Health Evidence Review Commission's Value-based Benefits Subcommittee
September 28, 2017 8:00 AM - 1:00 PM
Clackamas Community College Wilsonville Training Center, Room 111-112 29373 SW Town Center Loop E, Wilsonville, Oregon, 97070
Section 1.0 Call to Order AGENDA VALUE-BASED BENEFITS SUBCOMMITTEE September 28, 2017 8:00am - 1:00pm Wilsonville Training Center, Rooms 111-112 29353 SW Town Center Loop E Wilsonville, Oregon 97070 A working lunch will be served at approximately 12:00 PM All times are approximate
I. Call to Order, Roll Call, Approval of Minutes – Kevin Olson 8:00 AM
II. Staff report – Ariel Smits, Cat Livingston, Darren Coffman 8:05 AM A. Chronic Pain Task Force meeting report B. Errata C. Retreat
III. Straightforward/Consent agenda – Ariel Smits 8:15 AM A. Consent table B. Straightforward Modifications to the Prioritized List Changes: Continuous Glucose Monitoring in Diabetes Mellitus C. Straightforward changes to the PPI guideline for Barrett’s esophagus with dysplasia D. Tobacco cessation guideline clarification
IV. Advisory Panel reports 8:25 AM A. OHAP 1. 2018 CDT code placement recommendations
V. Previous discussion items 8:30 AM A. Consideration for prioritization on lines 500/660, Services with Minimal or No Clinical Benefit and/or Low Cost-Effectiveness 1. New medications for the treatment of Duchenne muscular dystrophy i. deflazacort (Emflaza) ii. etepliren (Exondys 51)
VI. New discussion items 9:30 AM A. Testicular prostheses B. Capsulorrhaphy for recurrent shoulder dislocation C. Transcutaneous neurostimulators D. Physical therapy for interstitial cystitis E. Acute peripheral nerve injuries F. SOI on role of Prioritized List in Coverage G. Graphs, flaps and pedicles
Health Evidence Review Commission (503) 373-1985 H. IT band syndrome
VII. Coverage guidances 11:30 AM A. Colon cancer screening modalities
VIII. Public comment 12:55 PM
IX. Adjournment – Kevin Olson 1:00 PM
Health Evidence Review Commission (503) 373-1985
Value-based Benefits Subcommittee Recommendations Summary For Presentation to: Health Evidence Review Commission on August 10, 2017
For specific coding recommendations and guideline wording, please see the text of the 08/10/2017 VbBS minutes.
RECOMMENDED CODE MOVEMENT (effective 10/1/2017 unless otherwise noted) • Various straightforward coding changes were made • Add limited coverage for lattice degeneration • Move the frenotomy procedure code from one uncovered line to another, more appropriate uncovered line • Add coverage for orthodontics for patients with craniofacial anomalies with a new guideline. Add additional facial and dental reconstruction procedures codes for these patients as well. [effective January 1, 2018] • Add the HCPCS code for counseling for alcohol misuse to the substance use disorder line • Psychological testing CPT codes were made diagnostic rather than included on the Prioritized List or Ancillary File • Re-add the HCPCS code for supported employment to the lines where it appeared on the October, 2016 Prioritized List and remove from the Ancillary File • Add the 2018 ICD-10 codes to various HSD files and lines on the Prioritized List • Delete the remaining CPT codes for sinus surgery from the acute sinusitis line • Move recurrent acute rhinosinusitis (RARS) from the acute sinusitis line to the chronic sinusitis line • Delete the procedure codes for insertion, maintenance and removal of intrathecal/epidural pumps from the central nervous system (CNS) cancer lines due to no longer being used for this indication • Delete the procedure codes for orthoptic and/or pleoptic training from all but 1 line with a coding specification limiting use to 3 diagnoses
RECOMMENDED GUIDELINE CHANGES (effective 10/1/2017 unless otherwise noted) • Add a new guideline regarding lattice degeneration, round holes, and retinal tears • Edit the frenulectomy guideline to add a CDT code • Edit the preventive dental guideline to delete reference to dental assessments and to add a CPT procedure code in place of a CDT code • Edit the silver diamine fluoride guideline to specify that this application is only covered for the treatment of caries, not for the prevention of caries • Add a new multisector intervention statement on the Prevention of Early Childhood Caries • Edit the acupuncture guideline to correct the line number for post-stroke depression and to soften the visit limits for this diagnosis • Edit the sinus surgery guideline note to clarify when recurrent acute rhinosinusitis and chronic sinusitis qualify for surgery
Value-based Benefits Subcommittee Summary Recommendations, 8/10/2017
• Add a new guideline clarifying coverage for insertion, maintenance and removal of intrathecal/epidural pump systems for medical delivery • Make extensive edits to the spine surgery guideline to improve readability and to clarify intent • Make extensive edits to the new guidelines on services with minimal or no clinical benefit and/or low cost-effectiveness; the previous Services Recommended for Non-Coverage entries were incorporated into these guidelines [effective January 1, 2018] • Edit the enzyme replacement therapy guideline to clarify which lines were referenced • Edit the continuous glucose monitoring guideline to broaden coverage to a larger group of patients with type 1 diabetes [effective January 1, 2018]
VALUE-BASED BENEFITS SUBCOMMITTEE Clackamas Community College Wilsonville Training Center, Rooms 111-112 Wilsonville, Oregon August 10, 2017 8:00 AM – 1:00 PM
Members Present: Kevin Olson, MD, Chair; David Pollack, MD; Susan Williams, MD (via phone); Mark Gibson; Holly Jo Hodges, MD; Gary Allen, DMD.
Members Absent: Vern Saboe, DC; Irene Croswell, RPh.
Staff Present: Darren Coffman; Ariel Smits, MD, MPH; Cat Livingston, MD, MPH; Denise Taray, RN; Daphne Peck (via phone).
Also Attending: Kim Wentz, MD, MPH and Bruce Austin, DMD (via phone)( OHA HSD); Judah Garfinkle, DDS (via phone); Andreas Lauer, MD (via phone) (OHSU); Laura Keller (American Diabetes Association); Carly Rodriguez and Jim Rickards, MD (MODA Health); Mike Donabedian and Lisa Borland (Sarepta Therapeutics); Jamie Saukko; Billy Ellsworth; Terri Ellsworth; Tomas Welken, MD and Elena Burns (Dexcom).
Roll Call/Minutes Approval/Staff Report
The meeting was called to order at 8:15 am and roll was called. Minutes from the May 18, 2017 VbBS meeting were reviewed and approved.
Smits reviewed the errata and there were no questions or concerns.
Coffman announced that Pollack is resigning from VbBS at the end of the year due to retirement. Pollack has been a member of HSC/HERC or one of their subcommittees since the inception of OHP legislation in 1989. He was thanked for his extensive service. Coffman also announced that Croswell’s term is completed at the end of the year and he is working with the pharmacy board to identify a new pharmacy member for VbBS.
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Topic: Straightforward/Consent Agenda
Discussion: There was no discussion about the consent agenda items.
Recommended Actions: 1) Add 44310 (Ileostomy or jejunostomy, non-tube) to line 220 CANCER OF STOMACH 2) Add 35251 (Repair blood vessel with vein graft; intra-abdominal) and 35281 (Repair blood vessel with graft other than vein; intra-abdominal) and 64680 (Destruction by neurolytic agent, with or without radiologic monitoring; celiac plexus) to line 321 CANCER OF PANCREAS 3) Add 38542 (Dissection, deep jugular node(s)) to line 280 CANCER OF SKIN, EXCLUDING MALIGNANT MELANOMA 4) Add 49255 (Omentectomy, epiploectomy, resection of omentum) to line 243 CANCER OF OVARY 5) Add 67840 (Excision of lesion of eyelid (except chalazion) without closure or with simple direct closure) to line 280 CANCER OF SKIN, EXCLUDING MALIGNANT MELANOMA 6) Add 92002-92014 (Ophthalmological services: medical examination and evaluation) and 92081-92083 (Visual field examination) to line 130 BENIGN NEOPLASM OF THE BRAIN AND SPINAL CORD 7) Add 65435 (Removal of corneal epithelium; with or without chemocauterization (abrasion, curettage)) and 65450 (Destruction of lesion of cornea by cryotherapy, photocoagulation or thermocauterization) to line 117 CANCER OF EYE AND ORBIT 8) Add 99356 and 99357 (Prolonged service in the inpatient or observation setting, requiring unit/floor time beyond the usual service) to all lines containing other prolonged E&M inpatient CPT codes (i.e., 99358 and 99359) on which 99356 and 99357 do not already appear 9) Add 99468-99480 (Initial/subsequent inpatient neonatal critical care) to line 152 ACQUIRED HEMOLYTIC ANEMIAS 10) Remove 49424 (Contrast injection for assessment of abscess or cyst via previously placed drainage catheter or tube) from lines 51,105,368,427,570,574 a. Advise HSD to place 49424 on the Diagnostic Procedures File 11) Add 13133 (Repair, complex, forehead, cheeks, chin, mouth, neck, axillae, genitalia, hands and/or feet; each additional 5 cm or less) and 99406 & 99407 (Smoking and tobacco use cessation counseling visit; intermediate) to line 1 PREGNANCY 12) Add 99460-99463 (Initial and subsequent hospital or birthing center care, per day, for evaluation and management) to lines 23 LOW BIRTH WEIGHT (1500-2500 GRAMS), 105 CONGENITAL ANOMALIES OF DIGESTIVE SYSTEM AND ABDOMINAL WALL EXCLUDING NECROSIS; CHRONIC INTESTINAL PSEUDO-OBSTRUCTION, and 146 CONDITIONS INVOLVING THE TEMPERATURE REGULATION OF NEWBORNS 13) Add 97530 (Therapeutic activities, direct (one-on-one) patient contact (use of dynamic activities to improve functional performance), each 15 minutes) to line 353 MILD/MODERATE BIRTH TRAUMA FOR BABY
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14) Add 31290 and 31291 (Nasal/sinus endoscopy, surgical, with repair of cerebrospinal fluid leak; ethmoid region/sphenoid region) to line 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT 15) Add 96150-96155 (Health and behavior assessment) to lines 111 GIANT CELL ARTERITIS, POLYMYALGIA RHEUMATICA AND KAWASAKI DISEASE and 210 SUPERFICIAL ABSCESSES AND CELLULITIS 16) Add 29075 (Application, cast; elbow to finger (short arm)) to line 467 OSTEOARTHRITIS AND ALLIED DISORDERS 17) Add 25230 (Radial styloidectomy) to line 361 RHEUMATOID ARTHRITIS, OSTEOARTHRITIS, OSTEOCHONDRITIS DISSECANS, AND ASEPTIC NECROSIS OF BONE 18) Add 28304 (Osteotomy, tarsal bones, other than calcaneus or talus) to line 530 DEFORMITIES OF UPPER BODY AND ALL LIMBS 19) Add 27033 (Arthrotomy, hip, including exploration or removal of loose or foreign body) and 29822 and 29823 (Arthroscopy, shoulder, surgical; debridement) to line 364 DEFORMITY/CLOSED DISLOCATION OF MAJOR JOINT AND RECURRENT JOINT DISLOCATIONS 20) Add 20610 and 26011 (Arthrocentesis, aspiration and/or injection, major joint or bursa (eg, shoulder, hip, knee, subacromial bursa) to line 361 RHEUMATOID ARTHRITIS, OSTEOARTHRITIS, OSTEOCHONDRITIS DISSECANS, AND ASEPTIC NECROSIS OF BONE 21) Add 21198 (Osteotomy, mandible, segmental) to line 561 BENIGN NEOPLASM OF BONE AND ARTICULAR CARTILAGE INCLUDING OSTEOID OSTEOMAS; BENIGN NEOPLASM OF CONNECTIVE AND OTHER SOFT TISSUE 22) Add M35.01 (Sicca syndrome with keratoconjunctivitis) to line 476 KERATOCONJUNCTIVITIS 23) Add 27360 (Partial excision (craterization, saucerization, or diaphysectomy) bone, femur, proximal tibia and/or fibula (eg, osteomyelitis or bone abscess)) and 27460 (Partial excision (craterization, saucerization, or diaphysectomy), bone (eg, osteomyelitis); tibia) to line 188 ACUTE OSTEOMYELITIS 24) Add 26910 (Amputation, metacarpal, with finger or thumb (ray amputation), single, with or without interosseous transfer) to line 136 OPEN FRACTURE/DISLOCATION OF EXTREMITIES 25) Add 26735 (Open treatment of phalangeal shaft fracture, proximal or middle phalanx, finger or thumb, includes internal fixation, when performed, each) and 27132 (Conversion of previous hip surgery to total hip arthroplasty, with or without autograft or allograft) and 27236 (Open treatment of femoral fracture, proximal end, neck, internal fixation or prosthetic replacement) to line 447 MALUNION AND NONUNION OF FRACTURE 26) Add 27254 (Open treatment of hip dislocation, traumatic, with acetabular wall and femoral head fracture, with or without internal or external fixation) and 27269 (Open treatment of femoral fracture, proximal end, head, includes internal fixation, when performed) to line 85 FRACTURE OF HIP 27) Add 27360 (Treatment of intertrochanteric, peritrochanteric, or subtrochanteric femoral fracture; with intramedullary implant, with or without interlocking screws and/or cerclage), 27570 (Manipulation of knee joint under general anesthesia (includes application of traction or other fixation devices)), 29882 (Arthroscopy, knee, surgical; with meniscus repair (medial OR lateral)), 27620 (Arthrotomy, ankle, with joint exploration, with or without biopsy, with or without removal of loose or foreign body) and 29899 (Arthroscopy, ankle (tibiotalar and
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fibulotalar joints), surgical; with ankle arthrodesis) to line 360 CLOSED FRACTURE OF EXTREMITIES (EXCEPT MINOR TOES) 28) Add 92978 (Endoluminal imaging of coronary vessel or graft using intravascular ultrasound (IVUS) or optical coherence tomography (OCT) during diagnostic evaluation and/or therapeutic intervention) and 92979 (each additional vessel) to line 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT 29) Add 34001-34203 (Embolectomy or thrombectomy, with or without catheter), 37220-37235 (Revascularization, endovascular, open or percutaneous, various arteries of the leg), 37236- 37237 (Transcatheter placement of an intravascular stent(s) (except lower extremity artery(s) for occlusive disease, cervical carotid, extracranial vertebral or intrathoracic carotid, intracranial, or coronary), open or percutaneous) and 37238-37239 (Transcatheter placement of an intravascular stent(s), open or percutaneous) to line 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT 30) Add L60.0 (Ingrowing nail) to line 588 DISEASE OF NAILS, HAIR AND HAIR FOLLICLES 31) Add line 64 METABOLIC DISORDERS to GN67 ENZYME REPLACEMENT THERAPY 32) Remove 26200 (Excision or curettage of bone cyst or benign tumor of metacarpal) from line 205 CANCER OF BONES 33) Add 92928-92929 (Percutaneous transcatheter placement of intracoronary stent(s), with coronary angioplasty when performed), 92933-92934 (Percutaneous transluminal coronary atherectomy, with intracoronary stent, with coronary angioplasty when performed), 92937- 92938 (Percutaneous transluminal revascularization of or through coronary artery bypass graft (internal mammary, free arterial, venous), any combination of intracoronary stent, atherectomy and angioplasty, including distal protection when performed) and 92943- 92944 (Percutaneous transluminal revascularization of chronic total occlusion, coronary artery, coronary artery branch, or coronary artery bypass graft, any combination of intracoronary stent, atherectomy and angioplasty) to line 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT 34) Add the following lower extremity amputation CPT codes to line 384 CHRONIC ULCER OF SKIN a. 27880-27886 Amputation, leg, through tibia and fibula; various techniques b. 27888 Amputation, ankle, through malleoli of tibia and fibula (eg, Syme, Pirogoff type procedures), with plastic closure and resection of nerves c. 28800 Amputation, foot; midtarsal (eg, Chopart type procedure) d. 28804 Amputation, foot; transmetatarsal e. 28805 Amputation, foot; transmetatarsal f. 28820 Amputation, toe; metatarsophalangeal joint g. 28825 Amputation, toe; interphalangeal joint 35) Add the following CPT codes to line 67 SPONTANEOUS ABORTION; MISSED ABORTION a. 59855 Induced abortion, by 1 or more vaginal suppositories (eg, prostaglandin) with or without cervical dilation (eg, laminaria), including hospital admission and visits, delivery of fetus and secundines; b. 59856 …with dilation and curettage and/or evacuation c. 59857 …with hysterotomy (failed medical evacuation)
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36) Add HCPCS code S0199 (Medically induced abortion by oral ingestion of medication including all associated services and supplies) to line 67 SPONTANEOUS ABORTION; MISSED ABORTION 37) Remove the following ICD-10 codes from the dysfunction lines (lines 75,297,350,382) and add to line 2 BIRTH OF INFANT: a. P39.3 Neonatal urinary tract infection b. P39.4 Neonatal skin infection c. P39.8 Other specified infections specific to the perinatal period d. P39.9 Infection specific to the perinatal period, unspecified i. Additionally, remove P39.9 from line 186 Septicemia 38) Add CPT 20650 (Insertion of wire or pin with application of skeletal traction, including removal), 27703 (Arthroplasty, ankle; revision, total ankle), 27704 (Removal of ankle implant), 27125 (Hemiarthroplasty, hip, partial (eg, femoral stem prosthesis, bipolar arthroplasty)), 27448 (Osteotomy, femur, shaft or supracondylar; without fixation), 27556 (Open treatment of knee dislocation, includes internal fixation, when performed; without primary ligamentous repair or augmentation/reconstruction), 27882 (Amputation, leg, through tibia and fibula; open, circular (guillotine)) and 29819 (Arthroscopy, shoulder, surgical; with removal of loose body or foreign body) to line 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT
MOTION: To approve the recommendations stated in the consent agenda. CARRIES 6-0.
Topic: Lattice degeneration
Discussion: Smits reviewed the summary document. Olson requested a definition for the term “young” in the proposed guideline. Lauer replied that “young” refers in this situation to when the vitreous is still attached to the retina, which varies by chronological age. The suggestion was made to restrict to persons under age 65. Gibson noted that the literature gave no evidence of a definition of young for lattice degeneration. There was discussion of not having an age limit, but Lauer felt that this would result in a significant increase in the number of patients who would qualify for treatment under the guideline, and recommended an age limit. Olson noted that a specific age would be easier to administer through the PA process. The group decided on younger than age 65 as an age limit and modified the proposed guideline.
Recommended Actions: 1) Add ICD-10 H35.41 (Lattice degeneration) to line 379 RETINAL TEAR and keep on line 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY 2) Adopt a new guideline for lines 379 and 658 as shown in Appendix A 3) Add unspecified retinal tears (ICD-10 H33.30) and round holes (ICD-10 H33.32) to line 658 and keep on line 379
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MOTION: To approve the code and guideline note changes as amended. CARRIES 6-0.
Topic: Oral Health Advisory Panel (OHAP) report
Discussion: Smits reviewed the OHAP minutes and the two topics with action items. There was no discussion about frenulectomy and minimal discussion on the orthodontics for craniofacial anomalies topic.
The early childhood caries multisector intervention was discussed after Livingston presented the draft box language on the Multisector Intervention Report on the Prevention of Early Childhood Caries. Wentz asked for clarification for some of the interventions listed in the “insufficient or conflicting evidence” category. Livingston clarified that it varied, some found negative or conflicting evidence but most were insufficient.
Pollack raised the point that Scandinavian countries have much lower rates of caries prevention than we do. Allen discussed that they generally have really aggressive school- based dental prevention work. There was a question about whether they used community water fluoridation and Allen clarified that they used topical fluoride and had comprehensive public health programs in the schools. Allen discussed that there are barriers for dental plans to work with the schools in Oregon. Anecdotally, when schools and DCOs are working together, there are excellent preliminary results. Austin also clarified that even when some European countries don’t have fluoridated water, they instead fluoridate salt or milk, leading to improved oral health compared to Oregon.
Livingston reviewed the coding suggestions, which involved removing a dental code for fluoride varnish on Line 3, the prevention line. Hodges queried whether there were problems with physical health providers using dental codes. The group agreed that while it appears that physical health providers can use dental codes, now that there is a code for physical health providers to use, keeping physical and dental codes and separate lines made sense, and it was not thought to provide a barrier to fluoride varnish coverage to have the physical health varnish codes on line 3 and the dental varnish codes on the preventive dental line, Line 57.
Wentz raised a concern about potential unintended consequences from taking out the risk assessment component of the guideline note. Allen clarified that risk assessment is being used as a measure of integration of oral health and physical health. Livingston addressed the changing recommendation by the USPSTF. Previously the recommendation was to apply fluoride varnish to only higher risk children but the most recent USPSTF recommendations recommend primary care clinicians apply fluoride varnish in all children from the first tooth eruption to age 5. Based on insufficient evidence of effectiveness of risk assessment, the non-relationship with fluoride varnish application and current non-payment, the group was comfortable with removal of the language around risk assessment in the guideline note.
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Livingston discussed a potential modification to the guideline note on silver diamine fluoride to clarify its inclusion for treatment of caries rather than for prevention. Allen clarified that silver diamine fluoride will not cause permanent staining of intact enamel and that advocates that use this would apply it to noncaries areas. Allen agreed with the assessment of insufficient evidence for the use of silver diamine fluoride for prevention of caries, and thought the assessment of insufficient evidence was appropriate. Wentz asked if there was mercury in silver diamine fluoride and Allen confirmed mercury is not present. Allen stated he thought the multisector intervention report appropriately reflected the evidence.
There was discussion about possible changes to guideline note 91 about silver diamine fluoride. Coffman clarified that this guideline modification reaffirms what was previously decided. Allen confirmed it does not further limit use; it is just a helpful clarification.
Allen commended the staff for the work done, and expressed appreciation of the evidence review for the Multisector Intervention Report for the Prevention of Early Childhood Caries.
The VbBS decided to accept the staff suggested modifications for GN 17 and to also accept the staff suggested modifications to GN91.
Recommended Actions: Effective October 1, 2017 1) Remove CPT 40806 (Incision of labial frenum (frenotomy)) from line 599 TONGUE TIE AND OTHER ANOMALIES OF TONGUE and add to line 665 MISCELLANEOUS CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY 2) Add D7960 (FRENULECTOMY - ALSO KNOWN AS FRENECTOMY OR FRENOTOMY - SEPARATE PROCEDURE NOT INCIDENTAL TO ANOTHER PROCEDURE) to line 19FEEDING PROBLEMS IN NEWBORNS 3) Modify GN 139 as shown in Appendix B 4) Modify GN 17 as shown in Appendix B 5) Modify GN 91 as shown in Appendix B 6) Add a Multisector Intervention Statement: Prevention of Early Childhood Caries as shown in Appendix D
Effective January 1, 2018 1) Add CPT 21110 (Application of interdental fixation device for conditions other than fracture or dislocation, includes removal) to line 305 CLEFT PALATE AND/OR CLEFT LIP 2) Add ICD-10 Q67.4 (Other congenital deformities of skull, face and jaw) and Q74.0 (Other congenital malformations of upper limb(s), including shoulder girdle) to line 261 DEFORMITIES OF HEAD 3) Add orthodontic and craniofacial surgery CDT codes (D7111, D7140, D7210, D7220, D7230, D7240, D7280, D7283, D7940, D7941, D7943- D7953, D7955, D8010, D8020, D8030, D8040, D8050, D8060, D8070, D8080, D8090, D8210, D8220, D8660, D8670, D8680, D8681, D8690-D8694) to line 261 DEFORMITIES OF HEAD
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4) Add craniofacial surgery CPT codes (21110, 21120-21123, 21193-21199, 21206, 21210, 21215) to line 261 DEFORMITIES OF HEAD 5) Add advanced imaging CDT (D0364-D0367) codes to line 261 DEFORMITIES OF HEAD 6) Adopt a new guideline note for line 261 as shown in Appendix A
MOTION: To recommend the code and guideline note changes as presented. CARRIES 6-0.
Topic: Behavioral Health Advisory Panel (BHAP) report
Discussion: Smits reviewed the BHAP minutes and the summarized action items. She discussed the BHAP recommendation to add buprenorphine implants to line 500/660, which she noted that staff is working with P&T staff and OHA leadership to determine the best strategy for dealing with this topic. Livingston summarized the discussion regarding MAT for substance rehabilitation programs; she is working with local workgroups to fine- tune proposed guideline language to bring back to a future VbBS meeting.
Smits reviewed the supported employment topic and there was no discussion.
Recommended Actions: 1) Add HCPCS G0443 (Brief face-to-face behavioral counseling for alcohol misuse, 15 minutes) to line 4 SUBSTANCE USE DISORDER 2) Change line 442 title to STEREOTYPY/HABIT DISORDER AND SELF-ABUSIVE BEHAVIOR DUE TO NEUROLOGICAL DYSFUNCTION STEREOTYPED MOVEMENT DISORDER WITH SELF-INJURIOUS BEHAVIOR DUE TO NEURODEVELOPMENTAL DISORDER 3) Remove CPT 96101 (Psychological testing (includes psychodiagnostic assessment of emotionality, intellectual abilities, personality and psychopathology, eg, MMPI, Rorschach, WAIS), per hour of the psychologist's or physician's time, both face-to-face time administering tests to the patient and time interpreting these test results and preparing the report) from all lines on the Prioritized List a. Advise HSD to place CPT 96101 on the Diagnostic Work Up File 4) Advise HSD to move CPT 96102 (Psychological testing (includes psychodiagnostic assessment of emotionality, intellectual abilities, personality and psychopathology, eg, MMPI and WAIS), with qualified health care professional interpretation and report, administered by technician, per hour of technician time, face-to-face) and CPT 96103 (Psychological testing (includes psychodiagnostic assessment of emotionality, intellectual abilities, personality and psychopathology, eg, MMPI), administered by a computer, with qualified health care professional interpretation and report) from the Ancillary File to the Diagnostic Work Up File 5) Modify GN92 as shown in Appendix B
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6) Add HCPCS H2023 (Supported employment, per 15 minutes) to the lines where it appeared on the October, 2016 Prioritized List and advise HSD to remove H2023 from the Ancillary File
MOTION: To recommend the code and guideline note changes as presented. CARRIES 6-0.
Topic: 2018 ICD-10 code placement
Discussion: Smits reviewed the consent ICD-10 placement spreadsheet which had previously been sent to members. No codes were pulled out for further review. The only ICD-10 code from the group included in the issues document pulled out for further discussion was Z40.03 (Encounter for prophylactic removal of fallopian tube(s)). There was discussion about putting this code on the Informational File until the coverage guidance on this topic was reviewed. The final decision was to add it to line 195 CANCER OF BREAST; AT HIGH RISK OF BREAST CANCER.
Recommended Actions: 1) The 2018 ICD-10 codes were placed as shown in the spreadsheet in Appendix C. 2) The following coding specification was added to line 386, deleted from line 153, and kept on line 635 in the modified form shown below: a. “ICD-10 F50.89 is included on Line 153 for avoidant/ restrictive food intake disorder and on Line 386 for psychogenic loss of appetite. ICD-10 F50.89 is included on Line 635 for pica in adults and for all other diagnoses using this code.”
MOTION: To recommend the code placements as presented. CARRIES 6-0.
Topic: Recurrent acute sinusitis treatment
Discussion: Smits reviewed the summary document. Hodges requested that the modified sinus surgery guideline contain a definition for chronic sinusitis. Chronic sinusitis is defined as “twelve weeks or longer of 2 or more signs and symptoms with documented inflammation based on imaging or direct visualization.” Similar wording was incorporated into the modified guideline note. There was discussion about the prioritization of recurrent acute sinusitis (RARS). The final decision was to place RARS on the chronic sinusitis line to pair with surgeries. This decision was largely based on the fact that, while the evidence of effectiveness is limited, this service has been provided for a long period of time and removing surgery for this condition would require evidence of ineffectiveness. Additionally, while the quality of evidence is low, the evidence is positive/demonstrates benefit.
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The VbBS requested that chronic, acute and recurrent acute sinusitis be placed on the list of topics for the 2020 Biennial Review. Recommended Actions: 1) Remove CPT 31256 (Nasal/sinus endoscopy, surgical, with maxillary antrostomy) from line 369 ACUTE SINUSITIS 2) Remove the following CPT codes from line 369 ACUTE SINUSITIS a. 31020 Sinusotomy, maxillary (antrotomy); intranasal b. 31030 Sinusotomy, maxillary (antrotomy); radical (Caldwell-Luc) without removal of antrochoanal polyps c. 31032 Sinusotomy, maxillary (antrotomy); radical (Caldwell-Luc) with removal of antrochoanal polyps d. 31040 Pterygomaxillary fossa surgery, any approach e. 31050 Sinusotomy, sphenoid, with or without biopsy; f. 31051 Sinusotomy, sphenoid, with or without biopsy; with mucosal stripping or removal of polyp(s) g. 31070-31087 Sinusotomy frontal h. 61782 Stereotactic computer-assisted (navigational) procedure; cranial, extradural (List separately in addition to code for primary procedure) 3) Change the treatment description for line 369 to MEDICAL AND SURGICAL TREATMENT 4) Remove the following recurrent acute rhinosinusitis diagnosis codes from line 369 ACUTE SINUSITIS and add to line 469 CHRONIC SINUSITIS a. J01.01 Acute recurrent maxillary sinusitis b. J01.11 Acute recurrent frontal sinusitis c. J01.21 Acute recurrent ethmoidal sinusitis d. J01.31 Acute recurrent sphenoidal sinusitis e. J01.41 Acute recurrent pansinusitis f. J01.81 Other acute recurrent sinusitis g. J01.91 Acute recurrent sinusitis, unspecified 5) Change line title of line 469 to RECURRENT ACUTE RHINOSINUSITIS; CHRONIC SINUSITIS 6) Modify GN35 as shown in Appendix B a. Staff was given permission to add other lines to GN35 as needed for the diagnoses included in sections C-G Upon further review, these lines were determined to be i. 292 CANCER OF ORAL CAVITY, PHARYNX, NOSE AND LARYNX ii. 509 NASAL POLYPS, OTHER DISORDERS OF NASAL CAVITY AND SINUSES
MOTION: To recommend the code and guideline note changes as amended. CARRIES 6-0.
Topic: Physical therapy for interstitial cystitis
Tabled until September, 2017 VbBS meeting
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Topic: Intrathecal/epidural pumps
Discussion: Smits reviewed the summary document. There was discussion about whether a patient receiving oral opioids in addition to opioids through a pump qualified as “continuing to receive adequate benefit” from the pump to qualify for maintenance services. Hodges felt that receiving oral opioids indicated inadequate pain control from the pump. The group decided to leave this decision up to the individual case reviews.
There was discussion about whether broken pumps should be replaced for patients who were receiving good benefit from them for non-covered indications such as low back pain. The decision was that the evidence finds increased harms from the pumps vs. other types of therapy for chronic pain conditions and, therefore, replacement should not be covered.
Olson noted that current oncology therapy does not include administration of chemotherapy for central nervous system (CNS) malignancies via implanted pumps. This indication was removed from the proposed guideline and the CPT codes will be taken off the CNS cancer lines. There was discussion about adding the codes to all the cancer lines for the palliative indication. The decision was that this therapy would be covered as an exception or under the palliative care SOI and did not need to be on every cancer line.
Specific edits were discussed for the proposed new guideline note. The VbBS felt that when the pumps are used for palliation of pain due to active, life-shortening cancer, there should not be a restriction based on the amount of pain relief. The restriction that the patient needed “at least a 50% reduction in pain relief” in cancer palliation was changed to “The patient has a favorable response to a trial intrathecal dosage of the analgesic drug prior to pump implantation.” This was due to the need for compassionate care of this group of patients.
For maintenance of pumps, the VbBS added wording that the pump itself as well as the administered medications needed to have no complications in order to allow continued usage. Also, the patient needed to exhibit they were “continuing to receive adequate benefit from the pump-delivered medication” rather than needing to be “receiving significant benefit in posture, function, or ability to perform ADLs.” This wording would be more consistent with chronic pain indications. The VbBS intends that pumps that are performing well and which are providing patients with adequate benefit should be maintained (e.g. medications refills, electronic analysis) regardless of the initial diagnosis for insertion. However, insertion of new pumps and pump replacements will only be covered for spasticity and palliation for life-shortening, active cancer pain.
Recommended Actions: 1) Remove the following CPT codes from line 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT. Only allow maintenance and removal of such pumps on this line.
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a. 62350 Implantation, revision or repositioning of tunneled intrathecal or epidural catheter, for long-term medication administration via an external pump or implantable reservoir/infusion pump; without laminectomy b. 62351 …with laminectomy c. 62360 Implantation or replacement of device for intrathecal or epidural drug infusion; subcutaneous reservoir d. 62361 …nonprogrammable pump e. 62362 …programmable pump, including preparation of pump, with or without programming 2) Add ICD-10 Z45.49 (Encounter for adjustment and management of other implanted nervous system device) to lines 75,97,130,239,242,290,299,402,403,495 3) Add CPT 62350-62351, 62360-62362 to line 297 NEUROLOGICAL DYSFUNCTION IN POSTURE AND MOVEMENT CAUSED BY CHRONIC CONDITIONS 4) Add CPT 62320-62323 (Injection(s), of diagnostic or therapeutic substance(s) (eg, anesthetic, antispasmodic, opioid, steroid, other solution), not including neurolytic substances, including needle or catheter placement, interlaminar epidural or subarachnoid) to line 495 SPASTIC DIPLEGIA 5) Remove CPT 62350-62370 (Implantation, revision or repositioning or maintenance or removal of tunneled intrathecal or epidural catheter, for long-term medication administration via an external pump or implantable reservoir/infusion pump) from lines a. 97 CHILDHOOD LEUKEMIAS b. 130 BENIGN NEOPLASM OF THE BRAIN AND SPINAL CORD c. 239 ACUTE LYMPHOCYTIC LEUKEMIAS (ADULT) AND MULTIPLE MYELOMA d. 242 ACUTE PROMYELOCYTIC LEUKEMIA e. 299 CANCER OF BRAIN AND NERVOUS SYSTEM f. 402 ACUTE MYELOID LEUKEMIA g. 403 MYELOID DISORDERS 1) Adopt a new guideline as shown in Appendix A 2) Add an entry to GN169 regarding intrathecal or epidural drug infusion device insertion or replacement or revision for chronic non-malignant pain or any indication other than spasticity, pain due to active life-limiting malignancy, or treatment of active CNS malignancy as shown in Appendix B
MOTION: To recommend the code and guideline note changes as amended. CARRIES 6-0.
Topic: Acute peripheral nerve injuries
Tabled until September, 2017 VbBS meeting
Topic: Testicular prostheses
Tabled until September, 2017 VbBS meeting
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Topic: Capsulorrhaphy for recurrent shoulder dislocation
Tabled until September, 2017 VbBS meeting
Topic: Transcutaneous neurostimulators
Tabled until September, 2017 VbBS meeting
Topic: State of Intent 1 Palliative Care revisions
Discussion: Discussed at HERC.
Recommended Actions: 1) See HERC 8/10/17 minutes
Topic: Vision training
Discussion: Smits reviewed the evidence summary. There was no discussion as the recommendation actions corresponding limiting the treatment to those conditions previously found by the Health Services Commission to result in benefit.
Recommended Actions: 1) Remove CPT 92065 (Orthoptic and/or pleoptic training, with continuing medical direction and evaluation) from lines 356 STRABISMUS DUE TO NEUROLOGIC DISORDER and 375 AMBLYOPIA 2) Add a new coding specification to line 399 STRABISMUS WITHOUT AMBLYOPIA AND OTHER DISORDERS OF BINOCULAR EYE MOVEMENTS; CONGENITAL ANOMALIES OF EYE; LACRIMAL DUCT OBSTRUCTION IN CHILDREN a. “CPT 92065 is included on line 399 only for pairing with ICD-10 H50.31 (Intermittent monocular esotropia), H50.32 (Intermittent alternating esotropia), and H50.33 (Intermittent alternating exotropia).”
MOTION: To recommend the code and coding specification changes as presented. CARRIES 6-0.
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Topic: Back surgery guideline
Discussion: Smits reviewed the summary document, which contains a significantly edited back surgery guideline based on extensive feedback from CCO medical directors, back surgeons, CCO benefit reviewers and other stakeholders. Smits noted that the OHSU spine surgery group requested consideration of 3 mm of translation rather than 5 mm as the definition of spondylolisthesis. However, the VbBS elected to stay with the 5 mm definition.
Recommended Actions: 1) Add the following radiculopathy ICD-10 codes to line 351 CONDITIONS OF THE BACK AND SPINE WITH URGENT SURGICAL INDICATIONS . M47.2 Other spondylosis with radiculopathy . M50.1 Cervical disc disorder with radiculopathy . M51.1 Intervertebral disc disorders with radiculopathy, thoracic, lumbar or sacral . M54.1 Radiculopathy 2) Modify GN 37 as shown in Appendix B
MOTION: To recommend the guideline note changes as presented. CARRIES 6-0.
Note: HERC staff made grammatical edits to GN37 after the meeting to clarify the intent. This additional wording is indicated in purple in Appendix B.
Topic: Guidelines for treatments with marginal or no clinical benefit/low cost- effectiveness
Discussion: Smits introduced the summary regarding the addition of previous Services Recommended for Non-Coverage (SRNC) entries to GN168 and GN169. There was minimal discussion; there were comments about how moving the previous SNRC entries to the guidelines will make them far more visible and useful to stakeholders. Staff noted that they will look through minutes of other meetings in 2017 and capture any other entries that were approved. It was noted that GN67 also needs modification based on staff review, to clarify where enzyme replacement therapy is prioritized. There was no discussion of this.
Smits introduced the summary regarding the staff proposal about how to incorporate medications of low importance into lines 500/660 and GN168/GN169. VbBS members asked about the timeline for bringing new drug to HERC for consideration for prioritization on one of these lines. Coffman replied that there would be a delay between when a new drug is released and when the HERC considered it for one of these lines, based on the P&T review/meeting schedule, and the need for the OHA Director to approve any P&T recommendation for the HERC to consider a drug for one of these lines.
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There was discussion regarding what additional input VbBS felt that it needed when considering drugs for lines 500/660. Williams wondered if the VbBS pharmacy member could be also a member of P&T. Coffman replied that this was not possible, as the VbBS/HERC pharmacist was required to be a retail pharmacist, appointed by the Governor and approved by the Senate. However, the P&T has indicated their openness to having members present at HERC/VBBS meetings. VbBS members felt this would be helpful. Additionally, Kim Wentz brought up that she also staffs P&T and can be a resource, and reviews P&T recommendations prior to OHA Director approval. VbBS members requested that HERC staff prepare a summary for any medication brought to the subcommittee, including a summary of the disease, its natural history, other available/standard treatments, and any other information staff feels would be helpful. Wentz pointed out that much of this information is already included in the P&T review. There was discussion about inviting disease experts to the meeting to provide expert testimony/answer questions.
Public comment: • Lisa Borland: with Serepta therapeutics. Ms. Borland indicated that she was attending the meeting to answer any questions about Exondys 51. Exondys 51 was approved by FDA for a very specific subset of patients with Duchenne muscular dystrophy (DMD) (13%, representing about 1,000 patients across the US). Exondys 51 gained approval through the accelerated approval pathway to allow medications to come out for rare conditions. There were no subcommittee questions. • Jamie Saukko: on behalf of son with DMD from Eugene. His son desperately in need of Exondys 51. DMD is a fatal diagnosis with no treatment other than Exondys 51. His condition is deteriorating daily and needs to be on this medication before further damage is done. This drug with help his son and others produce dystrophin, as clinical trials showed improvement in dystrophin level. It will not change the eventual end, but will improve function for some time. He thinks the medication should be covered, regardless of age and ability to walk. Everyone who qualifies should have access to this drug. • Jim Rickards, MD from MODA Health: Dr. Rickards stated that the role of the HERC in reviewing medical evidence of effectiveness of medications of marginal or no clinical benefit is important. Paying for these high cost drugs reduces ability to fund other things. He reviewed lack of clinical efficacy for Exondys 51. As a steward of Medicaid dollars, MODA recommends the HERC review these drugs and place on appropriate lines. • Billy Ellsworth: Billy is a patient with DMD from Pittsburg. He has been receiving Exondys 51 since 2011, and feels it has helped maintain his strength and ability to walk and be independent. He is sad at thought of not getting this drug and losing his independence. He sees other boys with DMD who are much worse that he is. He feels the drug is effective and helps him continue to walk. He asked that HERC please support coverage of this drug.
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• Terri Ellsworth (mother of Billy): Billy is 16 ½ and has been receiving this drug for 6 yrs. Their family flew across country to testify because of their strong feeling that the drug is effective. Ms. Ellsworth testified about what other parents go through caring for their sons with DMD. Billy can do most ADLs himself. Ms. Ellsworth does not feel that Billy is an outlier. Prior to starting Exondys 51 he was an extreme toe walker, a sign of the end of the ability to ambulate. He is now able to walk, with improved toe walking. A little dystrophin is better than no dystrophin for clinical impact. She feels this drug has a significant impact on patients and families. This is a rare disease and all drugs for rare diseases are expensive. This drug is FDA approved. Medicaid did approve Exondys 51 in Oregon. She requested that DMD experts be sought out for future discussions.
Recommended Actions: 1) Adopt the changes to GN67, GN168 and GN169 as shown in Appendix B 2) HERC staff will continue to work with P&T and OHA leadership on the topic of drugs of low clinical benefit and/or low cost-effectiveness and bring back Exondys 51 and deflazacort to discuss further at the September VbBS meeting.
MOTION: To recommend the guideline note changes as presented. CARRIES 6-0.
Topic: Coverage Guidance—Continuous glucose monitoring (CGM)
Discussion: Obley reviewed the evidence document. There was discussion about the evidence being weak, and mainly for non-critical outcomes. There was concern of the use of intermediate outcomes, such as hemoglobin A1c changes, in the literature.
There was discussion about the fact that pregnant women typically have a diagnosis code in the O series, even if they have another diagnosis such as type 1 diabetes. Coffman noted that there is an O code for preexisting type 1 DM in pregnancy [O24.01 series] and this was proposed for addition to line 8 TYPE 1 DIABETES MELLITUS.
There was discussion about the increased cost of CGM vs traditional finger stick monitoring; CGM was acknowledged to be higher cost. There was discussion about whether these higher costs were justified. Additionally, there was discussion about whether patients should have CGM therapy for life or just long enough to learn how to detect hypoglycemia. Obley commented about the expert testimony heard at HTAS on neurocognitive damage in kids with even modest hypoglycemia; therefore, it was important to have long-term use. There was discussion about how children and pregnant women (or their fetuses) were at higher risk for long-term sequelae from hypoglycemia and therefore CGM was more justified than in non-pregnant adults.
There was discussion about how the evidence is similar for type 1 and type 2 diabetes, but the proposal is to cover CGM only for type 1 diabetes. Shaffer noted that the expert
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testimony heard at HTAS was to cover type 1 diabetic patients, but not type 2 due to the smaller evidence base for the type 2 population. It was noted that studies are underway in the type 2 population and therefore the evidence base may become more robust in the near future.
Public comment: • Laura Keller with the American Diabetes Association: Children do not have a lot of studies on them, so data is not as robust. The ADA believes the significance of the drop in HbA1c would be greater if the trials were longer. Kids need blood sugar in a certain range to learn in school and test well. Adults need blood sugar at certain levels to perform well and some jobs do not allow finger testing. Pregnant women with CBGs out of range can cause fetal damage. She supported the guidelines as written. She also acknowledges lack of evidence for type 2 patients on insulin. There are studies in progress that might give better data in this population in the next few years. • Tomas Welken, MD, senior medical director with Dexcom: CMS criteria do not differentiate between type 1 and type 2 on insulin. The criteria is listed as: Diabetic, on 3 or more insulin injections a day, testing blood sugar 4 or more times per day.
Recommended Actions: 1) Add O24.01 (Pre-existing type 1 diabetes mellitus, in pregnancy) to line 8 TYPE 1 DIABETES MELLITUS 2) Revise Guideline Note 108 as shown in Appendix B 3) Add an entry to GN168 regarding retrospective (professional) continuous glucose monitoring with the CPT codes 95250-95251 o Note: subsequent input from stakeholders and OHA staff indicated that this was not the correct CPT code series for this service. HERC staff will work with stakeholders to revise this recommendation and bring back as an issue for the September, 2017 VbBS meeting.
MOTION: To approve the recommended changes to the Prioritized List based on the draft Continuous Glucose Monitoring in Diabetes Mellitus coverage guidance scheduled for review by HERC at their August 10, 2017 meeting. CARRIES 6-0.
Public Comment:
No additional public comment was received.
Issues for next meeting: • Physical therapy for interstitial cystitis • Acute peripheral nerve injuries • Testicular prostheses
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• Capsulorrhaphy for recurrent shoulder dislocation • Transcutaneous neurostimulators • Medications for consideration for line 500/660, services with minimal or no clinical benefit and/or low cost-effectiveness
Next meeting:
September 28, 2017 at Clackamas Community College, Wilsonville Training Center, Wilsonville, Oregon, Rooms 111-112.
Adjournment:
The meeting adjourned at 1:30 PM.
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Appendix A New Guideline Notes
Effective October 1, 2017
GUIDELINE NOTE XXX LATTICE DEGENERATION, ASYMPTOMATIC RETINAL BREAKS AND ROUND HOLES Lines 379,658 Lattice degeneration is included on line 379 only for pairing with ophthalmologic visits and dilated eye exams, and only for patients at high risk of retinal detachment: A) Patients under the age of 65 years with round holes and myopic vision B) Patients with a history of retinal detachment in the other eye C) Patients with biologic family member with history of retinal tear or retinal detachment Otherwise, lattice degeneration is included on line 658.
Retinal breaks and round holes are only included for pairing with treatment (other than ophthalmologic visits and dilated eye exams) on line 379 when they are symptomatic, the result of trauma, or are horseshoe breaks. Otherwise, these diagnoses are included on line 658.
GUIDELINE NOTE XXX INTRATHECAL OR EPIDURAL DRUG INFUSION Lines 75,290,297,495
Implantation, revision and replacement of devices for intrathecal or epidural drug infusion systems is only included on these lines when the patient meets the criteria for at least one of the categories (A or B) below: A) Placed for administration of baclofen for spasticity where all of the following (1-3) occur: 1) The patient has had an adequate trial of non-invasive methods of spasticity control and not had adequate control of spasticity or had intolerable side effects with these methods. 2) The spasticity is causing difficulties with at least one of the following (a, b or c): a) Posture or function b) Balance or locomotion c) Self-care (or ease of care by parents or caregivers) 3) The patient has a favorable response to a trial intrathecal dosage of the anti- spasmodic drug prior to pump implantation. B) Palliation for severe, intractable pain due to life-limiting active cancer which 1) Has not been responsive to non-invasive systemic pain control strategies or had intolerable side effects from such strategies AND 2) Where the patient has a favorable response to a trial of an intrathecal dose of the analgesic drug prior to pump implantation.
Intrathecal or epidural drug infusion pump insertion, revision, and replacement are not included on these lines for use with chronic non-malignant pain and all other indications not listed above. Removal of pumps placed for such indications is included on Line 290.
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix A A-1 Appendix A New Guideline Notes
Maintenance (i.e. reprogramming, medication refill) of epidural or intrathecal medication infusion pumps for any condition is only included on these lines for patients who A) Have no significant complications with the current medication regimen or pump delivery system AND B) Are continuing to receive adequate benefit from the pump-delivered medication.
Maintenance (but not replacement) of these infusion systems may be paired with ICD-10-CM Z45.49 (Encounter for adjustment and management of other implanted nervous system device).
Effective January 1, 2018
GUIDELINE NOTE XXX ORTHODONTICS AND CRANIOFACIAL SURGERY FOR CRANIOFACIAL ANOMALIES Line 261 Orthodontics and craniofacial surgery are included on this line only for pairing with craniofacial anomaly diagnoses when there is significant malocclusion expected to result in difficulty with mastication, speech, or other oral function. Advanced dental imaging is included on this line only when required for surgical planning for repair of craniofacial anomalies.
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix A A-2 Appendix B Modified Guideline Notes
Effective October 1, 2017
GUIDELINE NOTE 17, PREVENTIVE DENTAL CARE Lines 3,57 Dental cleaning is limited to once per 12 months for adults and twice per 12 months for children up to age 19 (D1110, D1120). More frequent dental cleanings may be required for certain higher risk populations. Additionally, assessment (D0191) may be performed once per 12 months for adults and twice per 12 months for children up to age 19.
Fluoride varnish (D1206,99188) is included on Line 3 for use with children 18 and younger during well child preventive care visits. Fluoride treatments (D1206 and D1208) are included on Line 57 PREVENTIVE DENTAL SERVICES for use with adults and children during dental visits. The total number of fluoride applications provided in all settings is not to exceed four per twelve months for a child at high risk for dental caries and two per twelve months for a child not at high risk. The number of fluoride treatments is limited to once per 12 months for average risk adults and up to four times per 12 months for high risk adults.
GUIDELINE NOTE 35, SINUS SURGERY Lines 369292,469,509 Sinus surgery (other than adenoidectomy) is indicated in when at least one of the following circumstances: occur (A-G): A) Recurrent acute rhinosinusitis, defined as 4 or more episodes of acute bacterial rhinosinusitis in one year OR B) Failure of without signs or symptoms of rhinosinusitis between episodes and have failed optimal medical management defined as nasal steroid therapy of and nasal saline therapy, in patients who are compliant with oral antibiotics and/or oral corticosteroids for management of acute episodes of rhinosinusitis OR C) Chronic sinusitis including alldefined as 12 weeks of continuous symptoms without improvement with one of the following: (1-3): • Several courses of antibiotics AND • Trial of inhaled and/or oral steroids AND • Allergy assessment and treatment when indicated
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AND
• One or more of the following: 1) Findings of obstruction of active infection on CT scan OR 2) Symptomatic mucocele OR 3) Negative CT scan but significant disease found on nasal endoscopy
AND
Failure of medical therapy defined as (1-2) 1) Two or more courses of antibiotics with adequate doses AND 2) Trial of inhaled and/or oral steroids (2 or more courses of adequate doses of one or both) OR D) Nasal polyposis causing or contributing to sinusitis OR E) Complications of sinusitis including subperiosteal or orbital abscess, Pott’s puffy tumor, brain abscess or meningitis OR F) Invasive or allergic fungal sinusitis OR G) Tumor of nasal cavity or sinuses OR H) CSF rhinorrhea
Adenoidectomy (CPT 42830, 42835) is included on Line 469 only for treatment of children with chronic sinusitis who fail appropriate medical therapy.
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-2 Appendix B Modified Guideline Notes
GUIDELINE NOTE 37, SURGICAL INTERVENTIONS FOR CONDITIONS OF THE BACK AND SPINE OTHER THAN SCOLIOSIS Lines 351,532 Spondylolisthesis (ICD-10-CM M43.1, Q76.2) is included on Line 351 only when it results in spinal stenosis with signs and symptoms of neurogenic claudication. Otherwise, these diagnoses are included on Line 532. Decompression and fusion surgeries are both included on these lines for spondylolisthesis.
Surgical correction of spinal stenosis (ICD-10-CM M48.0) is only included on Line 351 for patients with: Spine surgery is included on Line 351 only in the following circumstances: A) Decompressive surgery to treat debilitating symptoms due to central or foraminal spinal stenosis, and only when the patient meets the following criteria (1 and either 2 or 3): 1) Has MRI evidence of moderate toor severe central or foraminal spinal stenosis AND 2) A history ofHas neurogenic claudication, or OR 2)3) Has objective evidence of neurologic impairment consistent with the MRI findings. Neurologic impairment is defined as objective evidence of one or more of the following: a) Markedly abnormal reflexes b) Segmental muscle weakness c) Segmental sensory loss d) EMG or NCV evidence of nerve root impingement e) Cauda equina syndrome f) Neurogenic bowel or bladder g) Long tract abnormalities Otherwise, these diagnoses are included on Line 532. Only decompression surgery is included on these lines for Foraminal or central spinal stenosis; spinal causing only radiating pain (e.g. radiculopathic pain) is included only on Line 532.
B) Spinal fusion procedures are not included on either lineLine 351 for patients with MRI evidence of moderate or severe central spinal stenosis unless:only when one of the following conditions are met: 1) Spinal stenosis is in the cervical spine OR (with or without spondylolisthesis is present) which results in objective neurologic impairment as defined above OR
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-3 Appendix B Modified Guideline Notes
2) there is sSpinal stenosis in the thoracic or lumbar spine caused by spondylolisthesis resulting in signs and symptoms of neurogenic claudication and which correlate with xray flexion/extension films showing at least a 5 mm translation OR 3) Pre-existing or expected post-surgical spinal instability (e.g. degenerative scoliosis >10 deg, >50% of foraminalfacet joints per level expected to be resected.)
For all other indications, spine surgery is included on Line 532.
GUIDELINE NOTE 67, ENZYME REPLACEMENT THERAPY Lines 151147,656660 Enzyme replacement therapy for infantile Pompe’s disease is included on Line 151147. All other enzyme replacement therapies are included on Line 656660.
GUIDELINE NOTE 91, CARIES ARRESTING MEDICAMENT APPLICATION Line 348 D1354 is limited to silver diamine fluoride applications for the treatment (rather than prevention) of caries, with a maximum of two applications per year.
GUIDELINE NOTE 92, ACUPUNCTURE Lines 1,5,206,208,366,407,415,467,543 Inclusion of acupuncture (CPT 97810-97814) on the Prioritized List has the following limitations:
Line 1 PREGNANCY Acupuncture pairs on Line 1 for the following conditions and codes. Hyperemesis gravidarum ICD-10-CM: O21.0, O21.1 Acupuncture pairs with hyperemesis gravidarum when a diagnosis is made by the maternity care provider and referred for acupuncture treatment for up to 12 sessions of acupressure/acupuncture per pregnancy.
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-4 Appendix B Modified Guideline Notes
Breech presentation ICD-10-CM: O32.1 Acupuncture (and moxibustion) is paired with breech presentation when a referral with a diagnosis of breech presentation is made by the maternity care provider, the patient is between 33 and 38 weeks gestation, for up to 6 session per pregnancy. Back and pelvic pain of pregnancy ICD-10-CM: O99.89 Acupuncture is paired with back and pelvic pain of pregnancy when referred by maternity care provider/primary care provider for up to 12 sessions per pregnancy. Line 5 TOBACCO DEPENDENCE Acupuncture is included on this line for a maximum of 12 sessions per quit attempt up to two quit attempts per year; additional sessions may be authorized if medically appropriate. Line 208 DEPRESSION AND OTHER MOOD DISORDERS, MILD OR MODERATE 206 CHRONIC ORGANIC MENTAL DISORDERS INCLUDING DEMENTIAS Acupuncture is paired with the treatment of post-stroke depression only. Treatments may be billed to a maximum of 30 minutes face-to-face time and limited to 12 total sessions per year, with documentation of meaningful improvement; patients may have additional visits authorized beyond these limits if medically appropriate. Line 366 SCOLIOSIS Acupuncture is included on this line with visit limitations as in Guideline Note 56 NON-INTERVENTIONAL TREATMENTS FOR CONDITIONS OF THE BACK AND SPINE. Line 407 CONDITIONS OF THE BACK AND SPINE Acupuncture is included on this line with visit limitations as in Guideline Note 56 NON-INTERVENTIONAL TREATMENTS FOR CONDITIONS OF THE BACK AND SPINE. Line 415 MIGRAINE HEADACHES Acupuncture pairs on Line 415 for migraine (ICD-10-CM G43.0, G43.1, G43.5, G43.7, G43.8, G43.9), for up to 12 sessions per year. Line 467 OSTEOARTHRITIS AND ALLIED DISORDERS
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-5 Appendix B Modified Guideline Notes
Acupuncture pairs on Line 467 for osteoarthritis of the knee only (ICD-10-CM M17), for up to 12 sessions per year. *Line 543 TENSION HEADACHES Acupuncture is included on Line 543 for treatment of tension headaches (ICD-10-CM G44.2), for up to 12 sessions per year.
The development of this guideline note was informed by a HERC coverage guidance. See http://www.oregon.gov/oha/HPA/CSI- HERC/Pages/Evidence-based-Reports.aspx
*Below the current funding line.
GUIDELINE NOTE 108, CONTINUOUS BLOOD GLUCOSE MONITORING Line 8 Real-time continuous glucose monitoring (CGM) is included on Line 8 for: A) Adults with type 1 diabetes mellitus not on insulin pump management: 1) Who have received or will receive diabetes education specific to the use of CGM AND 2) Who have used the device for at least 50% of the time at their first follow-up visit AND 3) Who have baseline HbA1c levels greater than or equal to 8.0%, frequent or severe hypoglycemia, or impaired awareness of hypoglycemia (including presence of these conditions prior to initiation of CGM). Services related to real-time continuous blood glucose monitoring (for long-term use) or retrospective glucose monitoring (for short- term use) are included on Line 8 only when insulin pump management is being considered, initiated, or utilized and only when the patient has at least one of the following despite compliance with treatment: • HbA1c levels greater than 8.0%, or A) recurrent hypoglycemia with at least three events in the past six months. B) Adults with type 1 diabetes on insulin pump management (including the CGM-enabled insulin pump): 1) Who have received or will receive diabetes education specific to the use of CGM AND 2) Who have used the device for at least 50% of the time at their first follow-up visit. C) Women with type 1 diabetes who are pregnant or who plan to become pregnant within six months without regard to HbA1c levels. D) Children and adolescents under age 21 with type 1 diabetes: 1) Who have received or will receive diabetes education specific to the use of CGM AND
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2) Who have used the device for at least 50% of the time at their first follow-up visit.
GUIDELINE NOTE 139, FRENOTOMY FOR TONGUE-TIE IN NEWBORNS Lines 19,599 ICD-10-CM Q38.1 (Ankyloglossia) is included on Line 19 for pairing with CPT 41010 (Frenotomy) and CDT D7960 only when the ankyloglossia interferes with breastfeeding. Otherwise, Q38.1 and CPT 41010 are included on Line 599.
Effective January 1, 2018 GUIDELINE NOTE 168, TREATMENTS WITH MARGINAL CLINICAL BENEFIT OR LOW COST-EFFECTIVENESS FOR CERTAIN CONDITIONS
The following treatments are prioritized on Line 500 for the conditions listed here:
Condition Procedure Treatment Rationale Last Review Code Stroke 61630 Balloon angioplasty, Similar or worse March 2016 intracranial (eg, outcomes than standard atherosclerotic stenosis), therapies percutaneous Bladder 64566 Posterior tibial Minimally effective, no December, 2010 incontinence neurostimulation evidence of long-term effectiveness Hearing loss 69710 Implantation or Less effective than other June, 2014, Aug. 2015 replacement of therapies electromagnetic bone conduction hearing device HCPCS L8690- in temporal bone L8693 Auditory osseointegrated device
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-7 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code Cystic fibrosis, 94669 Mechanical chest wall More costly than equally October, 2016 other chronic lung oscillation effective therapies conditions Screening for ocular 99177 Photoscreening More costly than equally November, 2015 disorders effective methods of screening
GUIDELINE NOTE 169, TREATMENTS THAT HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS FOR CERTAIN CONDITIONS; UNPROVEN TREATMENTS
The following treatments are prioritized on Line 660, CONDITIONS FOR WHICH CERTAIN TREATMENTS HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS; UNPROVEN TREATMENTS for the conditions listed here:
Condition Procedure Treatment Rationale Last Review Code Tissue 15777 Acellular dermal matrix for soft Greater harms than March, 2015 reconstruction, tissue reinforcement (eg, other effective breast breast, trunk) therapies reconstruction Spinal conditions 22867-22870 Insertion of interlaminar/ Insufficient evidence of November, 2016 interspinous process effectiveness stabilization/ distraction device, without fusion, including image guidance when performed, with open decompression, lumbar All indications 31627 Computer assisted Insufficient evidence of December, 2009
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Condition Procedure Treatment Rationale Last Review Code bronchoscopy effectiveness All respiratory 31647- Bronchial valve Insufficient evidence of December, 2012 conditions 31649, insertion/removal/replacement effectiveness 31651 All respiratory 31660-31661 Bronchial thermoplasty Insufficient evidence of January, 2014 conditions effectiveness Cardiac conditions 33340 Percutaneous transcatheter Insufficient evidence of November, 2016 closure of the left atrial effectiveness appendage with endocardial implant Neonatal 36456 Partial exchange transfusion, No evidence of November, 2016 polycythemia blood, plasma or crystalloid effectiveness, evidence necessitating the skill of a of possible harm physician or other qualified health care professional, newborn Sleep apnea 41512 Tongue base suspension No clinically important January, 2014 benefit All indications 43252, Optical endomicroscopy Insufficient evidence of December, 2012 88375 effectiveness GI conditions 43284 Laproscopy, surgical, Insufficient evidence of November, 2016 esophageal sphincter effectiveness augmentation procedure, placement of sphincter augmentation device (ie, magnetic band) Genitourinary 50705 Ureteral embolization or Insufficient evidence of November, 2015 conditions occlusion effectiveness
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-9 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code All prostatic 53855 Temporary prostatic stents Insufficient evidence of October, 2015 conditions effectiveness Stress incontinence 53860 Transurethral radiofrequency Insufficient evidence of December, 2010 micro-remodeling of the effectiveness bladder neck and urethra for stress incontinence Uterine fibroids 58674 Laparoscopy, surgical, ablation Insufficient evidence of November, 2016 of uterine fibroid(s) effectiveness Stroke, intracrancial 61635 Transcather placement of Results in significantly March 2016 vasospasm intravascular stent(s), worse outcomes than intracranial (eg, atherosclerotic medical management stenosis), including balloon angioplasty, if performed Intracranial 61640-61642 Balloon dilation of intracranial Evidence of harm March, 2016 vasospasm vasospasm, percutaneous. Chronic non- 62350- Intrathecal or epidural drug Significantly greater August, 2017 malignant pain or 62351, infusion device insertion or harms that other any indication other 62360-62362 replacement or revision effective treatments than spasticity, pain due to active life- limiting malignancy, or treatment of active CNS malignancy Spinal conditions 62380 Endoscopic decompression of Insufficient evidence of November, 2016 spinal cord, nerve root(s), effectiveness including laminotomy, partial facetectomy, foraminotomy,
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-10 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code discectomy and/or excision of herniated intervertebral disc Neck and thoracic 64479-64480 Transforaminal epidural steroid Insufficient evidence of March, 2015 spine conditions injections benefit Coverage Guidance Blog
Neck and thoracic 64490-64492 Facet joint injections Insufficient evidence of March, 2015 spine conditions benefit Coverage Guidance Blog Neck and thoracic 64633-64634 Radiofrequency ablation Insufficient evidence of March, 2015 spine pain and benefit radiculopathy Coverage Guidance Blog Low back pain and 64635-64636 Radiofrequency ablation Insufficient evidence of November, 2014 radiculopathy benefit
Coverage Guidance Blog Chronic pain, CPT 64550, Cranial electrical stimulation No clinically important May, 2017 anxiety, depression, 97014, benefit for chronic pain; insomnia, all other 97032 insufficient evidence of indications HCPCS effectiveness for all E0720, E0730 other indications Glaucoma 66174-66175 Transluminal dilation of Insufficient evidence of December, 2010 aqueous outflow canal effectiveness Angina, coronary 75571 CT coronary calcium scoring Insufficient evidence of August 2013 artery disease, chest benefit, unclear harms pain, other cardiac of radiation exposure conditions Coverage Guidance Blog
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-11 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code Angina, coronary 75572 Computed tomography, heart, December, 2009 artery disease, chest with contrast material, for pain, other cardiac evaluation of cardiac structure conditions and morphology Angina, coronary 75574 Computed tomography, heart Insufficient evidence of August, 2013 artery disease, chest benefit, unclear harms pain, other cardiac of radiation exposure conditions Coverage Guidance Blog Screening for 77086 Vertebral fracture assessment Insufficient evidence of October, 2015 osteoporosis using DXA effectiveness Skin conditions 77767 Remote afterloading high dose Insufficient evidence of October and November rate radionuclide skin surface effectiveness 2015 brachytherapy, includes basic dosimetry Angina, coronary 78459 Myocardial imaging, positron Insufficient evidence of January, 2015 artery disease, chest emission tomography (PET), benefit, unclear harms pain, other cardiac metabolic evaluation of radiation exposure conditions Coverage Guidance Blog Angina, coronary 78491-78492 Myocardial imaging, positron Insufficient evidence of January, 2015 artery disease, chest emission tomography (PET), benefit, unclear harms pain, other cardiac perfusion of radiation exposure conditions Coverage Guidance Blog Screening for 81327 SEPT9 (Septin 9) (eg. Colorectal Insufficient evidence of November, 2016 colorectal cancer cancer) methylation analysis effectiveness Prenatal screening 81422 Fetal chromosomal Insufficient evidence of November, 2016
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-12 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code microdeletion(s) genomic effectiveness sequence analysis (eg. DiGeorge syndrome, Cri-du- chat syndrome), circulating cell-free fetal DNA in maternal blood Diagnosis, risk 81493 Coronary artery disease, Insufficient evidence of November, 2015 stratification or mRNA, gene expression effectiveness evaluation of profiling coronary artery disease Cancer tissue test 81504 Biomarker tests for tumor Insufficient evidence of August, 2015 tissue: effectiveness. More • Mammaprint, Mammostrat costly than equally and ImmunoHistoCHemistry effective therapies for 4 (IHC4) for breast cancer this condition • Microsatellite instability (MSI) for colorectal cancer Coverage Guidance Blog • Urovysion for bladder cancer • Prolaris for prostate cancer • Multiple molecular testing to select targeted cancer therapy Prostate cancer 81539 Oncology (high-grade prostate Insufficient evidence of November, 2016 screening cancer), biochemical assay of effectiveness four proteins (Total PSA, Free PSA, Intact PSA, and human
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-13 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code kallikrein-2[hk2]), utilizing plasma or serum, prognostic algorithm reported as a probability score Diagnostic testing 83987 pH; exhaled breath Insufficient evidence of December, 2009 condensate effectiveness Diagnostic testing 84145 Procalcitonin (PCT) Insufficient evidence of December, 2009 effectiveness Diagnostic testing 84431 Thromboxane metabolite(s) Insufficient evidence of December, 2009 effectiveness Diagnostic testing 86305 Human epididymis protein 4 Insufficient evidence of December, 2009 (HE4) effectiveness Diagnostic testing 88738 Hemoglobin (HGB), Insufficient evidence of December, 2009 quantitative, transcutaneous effectiveness Any indication 90880 Hypnotherapy No clinically important August, 2015 benefit Gastrointestinal 91112 Gastrointestinal transit and Insufficient evidence of December, 2012 conditions pressure measurement effectiveness Any indication 93050 Arterial pressure waveform Insufficient evidence of November, 2015 analysis for assessment of effectiveness central arterial pressure Any indication 93740 Temperature gradient studies Insufficient evidence of October, 2015 including breast effectiveness cancer screening Sleep apnea, other 95803 Actigraphy No clinically important January, 2009 sleep disorders benefit Diagnosis of skin 96931-96935 Reflectance confocal Insufficient evidence of November, 2015
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-14 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code lesions microscopy for non-melanoma effectiveness skin lesions Diagnosis of skin 96936 Reflectance confocal Insufficient evidence of November, 2016 lesions microscopy (RCM) for cellular effectiveness and subcellular imaging of skin. Musculoskeletal 97022 Application of a modality; Evidence of harm May, 2016 conditions, wounds whirlpool Musculoskeletal 97024 Application of a modality; Insufficient evidence of May, 2016 conditions diathermy (eg, microwave) effectiveness
Musculoskeletal 97028 Application of a modality; Insufficient evidence of May, 2016 conditions ultraviolet effectiveness
Musculoskeletal 97034 Application of a modality; Insufficient evidence of May, 2016 conditions contrast baths effectiveness Musculoskeletal 97036 Application of a modality; Evidence of harm May, 2016 conditions, wounds Hubbard tank Wounds 97610 Low frequency, non-contact, No clinically important October, 2013 non-thermal ultrasound benefit Any indication D0422 Collection and preparation of Insufficient evidence of October, 2015 genetic sample material for effectiveness laboratory analysis and report D0423 Genetic test for susceptibility to diseases – specimen analysis Any indication D9932- Cleaning and inspection of Insufficient evidence of October, 2015 D9935 removable complete or partial effectiveness denture, maxillary or mandibular
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-15 Appendix B Modified Guideline Notes
Condition Procedure Treatment Rationale Last Review Code All conditions except S9357 Enzyme replacement therapy No clinically important August, 2012 Pompe’s disease benefit
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix B B-16 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement A04.71 Enterocolitis due to Clostridium difficile, recurrent 150 ENTERIC INFECTIONS AND OTHER BACTERIAL FOOD POISONING A04.72 Enterocolitis due to Clostridium difficile, not specified as recurrent 150 ENTERIC INFECTIONS AND OTHER BACTERIAL FOOD POISONING C96.20 Malignant mast cell neoplasm, unspecified 162 NON-HODGKIN'S LYMPHOMAS C96.21 Aggressive systemic mastocytosis 162 NON-HODGKIN'S LYMPHOMAS C96.22 Mast cell sarcoma 162 NON-HODGKIN'S LYMPHOMAS C96.29 Other malignant mast cell neoplasm 162 NON-HODGKIN'S LYMPHOMAS D47.01 Cutaneous mastocytosis 162 NON-HODGKIN'S LYMPHOMAS D47.02 Systemic mastocytosis 162 NON-HODGKIN'S LYMPHOMAS D47.09 Other mast cell neoplasms of uncertain behavior 162 NON-HODGKIN'S LYMPHOMAS E11.10 Type 2 diabetes mellitus with ketoacidosis without coma 30 TYPE 2 DIABETES MELLITUS E11.11 Type 2 diabetes mellitus with ketoacidosis with coma 30 TYPE 2 DIABETES MELLITUS E85.81 Light chain (AL) amyloidosis 239 ACUTE LYMPHOCYTIC LEUKEMIAS (ADULT) AND MULTIPLE MYELOMA 265 MULTIPLE MYELOMA
E85.82 Wild-type transthyretin-related (ATTR) amyloidosis 239 ACUTE LYMPHOCYTIC LEUKEMIAS (ADULT) AND MULTIPLE MYELOMA 265 MULTIPLE MYELOMA
E85.89 Other amyloidosis 239 ACUTE LYMPHOCYTIC LEUKEMIAS (ADULT) AND MULTIPLE MYELOMA 265 MULTIPLE MYELOMA
F10.11 Alcohol abuse, in remission 4 SUBSTANCE USE DISORDER F11.11 Opioid abuse, in remission 4 SUBSTANCE USE DISORDER F12.11 Cannabis abuse, in remission 4 SUBSTANCE USE DISORDER F13.11 Sedative, hypnotic or anxiolytic abuse, in remission 4 SUBSTANCE USE DISORDER F14.11 Cocaine abuse, in remission 4 SUBSTANCE USE DISORDER F15.11 Other stimulant abuse, in remission 4 SUBSTANCE USE DISORDER F16.11 Hallucinogen abuse, in remission 4 SUBSTANCE USE DISORDER F18.11 Inhalant abuse, in remission 4 SUBSTANCE USE DISORDER F19.11 Other psychoactive substance abuse, in remission 4 SUBSTANCE USE DISORDER F50.82 Avoidant/restrictive food intake disorder 153 FEEDING AND EATING DISORDERS OF INFANCY OR CHILDHOOD G12.23 Primary lateral sclerosis 75,297,350,382 G12.24 Familial motor neuron disease 75,297,350,382 G12.25 Progressive spinal muscle atrophy 75,297,350,382
C-1/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement H44.2A1 Degenerative myopia with choroidal neovascularization, right eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2A2 Degenerative myopia with choroidal neovascularization, left eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2A3 Degenerative myopia with choroidal neovascularization, bilateral eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE
H44.2A9 Degenerative myopia with choroidal neovascularization, unspecified 453 DEGENERATION OF MACULA AND POSTERIOR POLE eye H44.2B1 Degenerative myopia with macular hole, right eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2B2 Degenerative myopia with macular hole, left eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2B3 Degenerative myopia with macular hole, bilateral eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2B9 Degenerative myopia with macular hole, unspecified eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2C1 Degenerative myopia with retinal detachment, right eye 284 RETINAL DETACHMENT AND OTHER RETINAL DISORDERS H44.2C2 Degenerative myopia with retinal detachment, left eye 284 RETINAL DETACHMENT AND OTHER RETINAL DISORDERS H44.2C3 Degenerative myopia with retinal detachment, bilateral eye 284 RETINAL DETACHMENT AND OTHER RETINAL DISORDERS H44.2C9 Degenerative myopia with retinal detachment, unspecified eye 284 RETINAL DETACHMENT AND OTHER RETINAL DISORDERS H44.2D1 Degenerative myopia with foveoschisis, right eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2D2 Degenerative myopia with foveoschisis, left eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2D3 Degenerative myopia with foveoschisis, bilateral eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2D9 Degenerative myopia with foveoschisis, unspecified eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2E1 Degenerative myopia with other maculopathy, right eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2E2 Degenerative myopia with other maculopathy, left eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2E3 Degenerative myopia with other maculopathy, bilateral eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H44.2E9 Degenerative myopia with other maculopathy, unspecified eye 453 DEGENERATION OF MACULA AND POSTERIOR POLE H54.0X33 Blindness right eye category 3, blindness left eye category 3 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X34 Blindness right eye category 3, blindness left eye category 4 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X35 Blindness right eye category 3, blindness left eye category 5 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION
C-2/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement H54.0X43 Blindness right eye category 4, blindness left eye category 3 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X44 Blindness right eye category 4, blindness left eye category 4 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X45 Blindness right eye category 4, blindness left eye category 5 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X53 Blindness right eye category 5, blindness left eye category 3 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X54 Blindness right eye category 5, blindness left eye category 4 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.0X55 Blindness right eye category 5, blindness left eye category 5 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1131 Blindness right eye category 3, low vision left eye category 1 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1132 Blindness right eye category 3, low vision left eye category 2 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1141 Blindness right eye category 4, low vision left eye category 1 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1142 Blindness right eye category 4, low vision left eye category 2 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1151 Blindness right eye category 5, low vision left eye category 1 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION
C-3/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement H54.1152 Blindness right eye category 5, low vision left eye category 2 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1213 Low vision right eye category 1, blindness left eye category 3 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1214 Low vision right eye category 1, blindness left eye category 4 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1215 Low vision right eye category 1, blindness left eye category 5 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1223 Low vision right eye category 2, blindness left eye category 3 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1224 Low vision right eye category 2, blindness left eye category 4 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.1225 Low vision right eye category 2, blindness left eye category 5 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.2X11 Low vision right eye category 1, low vision left eye category 1 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.2X12 Low vision right eye category 1, low vision left eye category 2 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.2X21 Low vision right eye category 2, low vision left eye category 1 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION H54.2X22 Low vision right eye category 2, low vision left eye category 2 382 DYSFUNCTION RESULTING IN LOSS OF ABILITY TO MAXIMIZE LEVEL OF INDEPENDENCE IN SELF- DIRECTED CARE CAUSED BY CHRONIC CONDITIONS THAT CAUSE NEUROLOGICAL DYSFUNCTION
C-4/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement H54.413A Blindness right eye category 3, normal vision left eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.414A Blindness right eye category 4, normal vision left eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.415A Blindness right eye category 5, normal vision left eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.42A3 Blindness left eye category 3, normal vision right eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.42A4 Blindness left eye category 4, normal vision right eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.42A5 Blindness left eye category 5, normal vision right eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.511A Low vision right eye category 1, normal vision left eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.512A Low vision right eye category 2, normal vision left eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.52A1 Low vision left eye category 1, normal vision right eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY H54.52A2 Low vision left eye category 2, normal vision right eye 658 SENSORY ORGAN CONDITIONS WITH NO OR MINIMALLY EFFECTIVE TREATMENTS OR NO TREATMENT NECESSARY I21.9 Acute myocardial infarction, unspecified 73 ACUTE AND SUBACUTE ISCHEMIC HEART DISEASE, MYOCARDIAL INFARCTION I21.A1 Myocardial infarction type 2 73 ACUTE AND SUBACUTE ISCHEMIC HEART DISEASE, MYOCARDIAL INFARCTION I21.A9 Other myocardial infarction type 73 ACUTE AND SUBACUTE ISCHEMIC HEART DISEASE, MYOCARDIAL INFARCTION I27.20 Pulmonary hypertension, unspecified 102 HEART FAILURE I27.21 Secondary pulmonary arterial hypertension 102 HEART FAILURE I27.22 Pulmonary hypertension due to left heart disease 102 HEART FAILURE I27.23 Pulmonary hypertension due to lung diseases and hypoxia 102 HEART FAILURE I27.24 Chronic thromboembolic pulmonary hypertension 102 HEART FAILURE I27.29 Other secondary pulmonary hypertension 102 HEART FAILURE I27.83 Eisenmenger's syndrome 102 HEART FAILURE
C-5/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement I50.810 Right heart failure, unspecified 102 HEART FAILURE I50.811 Acute right heart failure 102 HEART FAILURE I50.812 Chronic right heart failure 102 HEART FAILURE I50.813 Acute on chronic right heart failure 102 HEART FAILURE I50.814 Right heart failure due to left heart failure 102 HEART FAILURE I50.82 Biventricular heart failure 102 HEART FAILURE I50.83 High output heart failure 102 HEART FAILURE I50.84 End stage heart failure 102 HEART FAILURE I50.89 Other heart failure 102 HEART FAILURE K06.010 Localized gingival recession, unspecified 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.011 Localized gingival recession, minimal 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.012 Localized gingival recession, moderate 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.013 Localized gingival recession, severe 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.020 Generalized gingival recession, unspecified 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.021 Generalized gingival recession, minimal 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.022 Generalized gingival recession, moderate 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K06.023 Generalized gingival recession, severe 223 DENTAL CONDITIONS (EG. PERIODONTAL DISEASE) K56.50 Intestinal adhesions [bands], unspecified as to partial versus complete 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS obstruction FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.51 Intestinal adhesions [bands], with partial obstruction 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.52 Intestinal adhesions [bands] with complete obstruction 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.600 Partial intestinal obstruction, unspecified as to cause 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.601 Complete intestinal obstruction, unspecified as to cause 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
C-6/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement K56.609 Unspecified intestinal obstruction, unspecified as to partial versus 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS complete obstruction FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.690 Other partial intestinal obstruction 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.691 Other complete intestinal obstruction 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K56.699 Other intestinal obstruction unspecified as to partial versus complete 46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS obstruction FOREIGN BODY IN GI TRACT WITH RISK OF PERFORATION OR OBSTRUCTION
K91.30 Postprocedural intestinal obstruction, unspecified as to partial versus 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT complete K91.31 Postprocedural partial intestinal obstruction 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT
K91.32 Postprocedural complete intestinal obstruction 290 COMPLICATIONS OF A PROCEDURE ALWAYS REQUIRING TREATMENT
L97.105 Non-pressure chronic ulcer of unspecified thigh with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.106 Non-pressure chronic ulcer of unspecified thigh with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.108 Non-pressure chronic ulcer of unspecified thigh with other specified 384 CHRONIC ULCER OF SKIN severity L97.115 Non-pressure chronic ulcer of right thigh with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.116 Non-pressure chronic ulcer of right thigh with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.118 Non-pressure chronic ulcer of right thigh with other specified severity 384 CHRONIC ULCER OF SKIN
L97.125 Non-pressure chronic ulcer of left thigh with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis
C-7/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement L97.126 Non-pressure chronic ulcer of left thigh with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.128 Non-pressure chronic ulcer of left thigh with other specified severity 384 CHRONIC ULCER OF SKIN
L97.205 Non-pressure chronic ulcer of unspecified calf with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.206 Non-pressure chronic ulcer of unspecified calf with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.208 Non-pressure chronic ulcer of unspecified calf with other specified 384 CHRONIC ULCER OF SKIN severity L97.215 Non-pressure chronic ulcer of right calf with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.216 Non-pressure chronic ulcer of right calf with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.218 Non-pressure chronic ulcer of right calf with other specified severity 384 CHRONIC ULCER OF SKIN
L97.225 Non-pressure chronic ulcer of left calf with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.226 Non-pressure chronic ulcer of left calf with bone involvement without 384 CHRONIC ULCER OF SKIN evidence of necrosis L97.228 Non-pressure chronic ulcer of left calf with other specified severity 384 CHRONIC ULCER OF SKIN L97.305 Non-pressure chronic ulcer of unspecified ankle with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.306 Non-pressure chronic ulcer of unspecified ankle with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.308 Non-pressure chronic ulcer of unspecified ankle with other specified 384 CHRONIC ULCER OF SKIN severity L97.315 Non-pressure chronic ulcer of right ankle with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.316 Non-pressure chronic ulcer of right ankle with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.318 Non-pressure chronic ulcer of right ankle with other specified severity 384 CHRONIC ULCER OF SKIN
C-8/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement L97.325 Non-pressure chronic ulcer of left ankle with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.326 Non-pressure chronic ulcer of left ankle with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L97.328 Non-pressure chronic ulcer of left ankle with other specified severity 384 CHRONIC ULCER OF SKIN
L97.405 Non-pressure chronic ulcer of unspecified heel and midfoot with 384 CHRONIC ULCER OF SKIN muscle involvement without evidence of necrosis L97.406 Non-pressure chronic ulcer of unspecified heel and midfoot with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.408 Non-pressure chronic ulcer of unspecified heel and midfoot with other 384 CHRONIC ULCER OF SKIN specified severity L97.415 Non-pressure chronic ulcer of right heel and midfoot with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.416 Non-pressure chronic ulcer of right heel and midfoot with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.418 Non-pressure chronic ulcer of right heel and midfoot with other 384 CHRONIC ULCER OF SKIN specified severity L97.425 Non-pressure chronic ulcer of left heel and midfoot with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.426 Non-pressure chronic ulcer of left heel and midfoot with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.428 Non-pressure chronic ulcer of left heel and midfoot with other 384 CHRONIC ULCER OF SKIN specified severity L97.505 Non-pressure chronic ulcer of other part of unspecified foot with 384 CHRONIC ULCER OF SKIN muscle involvement without evidence of necrosis L97.506 Non-pressure chronic ulcer of other part of unspecified foot with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.508 Non-pressure chronic ulcer of other part of unspecified foot with 384 CHRONIC ULCER OF SKIN other specified severity L97.515 Non-pressure chronic ulcer of other part of right foot with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis
C-9/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement L97.516 Non-pressure chronic ulcer of other part of right foot with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.518 Non-pressure chronic ulcer of other part of right foot with other 384 CHRONIC ULCER OF SKIN specified severity L97.525 Non-pressure chronic ulcer of other part of left foot with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.526 Non-pressure chronic ulcer of other part of left foot with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.528 Non-pressure chronic ulcer of other part of left foot with other 384 CHRONIC ULCER OF SKIN specified severity L97.805 Non-pressure chronic ulcer of other part of unspecified lower leg with 384 CHRONIC ULCER OF SKIN muscle involvement without evidence of necrosis L97.806 Non-pressure chronic ulcer of other part of unspecified lower leg with 384 CHRONIC ULCER OF SKIN bone involvement without evidence of necrosis L97.808 Non-pressure chronic ulcer of other part of unspecified lower leg with 384 CHRONIC ULCER OF SKIN other specified severity L97.815 Non-pressure chronic ulcer of other part of right lower leg with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.816 Non-pressure chronic ulcer of other part of right lower leg with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.818 Non-pressure chronic ulcer of other part of right lower leg with other 384 CHRONIC ULCER OF SKIN specified severity L97.825 Non-pressure chronic ulcer of other part of left lower leg with muscle 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.826 Non-pressure chronic ulcer of other part of left lower leg with bone 384 CHRONIC ULCER OF SKIN involvement without evidence of necrosis L97.828 Non-pressure chronic ulcer of other part of left lower leg with other 384 CHRONIC ULCER OF SKIN specified severity L97.905 Non-pressure chronic ulcer of unspecified part of unspecified lower leg 384 CHRONIC ULCER OF SKIN with muscle involvement without evidence of necrosis L97.906 Non-pressure chronic ulcer of unspecified part of unspecified lower leg 384 CHRONIC ULCER OF SKIN with bone involvement without evidence of necrosis
C-10/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement L97.908 Non-pressure chronic ulcer of unspecified part of unspecified lower leg 384 CHRONIC ULCER OF SKIN with other specified severity L97.915 Non-pressure chronic ulcer of unspecified part of right lower leg with 384 CHRONIC ULCER OF SKIN muscle involvement without evidence of necrosis L97.916 Non-pressure chronic ulcer of unspecified part of right lower leg with 384 CHRONIC ULCER OF SKIN bone involvement without evidence of necrosis L97.918 Non-pressure chronic ulcer of unspecified part of right lower leg with 384 CHRONIC ULCER OF SKIN other specified severity L97.925 Non-pressure chronic ulcer of unspecified part of left lower leg with 384 CHRONIC ULCER OF SKIN muscle involvement without evidence of necrosis L97.926 Non-pressure chronic ulcer of unspecified part of left lower leg with 384 CHRONIC ULCER OF SKIN bone involvement without evidence of necrosis L97.928 Non-pressure chronic ulcer of unspecified part of left lower leg with 384 CHRONIC ULCER OF SKIN other specified severity L98.415 Non-pressure chronic ulcer of buttock with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L98.416 Non-pressure chronic ulcer of buttock with bone involvement without 384 CHRONIC ULCER OF SKIN evidence of necrosis L98.418 Non-pressure chronic ulcer of buttock with other specified severity 384 CHRONIC ULCER OF SKIN L98.425 Non-pressure chronic ulcer of back with muscle involvement without 384 CHRONIC ULCER OF SKIN evidence of necrosis L98.426 Non-pressure chronic ulcer of back with bone involvement without 384 CHRONIC ULCER OF SKIN evidence of necrosis L98.428 Non-pressure chronic ulcer of back with other specified severity 384 CHRONIC ULCER OF SKIN L98.495 Non-pressure chronic ulcer of other sites with muscle involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L98.496 Non-pressure chronic ulcer of other sites with bone involvement 384 CHRONIC ULCER OF SKIN without evidence of necrosis L98.498 Non-pressure chronic ulcer of other sites with other specified severity 384 CHRONIC ULCER OF SKIN
M33.03 Juvenile dermatomyositis without myopathy 78 DERMATOMYOSITIS, POLYMYOSITIS M33.13 Other dermatomyositis without myopathy 78 DERMATOMYOSITIS, POLYMYOSITIS M33.93 Dermatopolymyositis, unspecified without myopathy 78 DERMATOMYOSITIS, POLYMYOSITIS
C-11/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement M48.061 Spinal stenosis, lumbar region without neurogenic claudication 351 CONDITIONS OF THE BACK AND SPINE WITH URGENT SURGICAL INDICATIONS 407 CONDITIONS OF THE BACK AND SPINE 532 CONDITIONS OF THE BACK AND SPINE WITHOUT URGENT SURGICAL INDICATIONS M48.062 Spinal stenosis, lumbar region with neurogenic claudication 351 CONDITIONS OF THE BACK AND SPINE WITH URGENT SURGICAL INDICATIONS 407 CONDITIONS OF THE BACK AND SPINE 532 CONDITIONS OF THE BACK AND SPINE WITHOUT URGENT SURGICAL INDICATIONS N63.0 Unspecified lump in unspecified breast Diagnostic Workup File (DWF) N63.10 Unspecified lump in the right breast, unspecified quadrant Diagnostic Workup File (DWF) N63.11 Unspecified lump in the right breast, upper outer quadrant Diagnostic Workup File (DWF) N63.12 Unspecified lump in the right breast, upper inner quadrant Diagnostic Workup File (DWF) N63.13 Unspecified lump in the right breast, lower outer quadrant Diagnostic Workup File (DWF) N63.14 Unspecified lump in the right breast, lower inner quadrant Diagnostic Workup File (DWF) N63.20 Unspecified lump in the left breast, unspecified quadrant Diagnostic Workup File (DWF) N63.21 Unspecified lump in the left breast, upper outer quadrant Diagnostic Workup File (DWF) N63.22 Unspecified lump in the left breast, upper inner quadrant Diagnostic Workup File (DWF) N63.23 Unspecified lump in the left breast, lower outer quadrant Diagnostic Workup File (DWF) N63.24 Unspecified lump in the left breast, lower inner quadrant Diagnostic Workup File (DWF) N63.31 Unspecified lump in axillary tail of the right breast Diagnostic Workup File (DWF) N63.32 Unspecified lump in axillary tail of the left breast Diagnostic Workup File (DWF) N63.41 Unspecified lump in right breast, subareolar Diagnostic Workup File (DWF) N63.42 Unspecified lump in left breast, subareolar Diagnostic Workup File (DWF) O00.101 Right tubal pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.102 Left tubal pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.109 Unspecified tubal pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.111 Right tubal pregnancy with intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.112 Left tubal pregnancy with intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.119 Unspecified tubal pregnancy with intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.201 Right ovarian pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.202 Left ovarian pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA
C-12/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement O00.209 Unspecified ovarian pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.211 Right ovarian pregnancy with intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.212 Left ovarian pregnancy without intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O00.219 Unspecified ovarian pregnancy with intrauterine pregnancy 41 ECTOPIC PREGNANCY; HYDATIDIFORM MOLE; CHORIOCARCINOMA O36.8310 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, not applicable or unspecified O36.8311 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, fetus 1 O36.8312 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, fetus 2 O36.8313 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, fetus 3 O36.8314 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, fetus 4 O36.8315 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, fetus 5 O36.8319 Maternal care for abnormalities of the fetal heart rate or rhythm, first 1 PREGNANCY trimester, other fetus O36.8320 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, not applicable or unspecified O36.8321 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, fetus 1 O36.8322 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, fetus 2 O36.8323 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, fetus 3 O36.8324 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, fetus 4 O36.8325 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, fetus 5 O36.8329 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY second trimester, other fetus
C-13/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement O36.8330 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, not applicable or unspecified O36.8331 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, fetus 1 O36.8332 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, fetus 2 O36.8333 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, fetus 3 O36.8334 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, fetus 4 O36.8335 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, fetus 5 O36.8339 Maternal care for abnormalities of the fetal heart rate or rhythm, third 1 PREGNANCY trimester, other fetus O36.8390 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, not applicable or unspecified O36.8391 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, fetus 1 O36.8392 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, fetus 2 O36.8393 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, fetus 3 O36.8394 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, fetus 4 O36.8395 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, fetus 5 O36.8399 Maternal care for abnormalities of the fetal heart rate or rhythm, 1 PREGNANCY unspecified trimester, other fetus P29.30 Pulmonary hypertension of newborn 81 PATENT DUCTUS ARTERIOSUS; AORTIC PULMONARY FISTULA/WINDOW
P29.38 Other persistent fetal circulation 81 PATENT DUCTUS ARTERIOSUS; AORTIC PULMONARY FISTULA/WINDOW
C-14/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement P78.84 Gestational alloimmune liver disease 105 CONGENITAL ANOMALIES OF DIGESTIVE SYSTEM AND ABDOMINAL WALL EXCLUDING NECROSIS; CHRONIC INTESTINAL PSEUDO-OBSTRUCTION 312 CIRRHOSIS OF LIVER OR BILIARY TRACT; BUDD-CHIARI SYNDROME; HEPATIC VEIN THROMBOSIS; INTRAHEPATIC VASCULAR MALFORMATIONS; CAROLI'S DISEASE Tx: Liver transplant
P83.81 Umbilical granuloma 648 EDEMA AND OTHER CONDITIONS INVOLVING THE SKIN OF THE FETUS AND NEWBORN P83.88 Other specified conditions of integument specific to newborn 648 EDEMA AND OTHER CONDITIONS INVOLVING THE SKIN OF THE FETUS AND NEWBORN P91.811 Neonatal encephalopathy in diseases classified elsewhere 27 INTRACRANIAL HEMORRHAGES; CEREBRAL CONVULSIONS, DEPRESSION, COMA, AND OTHER ABNORMAL CERERAL SIGNS OF THE NEWBORN
P91.819 Neonatal encephalopathy, unspecified 27 INTRACRANIAL HEMORRHAGES; CEREBRAL CONVULSIONS, DEPRESSION, COMA, AND OTHER ABNORMAL CERERAL SIGNS OF THE NEWBORN
P91.88 Other specified disturbances of cerebral status of newborn 27 INTRACRANIAL HEMORRHAGES; CEREBRAL CONVULSIONS, DEPRESSION, COMA, AND OTHER ABNORMAL CERERAL SIGNS OF THE NEWBORN
Q53.111 Unilateral intraabdominal testis 98 UNDESCENDED TESTICLE Q53.112 Unilateral inguinal testis 98 UNDESCENDED TESTICLE Q53.13 Unilateral high scrotal testis 98 UNDESCENDED TESTICLE Q53.211 Bilateral intraabdominal testes 98 UNDESCENDED TESTICLE Q53.212 Bilateral inguinal testes 98 UNDESCENDED TESTICLE Q53.23 Bilateral high scrotal testes 98 UNDESCENDED TESTICLE R06.03 Acute respiratory distress Diagnostic Workup File (DWF) R39.83 Unilateral non-palpable testicle Diagnostic Workup File (DWF) R39.84 Bilateral non-palpable testicles Diagnostic Workup File (DWF) T07.XXXA Unspecified multiple injuries, initial encounter 638 SUPERFICIAL WOUNDS WITHOUT INFECTION AND CONTUSIONS T07.XXXD Unspecified multiple injuries, subsequent encounter 638 SUPERFICIAL WOUNDS WITHOUT INFECTION AND CONTUSIONS
T07.XXXS Unspecified multiple injuries, sequela 638 SUPERFICIAL WOUNDS WITHOUT INFECTION AND CONTUSIONS T14.8XXA Other injury of unspecified body region, initial encounter 607 DISORDERS OF SOFT TISSUE
C-15/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement T14.8XXD Other injury of unspecified body region, subsequent encounter 607 DISORDERS OF SOFT TISSUE
T14.8XXS Other injury of unspecified body region, sequela 607 DISORDERS OF SOFT TISSUE T14.90XA Injury, unspecified, initial encounter Undefined Diagnosis File T14.90XD Injury, unspecified, subsequent encounter Undefined Diagnosis File
T14.90XS Injury, unspecified, sequela Undefined Diagnosis File T14.91XA Suicide attempt, initial encounter Diagnostic Workup File (DWF) T14.91XD Suicide attempt, subsequent encounter Diagnostic Workup File (DWF)
T14.91XS Suicide attempt, sequela Informational Diagnosis File V86.05XA Driver of 3- or 4- wheeled all-terrain vehicle (ATV) injured in traffic Informational Diagnosis File accident, initial encounter V86.05XD Driver of 3- or 4- wheeled all-terrain vehicle (ATV) injured in traffic Informational Diagnosis File accident, subsequent encounter V86.05XS Driver of 3- or 4- wheeled all-terrain vehicle (ATV) injured in traffic Informational Diagnosis File accident, sequela V86.06XA Driver of dirt bike or motor/cross bike injured in traffic accident, initial Informational Diagnosis File encounter V86.06XD Driver of dirt bike or motor/cross bike injured in traffic accident, Informational Diagnosis File subsequent encounter V86.06XS Driver of dirt bike or motor/cross bike injured in traffic accident, Informational Diagnosis File sequela V86.15XA Passenger of 3- or 4- wheeled all-terrain vehicle (ATV) injured in traffic Informational Diagnosis File accident, initial encounter V86.15XD Passenger of 3- or 4- wheeled all-terrain vehicle (ATV) injured in traffic Informational Diagnosis File accident, subsequent encounter V86.15XS Passenger of 3- or 4- wheeled all-terrain vehicle (ATV) injured in traffic Informational Diagnosis File accident, sequela V86.16XA Passenger of dirt bike or motor/cross bike injured in traffic accident, Informational Diagnosis File initial encounter V86.16XD Passenger of dirt bike or motor/cross bike injured in traffic accident, Informational Diagnosis File subsequent encounter
C-16/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement V86.16XS Passenger of dirt bike or motor/cross bike injured in traffic accident, Informational Diagnosis File sequela V86.25XA Person on outside of 3- or 4- wheeled all-terrain vehicle (ATV) injured Informational Diagnosis File in traffic accident, initial encounter V86.25XD Person on outside of 3- or 4- wheeled all-terrain vehicle (ATV) injured Informational Diagnosis File in traffic accident, subsequent encounter V86.25XS Person on outside of 3- or 4- wheeled all-terrain vehicle (ATV) injured Informational Diagnosis File in traffic accident, sequela V86.26XA Person on outside of dirt bike or motor/cross bike injured in traffic Informational Diagnosis File accident, initial encounter V86.26XD Person on outside of dirt bike or motor/cross bike injured in traffic Informational Diagnosis File accident, subsequent encounter V86.26XS Person on outside of dirt bike or motor/cross bike injured in traffic Informational Diagnosis File accident, sequela V86.35XA Unspecified occupant of 3- or 4- wheeled all-terrain vehicle (ATV) Informational Diagnosis File injured in traffic accident, initial encounter V86.35XD Unspecified occupant of 3- or 4- wheeled all-terrain vehicle (ATV) Informational Diagnosis File injured in traffic accident, subsequent encounter V86.35XS Unspecified occupant of 3- or 4- wheeled all-terrain vehicle (ATV) Informational Diagnosis File injured in traffic accident, sequela V86.36XA Unspecified occupant of dirt bike or motor/cross bike injured in traffic Informational Diagnosis File accident, initial encounter V86.36XD Unspecified occupant of dirt bike or motor/cross bike injured in traffic Informational Diagnosis File accident, subsequent encounter V86.36XS Unspecified occupant of dirt bike or motor/cross bike injured in traffic Informational Diagnosis File accident, sequela V86.45XA Person injured while boarding or alighting from a 3- or 4- wheeled all- Informational Diagnosis File terrain vehicle (ATV), initial encounter V86.45XD Person injured while boarding or alighting from a 3- or 4- wheeled all- Informational Diagnosis File terrain vehicle (ATV), subsequent encounter V86.45XS Person injured while boarding or alighting from a 3- or 4- wheeled all- Informational Diagnosis File terrain vehicle (ATV), sequela
C-17/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement V86.46XA Person injured while boarding or alighting from a dirt bike or Informational Diagnosis File motor/cross bike, initial encounter V86.46XD Person injured while boarding or alighting from a dirt bike or Informational Diagnosis File motor/cross bike, subsequent encounter V86.46XS Person injured while boarding or alighting from a dirt bike or Informational Diagnosis File motor/cross bike, sequela V86.55XA Driver of 3- or 4- wheeled all-terrain vehicle (ATV) injured in nontraffic Informational Diagnosis File accident, initial encounter V86.55XD Driver of 3- or 4- wheeled all-terrain vehicle (ATV) injured in nontraffic Informational Diagnosis File accident, subsequent encounter V86.55XS Driver of 3- or 4- wheeled all-terrain vehicle (ATV) injured in nontraffic Informational Diagnosis File accident, sequela V86.56XA Driver of dirt bike or motor/cross bike injured in nontraffic accident, Informational Diagnosis File initial encounter V86.56XD Driver of dirt bike or motor/cross bike injured in nontraffic accident, Informational Diagnosis File subsequent encounter V86.56XS Driver of dirt bike or motor/cross bike injured in nontraffic accident, Informational Diagnosis File sequela V86.65XA Passenger of 3- or 4- wheeled all-terrain vehicle (ATV) injured in Informational Diagnosis File nontraffic accident, initial encounter V86.65XD Passenger of 3- or 4- wheeled all-terrain vehicle (ATV) injured in Informational Diagnosis File nontraffic accident, subsequent encounter V86.65XS Passenger of 3- or 4- wheeled all-terrain vehicle (ATV) injured in Informational Diagnosis File nontraffic accident, sequela V86.66XA Passenger of dirt bike or motor/cross bike injured in nontraffic Informational Diagnosis File accident, initial encounter V86.66XD Passenger of dirt bike or motor/cross bike injured in nontraffic Informational Diagnosis File accident, subsequent encounter V86.66XS Passenger of dirt bike or motor/cross bike injured in nontraffic Informational Diagnosis File accident, sequela V86.75XA Person on outside of 3- or 4- wheeled all-terrain vehicle (ATV) injured Informational Diagnosis File in nontraffic accident, initial encounter
C-18/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement V86.75XD Person on outside of 3- or 4- wheeled all-terrain vehicle (ATV) injured Informational Diagnosis File in nontraffic accident, subsequent encounter V86.75XS Person on outside of 3- or 4- wheeled all-terrain vehicle (ATV) injured Informational Diagnosis File in nontraffic accident, sequela V86.76XA Person on outside of dirt bike or motor/cross bike injured in nontraffic Informational Diagnosis File accident, initial encounter V86.76XD Person on outside of dirt bike or motor/cross bike injured in nontraffic Informational Diagnosis File accident, subsequent encounter V86.76XS Person on outside of dirt bike or motor/cross bike injured in nontraffic Informational Diagnosis File accident, sequela V86.95XA Unspecified occupant of 3- or 4- wheeled all-terrain vehicle (ATV) Informational Diagnosis File injured in nontraffic accident, initial encounter V86.95XD Unspecified occupant of 3- or 4- wheeled all-terrain vehicle (ATV) Informational Diagnosis File injured in nontraffic accident, subsequent encounter V86.95XS Unspecified occupant of 3- or 4- wheeled all-terrain vehicle (ATV) Informational Diagnosis File injured in nontraffic accident, sequela V86.96XA Unspecified occupant of dirt bike or motor/cross bike injured in Informational Diagnosis File nontraffic accident, initial encounter V86.96XD Unspecified occupant of dirt bike or motor/cross bike injured in Informational Diagnosis File nontraffic accident, subsequent encounter V86.96XS Unspecified occupant of dirt bike or motor/cross bike injured in Informational Diagnosis File nontraffic accident, sequela Z36.0 Encounter for antenatal screening for chromosomal anomalies 1 PREGNANCY Z36.1 Encounter for antenatal screening for raised alphafetoprotein level 1 PREGNANCY Z36.2 Encounter for other antenatal screening follow-up 1 PREGNANCY Z36.3 Encounter for antenatal screening for malformations 1 PREGNANCY Z36.4 Encounter for antenatal screening for fetal growth retardation 1 PREGNANCY Z36.5 Encounter for antenatal screening for isoimmunization 1 PREGNANCY Z36.81 Encounter for antenatal screening for hydrops fetalis 1 PREGNANCY Z36.82 Encounter for antenatal screening for nuchal translucency 1 PREGNANCY Z36.83 Encounter for fetal screening for congenital cardiac abnormalities 1 PREGNANCY Z36.84 Encounter for antenatal screening for fetal lung maturity 1 PREGNANCY Z36.85 Encounter for antenatal screening for Streptococcus B 1 PREGNANCY
C-19/20 Appendix C 2018 ICD-10-CM Codes Code Description Recommended Placement Z36.86 Encounter for antenatal screening for cervical length 1 PREGNANCY Z36.87 Encounter for antenatal screening for uncertain dates 1 PREGNANCY Z36.88 Encounter for antenatal screening for fetal macrosomia 1 PREGNANCY Z36.89 Encounter for other specified antenatal screening 1 PREGNANCY Z36.8A Encounter for antenatal screening for other genetic defects 1 PREGNANCY Z36.9 Encounter for antenatal screening, unspecified 1 PREGNANCY Z40.03 Encounter for prophylactic removal of fallopian tube(s ) 195 CANCER OF BREAST; AT HIGH RISK OF BREAST CANCER Z71.82 Exercise counseling 325 OBESITY (ADULT BMI ≥ 30, CHILDHOOD BMI ≥ 95TH PERCENTILE) AND OVERWEIGHT IN ADULTS (BMI >25) WITH CARDIOVASCULAR RISK FACTORS 589 OBESITY (ADULT BMI ≥ 30, CHILDHOOD BMI ≥ 95TH PERCENTILE) AND OVERWEIGHT IN ADULTS (BMI >25) WITH CARDIOVASCULAR RISK FACTORS 625 PREVENTION SERVICES WITH LIMITED OR NO EVIDENCE OF EFFECTIVENESS
Z71.83 Encounter for nonprocreative genetic counseling Diagnostic Workup File (DWF) Z91.841 Risk for dental caries, low 57 PREVENTIVE DENTAL SERVICES Z91.842 Risk for dental caries, moderate 57 PREVENTIVE DENTAL SERVICES Z91.843 Risk for dental caries, high 57 PREVENTIVE DENTAL SERVICES Z91.849 Unspecified risk for dental caries 57 PREVENTIVE DENTAL SERVICES
C-20/20 Appendix D Multisector Interventions Multisector Interventions: Prevention of Early Childhood Caries
Evidence supports • Community water fluoridation • Fluoride varnish, including applied in a primary care setting • Fluoride gel • Oral fluoride supplementation • Community-based programs that combine oral health education with supervised toothbrushing
Limited evidence supports • Motivational interviewing towards caregivers
Insufficient or conflicting evidence on: • Anticipatory guidance/oral health education alone • Encouragement of preventive dental visits • Risk assessment • Xylitol products • Chlorhexidine • Silver diamine fluoride • School-based behavioral interventions • Breastfeeding interventions
Value-based Benefits Subcommittee Minutes, 8/10/2017 Appendix D-1 Section 3.0 Consent Agenda- Straightforward Items Consent Agenda Issues—September, 2017
Code Code Description Line(s) Involved Issue Recommendation(s) 20552 Injection(s); single or multiple 425 ACUTE PERIPHERAL MOTOR HSD requested removal of 20552 Remove 20552 and 20553 from trigger point(s), 1 or 2 AND DIGITAL NERVE INJURY and 20553 from line 431 as there line 425 muscle(s) are no appropriate diagnoses on 20553 3 or more muscles this line. 20552 and 20553 also appear on lines 501,503,586,590 26460 Tenotomy, extensor, hand or 292 NEUROLOGICAL HSD requested that 26460 pair Add 26460 to line 292 finger, open, each tendon DYSFUNCTION IN POSTURE AND with M24.542 (Contracture, left MOVEMENT CAUSED BY CHRONIC hand). 26460 is on lines CONDITIONS 208,285,359,415,425,503,525 10030 Image-guided fluid collection 422 COMPLICATIONS OF A HSD requested that 10030 pair Add 10030 to line 422 drainage by catheter (eg, PROCEDURE USUALLY REQUIRING with M96.842 (Postprocedural abscess, hematoma, seroma, TREATMENT seroma of a musculoskeletal lymphocele, cyst), soft tissue structure following a (eg, extremity, abdominal wall, musculoskeletal system neck), percutaneous procedure). 10030 is on lines 47,206,236,285,402.
29130 Application of finger splint; 441 MALUNION AND NONUNION HSD requested that 29130 pair Add 29130 to line 441 static OF FRACTURE with S62.627K (Displaced fracture of medial phalanx of left little finger, subsequent encounter for fracture with nonunion). 29130 is on lines 132, 206, 208, 289, 355, 359, 376, 525
28300 Osteotomy; calcaneus (eg, 355 CLOSED FRACTURE OF HSD requested that 28300 pair Add 28300 to line 355 Dwyer or Chambers type EXTREMITIES (EXCEPT MINOR with S92.001A (Unspecified procedure), with or without TOES) fracture of right calcaneus, initial internal fixation encounter for closed fracture). 28300 is on lines 292,359,525,540,575
1 Consent Agenda Issues—September, 2017
Code Code Description Line(s) Involved Issue Recommendation(s) 29894 Arthroscopy, ankle (tibiotalar 355 CLOSED FRACTURE OF HSD requested that 29894 pair Add 29894 to line 355 and fibulotalar joints), surgical; EXTREMITIES (EXCEPT MINOR with S92.141A (Displaced dome with removal of loose body or TOES) fracture of right talus, initial foreign body encounter for closed fracture). 29894 is on lines 132,153,356,359. These lines include the open fracture line 37184 Primary percutaneous 285 COMPLICATIONS OF A HSD requested that 37184 pair Add 37184 and 37185 to line 285 transluminal mechanical PROCEDURE ALWAYS REQUIRING with T82.818A (Embolism due to thrombectomy, noncoronary, TREATMENT vascular prosthetic devices, non-intracranial, arterial or implants and grafts, initial arterial bypass graft, including encounter). 37184 and 37185 are fluoroscopic guidance and on lines 236,254,349,446 intraprocedural pharmacological thrombolytic injection(s); initial vessel 37185 second and all subsequent vessel(s) within the same vascular family 37211 Transcatheter therapy, arterial 285 COMPLICATIONS OF A HSD requested that 37212 pair Add 37211 and 37212 to line 285 infusion for thrombolysis, any PROCEDURE ALWAYS REQUIRING with T82.868A (Thrombosis due to method, including radiological TREATMENT vascular prosthetic devices, supervision and interpretation, implants and grafts, initial initial treatment day encounter). 37211 is on lines 37212 venous 254,317,349,446. 37212 is on lines 47, 79, 280.
2 Consent Agenda Issues—September, 2017
96150- Health and behavior 10 Galactosemia 96154-5 (Health and behavior Add 96150-96153 to lines 10, 13- 96153 intervention, each 15 minutes, 13 Congenital hypothyroidism intervention, family) appear on 15, 33, 44, 48, 64, 67, 77, 85, 87, 14 Phenylketonuria (PKU) approximately 30 more lines that 89, 101, 103, 105, 130 15 Congenital infectious diseases 96150-96153 (Health and 33 Spina bifida behavior intervention, non- 44 Coarctation of the aorta family). The additional lines are all 48 Chronic respiratory disease congenital birth defects or inborn arising in the neonatal perio... errors of metabolism. These 64 Congenital anomalies of upper diagnoses are appropriate for alimentary tract, excluding... family interventions, but may also 67 Ventricular septal defect be appropriate for individual 77 Patent ductus arteriosus… interventions when the child 87 Congenital anomalies of becomes old enough to manage genitourinary system his/her own condition. 89 Discordant cardiovascular connections Other lines suggested for addition 101 Congenital anomalies of of 96150-96153 only affect infants digestive system… and any sequelae would be coded 103 Poisoning by ingestion… with a dysfunction diagnosis. 105 Tetralogy of Fallot… Therefore these lines are 111 Congenital heart block… appropriate only for family 130 Total anomalous pulmonary interventions: venous connection 11 Respiratory conditions of fetus and newborn 16 Low birth weight… 17 Neonatal myasthenia gravis 23 Intracranial hemorrhages… 24 Endocrine and metabolic disturbances specific to the fetu... 28 Drug withdrawal syndrome… 31 Severe birth trauma for baby… 32 Hematological disorders of fetus and newborn 348 Mild/moderate birth trauma for baby
3
Consent Agenda Issues—September, 2017
Code Code Description Line(s) Involved Issue Recommendation(s) L08.9 Local infection of the skin and 206 SUPERFICIAL ABSCESSES AND L08.9 currently appears only on Add L08.9 to lines 206 and 385 subcutaneous tissue, CELLULITIS line 625. A CCO medical director unspecified 385 SUPERFICIAL INJURIES WITH requested that it be placed on the Remove L08.9 from line 625 INFECTION same lines as L08.89 (Other 631 BENIGN NEOPLASMS OF SKIN specified local infections of the AND OTHER SOFT TISSUES skin and subcutaneous tissue) to allow treatment which is on lines 206 and 385. P39.3 Neonatal urinary tract infection 2 BIRTH OF AN INFANT In August, 2017, P39.3, P39.4, For January 1, 2018, remove P39.4 Neonatal skin infection 43 NEONATAL INFECTIONS OTHER P39.8 and P39.9 were removed P39.3, P39.4, P39.8 and P39.9 P39.8 Other specified infections THAN SEPSIS from the dysfunction lines and from line 2. specific to the perinatal period added to line 2, effective October P39.9 Infection specific to the 1, 2017. However, as part of the perinatal period, unspecified biennial review effective January 1, 2018, these diagnoses were to be included on the revised line 43 which is a more appropriate placement. 58150 Total abdominal hysterectomy 1 PREGNANCY Line 1 currently contains only one Add 58150, 58180, 58260-58262, (corpus and cervix), hysterectomy code (CPT 59525 58290-58291, 58541-58544, and 58180 Supracervical abdominal (Subtotal or total hysterectomy 58550-58573 to line 1 hysterectomy (subtotal after cesarean delivery (List hysterectomy) separately in addition to code for 58260- Vaginal hysterectomy primary procedure)). There are 58262, many obstetrical complications 58290- which may require a hysterectomy 58291 outside of a cesarean delivery. 58541- Laparoscopy, surgical, HSD as requested that 58544 supracervical hysterectomy hysterectomy CPT codes be added 58550- Laparoscopy, surgical, with to line 1. 58554 vaginal or total hysterectomy 58570- 58573
4 Consent Agenda Issues—September, 2017
Code Code Description Line(s) Involved Issue Recommendation(s) 62143 Replacement of bone flap or 196 SUBARACHNOID AND HSD requested that 62143 be Add 62143 to line 196 prosthetic plate of skull INTRACEREBRAL added to line 196 to pair with HEMORRHAGE/HEMATOMA; Q28.2 (Arteriovenous CEREBRAL ANEURYSM; malformation of cerebral vessels). COMPRESSION OF BRAIN 62143 is on lines 47,92,126,257,294 77332- Treatment devices, design and 440 TRIGEMINAL AND OTHER HSD requested that 77334 be Add 77332-77334 to lines 440 and 77334 construction; NERVE DISORDERS paired with Bell’s palsy. 77334 is 458 simple/intermediate/complex 458 CENTRAL PTERYGIUM on 48 lines, but is missing from a AFFECTING VISION few lines with radiation therapy. 77332 and 77333 are similar codes for less complex treatment devices. All three codes appear on the same 48 lines currently. These three codes are missing from a few radiation therapy lines for benign conditions. .
5 Straightforward Modifications to the Prioritized List Changes: Continuous Glucose Monitoring in Diabetes Mellitus
Question: What modifications are required for the changes to the Prioritized List for retrospective continuous glucose monitoring?
Question source: HERC Staff, HSD staff, providers, manufacturer
Issue: In August, 2017, VBBS and HERC adopted changes to the Prioritized List based on recommendations in the Coverage Guidance on Continuous Glucose Monitoring. Stakeholder feedback after the meeting led to HERC staff not proceeding with the accepted changes for retrospective glucose monitoring. The recommendation was to add retrospective (professional) continuous glucose monitoring (CPT 95250-95251 Glucose monitoring by SQ device) to line 500 and GN168 as shown below, and remove from line 8 TYPE 1 DIABETES MELLITUS effective January 1, 2018.
GUIDELINE NOTE 168, TREATMENTS WITH MARGINAL CLINICAL BENEFIT OR LOW COST- EFFECTIVENESS FOR CERTAIN CONDITIONS The following treatments are prioritized on Line 500, CONDITIONS FOR WHICH CERTAIN TREATMENTS RESULT IN MARGINAL CLINICAL BENEFIT OR LOW COST-EFFECTIVENESS, for the conditions listed here:
CONDITION CPT/HCPCS TREATMENT Rational Date of last Code Review Diabetes mellitus 95250-95251 Retrospective Limited evidence of clinical August, 2017 (professional) utility continuous glucose monitoring
Stakeholders informed HERC staff that CPT 95250-95251 are actually used for several services in addition to professional retrospective glucose monitoring. These codes can be used for the situation in which a patient is given a trial period of CGM prior to purchasing a personal CGM. CPT code 95250 can also be used for the training given to the patient for either the personal/real-time (for long-term use) or professional/retrospective CGM (lent to the patient from the facility for short-term use). CPT 95251 is used for the reading of data and interpretation for either device.
Internal discussion amongst HERC staff and HSD staff have led to the recommendation to continue to include CPT 95250-95251 on line 500/GN168, but to also add them back to line 8 TYPE 1 DIABETES MELLITUS with a coding specification.
1
Straightforward Modifications to the Prioritized List Changes: Continuous Glucose Monitoring in Diabetes Mellitus
HERC Staff Recommendations: 1) Reverse the August 2017 decision to remove CPT 95250 and 95251 from line 8 TYPE 1 DIABETES MELLITUS 2) Add a coding specification to line 8 TYPE 1 DIABETES MELLITUS as shown below a. “CPT 95250 and 95251 are included on this line for services related to real-time CGM but not to retrospective (professional) CGM.” 3) Affirm the addition of the entry to GN168 as shown below (effective January 1, 2018)
GUIDELINE NOTE 168, TREATMENTS WITH MARGINAL CLINICAL BENEFIT OR LOW COST-EFFECTIVENESS FOR CERTAIN CONDITIONS The following treatments are prioritized on Line 500, CONDITIONS FOR WHICH CERTAIN TREATMENTS RESULT IN MARGINAL CLINICAL BENEFIT OR LOW COST-EFFECTIVENESS, for the conditions listed here:
CONDITION CPT/HCPCS TREATMENT Rational Date of last Code Review Diabetes mellitus 95250-95251 Retrospective Limited evidence of clinical August, 2017 (professional) utility continuous glucose monitoring
2
Barrett’s Esophagus Straightforward Change
Question: how should GN144 be modified to clarify coverage of proton pump inhibitor (PPI) therapy for Barrett’s esophagus with dysplasia?
Question source: HERC staff
Issue: Barrett’s esophagus with dysplasia (ICD-10 K22.71) is on line 314 CANCER OF ESOPHAGUS; BARRETT'S ESOPHAGUS WITH DYSPLASIA. However, the guideline regarding PPI therapy does not list 314 as a line eligible for long term PPI therapy. As reviewed in January, 2016, PPI therapy is indicated for Barrett’s esophagus with or without dysplasia. At the January, 2016 meeting, the HERC affirmed the addition of Barrett’s esophagus with dysplasia to line 314 and modified GN144 PROTON PUMP INHIBITOR THERAPY FOR GASTROESOPHAGEAL REFLUX DISEASE (GERD) to clarify that Barrett’s esophagus without dysplasia is on line 385 and treatment includes long term proton pump inhibitor therapy. There is no mention of the higher grade Barrett’s diagnosis being eligible for long term PPI therapy, presumably because such therapy was not for GERD. Recently, HERC staff was contacted by a CCO on behalf of a gastroenterologist to clarify when long term PPI therapy is a covered services.
Current Prioritized List status: ICD10 K22.70 (Barrett’s esophagus) is on line 385 ICD10 K22.71 (Barrett’s esophagus with dysplasia) is on line 314 CANCER OF ESOPHAGUS; BARRETT'S ESOPHAGUS WITH DYSPLASIA
HERC staff recommendation: 1) Modify GN144 as shown below
GUIDELINE NOTE 144, PROTON PUMP INHIBITOR THERAPY FOR GASTROESOPHAGEAL REFLUX DISEASE (GERD) Lines 314,385,516 Short term treatment (up to 8 weeks) of GERD without Barrett’s (ICD-10 K20.8, K20.9, K21.0, K21.9) with proton pump inhibitor therapy is included on Line 385. Long term treatment is included on Line 516.
Long term proton pump inhibitor therapy is included on line 385 for Barrett’s esophagus (ICD-10 K22.70). and on line 314 for Barrett’s esophagus with dysplasia (ICD-10 K22.71).
1
Nicotine replacement tobacco cessation guideline
Question: Does the tobacco dependence guideline need modification?
Question source: Peter Mahr, MD, local provider
Issue: A local provider was finding difficulty with getting nicotine replacement therapy (specifically patches) covered by a CCO and contacted HERC to determine required coverage. In the follow up to that query, the following questions have arisen: Do CCOs need to cover without any copay or prior authorization all FDA- approved pharmacotherapies? o All types (i.e. the variety of nicotine replacement therapies including gum, lozenges, patches, nasal spray, inhaler; varenicline, buproprion) o All brands
Also, the weblink needs updating.
Prioritized List Status GUIDELINE NOTE 4, Tobacco dependence, including during pregnancy Lines 1,5 Pharmacotherapy and behavioral counseling are included on this line, alone or in combination, for at least 2 quit attempts per year. A minimum of four counseling sessions of at least 10 minutes each (group or individual, telephonic or in person) are included for each quit attempt. More intensive interventions and group therapy are likely to be the most effective behavioral interventions. During pregnancy, additional intensive behavioral counseling is strongly encouraged. All tobacco cessation interventions during pregnancy are not subject to limits.
Inclusion on this line follows the minimum standard criteria as defined in the Oregon Public Health Division “Standard Tobacco Cessation Coverage” (based on the Patient Protection and Affordable Care Act), available here: https://public.health.oregon.gov/PreventionWellness/TobaccoPrevention/Pages /pubs.aspx. The USPSTF has also made “A” recommendations for screening, counseling, and treatment of pregnant and nonpregnant adults, included in Guideline Note 106.
The development of this guideline note was informed by a HERC coverage guidance. See http://www.oregon.gov/oha/HPA/CSI-HERC/Pages/Evidence- based-Reports.aspx
HERC Staff Summary The intent of the guideline note would be met if at least one medication within each category is covered fully with no PA or co-pays. For examples, if there are two different brands of patches, with significantly different cost, it is reasonable for a CCO to choose to offer a cheaper patch. However, they must also make available all the variety of
Nicotine replacement tobacco cessation guideline, Issue #1311 Page 1
Nicotine replacement tobacco cessation guideline different options of pharmacotherapy (patches, gum, lozenges, spray, inhaler, varenicline, buproprion).
HERC Staff Recommendations: 1) Update the hyperlink to the public health Standard Tobacco Cessation Coverage document 2) Modify guideline note 4 to clarify coverage of pharmacotherapy as follows: GUIDELINE NOTE 4, Tobacco dependence, including during pregnancy Lines 1,5 Pharmacotherapy and behavioral counseling are included on this line, alone or in combination, for at least 2 quit attempts per year.
Pharmacotherapy includes all of the FDA-approved cessation medications in all approved forms (nicotine gum, nicotine patch, nicotine lozenge, nicotine nasal spray, nicotine inhaler, varenicline, and bupropion). At least one option (brand or generic) for each of these listed therapies is included on these lines with no prior authorization requirement for at least two quit attempts per year. Each quit attempt can include concurrent use of either two nicotine replacement dosage forms or one nicotine replacement form plus bupropion SR.
A minimum of four counseling sessions of at least 10 minutes each (group or individual, telephonic or in person) are included for each quit attempt. More intensive interventions and group therapy are likely to be the most effective behavioral interventions. During pregnancy, additional intensive behavioral counseling is strongly encouraged. All tobacco cessation interventions during pregnancy are not subject to limits.
Inclusion on this line follows the minimum standard criteria as defined in the Oregon Public Health Division “Standard Tobacco Cessation Coverage” (based on the Patient Protection and Affordable Care Act), available here: https://public.health.oregon.gov/PreventionWellness/TobaccoPrevention/Pages /pubs.aspx. http://www.oregon.gov/oha/PH/PREVENTIONWELLNESS/TOBACCOPREVENTION /Documents/tob_cessation_coverage_standards.pdf. The USPSTF has also made “A” recommendations for screening, counseling, and treatment of pregnant and nonpregnant adults, included in Guideline Note 106.
The development of this guideline note was informed by a HERC coverage guidance. See http://www.oregon.gov/oha/HPA/CSI-HERC/Pages/Evidence- based-Reports.aspx
Nicotine replacement tobacco cessation guideline, Issue #1311 Page 2
Section 4.0 New Codes 2018 CDT codes
CDT Code Code description Proposed Placement Comments
D0411 HbA1c in-office point of service Diagnostic Procedures File Covered as diagnostic for medical offices. Supports testing medical/dental integration. HSD will consider rules for frequency D5511 repair broken complete denture 451 DENTAL CONDITIONS (EG. MISSING Similar denture repair CDT codes are on line 451. Replaces D5510 base, mandibular TEETH, PROSTHESIS FAILURE) Treatment which was on line 267; OHAP felt that 451 was a more REMOVABLE PROSTHODONTICS (E.G. FULL appropriate line for placement. HSD will prepared rules regarding AND PARTIAL DENTURES, RELINES) repair of broken dentures
D5512 repair broken complete denture 451 See above base, maxillary D5611 repair resin partial denture base, 451 Replaces D5610 which was on line 451 mandibular D5612 repair resin partial denture base, 451 See above maxillary D5621 repair cast partial framework, 451 Replaces D5620 which is on line 451 mandibular Initial cast partial dentures are not covered, but OHAP felt that a pre-existing partial should be repaired if otherwise working well.
D5622 repair cast partial framework, 451 See D5621 above maxillary D6096 remove broken implant retaining 344 DENTAL CONDITIONS (EG. SEVERE Other implant removal CDT codes (i.e. CDT D6100 (IMPLANT screw CARIES, INFECTION) Treatment: ORAL REMOVAL, BY REPORT)) were added to line 344 as a biennial SURGERY (I.E. EXTRACTIONS AND OTHER review change in February, 2017 effective January 1, 2018. INTRAORAL SURGICAL PROCEDURES) Current placement of all implant related CDT codes is line 616. OHAP felt that broken screws should be covered for removal.
1 2018 CDT codes
CDT Code Code description Proposed Placement Comments
D6118 implant/abutment supported interim 616 DENTAL CONDITIONS (EG. MISSING All similar impant insertion CDT codes are on line 616. Only fixed denture for edentulous arch – TEETH) Treatment: IMPLANTS (I.E. IMPLANT implant removal codes were added to line 344 with biennial mandibular PLACEMENT AND ASSOCIATED CROWN OR review PROSTHESIS) D6119 implant/abutment supported interim 616 See above fixed denture for edentulous arch – maxillary D7296 corticotomy – one to three teeth or 615 DENTAL CONDITIONS (EG. This is an orthodontic procedure used only for adults, not tooth spaces, per quadrant MALOCCLUSION) children. Therefore does not belong on the craniofacial anomaly or cleft palate lines. D7297 corticotomy four or more teeth or 615 DENTAL CONDITIONS (EG. See D7297 above tooth spaces, per quadrant MALOCCLUSION) D7979 non – surgical sialolithotomy 498 SIALOLITHIASIS, MUCOCELE, Sialoadenitis and sialolithiasis are on lines 323 SIALOADENITIS, DISTURBANCE OF SALIVARY SECRETION, ABSCESS, FISTULA OF SALIVARY GLANDS and 498, as are the CPT OTHER AND UNSPECIFIED DISEASES OF codes for sailolithotomy (42330-42340). D7980 SALIVARY GLANDS (SIALOLITHOTOMY) is also on lines 323 and 498. OHAP recommended placement of the dental codes only on 498, leaving 323 as a medical line.
NOTE: Remove D7980 (SIALOLITHOTOMY) from line 323.
D8695 removal of fixed orthodontic 267 Dental conditions (time sensitive OHAP recommended that fixed appliances always be removed if appliance(s) - other than at events) Tx Urgent dental services needed. Orthodontic appliances may be applied for many conclusion of treatment diagnoses if a patient has this procedure done prior to coming on OHP. If the appliance is still in place, it can lead to poor oral hygiene and pathology and should be removed if the orthodontic treatment is not planned to be continued.
D9222 deep sedation/general anesthesia – Ancillary Procedures File Code D9222 billed for 1st 15 minutes and D9223 to be billed for first 15 minutes each 15 increment after. D9223 is Ancillary. Similar medical anesthesia CPT codes are Ancillary
2 2018 CDT codes
CDT Code Code description Proposed Placement Comments
D9239 intravenous moderate (conscious) Ancillary Procedures File Similar CDT codes (D9241-D9248) for moderate conscious sedation/analgesia- first 15 minutes sedation are Ancillary. Code D9239 first 15 minutes and D9243 for each 15 after. D9243 is Ancillary D9995 teledentistry – synchronous; real- 54 DENTAL CONDITIONS (EG. INFECTION, Line 54 includes other place of service codes such as D9410 time encounter PAIN, TRAUMA) HOUSE/EXTENDED CARE FACILITY CALL and D9420 HOSPITAL OR AMBULATORY SURGICAL CENTER CALL
HSD will prepare rules regarding use of the teledentristry codes
D9996 teledentistry – asynchronous; 54 DENTAL CONDITIONS (EG. INFECTION, See above information stored and forwarded to PAIN, TRAUMA) dentist for subsequent review
3
MINUTES
Health Evidence Review Commission’s Oral Health Advisory Panel (OHAP)
Clackamas Community College Wilsonville Training Center, Room 155 September 18, 2017 10:30 AM – 12:00 PM
Members Present: Gary Allen, DMD, Chair (by phone); Bruce Austin, DMD (by phone); Patricia Parker, DMD (by phone); Karen Nolon; Alison Noble (by phone); Laura McKeane (by phone).
Members Absent: Eli Schwarz, DDS, MPH, PhD; Len Barozzini, DDS; Deborah Loy.
Staff Present: Darren Coffman; Ariel Smits, MD, MPH (by phone).
Also Attending: Kellie Skenandore (OHA).
Roll Call/Minutes Approval/Staff Report
The meeting was called to order at 10:30 am and roll was called. Laura McKeane and Alison Noble were welcomed to the advisory panel. Minutes from June 26, 2017 were reviewed and approved.
Topic: 2018 CDT Code Placement Recommendations
Actions: The 2018 CDT codes were discussed. The staff recommendations for placement were accepted except as outlined below. See the attached spreadsheet for comments and discussion about the new codes with no change in the staff recommendations.
1. D7979 (non–surgical sialolithotomy) was proposed for lines 323 SIALOADENITIS, ABSCESS, FISTULA OF SALIVARY GLANDS and 498 SIALOLITHIASIS, MUCOCELE, DISTURBANCE OF SALIVARY SECRETION, OTHER AND UNSPECIFIED DISEASES OF SALIVARY GLANDS. There was general consensus that this code should not be covered except in cases when the stone was causing infection or other pathology. In that case, the sialiolithotomy would be covered under the medical codes for sialolithotomy (CPT 42330-42340). The group recommended that sialolithotomy (surgical or non-surgical) when done in the dental office should be only on line 498. Medical sialolithotomy CPT codes should be on line 323 and 498. Therefore, D7979
OHAP Minutes 9/18/2017 Page 1
should only be added to line 498. Additionally, D7980 (SIALOLITHOTOMY) should be removed from 323 and remain on line 498. 2. D8695 (removal of fixed orthodontic appliance(s) - other than at conclusion of treatment). Staff recommendation was to add to all lines with orthodontic codes: 42 CLEFT PALATE WITH AIRWAY OBSTRUCTION, 257 DEFORMITIES OF HEAD, 300 CLEFT PALATE AND/OR CLEFT LIP, and 615 DENTAL CONDITIONS (EG. MALOCCLUSION). The OHAP members felt that there should be coverage for removal of an orthodontic appliance if placed prior to OHP coverage, particularly if the appliance is causing pathology. There was further discussion that retained fixed appliances would always eventually cause issues if only due to lack of ability to maintain oral hygiene. Line 267 DENTAL CONDITIONS (TIME SENSITIVE EVENTS) Tx: URGENT DENTAL SERVICES was proposed as a more appropriate line placement.
Public Comment:
No public comment was received.
Issues for next meeting:
HERC staff will accept issues from members and other stakeholders as they arise over the year and bring them to the next OHAP meeting, tentatively scheduled for late next spring or early summer.
Next meeting: o TBD
OHAP Minutes 9/18/2017 Page 2
Section 5.0 Previously Discussed Items New Medications for the Treatment of Duchenne Muscular Dystrophy
Question: How should new medications for the treatment of Duchenne muscular dystrophy (DMD) be prioritized? 1) deflazacort (Emflaza) 2) eteplirsen (Exondys 51)
Question source: Pharmacy and Therapeutics (P&T) staff, OHA leadership
Issue: What is Duchenne muscular dystrophy (DMD)? DMD is an X-linked recessive genetic disorder that is the most common type of muscular dystrophy, affecting 1 in 5,000 males at birth. Currently, in the Oregon Health Plan (OHP) population, approximately 70 fee-for-service patients and more than 300 patients enrolled in coordinated care organizations have a diagnosis of muscular dystrophy (all types, not necessarily DMD). DMD results in muscle weakness beginning at age 2-4 that progresses quickly. Most affected boys lose the ability to walk between ages 9 and 14. Most patients eventually become ventilator dependent, and life expectancy is approximately age 26. The usual cause of death is respiratory failure. Women with one copy of the defective gene may show mild symptoms.
What causes DMD? DMD is caused by a mutation in the gene for the protein dystrophin. Dystrophin is important to maintain the muscle fiber's cell membrane. Dystrophin is necessary for normal muscle function; loss of dystrophin results in degeneration of muscle fibers and results in muscle weakness.
How is DMD usually treated? No cure for muscular dystrophy is known. Treatment is supportive and includes physical therapy, braces, and corrective surgery to help with some symptoms. Medications used include steroids to slow muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants to delay damage to dying muscle cells. Cardiac pacemakers may be required due to acquired cardiomyopathy; ventilatory support is also frequently required later in the course of the disease.
What is the importance of dystrophin levels in DMD? In untreated patients with DMD, documented dystrophin levels typically range from 0 to 0.4% of normal healthy patients. Experts suggest that dystrophin levels less than 3% of normal are typically associated with a phenotype of DMD. It is unclear whether increases in dystrophin protein level in patients with DMD correlate to clinical outcomes. Similarly, the minimum change in dystrophin level which may result in a clinical improvement has not been established. Some experts suggest that very minimal improvements may constitute a beneficial change in dystrophin level while others suggest that dystrophin levels at 10-20% of normal would likely correlate to clinically significant changes in muscle symptoms or function. In patients with Becker muscular dystrophy, a less severe form of muscular dystrophy, dystrophin protein levels
1
New Medications for the Treatment of Duchenne Muscular Dystrophy are on average 80% of normal. In the P&T review, no studies were found which compared change in dystrophin protein level and the change in clinical outcomes for patients with DMD.
2
New Medications for the Treatment of Duchenne Muscular Dystrophy
New medications 1) Deflazacort (Emflaza) a. General i. Deflazacort is a corticosteroid which has been on the market in Europe and other countries for decades, but only recently achieved FDA approval in the United States. ii. Guidelines from the American Academy of Neurology recommend either deflazacort or prednisone as first-line treatment in children over 5 years of age to improve muscle and pulmonary function and reduce risk of scoliosis b. Evidence (see the P&T medication review) i. The P&T review was based primarily on an April, 2017 Drug Effectiveness Review Project (DERP) report. 1. Studies: 4 RCTs (N=348 total), 3 systematic reviews, and one guideline (all included males at least age 5 with DMD, comparing deflazacort to prednisone). Overall evidence from these trials was graded as poor quality due to significant methodological flaws and lack of reported data. 2. RCT: N=196, included both Duchenne and Becker muscular dystrophy patients (very different types of disease), 12 week crossover study. Patients followed for 1 year, no difference in muscle strength was seen between deflazacort and prednisone. Patients randomized to deflazacort had less weight gain (5.05 kg) compared to prednisone (8.45 kg; MD 3.4 kg; p<0.0001) over the course of 1 year. However, incidence of cataracts was higher with deflazacort (6.6%) at 1 year compared to prednisone (4.4%; p- value not reported). The adverse event data was considered of too poor a quality to make any conclusions. 3. RCT: N=100, no difference in muscle strength found at 2 yrs between types of steroids 4. RCT: N=18, no difference in muscle strength found at 2 yrs between types of steroids 5. RCT: N=34, no statistically significant difference in muscle strength found at 18 months between types of steroids ii. Summary of findings: 1. There is insufficient evidence to evaluate differences between deflazacort and other corticosteroids for DMD or other conditions. 2. Overall, there is insufficient evidence to evaluate differences in adverse effects between deflazacort and other oral
3
New Medications for the Treatment of Duchenne Muscular Dystrophy
corticosteroids. Evidence is limited by small sample sizes, lack of reported methodology and outcomes, and use of historical controls from a population of patients outside of the United States. c. Cost i. Wholesale acquisition cost of deflazacort
42998050101 DEFLAZACORT - EMFLAZA ORAL 6 MG TABLET 09 - WHN $43.61000 DEFLAZACORT 42998050203 ORAL 18 MG - EMFLAZA TABLET 09 - WHN $130.83333 DEFLAZACORT 42998050303 ORAL 30 MG - EMFLAZA TABLET 09 - WHN $218.06666 DEFLAZACORT 42998050403 ORAL 36 MG - EMFLAZA TABLET 09 - WHN $243.00000 DEFLAZACORT 42998050521 ORAL 22.75MG/ML - EMFLAZA ORAL SUSP 09 - WHN $221.00000 ii. FDA approved dosing for deflazacort: 0.9 mg/kg/day 1. Estimated cost per year for a 25 kg patient based on this WAC: approximately $63,670 (four 6 mg tablets a day) 2. Deflazacort is available as a generic medication in Europe for approximately $1000/yr iii. Wholesale acquisition cost of prednisone is $0.05 per 20 mg tablet. 1. Estimated cost per year per patient: $55
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New Medications for the Treatment of Duchenne Muscular Dystrophy
2) eteplirsen (Exondys 51) a. General: In approximately 13% of patients with DMD, the cause is a mutation in exon 51 of the pre-mRNA. Eteplirsen binds to exon 51 of dystrophin pre-mRNA leading to exclusion of this exon and formation of a partially functional, truncated dystrophin protein. b. Estimated prevalence of patients with Duchenne muscular dystrophy (DMD) and an exon 51 mutation is approximately 1 in 27,000 people (13% of DMD patients) i. Oregon OHP patients with DMD and the exon 51 mutation: estimated to be 35-50 patients ii. Estimates are that 60-80% of DMD patients have an exon mutation that may eventually be treatable with eteplirsen or similar medications (estimated to be 250-300 OHP patients) c. Eteplirsen has conditional FDA approval with a specification in the medication labeling that it “has no proven clinical benefit.” Final FDA approval will depend on the results of a large ongoing trial expected to have published results in the next few years. i. Within the FDA, there was intense and unprecedented disagreement concerning eteplirsen's approval, which was made public when the FDA commissioner released a document summarizing in detail the internal controversies surrounding the eteplirsen review. In brief, the Director of the Office of Drug Evaluation, Dr. Ellis Unger, and the Division of Neurology Products, headed by Dr. Ronald Farkas, had initially rejected the eteplirsen application. However, they were overruled by Dr. Janet Woodcock, the Director of the Center for Drug Evaluation & Research. An internal FDA dispute resolution process was then initiated, culminating in an appeal to the FDA Commissioner, Dr. Robert Califf, who allowed Dr. Woodcock's approval decision to stand. Dr. Farkas and at least one other member of the eteplirsen review team resigned from the FDA. Although the reason for these resignations has not been made public, the timing led to speculation that they are related to the eteplirsen approval. d. Several similar medications treating different mutations of the dystrophin gene are in clinical trials e. Evidence (see the P&T medication review) i. 3 studies (N=25); 1 randomized placebo controlled trial and 2 open-label studies. All subjects were ambulatory. Primary outcome was dystrophin protein level in muscle tissue. Clinical outcomes included change in 6- minute walking distance. All studies found to be poor quality with significant methodologic flaws. 1. Study 1: RCT of 12 pts for 24 weeks (randomized (1:1:1) to eteplirsen 50 mg/kg weekly, eteplirsen 30 mg/kg weekly, or placebo). No difference was observed in the 6-minute walk
5
New Medications for the Treatment of Duchenne Muscular Dystrophy
distance at 24 weeks compared to placebo. Change in dystrophin level from baseline could not be assessed. 2. Study 2: extension of study 1 to 3.5 years. Control patients from study 1 were treated with eteplirsen (50 mg/kg weekly or 30 mg/kg weekly) and all patients were compared to historical controls from Belgium and Italy. Patients treated with eteplirsen had an average dystrophin level that was 0.93% of the normal protein level in healthy patients. No significant difference in 6 minute walk test was found at 48 weeks. Overall, compared to the historical control, patients treated with eteplirsen experienced a benefit of 162 meters at 36 months (3 years) in the 6MWT (p=0.0005). The manufacturer also claimed that only 2 patients (16.7%) treated with eteplirsen lost ambulation over 4 years compared to 76.9% (10/13) of untreated historical controls. However, when results are evaluated as a function of age, 6 patients (4 less than 14 years of age and 2 still ambulatory between 13 and 14 years of age) appear to have similar disease progression and functional decline compared to their age- matched, untreated historical controls. All patients treated with eteplirsen had progressive decline in other functional outcomes including NSAA scores with no apparent difference from the untreated historical control. a. Note: “There is a high risk of selection, performance, detection, and reporting bias in this study and efficacy results should not be considered in the decision-making process.” 3. Study 3: an ongoing, unpublished, interim analysis of an open- label study trial of 13 patients treated with eteplirsen 30 mg/kg weekly for 48 weeks. Mean change in dystrophin level from baseline to 48 weeks was 0.28% of normal (0.16% at baseline vs. 0.44% at 48 weeks; p=0.008). Change in dystrophin protein level has not been validated as a surrogate outcome in DMD and there is no evidence to support it is correlated to clinical outcomes. The minimum change in dystrophin level which may result in a clinical improvement has not been established. No functional outcomes were evaluated in this study. 4. P&T study critique: Efficacy of eteplirsen for DMD remains to be established. Data from Western blot analysis suggests that some patients may not respond to treatment with little to no improvement in dystrophin levels. The FDA recommended further post-marketing studies to evaluate efficacy at higher doses.
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New Medications for the Treatment of Duchenne Muscular Dystrophy
Studies failed to demonstrate improvement in functional outcomes even in patients treated for more than 4 years, and labeling for eteplirsen specifies that a clinical benefit has not been established. Furthermore, though a slight change in level of dystrophin level was observed (<1% of normal), changes did not correlate with any clinical improvement. It remains to be determined if changes in dystrophin correlate to clinical outcomes, and the FDA has required further studies to evaluate functional improvements in patients with DMD. FDA approval of eteplirsen was highly controversial because it conflicted with the recommendation by the external advisory committee who expressed multiple concerns with the studies, including: industry funding, blinding procedures, assays used, small sample size, and very minimal change from baseline. 5. Safety: The safety population included a total of 114 patients treated with at least one dose of eteplirsen. Only 36 patients have been treated for more than 6 months and 12 have been treated for more than 1 year. Serious adverse events occurred in 6 patients (5.3%) and were consistent with expected events for a population of patients with DMD. ii. Summary: Efficacy of eteplirsen for DMD remains to be established. The studies published to date were found to have serious methodological flaws. Studies failed to demonstrate improvement in functional outcomes even in patients treated for more than 4 years, and labeling for eteplirsen specifies that a clinical benefit has not been established. Furthermore, though a slight change in level of dystrophin level was observed (<1% of normal), changes do not correlate with any clinical improvement. Additionally, there are significant methodological concerns and a high risk of bias in available studies. f. Wholesale Acquisition Cost:
60923028410 ETEPLIRSEN - EXONDYS INTRAVEN 51 500MG/10ML VIAL 09 - WHN $800.00000 60923036302 ETEPLIRSEN - EXONDYS INTRAVEN 100 51 MG/2ML VIAL 09 - WHN $800.00000 1. Note: vials are single use. The cost is $800/ml regardless of vial size 2. A 25kg patient dosed at 30 mg/kg/week would require 750mg/wk (one 500mg vial at $8000 + three 100mg vials at $4800), giving an estimated yearly cost of $665,600 i. It is estimated that there are 35-50 OHP patients with DMD and the exon 51 mutation eligible for this therapy (this estimate is highly uncertain)
7
New Medications for the Treatment of Duchenne Muscular Dystrophy
Other state Medicaid coverage policies: States vary on coverage of eteplirsen, with some state Medicaid programs considering it experimental and others covering it for certain or all DMD patients.
HERC staff summary: Based on the Pharmacy and Therapeutics drug reviews, deflazacort has equal efficacy to prednisone at dramatically higher cost. The evidence quality was considered too poor to determine differences in side effect profiles between deflazacort and prednisone.
Eteplirsen has evidence of a small (<1%) increase in the surrogate outcome of dystrophin levels, but this increase does not have any known clinical significance. Additionally, there is no published evidence of improved clinical outcomes such as 6 minute walk distances, hospitalizations, etc. with eteplirsen treatment. This is a very high cost medication.
Stakeholder input already received on this topic: 1) P&T obtained input from Barry Russman, MD, Professor of Pediatrics and Neurology at OHSU, in preparing the report excerpted below 3) Two additional DMD experts were contacted by P&T for comments on the P&T review; no responses were received from these providers during report preparation 4) At the P&T meeting at which deflazacort and eteplirsen were discussed, public comment was taken from Erika Finanger, MD MS, Assistant Professor of Neurology and Pediatrics at OHSU and Co-Director, Muscular Dystrophy Association Clinic at Shriners Hospital Portland 5) Public comment from various patients and patient families was received at the P&T meeting at which deflazacort and eteplirsen were discussed 6) Public comment was received at the August, 2017 VBBS meeting: a) A patient and his mother and another parent of a child with DMD testified about their positive experiences with Exondys 51, and their belief that it slowed functional decline. They requested that this medication be covered by Oregon Medicaid. b) A representative of the manufacturer of Exondys 51 testified on the FDA approval of the drug and its indication. c) A CCO representative testified about the high cost of these drugs affecting the CCO ability to pay for other services and medications. He recommended the HERC consider how best to be stewards of Medicaid dollars in their deliberations on these medications.
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New Medications for the Treatment of Duchenne Muscular Dystrophy
HERC staff recommendations: 1) Prioritize deflazacort (Emflaza) for Duchenne muscular dystrophy to line 500 and add the following entry to GN168 as it is much less cost effective than alternative, equally effective therapies GUIDELINE NOTE 168, TREATMENTS WITH MARGINAL CLINICAL BENEFIT OR LOW COST-EFFECTIVENESS FOR CERTAIN CONDITIONS
The following treatments are prioritized on Line 500 for the conditions listed here: CONDITION CPT/HCPCS TREATMENT Rationale Date of Last Review/Link code to Meeting Minutes Duchenne Muscular Deflazacort (Emflaza) Marginal benefit/low September, 2017 Dystrophy cost-effectiveness compared to equally effective but much less expensive alternative corticosteroids
2) Prioritize eteplirsen (Exondys 51) to line 660 and add the following entry to GN169 due to no clinically important benefit shown in studies GUIDELINE NOTE 169, TREATMENTS THAT HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS FOR CERTAIN CONDITIONS; UNPROVEN TREATMENTS
The following treatments are prioritized on Line 660, CONDITIONS FOR WHICH CERTAIN TREATMENTS HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS; UNPROVEN TREATMENTS, for the conditions listed here: CONDITION CPT/HCPCS TREATMENT Rational Date of Last Review/Link Code to Meeting Minutes Duchenne Muscular Eteplirsen (Exondys 51) No clinically important September, 2017 Dystrophy benefit
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New Medications for the Treatment of Duchenne Muscular Dystrophy
10
© Copyright 2012 Oregon State University. All Rights Reserved
Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 | Fax 503-947-1119
OHSU Drug Effectiveness Review Project Summary Report – Deflazacort oral tablet
Date of Review: July 2017 End Date of Literature Searcy: 05/22/2017 Generic Name: deflazacort Brand Name (Manufacturer): Emflaza™ (PTC Therapeutics) Dossier Received: Yes
Research Questions: 1. What is the comparative efficacy or effectiveness of deflazacort compared to currently available corticosteroids in improving clinical outcomes (including improved muscle strength and mobility, prevention of long-term cardiac and pulmonary complications, and increased survival) in patients with Duchenne Muscular Dystrophy (DMD)? 2. Is deflazacort safe for treatment of DMD and what is the relative safety compared to other corticosteroids? 3. Are there any subgroups (based on age, gender, ethnicity, comorbidities, disease duration or severity) that would particularly benefit or be harmed from treatment with deflazacort?
Conclusions: The report conducted by the Drug Effectiveness Review Project (DERP) evaluated deflazacort for the treatment of DMD based on 4 randomized controlled trials (RCT), 3 systematic reviews, and one guideline. Four RCTs of poor methodological quality showed insufficient evidence that demonstrated no difference in muscle strength and motor outcomes between deflazacort and prednisone for patients with DMD. Similarly, there is a lack of quality evidence evaluating comparative differences in adverse effects between deflazacort and prednisone. Evidence that deflazacort is associated with significantly less weight gain (mean difference [MD] 2.91 to 4.1 kg) but more cataracts than prednisone was of insufficient quality. Due to significant methodological limitations of these trials and lack of reported data, the true treatment effect is likely to be substantially different from the estimated treatment effect. Two of these RCTs were completed more than 20 years ago, and only one included patients in the United States. As a result, these data may not be applicable to patients under the Oregon Health Plan (OHP) today. There was no comparative evidence of deflazacort and prednisone beyond 2 years of follow-up. There is insufficient evidence to evaluate differences between deflazacort and other corticosteroids for DMD or other conditions. Overall, there is insufficient evidence to evaluate differences in adverse effects between deflazacort and other oral corticosteroids. Evidence is limited by small sample sizes, lack of reported methodology and outcomes, and inadequate data in a United States population of patients.
Recommendations: Implement prior authorization criteria that restricts use to patients with DMD and documented contraindication or serious intolerance to oral corticosteroids (Appendix 3).
Author: Sarah Servid, PharmD Date: July 2017
Refer deflazacort to the Health Evidence Review Commission (HERC) for funding placement as a drug with high cost and marginal benefit compared to currently available low-cost oral corticosteroids.
Background: Duchenne muscular dystrophy (DMD) is a rare X-linked genetic disorder caused by the absence of a functional dystrophin protein. Duchenne’s is the most common type of muscular dystrophy occurring in approximately 1 in 7250 males between the ages of 5 to 24 years.1 Currently, in the Oregon Health Plan (OHP) population, approximately 70 fee-for-service patients and more than 300 patients enrolled in coordinated care organizations have a diagnosis of muscular dystrophy. Available claims data for OHP are unable to distinguish between patients with various types of muscular dystrophy. Based on the estimated prevalence of DMD, approximately 60 OHP patients with muscular dystrophy may be eligible for this medication. Patients with DMD experience progressive muscle deterioration leading to loss of ambulation and decreased muscle strength. Long-term complications include pulmonary problems, dilated cardiomyopathy, arrhythmias, and increased risk for thrombotic events. In many patients, these complications can lead to wheelchair dependence by age 12 and death before the age of 20.2 Only 25% of patients remain ambulatory by age 16.3 There is currently no curative treatment, and therapy focuses on improving symptoms, enhancing quality of life, and decreasing disease progression. Guidelines from the American Academy of Neurology recommend either deflazacort or prednisone as first-line treatment in children over 5 years of age to improve muscle and pulmonary function and reduce risk of scoliosis.2 Other non- pharmacological therapies which are often essential in disease management include physical therapy and use of support devices such as braces and wheelchairs. As the disease progresses, mechanical ventilation and spinal surgery may be used to improve pulmonary function and decrease pain from scoliosis and vertebral fractures.4
Deflazacort is a corticosteroid which has been on the market in Europe and other countries for decades, but only recently achieved FDA approval in the United States. Deflazacort was approved through the FDA priority review process for the treatment of DMD in patients age 5 years and older based on the results of 2 randomized active-comparator trials including 196 and 18 patients each. The primary outcome evaluated change in muscle strength measured by a modified Medical Research Council scale. The Medical Research Council scale (MRC) ranges from 0 to 10 points, with higher scores indicating greater strength. A score of 10 indicates the muscle is able to contract against full resistance and 0 represents no movement observed.1 Scores are typically assessed and summarized for several muscle groups in several positions (sitting, prone, supine, and lying on the side). The minimum clinically important difference with this scale has not been established. Other studies evaluated change in muscle function using timed function tests such as the time required to stand from a supine position or the time required to walk a certain distance. Other methods to evaluate functional improvement included use of the Motor Function Index which evaluates a patient’s ability to climb four 17 cm stairs, stand from a sitting position, and walk 10 meters on flat ground.5 Each test is evaluated on a 1-3 scale indicating if individuals are able to complete the task without assistance (1 point), accomplish the task with assistance (2 points), or are not able to complete the task (3 points).5 Total scores range from 3 to 9 with larger scores indicating more severe disease.5 The validity of this scale and minimum clinically important change has not been determined.
Deflazacort has also been studied for treatment on multiple conditions including idiopathic thrombocytic purpura, essential mixed cryoglobulinemia, juvenile chronic arthritis, nephrotic syndrome, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, solid organ transplant rejection, and urolithiasis.4 Randomized controlled trials have examined the efficacy or safety of deflazacort compared to other corticosteroids. However, long-term population-based studies indicate that oral prednisone may be associated with greater incidence of weight gain, hirsutism and cushingoid appearance, while deflazacort may have greater risk of cataracts.1,6,7 The DERP review summarizes comparative evidence of deflazacort versus other corticosteroids for the treatment of DMD. Evidence for other potential off-label conditions will also be considered in this report.
Author: S. Servid Date: July 2017
See Appendix 1 for Highlights of Prescribing Information from the manufacturer, including Boxed Warnings and Risk Evaluation Mitigation Strategies (if applicable), indications, dosage and administration, formulations, contraindications, warnings and precautions, adverse reactions, drug interactions and use in specific populations.
Methods: An April 2017 Drug Effectiveness Review Project (DERP) report compared deflazacort to prednisone for children with Duchenne Muscular Dystrophy was used to inform recommendations for this drug evaluation. The DERP report was supplemented with information from the manufacturer’s prescribing information and the FDA website. In addition, new evidence published since completion of the DERP report that evaluated use for FDA-approved indications or off-label conditions was identified. The Medline search strategy used for this review is available in Appendix 2, which includes dates, search terms and limits used. The Agency for Healthcare Research and Quality (AHRQ), the Cochrane Collaboration, National Institute for Health and Clinical Excellence (NICE), Department of Veterans Affairs, BMJ Clinical Evidence, and the Canadian Agency for Drugs and Technologies in Health (CADTH) resources were manually searched for high quality and relevant systematic reviews. Finally, the AHRQ National Guideline Clearinghouse (NGC) was searched for updated and recent evidence‐based guidelines.
The DERP is part of the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University. The purpose of the DERP reports is to make available information regarding the comparative clinical effectiveness and harms of different drugs. DERP reports are not usage guidelines, nor should they be read as an endorsement of or recommendation for any particular drug, use, or approach. OHSU does not recommend or endorse any guideline or recommendation developed by users of these reports. The original DERP report is available to Oregon Pharmacy and Therapeutics Committee members upon request. An executive summary report is publically available in the agenda packet and on the DURM website.
Summary Findings: Duchenne Muscular Dystrophy A total of 4 RCTs, 3 systematic reviews, and one guideline were identified in the DERP report. All trials included a similar population of patients (males at least age 5 with DMD), and all compared FDA-approved dosing of deflazacort 0.9 mg/kg/day to prednisone 0.75 mg/kg/day.2 Overall evidence from these trials was graded as poor quality due to significant methodological flaws and lack of reported data.2
The primary study used for FDA approval included 196 males from the United States and Canada randomized to deflazacort 0.9 mg/kg/day, deflazacort 1.2 mg/kg/day, prednisone 0.75 mg/kg/day, or placebo.2 At 12 weeks, patients in the placebo group were re-randomized to a treatment arm. The trial was completed in 1995, and at this time the distinction between types of muscular dystrophy was not well defined. As a result, this trial included patients with either Duchenne or Becker muscular dystrophy limiting applicability to patients with DMD today. The primary outcome was change in muscle strength at 12 weeks measured using a modified MRC index score.1 Scores are based on several muscle strength assessments and evaluated on a 0 to 10 point rating scale with lower scores indicating more severe disease.1,8 Secondary outcomes included muscle strength at 1 year, motor function, pulmonary function, disease severity, adverse effects, weight gain and change in growth. Outcomes are summarized in Table 1. Actual MRC scores at baseline, 12 weeks and 1 year were not reported and numbers represent the change in MRC score from baseline. Overall, there was no significant difference in muscle strength between patients treated with either corticosteroid at 12 weeks or 1 year.2 Compared to placebo at 12 weeks, these differences in MRC were statistically significant for both groups, though the clinical significance of 0.25 to 0.38 points is questionable.8 There was no difference between deflazacort and prednisone in timed motor function tests between groups at 1 year.2 Timed motor function tests included time to stand from a supine position, climb 4 stairs, run or walk 30 feet, or propel a wheelchair 30 feet.2 This evidence had several important limitations which decrease confidence in these results including potential conflicts of interest and lack of information on randomization methods, allocation concealment, and baseline disease severity between groups. Author: S. Servid Date: July 2017
Table 1. Mean change in MRC Score^ from Baseline (95% CI).8 12 weeks 1 year Placebo -0.1 (-0.23 to 0.03) - Deflazacort 0.9 mg/kg 0.15 (0.01 to 0.28)* 0.39 (0.25 to 0.54) Deflazacort 1.2 mg/kg 0.26 (0.12 to 0.40)* 0.38 (0.23 to 0.54) Prednisone 0.75 mg/kg 0.27 (0.13 to 0.41)* 0.23 (0.07 to 0.38) *Statistically different from placebo. ^MRC score was evaluated on a 0 to 10 point scale.
A second trial of 100 German patients also evaluated the comparative efficacy and safety of prednisone and deflazacort.2 Overall, data from this study were rated as poor quality due to significant methodological flaws and lack of reported data. Preliminary results of this RCT including 67 patients were published in 1995 and final results including all 100 patients were available in an unpublished conference report in 2000.2 Of the 100 patients enrolled, 80% remained in the trial at 2 years.2 Overall, there was no difference in muscle function or strength between groups. However, numerical data for these outcomes were not reported, and results from this trial were limited by highly disparate attrition rates between groups without use of an intention-to-treat analysis.2
The third RCT was double-blinded and included 18 Italian patients followed for 2 years.2 Patients were randomized to prednisone or deflazacort and reportedly stratified by disease severity and age.2 However, methods used for randomization and allocation concealment were unclear.2 Outcomes reported at 1 and 2 years included muscle strength, motor outcomes (reported descriptively) and weight gain. No difference was observed in muscle strength or functional scores at 2 years.2 This study was significantly limited by the small sample size, lack of reported outcomes, and significant risk of bias.2
Another RCT evaluated 34 Iranian patients randomized to deflazacort or prednisone.2 The study was limited by poor reporting of methodological methods including methods of randomization, allocation concealment, blinding, and baseline characteristics for each group.2 In addition, a significant portion of patients were lost to follow up with high differential rates between groups (17.6% in deflazacort vs. 29.4% in prednisone group) increasing risk of bias.2 The efficacy outcomes evaluated included change in the motor function index (Table 2) up to 18 months. The motor function index evaluates functional status on a 7-point scale (range 3-9) with larger scores indicating more severe disease.5 At 12 months, patients treated with deflazacort had a statistically significant increase from baseline in the mean motor function index compared to prednisone, but differences failed to achieve statistical significance at 18 months.2,5
Table 2. Motor function index reported as mean score (95% CI) and mean difference (MD) from baseline.5 Baseline 12 months 18 months Deflazacort 0.9 mg/kg 4.93 (95% CI 4.4 to 5.5) 4.36 (95% CI 3.7 to 5.0); MD -0.57 4.64 (95% CI 3.8 to 5.5); MD -0.29 Prednisone 0.75 mg/kg 5.0 (95% CI 4.6 to 5.5) 5.25 (95% CI 4.4 to 6.1); MD 0.25 5.75 (95% CI 4.4 to 7.2); MD 0.75 Mean difference between groups 0.82; p=0.001 1.04; p=0.128
Three systematic reviews also evaluated comparative efficacy and safety between prednisone and deflazacort.2 Though the RCTs included in these reviews differed, they all reached similar conclusions. Evidence for motor outcomes was graded as insufficient to very low quality demonstrating no difference in efficacy between deflazacort and prednisone.2
Author: S. Servid Date: July 2017
One guideline from the American Academy of Neurology on use of corticosteroids for treatment of DMD was included in the DERP report. Evidence supporting recommendations in this guideline included one RCT and multiple observational studies that evaluated the comparative effectiveness of deflazacort and prednisone.2 The majority of observational evidence included cohort or case-control studies with a defined control group, masked outcome assessment, and description of potential confounding factors.9 Overall, evidence was graded as moderate quality indicating moderate assessment of benefit versus risk, low quality indicating small benefit relative to risk, or very low quality indicating there is insufficient evidence to evaluate risk versus benefit. Due to limitations in the evidence, many recommendations are graded as low quality.2 No specific recommendations are made for any particular agent. Evidence supporting use of prednisone to improve strength and pulmonary function was rated as moderate quality.2 There was low quality evidence to support use of deflazacort to improve strength and pulmonary function, delay loss of ambulation by 1.4 to 2.5 years, and increase survival at 5 or 15 years.2 Evidence regarding survival was primarily derived from 3 observational studies which demonstrated increased mortality in untreated patients (21-43%) compared to those treated with deflazacort (3-11%).6 Six observational studies evaluated outcomes of muscle strength and ambulation with deflazacort treatment and demonstrated improvements in motor outcomes using various measures.6 In 3 of these studies, the age at which patients lost ambulation was improved by 1.4 to 2.5 years in patients treated with deflazacort compared to no treatment.6 Two additional studies evaluating both prednisone and deflazacort demonstrated improvements in age at loss of ambulation for both medications.6 Evidence evaluating the need for scoliosis surgery, delaying the onset of cardiomyopathy, and improving timed motor function tests was evaluated as low quality for both prednisone and deflazacort.2 Similarly, there was low quality evidence that deflazacort and prednisone provide similar improvements in motor function, and low quality evidence that deflazacort has less weight gain but greater risk for cataracts than prednisone.2 Direct comparative evidence included 2 observational studies that demonstrated no difference in functional motor outcomes over 1 year and 5.49 years each.6 In these studies, weight gain was more common in the first year of treatment (mean weight increase of 21.3% with prednisone vs. 9% with deflazacort) corresponding to a mean weight increase at 1 year of 5.08 kg in patients treated with prednisone compared to 2.17 kg in patients treated with deflazacort (p<0.05).6 However, one study noted no difference in weight in older children (12-15 years).6 Cataracts occurred more often in patients treated with deflazacort compared to prednisone, though results were not statistically significant.6 There was insufficient evidence to compare differences between therapies for other outcomes including pulmonary and cardiac function.2
Evidence evaluating adverse effects was also reported from these 4 RCTs. In the primary study used for FDA approval (n=196), patients randomized to deflazacort had less weight gain (5.05 kg) compared to prednisone (8.45 kg; MD 3.4 kg; p<0.0001) over the course of 1 year. However, incidence of cataracts was higher with deflazacort (6.6%) at 1 year compared to prednisone (4.4%; p-value not reported).2 Similar trends were noted between groups with evaluation of body mass index.2 Similarly in subsequent studies, patients treated with prednisone versus deflazacort reported higher incidence of weight gain leading to treatment discontinuation (data not reported) and more weight gain at 1 and 2 years (2.17 kg vs. 5.08 kg, p-value not reported and 4.6 kg vs. 8.7 kg; p<0.05, respectively). Another study reported that patients treated with prednisone had a greater mean percent increase in weight than patients treated with deflazacort at 12 months (21.7% vs. 13.0%; p=0.001) and 18 months (32% vs. 21.7%; p=0.046) corresponding to a mean 2.41 to 3.18 kg weight increase in patients treated with prednisone compared to deflazacort.2,5 One other study (n=100) also reported that more patients on deflazacort developed cataracts compared to patients treated with prednisone (36% vs. 3%, p-value not reported).2 However, evidence from these RCTs was limited by inadequate or unclear methods, lack of adequately reported data, and high and/or disparate attrition rates without use of intention-to-treat analyses.2 Systematic reviews evaluating adverse effects of deflazacort and prednisone also concluded that deflazacort was associated with less weight gain than prednisone though evidence was graded as very low quality indicating very little confidence in the estimated effect.2 Further studies are needed to evaluate comparative safety and adverse effects between deflazacort and other corticosteroids.
Author: S. Servid Date: July 2017
Because deflazacort is a corticosteroid, FDA labelling includes warnings and precautions for adverse effects which have been associated with corticosteroid use. Warnings are summarized in Appendix 1. Additional rare but serious adverse effects include effects on growth and development, myopathy, Kaposi’s sarcoma, thrombotic events, and anaphylaxis.10 Deflazacort suspension also includes benzyl alcohol preservative which has been associated with increased risk of serious and fatal reactions in infants and is not approved in children less than 5 years of age.10 Common adverse effects (occurring in >10% of patients compared to placebo at 12 weeks) included cushingoid appearance, weight gain, and increased appetite.10 Because clinical trials included a limited population of patients randomized to deflazacort and placebo (n=51 and 50), rates of adverse events may not be reflective of rates observed in clinical practice.10
Off-label Indications A high-quality systematic review published in 2012 examined the comparative efficacy and safety of deflazacort versus other corticosteroids for the treatment of nephrotic syndrome.11 The review included 3 single-center RCTs (n=91 patients total) in France, Denmark and Argentina.11 Patients were randomized to deflazacort or prednisone in 2 studies and to deflazacort or methylprednisolone in the third study.11 Two trials evaluated use in children and one evaluated adults with newly diagnosed nephrotic syndrome. Data for these trials were described descriptively as they did not consistently report similar outcomes and evaluated different populations. Two studies examine time to remission, with no apparent difference between patients randomized to deflazacort or another corticosteroid.11 In 1 study, the mean number of new relapses and the proportion of children who were relapse free at 1 year was improved with treatment of deflazacort compared to prednisone (MD 1.9; 0.9 vs. 2.8; p<0.002 and 60% vs. 10%; p=0.002, respectively).11 Another study reported no difference in the number of relapses after more than 4 years of follow-up.11 No significant difference was observed in mean growth velocity, fasting blood sugar, infection rate, or cushingoid symptoms when deflazacort was compared to other corticosteroids.11 One study did report a smaller mean decrease with deflazacort compared to prednisone in bone density (3.6 vs. 5.9 gHa; p<0.05) and bone mineral content (0.0050 vs. 0.0089 gHa/cm2/month; p<0.05) of the spine, while another study failed to achieve statistical significance between groups.11 Evidence was limited by lack of defined primary and secondary outcomes and small patient population.11 In addition, one trial failed to report adequate randomization methods, and in another, providers and outcome assessors were not blinded, increasing risk of bias.11
Randomized Controlled Trials: A total of 155 citations were manually reviewed from the initial literature search. The Medline search strategy used for this review is available in Appendix 2, which includes dates, search terms and limits used. After further review, 139 citations were excluded because of wrong study design (eg, observational), comparator (eg, no control or placebo-controlled), population (eg, healthy subjects), or outcome (eg, non-clinical). Several excluded trials examined effects on bone mineral density or content. However, bone mineral density can vary between instruments and trials did not report outcomes using standardized methods (i.e. T-score or Z-score) making interpretation of these outcomes difficult. The remaining 20 trials were critically evaluated for internal validity and risk of bias. Seven trials were excluded due to substantial flaws and lack of reported methods which significantly increase risk for selection bias (i.e. methods of randomization and allocation concealment, inclusion and exclusion criteria, and relevant baseline characteristics were not reported), and results should not be considered in the decision-making process. Results of the remaining trials which evaluate evidence for deflazacort in off-label conditions are summarized in the table below. Overall, evidence is limited by small population size, significant methodological flaws, and lack of reported outcomes which increases risk of bias. In addition, the majority of studies were completed outside the United States at a single medical center, and published more than 15 years ago limiting applicability to the OHP population today.
Author: S. Servid Date: July 2017
Table 3. Description of Comparative Clinical Trials. Study/Location Comparison Population/ Primary Outcome Results Study Limitations and Potential Sources of Location Bias Grosso S, et al. 1. Hydrocortisone daily and Children with Proportion of 1. 44% Patients and providers were not blinded and 2008.12 tapered at monthly drug-resistant patients with 2. 47% patients were allocated to groups on an intervals on the following epilepsy >50% decreased P=0.9 alternate basis at hospitalization increasing OL, RCT schedule: 10 mg/kg, 5 seizure frequency risk of bias. Allocation concealment was not mg/kg, 2.5 mg/kg, 1 Italy at 6 months reported. N=35 mg/kg, and 1 mg/kg on alternate days, thereafter Duration: 6 2. Deflazacort 0.75 mg/kg months Elli A, et al. 1. Deflazacort Kidney transplant No primary Acute rejection episodes Inclusion and exclusion criteria were not 1993.13 2. Methylprednisolone patients outcome specified. 1. 9 (36%) specified. Randomization and allocation Clinical outcomes 2. 11 (44%) concealment methods were unclear. Single-center, Dosing administered in a Italy included rejection p-value NS Baseline weight was higher in patients OL, RCT ratio of 6 mg deflazacort to episodes and treated with methylprednisolone (2.7kg). 4 mg methylprednisolone. weight gain at 1 Mean change in weight Open-label study increases risk of bias. N=50 Dose was tapered to 12 or year 1. 1.25 kg Primary and secondary outcomes were not 18 mg at 12 months. 2. 2.8 kg specified and multiple outcomes were Duration: 1 yr P<0.05 examined without methods to control for multiplicity increasing risk of reporting bias. Kim Y, et al. 1. Deflazacort Kidney transplant No primary 50% dose reduction of Randomization and allocation concealment, 1997.14 2. Prednisolone patients with pre- outcome specified. insulin or diabetic agents methods were unclear. Primary and or post-transplant Outcomes 1. 12 (30.8%) secondary outcomes were not specified and OL, single-site, Dose given in a ratio of 1 DM included change in 2. 2 (5%) multiple outcomes were examined without RCT mg to 1.2 mg of prednisone body weight, P=0.023 methods to control for multiplicity to deflazacort Korea insulin increasing risk of bias. N=82 requirements, Weight acute rejection, 1. 1.74 kg weight loss adverse effects 2. 0.58 kg weight loss Ferraris JR, et 1. Deflazacort 0.3 Children following No primary No specified primary Randomization and allocation concealment al. 2007.15 mg/kg/day kidney outcome specified. outcome. Multiple methods were unclear. Patients and 2. Methylprednisolone 0.2 transplantation Outcomes outcomes described providers were not blinded increasing risk of OL, MC, RCT mg/kg/day (mean time since included rates of descriptively. BMI was bias. Primary and secondary outcomes were transplantation adverse effects not significantly different not pre-specified and were evaluated post- N=31 was 2.1 years) compared to between groups. More hoc. Adverse effects were evaluated using baseline (growth, patients treated with multiple analyses increasing risk of reporting Duration: 3 yrs Argentina body weight, BMD, deflazacort had an bias. Multiple outcomes were described and effects on LDL<100 mg/dL descriptively. Use of concomitant lipid or (p<0.001) and normal glucose-lowering therapies was not
Author: S. Servid Date: July 2017
glucose and lipid glucose/insulin ratio addressed. Four patients (13%) were metabolism). (p=0.02) at 2 or 3 years. withdrawn from the study due to onset of puberty. Saviola GL, et 1. Deflazacort 7.5 mg/day Adults with active No specified ACR50 at 6 months Randomization and allocation concealment al. 2007.16 2. Methylprednisolone 4 RA or psoriatic primary outcomes. 1. 5/9 (55.5%) methods not stated. Patients and providers mg/day arthritis, naïve to Efficacy was 2. 6/11 (54.5%) were not blinded increasing risk of bias. Single-center, steroid treatment evaluated using p-value NR Primary and secondary outcomes were not OL, cross-over, At 6 months, patients were ACR score at 6 and specified. RCT allocated to the alternate Italy 12 months. ACR50 at 12 months treatment group 1. 6/9 (66.7%) N=21 2. 7/11 (63.6%) p-value NR Duration: 1 yr Messina O, et 1. Deflazacort 12 mg/day Patients with RA No primary Changes in joint Blinding performed with identical capsules. al. 1992.17 2. Prednisone 10 mg/day outcome specified. involvement, and Randomization generated with use of a Argentina Clinical outcomes morning stiffness NR. computer with allocation concealment. DB, RCT included change in Change in physical Primary and secondary outcomes were not joint involvement, activity was NS specified and multiple outcomes were N=16 morning stiffness, (described descriptively). examined without methods to control for and physical multiplicity increasing risk of bias. Duration: 1 yr activity 12 months. Study not powered to determine differences in outcomes. Loftus J, et al. 1. Deflazacort (mean dose Children with No primary No specified primary Randomization and blinding methods were 1991.18 9.07 mg/day) chronic juvenile outcome specified. outcome. No statistical not reported. Baseline weight was not 2. Prednisone (mean dose rheumatoid Outcomes difference was noted in reported. Primary and secondary outcomes DB, RCT 7.87 mg/day) arthritis included joint joint count, height, or were not specified and multiple outcomes count, height, fractures. were examined without methods to control N=34 Corticosteroids England weight, and for multiplicity increasing risk of bias. Study administered as alternate- fractures. Weight gain at 1 year was not powered to determine differences Duration: 1 yr day regimens and in a 1.2 was greater for in outcomes. Data on weight outcomes was to 1 mg ratio of deflazacort prednisone than not reported. to prednisone deflazacort; p<0.02 (described descriptively) Gray R, et al. 1. Deflazacort Adults with RA, No primary No primary outcome Randomization and allocation concealment 1991.19 2. Prednisone polymyalgia outcome specified. specified. No statistically methods were not reported. Patients rheumatic, mixed Clinical outcomes significant differences blinded using identically packaged Blinded, RCT Dose was fixed for first 15 connective tissue included weight, were observed between medications. Blinding of providers unclear. days then adjusted based disease, or severe early morning treatment groups for all Primary and secondary outcomes were not N=26 on clinical requirements eczema stiffness, grip clinical outcomes. specified and multiple outcomes were strength, pain and examined without methods to control for functional multiplicity increasing risk of bias. Study was
Author: S. Servid Date: July 2017
Duration: 3 assessments, and not powered to determine differences in months adverse effects outcomes. More patients in the deflazacort group began additional immunotherapy at the start of the study. Di Munno O, et 1. Deflazacort 24 mg daily Polymyalgia No primary Mean pain scores Randomization and allocation concealment al. 1995.20 2. Deflazacort 48 mg on rheumatica outcome specified. 1. -4.5 methods were unclear. Blinding achieved alternate days Clinical outcomes 2. -4.6 with use of identical packaging though Cross-over, DB, 3. Methylprednisolone 16 included pain 3. -6.3 tablets had different appearances. RCT mg daily scores (evaluated 4. -6.0 7 patients (23%) were excluded from the 4. Methylprednisolone 32 by visual analogue p-values NS between all analysis. Primary and secondary outcomes N=31 mg on alternate days scale) and were not specified and multiple outcomes morning stiffness Mean change in morning were examined without methods to control Duration: 12 After 2 weeks, dose was stiffness from baseline for multiplicity increasing risk of reporting weeks titrated based on clinical (minutes) bias. response. At 6 weeks 1. -83 patients were allocated to 2. -84 the alternate dosing 3. -132 regimen (daily vs. alternate 4. -116 day). Eberhardt R, et 1. Deflazacort Patients with RA Ritchie Index (an Ritchie index at 12 Randomization, allocation concealment, and al. 1994.21 2. Prednisone evaluation of 53 months (SD) blinding methods were unclear. Concomitant Germany joint groups each 1. 12.8 (7.46) use of other medications for RA and baseline DB, MC, RCT Mean daily dose was 8.5 scored on a 0-3 2. 9.8 (7.6) disease severity were not reported. 23 mg deflazacort and 7.3 mg scale; total range: P=0.4954 patients (30%) were lost to follow-up. N=76 prednisone. 0 to 159)
Duration: 12 months Lund B, et al. 1. Deflazacort Patients with Disease activity, Results described Randomization methods were unclear and 1987.22 2. Prednisone polymyalgia pain and descriptively. No baseline disease severity for each group was rheumatic tenderness difference was observed not reported. Multiple analyses performed DB, cross-over, Dosing administered in a evaluated using a in general disease without methods to control for multiplicity. RCT ratio of 1.2-1.8 mg Denmark visual analog scale activity, pain or Study not powered to determine differences deflazacort to 1 mg tenderness. in outcomes. N=30 prednisone for 2 week periods Rizzato G, et al. 1. Deflazacort Patients with No primary Fractures Randomization and allocation concealment 1997.23 2. Prednisone chronic outcome specified. 1. 1/28 (3.5%) methods were unclear. Disease duration was pulmonary Clinical outcomes 2. 5/30 (16.7%) longer for patients treated with deflazacort OL, RCT sarcoidosis p-value NR (5.6 vs. 3.5 years). Dose and duration of
Author: S. Servid Date: July 2017
Mean starting dose was 22 included fracture treatment were not equivalent. Open-label N=72 mg for each group and events trial further increases risk of bias. Primary tapered based on clinical and secondary outcomes were not specified Mean duration: requirements and multiple outcomes were examined 42 months without methods to control for multiplicity increasing risk of bias. Bone toxicity analysis only reported in 58 patients (80%). Ferrari A, et al. 1. Deflazacort 1.4 Autoimmune No primary Complete response Randomization and allocation concealment 1991.24 mg/kg/day thrombocytopenic outcome specified. 1. 2/11 (18%) methods were unclear. Open label design 2. Prednisone 1 mg/kg/day purpura Clinical efficacy 2. 2/12 (17%) increases risk of bias. Primary and secondary OL, RCT outcomes included outcomes were not specified and multiple Treatment was tapered complete response No treatment response outcomes were examined without methods N=27 upon complete response to (platelet count 1. 4/11 (36%) to control for multiplicity increasing risk of treatment (platelet count >150) and no 2. 4/12 (33%) bias. Duration: 24 >150) or completion of 4 response (platelet Four patients (14.8%) were excluded weeks weeks of treatment count <50) after p-values NS increasing risk of attrition bias. Study was 24 weeks not powered to determine differences in outcomes. Abbreviations: ACR50 = 50% improvement in the American College of Rheumatology criteria; BMD = bone mineral density; BMI = bod mass index; DMD = Duchenne Muscular Dystrophy; DXA = dual x-ray absorptiometry; ESRD = end-stage renal disease; MC = multicenter; MD = mean difference; NR = not reported; NS = not significant; OL = open-label; RA = rheumatoid arthritis; RCT = randomized clinical trial; SD = standard deviation; yrs = years.
Table 1. Pharmacology and Pharmacokinetic Properties.1,10 Parameter Corticosteroid prodrug which has anti-inflammatory and immunosuppressant properties. The exact mechanism in patients with Mechanism of Action Duchenne muscular dystrophy is unclear. Oral Bioavailability Not reported; area under the curve is unchanged upon administration with food Distribution and Protein binding = 40% Protein Binding Exact volume of distribution is unknown 68% excreted unchanged in urine Elimination 18% metabolized Half-Life Half-life of approximately 1.17 to 2.4 hours. Elimination is almost complete by 24 hours after a single dose. Converted to the active metabolite, 21-des-deflazacort by esterase Metabolism Metabolized via CYP3A4 and p-glycoprotein
Author: S. Servid Date: July 2017
References: 1. Deflazacort Medical Review. US Food and Drug Administration Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000TOC.cfm. 2. Carson S, Driver R, and Harrod C. Emflaza (deflazacort) for children with Duchenne muscular dystrophy: Comparative effectiveness versus prednisone. Portland, OR: Center for Evidence-based Policy, Oregon Health & Science University. April 2017. 3. Deflazacort Summary Review. US Food and Drug Administration Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208684,208685Orig1s000TOC.cfm. 4. Emflaza (deflazacort) tablets [product dossier]. Northbrook, IL: Marathon Pharmaceuticals LLC; 2017. 5. Karimzadeh P, and Ghazavi, A. Comparison of Deflazacort and Prednisone in Duchenne Muscular Dystrophy. Iranian Journal of Child Neurology. 2012;6(1):5-12. 6. Gloss D, Moxley RT, 3rd, Ashwal S, Oskoui M. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology. 2016;86(5):465-472. 7. Bello L, Gordish-Dressman H, Morgenroth LP, et al. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology. 2015;85(12):1048-1055. 8. Griggs R, Miller, JP, Greenberg, CR, et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology 2016;87(20):2123-2131. 9. American Academy of Neurology. 2011. Clinical Practice Guideline Process Manual, 2011 ed. St. Paul, MN: The American Academy of Neurology. 10. Emflaza (deflazacort) [package insert]. Northbrook, IL: Marathon Pharmaceuticals, LLC. February 2017. 11. Jat KR, Khairwa A. Deflazacort in comparison to other steroids for nephrotic syndrome. Indian J Nephrol. 2012;22(4):239-245. 12. Grosso S, Farnetani M, Mostardini R, Cordelli D, Berardi R, Balestri P. A comparative study of hydrocortisone versus deflazacort in drug-resistant epilepsy of childhood. Epilepsy Res. 2008;81(1):80-85. 13. Elli A, Rivolta R, Di Palo FQ, et al. A randomized trial of deflazacort versus 6-methylprednisolone in renal transplantation--immunosuppressive activity and side effects. Transplantation. 1993;55(1):209-212. 14. Kim YS, Kim MS, Kim SI, et al. Post-transplantation diabetes is better controlled after conversion from prednisone to deflazacort: a prospective trial in renal transplants. Transpl Int. 1997;10(3):197-201. 15. Ferraris JR, Pasqualini T, Alonso G, et al. Effects of deflazacort vs. methylprednisone: a randomized study in kidney transplant patients. Pediatr Nephrol. 2007;22(5):734-741. 16. Saviola G, Abdi Ali L, Shams Eddin S, et al. Compared clinical efficacy and bone metabolic effects of low-dose deflazacort and methyl prednisolone in male inflammatory arthropathies: a 12-month open randomized pilot study. Rheumatology. 2007;46(6):994-998. 17. Messina OD, Barreira JC, Zanchetta JR, et al. Effect of low doses of deflazacort vs prednisone on bone mineral content in premenopausal rheumatoid arthritis. J Rheumatol. 1992;19(10):1520-1526. 18. Loftus J, Allen R, Hesp R, et al. Randomized, double-blind trial of deflazacort versus prednisone in juvenile chronic (or rheumatoid) arthritis: a relatively bone-sparing effect of deflazacort. Pediatrics. 1991;88(3):428-436. 19. Gray RE, Doherty SM, Galloway J, Coulton L, de Broe M, Kanis JA. A double-blind study of deflazacort and prednisone in patients with chronic inflammatory disorders. Arthritis Rheum. 1991;34(3):287-295. 20. Di Munno O, Imbimbo B, Mazzantini M, Milani S, Occhipinti G, Pasero G. Deflazacort versus methylprednisolone in polymyalgia rheumatica: clinical equivalence and relative antiinflammatory potency of different treatment regimens. J Rheumatol. 1995;22(8):1492-1498.
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21. Eberhardt R, Kruger K, Reiter W, Gross W, Zwingers T. Long-term therapy with the new glucocorticosteroid deflazacort in rheumatoid arthritis. Double- blind controlled randomized 12-months study against prednisone. Arzneimittelforschung. 1994;44(5):642-647. 22. Lund B, Egsmose C, Jorgensen S, Krogsgaard MR. Establishment of the relative antiinflammatory potency of deflazacort and prednisone in polymyalgia rheumatica. Calcif Tissue Int. 1987;41(6):316-320. 23. Rizzato G, Riboldi A, Imbimbo B, Torresin A, Milani S. The long-term efficacy and safety of two different corticosteroids in chronic sarcoidosis. Respir Med. 1997;91(8):449-460. 24. Ferrari A, Pasqualetti D, Del Bianco P, Gandolfo GM, Chistolini A, Mazzucconi MG. Prednisone versus deflazacort in the treatment of autoimmune thrombocytopenic purpura: evaluation of clinical response and immunological modifications. Haematologica. 1991;76(4):342-345.
Author: S. Servid Date: July 2017
Appendix 1: Prescribing Information Highlights
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use EMFLAZA™ safely and effectively. See full prescribing information for EMFLAZA. Behavioral and Mood Disturbances: May include euphoria, EMFLAZA (deflazacort) tablets, for oral use insomnia, mood swings, personality changes, severe depression, EMFLAZA (deflazacort) oral suspension and psychosis (5.5) Initial U.S. Approval: 2017 Effects on Bones: Monitor for decreases in bone mineral density with chronic use of EMFLAZA (5.6)
Ophthalmic Effects: May include cataracts, infections, and ------INDICATIONS AND USAGE------EMFLAZA is a corticosteroid indicated for the treatment of Duchenne glaucoma; Monitor intraocular pressure if EMFLAZA is muscular dystrophy (DMD) in patients 5 years of age and older (1) continued for more than 6 weeks (5.7) Vaccination: Do not administer live or live attenuated vaccines to ------DOSAGE AND ADMINISTRATION------patients receiving immunosuppressive doses of corticosteroids The recommended once-daily dosage is approximately 0.9 (5.8) mg/kg/day administered orally (2.1) Serious Skin Rashes: Discontinue at the first sign of rash, unless Discontinue gradually when administered for more than a few the rash is clearly not drug related (5.9) days (2.2) ------ADVERSE REACTIONS------DOSAGE FORMS AND STRENGTHS------The most common adverse reactions (≥ 10% for EMFLAZA and Tablets: 6 mg, 18 mg, 30 mg, and 36 mg (3) greater than placebo) are Cushingoid appearance, weight increased, Oral Suspension: 22.75 mg/mL (3) increased appetite, upper respiratory tract infection, cough, pollakiuria, hirsutism, central obesity, and nasopharyngitis (6.1) ------CONTRAINDICATIONS------Hypersensitivity to deflazacort or any of the inactive ingredients in ------DRUG INTERACTIONS------EMFLAZA (4) Moderate or strong CYP3A4 inhibitors: Give one third of the recommended dosage of EMFLAZA (7.1) ------WARNINGS AND PRECAUTIONS------ Avoid use of moderate or strong CYP3A4 inducers with Alterations in Endocrine Function: Hypothalamic-pituitary- EMFLAZA, as they may reduce efficacy (7.1) adrenal axis suppression, Cushing’s syndrome, and hyperglycemia can occur; Monitor patients for these conditions To report SUSPECTED ADVERSE REACTIONS, contact with chronic use of EMFLAZA (2.2, 5.1) Marathon Pharmaceuticals, LLC at 1-866-562-4620 or Immunosuppression and Increased Risk of Infection: Increased [email protected] or FDA at 1-800-FDA-1088 risk of new, exacerbation, dissemination, or reactivation of latent or www.fda.gov/medwatch. infections, which can be severe and at times fatal; Signs and symptoms of infection may be masked (5.2) See 17 for PATIENT COUNSELING INFORMATION and FDA- Alterations in Cardiovascular/Renal Function: Monitor for approved patient labeling. elevated blood pressure and sodium, and for decreased potassium levels (5.3) Revised: 02/2017 Gastrointestinal Perforation: Increased risk in patients with certain GI disorders; Signs and symptoms may be masked (5.4)
Author: S. Servid Date: July 2017
Appendix 2: Literature search
Ovid MEDLINE(R) Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid MEDLINE(R) 1946 to Present
1 deflazacort.mp. 527
2 limit 1 to (english language and humans) 377
3 limit 2 to (clinical trial, all or clinical trial, phase iii or clinical trial, phase iv or clinical trial or comparative study or controlled clinical trial or meta 155 analysis or multicenter study or practice guideline or pragmatic clinical trial or randomized controlled trial or systematic reviews)
Appendix 3. Prior Authorization Criteria Drugs for Duchenne Muscular Dystrophy
Goal(s): Encourage use of corticosteroids which have demonstrated long-term efficacy Restrict use of eteplirsen and deflazacort to patients with Duchenne Muscular Dystrophy and limit use of deflazacort to patients with contraindications or serious intolerance to other oral corticosteroids
Length of Authorization: 6 months
Requires PA: Eteplirsen Deflazacort
Covered Alternatives: Current PMPDP preferred drug list per OAR 410-121-0030 at www.orpdl.org Searchable site for Oregon FFS Drug Class listed at www.orpdl.org/drugs/
Approval Criteria
1. What diagnosis is being treated? Record ICD10 code.
2. Is the diagnosis funded by OHP? Yes: Go to #3 No: Pass to RPh. Deny; not funded by the OHP.
Author: S. Servid Date: July 2017
Approval Criteria
3. Is the request for treatment of Duchenne Muscular Yes: Go to #4 No: Pass to RPh. Deny; Dystrophy? medical appropriateness.
Note: Eteplirsen and deflazacort are not indicated for other forms of muscular dystrophy or other diagnoses.
4. Is the request for continuation of eteplirsen treatment? Yes: Go to Renewal Criteria No: Go to #5
5. Is the request for deflazacort? Yes: Go to #6 No: Go to #8
6. Is the patient ≥ 5 years of age? Yes: Go to #7 No: Pass to RPh. Deny; medical appropriateness.
7. Does the patient have a documented contraindication or Yes: Approve for up to 12 No: Pass to RPh. Deny; intolerance to oral prednisone that is not expected to months. medical appropriateness. crossover to deflazacort? Document contraindication or Recommend trial of another oral intolerance reaction. corticosteroid.
8. Does the patient have a diagnosis of Duchenne Muscular Yes: Go to #9 No: Pass to RPh, Deny; Dystrophy with one of the following genetic mutations medical appropriateness. amenable to exon 51 skipping: Document genetic testing. Deletion of exons 45 to 50 Deletion of exons 48 to 50 Deletion of exons 49 and 50 Deletion of exon 50 OR Deletion of exon 52?
9. Has the patient been on a stable dose of corticosteroid for Yes: Go to #10 No: Pass to RPh. Deny; at least 6 months? medical appropriateness.
Author: S. Servid Date: July 2017
Approval Criteria
10. Has baseline functional assessment been evaluated using Yes: Document baseline No: Pass to RPh. Deny; a validated tool such as the 6-minute walk test or North Star functional assessment and medical appropriateness. Ambulatory Assessment? approve for up to 6 months
Renewal Criteria
1. Has the patient’s baseline functional status been Yes: Approve for up to 6 months No: Pass to RPh, Deny; maintained at or above baseline level or not declined more medical appropriateness. than expected given the natural disease progression? Document functional status.
P&T/DUR Review: 07/17 (SS) Implementation: TBD
Author: S. Servid Date: July 2017
© Copyright 2012 Oregon State University. All Rights Reserved
Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 | Fax 503-947-1119
New Drug Evaluation: Eteplirsen injection, intravenous
Date of Review: July 2017 End Date of Literature Search: 06/02/2017 Generic Name: eteplirsen injection Brand Name (Manufacturer): Exondys 51 (Sarepta Therapeutics, Inc.) Dossier Received: Yes
Research Questions: 1. What is the efficacy of eteplirsen compared to placebo or currently available treatments of Duchenne Muscular Dystrophy (DMD)? 2. Is eteplirsen safe for treatment of DMD? 3. Are there any subgroups (based on age, gender, ethnicity, comorbidities, disease duration or severity) that would particularly benefit or be harmed from treatment with eteplirsen?
Conclusions: Efficacy of eteplirsen for DMD remains to be established. Studies failed to demonstrate improvement in functional outcomes even in patients treated for more than 4 years, and labeling for eteplirsen specifies that a clinical benefit has not been established.1 Furthermore, though a slight change in level of dystrophin level was observed (<1% of normal), changes do not correlate with any clinical improvement. Additionally, there are significant methodological concerns and a high risk of bias in available studies. There is insufficient evidence that eteplirsen treatment in patients with DMD is associated with any clinical change in symptoms or functional status. Functional improvement was primarily evaluated using the 6-minute walk test (6MWT). In a single study of 12 patients, no difference was observed between patients treated with eteplirsen and placebo in the 6MWT at 24 or 48 weeks.1 A long-term extension study evaluating functional improvement assessed with the 6MWT or North Star Ambulatory Assessment (NSAA) over 36 months compared eteplirsen to a historical control group.2 However, significant limitations associated with this study including differing baseline characteristics between groups, inability to control for potential confounders, and differences in assessment methods limit confidence in these results. Labeling for eteplirsen specifies that a clinical benefit has not been established.3 Eteplirsen was primarily evaluated in 2 studies (n=24) which examined change in the level of dystrophin protein. After 3.5 years of treatment, patients treated with eteplirsen had an average dystrophin level that was 0.93% of the normal protein level in healthy patients (as evaluated by Western blot).1 Mean change in dystrophin level from baseline to 48 weeks was 0.28% of normal (0.16% at baseline vs. 0.44% at 48 weeks; p=0.008).1 Change in dystrophin protein level has not been validated as a surrogate outcome in DMD and there is no evidence to support it is correlated to clinical outcomes. The minimum change in dystrophin level which may result in a clinical improvement has not been established. There is insufficient evidence to evaluate safety of eteplirsen for treatment of DMD. The safety population included a total of 114 patients treated with at least one dose of eteplirsen. Only 36 patients have been treated for more than 6 months and 12 have been treated for more than 1 year.1 Serious adverse events occurred in 6 patients (5.3%) and were consistent with expected events for a population of patients with DMD.1 There is insufficient evidence to evaluate differences in specific populations or subgroups. Author: Sarah Servid, Pharm.D. Date: July 2017
Recommendations: Recommend implementation of prior authorization criteria limiting use to the population studied and requiring maintained functional status with continuation of therapy (Appendix 2). Due to the lack of evidence supporting clinical efficacy of eteplirsen for the treatment of Duchenne muscular dystrophy, consider referral of eteplirsen to the Health Evidence Review Commission (HERC) for funding placement as a medication with high cost and no clinically meaningful benefit.
Background: Duchenne muscular dystrophy (DMD) is a rare X-linked genetic disorder which results in the absence of a functional dystrophin protein. Duchenne’s is the most common type of muscular dystrophy occurring in approximately 1 in 5000 to 7250 patients age 5 to 24 years.1,4 Currently, in the Oregon Health Plan (OHP) population, approximately 70 fee-for-service patients and more than 300 patients enrolled in coordinated care organizations have a diagnosis of muscular dystrophy. Available claims data for OHP is unable to distinguish between patients with various types of muscular dystrophy. Based on this data and the estimated prevalence of mutations amenable to exon 51 skipping, approximately 3-4 OHP patients may be eligible for this medication. Without a functional dystrophin protein, muscle fibers degenerate and are eventually replaced with adipose and fibrotic tissue.1 Patients with DMD experience progressive muscle deterioration leading to pulmonary problems, dilated cardiomyopathy, arrhythmias, and increased risk for thrombotic events. In many patients, these complications lead to wheelchair dependence between the ages of 8-16 and death before the age of 20.1,5 Only 25% of patients remain ambulatory by age 16.1 There is currently no curative treatment, and therapy focuses on improving symptoms, enhancing quality of life, and decreasing disease progression.4 Guidelines from the American Academy of Neurology recommend glucocorticoids as first-line treatment in children over 5 years of age to improve muscle and pulmonary function and reduce risk of scoliosis.5 Other non-pharmacological therapies which are often essential in disease management include physical therapy and use of support devices such as braces and wheelchairs.4 As the disease progresses, mechanical ventilation and spinal surgery may be used to improve pulmonary function and decrease pain from scoliosis and vertebral fractures.4
Recently the FDA approved eteplirsen, an oligonucleotide indicated for patients with DMD who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping.3 In approximately 13% of patients with DMD, exon 51 is included in pre-mRNA and one or more nearby exons are deleted.1 This results in a shift in the reading-frame as the protein is formed and leads to reduction or absence of dystrophin protein. Eteplirsen binds to exon 51 of dystrophin pre-mRNA leading to exclusion of this exon, partially restoring the reading-frame, and forming a potentially functional, truncated dystrophin protein. In untreated patients with DMD, documented dystrophin levels typically range from 0 to 0.4% of normal healthy patients.1 Experts suggests that dystrophin levels less than 3% of normal are typically associated with a phenotype of DMD.1 It is unclear whether increases in dystrophin protein level in patients with DMD correlate to clinical outcomes. Similarly, the minimum change in dystrophin level which may result in a clinical improvement has not been established. Some experts suggest that very minimal improvements may constitute a beneficial change in dystrophin level while others suggest that dystrophin levels at 10-20% of normal would likely correlate to clinically significant changes in muscle symptoms or function.1,6 In patients with Becker muscular dystrophy, a less severe form of the muscular dystrophy, dystrophin protein levels are on average 80% of normal.1
Efficacy outcomes which are clinically important in patients with DMD include muscle strength, functional status, quality of life, disease progression, and mortality. Functional improvement is often evaluated using the 6-minute walk test (6MWT) and the North Star Ambulatory Assessment (NSAA) score. The 6MWT evaluates the distance a patient is able to walk in 6 minutes and evaluates both function and endurance.7 In healthy children less than 7 years of age, the distance patients are able to walk is expected to remain stable or improve over time with estimated mean walk distances ranging from 500-700 meters.2,8,9 The minimum clinically important difference in the 6MWT for patients with DMD is approximately 30 meters.7 The NSAA evaluates 17 functional activities including standing, walking, standing up from a chair, standing on 1 leg, climbing/descending step, moving from lying to sitting, rising from the floor, jumping, hopping, Author: S. Servid Date: July 2017 and running.1 Each item is evaluated on a 3 point scale with a total score ranging from 0 to 34. NSAA scores less than 16 are more often correlated with 6MWT of less than 300 meters and scores greater than 30 correlate moderately with 6MWT of more than 400 meters.10 The NSAA is considered a more comprehensive measure of functional status compared to other functional assessments, but score is often very dependent on patient effort.1 The minimum clinically important difference in NSAA score has not been determined. Other functional assessments include timed measures of rising from a sitting or supine position, 10-meter run/walking time, or time to climb 4 stairs.7
See Appendix 1 for Highlights of Prescribing Information from the manufacturer, indications, dosage and administration, formulations, contraindications, warnings and precautions, adverse reactions, drug interactions and use in specific populations.
Clinical Efficacy: Eteplirsen was evaluated in 3 poor quality studies with significant flaws (1 randomized placebo controlled trial and 2 open-label studies). All patients in these trials were ambulatory and on a stable dose of corticosteroids for at least 6 months. Study 1 was a double-blind, randomized, dose-response, placebo-controlled study for 24 weeks. It included 12 white, male, pediatric patients (age range 7-13, mean 9.4 years) with a mean 6-minute walking distance at baseline of 363 meters (substantially decreased from the mean distance of 500-700 meters expected in healthy children).11 Patients were randomized (1:1:1) to eteplirsen 50 mg/kg weekly, eteplirsen 30 mg/kg weekly, or placebo.11 After 24 weeks, patients were enrolled in a long-term open-label extension study (Study 2). In this study, patients initially randomized to the placebo group were re-randomized to eteplirsen 30 or 50 mg/kg/week for which data is available up to 240 weeks (4.6 years).1 The primary outcomes for these studies included the level of dystrophin protein in muscle tissue (measured as a percentage of the expected normal levels in healthy patients without DMD) and change in the 6MWT.11 Study 3 is an ongoing, unpublished, interim analysis of an open-label study which evaluated the change in dystrophin levels for 13 male patients treated with eteplirsen 30 mg/kg weekly for up to 48 weeks.1
No difference was observed in the 6MWT at 24 weeks compared to placebo.11 In addition, the long-term extension study failed to demonstrate a statistically significant difference in 6MWT upon comparison to placebo at 48 weeks.1 Since all patients were re-randomized to treatment, the manufacturer attempted to compare eteplirsen to a control group generated from two DMD natural history cohorts of patients in an open-label extension of the primary study. Patients were matched to 13 historical controls based on corticosteroid use, available longitudinal data for the 6MWT, age (less than or greater than 7 years), and genotype.1,2 Patients were not matched on the basis of the 6MWT distance though mean distance was similar between groups at baseline (363 vs. 358 meters).2 Overall, compared to the historical control, patients treated with eteplirsen experienced a benefit of 162 meters at 36 months (3 years) in the 6MWT (p=0.0005).1 The manufacturer also claimed that only 2 patients (16.7%) treated with eteplirsen lost ambulation over 4 years compared to 76.9% (10/13) of untreated historical controls.1 However, when results are evaluated as a function of age, 6 patients (4 less than 14 years of age and 2 still ambulatory between 13 and 14 years of age) appear to have similar disease progression and functional decline compared to their age-matched, untreated historical controls.1 All patients treated with eteplirsen had progressive decline in other functional outcomes including NSAA scores with no apparent difference from the untreated historical control.1
There are significant concerns and inherent limitations of using a historical control group and conclusions cannot be made from this fatally flawed study. Performance on the 6MWT is susceptible to expectation bias and coaching which significantly confounds the benefit observed in an open-label trial when compared to a historical cohort. For example, in patients treated with eteplirsen, the maximum distance achieved in the 6MWT was recorded, whereas the standard approach for historical controls was to classify patients as non-ambulatory if they were unable to complete the 6MWT.1 If a standard assessment for the 6MWT was applied to both groups, several patients treated with eteplirsen may have been classified as non-ambulatory. It is also unclear whether physical therapy programs were similar between the treatment group and historical control.1,2 In addition, there were significant differences between groups in steroid
Author: S. Servid Date: July 2017 regimens used and the mean age at initiation of steroid treatment (6.4 years in historical control vs. 5.2 years in treatment group).1 These differences affect interpretation and bias results in favor of eteplirsen treatment. Historical control patients also had a lower mean NSAA scores at baseline, indicating greater disease severity and could bias results in favor of eteplirsen treatment.1 The historical control population was selected after publication of results in eteplirsen trials and was not specified a priori. There is a high risk of selection, performance, detection, and reporting bias in this study and efficacy results should not be considered in the decision-making process.
The additional outcome in Study 1 and 2 was mean change in percent of dystrophin-positive fibers from baseline.1 Biopsies through week 48 were collected from the biceps and week 180 biopsies were collected from the deltoid.1 Because different muscle groups are known to have varying levels of dystrophin protein, comparisons of the deltoid biopsy at week 180 to earlier samples taken from the biceps are difficult to interpret. Evaluation of a different muscle group may result in varying levels of dystrophin protein. Dystrophin level was assessed using both immunofluorescence and Western blot techniques. These provide very different insight into perceived benefit of eteplirsen. Western blot is a quantitative method whereas immunofluorescence is used to identify localization of a protein in a particular tissue and is considered to be less quantitative.1 Due to significant methodological and technical issues with the initial analyses, the FDA concluded that the results were unreliable and uninterpretable.12 The FDA required a blinded re-analysis of available biopsies by 3 independent evaluators.1
After 3.5 years of treatment, patients treated with eteplirsen (both 30 and 50 mg/kg/week) had an average dystrophin level that was 0.93% of the normal protein level in healthy patients (as evaluated by Western blot).1 Approximately one-third of patients had no change in dystrophin level or changes that were below the level of quantification (0.24% of normal).1 Only one patient had a dystrophin level greater than 2% and none had a level greater than 3% of normal.1 Overall, re-analyzed biopsies did not confirm the initial study findings and did not support the dose dependent effect seen in earlier trials. In addition, there was a poor correlation between results of immunofluorescence and Western blot analyses, and results of the immunofluorescent tests varied between treatment groups.
Despite re-analysis of biopsy samples, there are several significant limitations which should be taken into consideration. Only 3 patients had baseline samples that were evaluable upon re-analysis, and therefore, the change in dystrophin level from baseline could not be assessed.1 Furthermore, immunofluorescent samples at 48 weeks (11 months) and Western blot analysis at 180 weeks (3.5 years) were processed differently and were not comparable with earlier samples.1 There was also significant intra-patient variability upon Western blot analysis at 180 weeks. At least 3 patients had analyses which differed by more than 0.7% of normal between samples evaluated at 180 weeks.1 Furthermore, the methods used to select the group of historical controls is unclear, and they may not represent a random sample of comparative patients, decreasing confidence in the results which indicate protein level was only 0.93% of normal.1 In addition, biopsy samples were stored for approximately 3 years before re-analyzed and the stability of the protein over time was not evaluated.1
Study 3 is an ongoing, unpublished, open-label study including 13 male patients treated with eteplirsen 30 mg/kg weekly for up to 48 weeks (mean age of 8.9 years).1 Data was available from 12 of these patients.1 The primary outcome evaluated change in dystrophin protein level (evaluated using Western blot analysis). No functional outcomes were evaluated in this study. Protein levels that were below the level of quantification (0.24%) were analyzed using several imputation methods including minimum (0%), maximum (0.24%), and actual measured values. Results were consistent between all analyses, and demonstrated statistically significant differences in dystrophin level compared to baseline.1 Mean change in dystrophin level from baseline to 48 weeks was 0.28% of normal (0.16% at baseline vs. 0.44% at 48 weeks; p=0.008).1 At 48 weeks, approximately 60% of patients treated in this study had no change in dystrophin level or had a change less than 0.25% compared to the normal level in a health patient. Only one patient had a dystrophin level greater than 1% and none had a level greater than 2% of normal.1 These changes in dystrophin levels are not clinically significant and do not translate into any clinical meaningful benefit.
Author: S. Servid Date: July 2017
Efficacy of eteplirsen for DMD remains to be established. Data from Western blot analysis suggests that some patients may not respond to treatment with little to no improvement in dystrophin levels.1 The FDA recommended further post-marketing studies to evaluate efficacy at higher doses.1 Studies failed to demonstrate improvement in functional outcomes even in patients treated for more than 4 years, and labeling for eteplirsen specifies that a clinical benefit has not been established.1 Furthermore, though a slight change in level of dystrophin level was observed (<1% of normal), changes did not correlate with any clinical improvement. It remains to be determined if changes in dystrophin correlate to clinical outcomes, and the FDA has required further studies to evaluate functional improvements in patients with DMD.3 FDA approval of eteplirsen was highly controversial because it conflicted with the recommendation by the external advisory committee who expressed multiple concerns with the studies, including: industry funding, blinding procedures, assays used, small sample size, and very minimal change from baseline.
Clinical Safety: The safety population included a total of 114 patients treated with at least 1 dose of eteplirsen. Only 36 patients have been treated for more than 6 months and 12 have been treated for more than 1 year.1 Because the population is small and the majority of these trials were not placebo-controlled, there is limited data available regarding adverse effects and safety. Serious adverse events occurred in 6 patients (5.3%) and included wound infection, vomiting, fractures, decreased oxygen saturation, and viral lymphadenitis.1 All events were thought to be unrelated to treatment. One patient, who had preexisting cardiomyopathy, experienced a decreased left ventricular ejection and discontinued treatment.1 In general, serious and severe adverse effects were consistent with expected events for a population of patients with DMD. However, there is insufficient data to assess short-term or long-term safety of eteplirsen.
Table 1. Pharmacology and Pharmacokinetic Properties.3 Parameter Eteplirsen binds to exon 51 of dystrophin pre-mRNA, resulting in exclusion of this exon during mRNA processing in patients with genetic Mechanism of Action mutations that are amenable to exon 51 skipping. Skipping of exon 51 allows for formation of a truncated dystrophin protein. Distribution and Protein binding: 6-17% Protein Binding Volume of distribution at steady state: 600 mL/kg Approximately 67% of eteplirsen is renally cleared Elimination Majority of drug elimination occurred within 24 hours Half-Life 3-4 hours Metabolism No hepatic metabolism apparent Abbreviations:
Comparative Clinical Efficacy: Clinically Relevant Endpoints: Primary Study Endpoint: 1) Functional or symptom improvement 1) Mean change in the percentage of dystrophin-positive fibers 2) Quality of life 2) Change in the 6-minute walk test at 48 weeks 3) Disease progression 4) Serious adverse events 5) Study withdrawal due to an adverse event
Author: S. Servid Date: July 2017
Table 2. Comparative Evidence Table. Ref./Study Drug Patient N Efficacy Endpoints ARR/ Safety ARR/ Risk of Bias/ Design Regimens/ Population NNT Outcomes NNH Applicability Duration 1. Mendell, 1. Eteplirsen Demographics: ITT: Primary Endpoints (ITT):1 No Risk of Bias (low/high/unclear): et al. 30 mg/kg/ - Mean age: 1. 4 Mean change in percent of serious or Selection Bias: UNCLEAR. Randomization methods and allocation 2013.11 week 9.4 years 2. 4 dystrophin-positive fibers from NA treatment NA concealment were unclear. Average baseline 6MWT in patients - Deflazacort 3. 4 baseline to 12 or 24 weeksϮ** -emergent randomized to 30 mg/kg/week was ~40 m less than other groups. Exondys 51 2. Eteplirsen 18-25 1. 13% adverse Performance Bias: UNCLEAR. Methods of blinding were not stated. FDA 50 mg/kg/ mg/day: 8/12 mITT: 2. 2% effects Placebo consisted of phosphate buffered saline. Placebo or eteplirsen was Medical week (67%) 1. 2 3. -1% reported diluted in normal saline and infused over 60 minutes. Review.1 - Prednisone: 2. 4 P-values NR at 48 Detection Bias: HIGH. Biopsy samples were not processed consistently at 3. Placebo/ 4/12 (33%) 3. 4 weeks. all time points leading to unclear changes over time. Use of Exondys 51 delayed tx - Mean Mean change in percent of immunofluorescent staining was less quantitative than Western blot FDA 6MWT: 363 Attrition: dystrophin-positive fibers from analysis. Re-analysis by blinded, independent pathologists (reported here) Summary After 24 m (range All patients baseline to 48 weeks** NA resulted in significantly differing protein levels. Analysis confirmed by Review.12 weeks 261-456) completed 1. 9% Western blot at 180 weeks. Multiple methodological limitations reduce patients in 48 weeks 2. 10% confidence in the results and limit ability to make conclusions regarding the placebo Key Inclusion 3. -1% dystrophin level. DB, PC, group were Criteria: P-values NR Attrition Bias: HIGH. All patients remained in the study up to 48 weeks. Phase IIB randomized - Boys age 7 to Use of ITT appropriate. The mITT population excludes 2 patients who had RCT to one of the 13 Mean percent of normal NA rapid disease progression and became non-ambulatory despite treatment treatment - Confirmed dystrophin at 180 weeks (SD) and increases in dystrophin-positive fibers. groups in an DMD with Western blot analysis12 Reporting Bias: HIGH. Funding provided by Sarepta Therapeutics who was open label deletions 1. 0.96% (0.95) involved in data interpretation and editing the manuscript. Results of extension potentially 2. 0.91% (0.79) multiple post-hoc analyses emphasized. Results of immunofluorescent study up to correctable assays may be misleading as they describe the percent of fibers stained 48 weeks. by exon 51 Mean change in 6MWT at 48 with an intensity above the background of the image and DO NOT Patients skipping weeks (SE) correspond to a percent of normal levels expected in a healthy patient. have been - 6MWT of 1. -153.4 m (38.7) NA continued in 200-400 m 2. 21 m (38.2) Applicability: the - On stable 3. -68.4 m (37.6) Patient: Small population limits ability to make conclusions. Patients were extension glucocorticoi p-values NR on stable dose of corticosteroid and ambulatory at baseline. study for d tx for ≥24 Intervention: Effective dose not established. greater than weeks Secondary Endpoints (ITT): Comparator: Placebo appropriate to determine efficacy. No dose-response 4 years. - Stable Mean change in 6MWT at 24 observed. Use of an open-label, non-controlled extension study after 24 cardiac and weeks (SE) weeks limits ability to make long-term efficacy or safety conclusions. pulmonary 1. -128.2 m (31.6) Outcomes: Dystrophin measured using immunofluorescence, confirmed function 2. -0.3 m (31.2) by Western blot. As reported, outcomes do not correspond to percent of 3. -25.8 m (30.6) normal levels expected in a healthy patient and may be misleading. Due to Key Exclusion p-values NR significant methodological issues, the change from baseline could not be Criteria: determined. Correlation of 6MWT or other functional outcomes with - None dystrophin levels is unclear. Setting: Initial 24 weeks conducted at Nationwide Children’s Hospital, open-label extension study conducted at 10 sites throughout the United States. Author: S. Servid Date: July 2017
Abbreviations [alphabetical order]: 6MWT = 6 minute walk test; ARR = absolute risk reduction; CI = confidence interval; DB = double blind; ITT = intention to treat; m = meters; mITT = modified intention to treat; N = number of subjects; NA = not applicable; NNH = number needed to harm; NNT = number needed to treat; NS = not significant; PC = placebo-controlled; PP = per protocol, RCT = randomized controlled trial; SE = standard error; tx = treatment **Percentages were evaluated with immunofluorescent assays and represent the percent of fibers stained with an intensity above the background of the image and DO NOT correspond to a percent of normal levels expected in a healthy patient. ϮData for 30mg/kg/week group collected at 24 weeks, 50mg/kg/week collected at 12 weeks, and placebo collected at both times.
References: 1. Exondys 51 Medical Review. US Food and Drug Administration Center for Drug Evaluation and Research. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206488Orig1s000MedR.pdf. Accessed February 2, 2017. 2. Mendell JR, Goemans N, Lowes LP, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79(2):257-271. 3. Exondys 51 (eteplirsen injection) [package insert] Cambridge, MA: Sarepta Therapeutics, Inc.; 2016. 4. Duchenne and Becker muscular dystrophies. In: DynaMed [internet database]. Ipswich, MA: EBSCO Publishing, Inc. Updated December 30, 2016. Accessed June 2, 2016. 5. Carson S, Driver R, and Harrod C. Emflaza (deflazacort) for children with Duchenne muscular dystrophy: Comparative effectiveness versus prednisone. Portland, OR: Center for Evidence-based Policy, Oregon Health & Science University. April 2017. 6. Wilton SD, Veedu RN, Fletcher S. The emperor's new dystrophin: finding sense in the noise. Trends Mol Med. 2015;21(7):417-426. 7. McDonald CM, Henricson EK, Abresch RT, et al. The 6-minute walk test and other clinical endpoints in duchenne muscular dystrophy: reliability, concurrent validity, and minimal clinically important differences from a multicenter study. Muscle Nerve. 2013;48(3):357-368. 8. Geiger R, Strasak A, Treml B, et al. Six-Minute Walk Test in Children and Adolescents. The Journal of Pediatrics. 2007;150(4):395-399.e392. 9. Ulrich S, Hildenbrand FF, Treder U, et al. Reference values for the 6-minute walk test in healthy children and adolescents in Switzerland. BMC Pulm Med. 2013;13(1):49. 10. Mazzone E, Martinelli D, Berardinelli A, et al. North Star Ambulatory Assessment, 6-minute walk test and timed items in ambulant boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2010;20(11):712-716. 11. Mendell JR, Rodino-Klapac LR, Sahenk Z, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013;74(5):637-647. 12. Exondys 51 Summary Review. US Food and Drug Administration Center for Drug Evaluation and Research. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/206488_summary%20review_Redacted.pdf. Accessed February 2, 2017.
Author: S. Servid Date: July 2017
Appendix 1: Prescribing Information Highlights
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights • Administer as an intravenous infusion over 35 to 60 minutes (2.1, do not include all the information needed to use EXONDYS 51™ safely 2.3) and effectively. See full prescribing information for EXONDYS 51. • Dilution required prior to administration (2.2)
EXONDYS 51 (eteplirsen) injection, for intravenous use
Initial U.S. Approval: 2016 DOSAGE FORMS AND STRENGTHS INDICATIONS AND USAGE Injection: • 100 mg/2 mL (50 mg/mL) in single-dose vial (3) EXONDYS 51 is an antisense oligonucleotide indicated for the treatment of • 500 mg/10 mL (50 mg/mL) in single-dose vial (3) Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 51 skipping. This ______indication is approved under accelerated approval based on an increase in CONTRAINDICATIONS dystrophin in skeletal muscle observed in some patients treated with None (4) EXONDYS 51 [see Clinical Studies (14)]. A clinical benefit of EXONDYS ______51 has not been established. Continued approval for this indication may be ADVERSE REACTIONS contingent upon verification of a clinical benefit in confirmatory trials. (1) The most common adverse reactions (incidence ≥35% and higher than placebo) were balance disorder and vomiting (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Sarepta DOSAGE AND ADMINISTRATION Therapeutics, Inc. at 1-888-SAREPTA (1-888-727-3782) or FDA at 1- • 30 milligrams per kilogram of body weight once weekly (2.1) 800FDA-1088 or www.fda.gov/medwatch. Revised: 09/2016
Author: S. Servid Date: July 2017
Appendix 2: Prior Authorization Criteria Drugs for Duchenne Muscular Dystrophy
Goal(s): Encourage use of corticosteroids which have demonstrated long-term efficacy Restrict use of eteplirsen and deflazacort to patients with Duchenne Muscular Dystrophy and limit use of deflazacort to patients with contraindications or serious intolerance to other oral corticosteroids
Length of Authorization: 6 months
Requires PA: Eteplirsen Deflazacort
Covered Alternatives: Current PMPDP preferred drug list per OAR 410-121-0030 at www.orpdl.org Searchable site for Oregon FFS Drug Class listed at www.orpdl.org/drugs/
Approval Criteria
1. What diagnosis is being treated? Record ICD10 code.
2. Is the diagnosis funded by OHP? Yes: Go to #3 No: Pass to RPh. Deny; not funded by the OHP.
3. Is the request for treatment of Duchenne Muscular Yes: Go to #4 No: Pass to RPh. Deny; Dystrophy? medical appropriateness.
Note: Eteplirsen and deflazacort are not indicated for other forms of muscular dystrophy or other diagnoses.
4. Is the request for continuation of eteplirsen treatment? Yes: Go to Renewal Criteria No: Go to #5
Author: S. Servid Date: July 2017
Approval Criteria
5. Is the request for deflazacort? Yes: Go to #6 No: Go to #8
6. Is the patient ≥ 5 years of age? Yes: Go to #7 No: Pass to RPh. Deny; medical appropriateness.
7. Does the patient have a documented contraindication or Yes: Approve for up to 12 No: Pass to RPh. Deny; intolerance to oral prednisone that is not expected to months. medical appropriateness. crossover to deflazacort? Document contraindication or Recommend trial of another oral intolerance reaction. corticosteroid.
8. Does the patient have a diagnosis of Duchenne Muscular Yes: Go to #9 No: Pass to RPh, Deny; Dystrophy with one of the following genetic mutations medical appropriateness. amenable to exon 51 skipping: Document genetic testing. Deletion of exons 45 to 50 Deletion of exons 48 to 50 Deletion of exons 49 and 50 Deletion of exon 50 OR Deletion of exon 52?
9. Has the patient been on a stable dose of corticosteroid for Yes: Go to #10 No: Pass to RPh. Deny; at least 6 months? medical appropriateness.
10. Has baseline functional assessment been evaluated using Yes: Document baseline No: Pass to RPh. Deny; a validated tool such as the 6-minute walk test or North Star functional assessment and medical appropriateness. Ambulatory Assessment? approve for up to 6 months
Renewal Criteria
1. Has the patient’s baseline functional status been Yes: Approve for up to 6 months No: Pass to RPh, Deny; maintained at or above baseline level or not declined more medical appropriateness. than expected given the natural disease progression? Document functional status.
Author: S. Servid Date: July 2017
P&T/DUR Review: 07/17 (SS) Implementation: TBD
Author: S. Servid Date: July 2017 Section 6.0 New Discussion Items Testicular Prosthetics
Question: Should testicular prosthetics be covered for reconstruction after various testicular surgeries or be considered cosmetic?
Question source: Ellen Pinney, OHA ombudsperson
Issue: Testicular prosthetics are covered after testicular removal for torsion or surgery for undescended testicle. However, they are not covered after surgery for testicular cancer or for gender dysphoria. Ms. Pinney contacted the HERC on behalf of a patient with testicular cancer who had a request for a testicular prosthetic denied as being cosmetic.
Review of minutes finds that testicular prosthetic insertion as a separate procedure (CPT 54660 Insertion of testicular prosthesis (separate procedure)) was added to the testicular torsion and undescended testes lines with the creation of the original Prioritized List in 1994. The placement of a prosthetic done at the time of orchiectomy (CPT 54520 Orchiectomy, simple (including subcapsular), with or without testicular prosthesis, scrotal or inguinal approach) is covered for a wide variety of indications.
The addition of testicular prosthetics (CPT 54660) was originally approved for the gender dysphoria line in 2013 and was in place until October 2016, when it was removed as part of a discussion regarding non- coverage for penile prostheses. This removal from the gender dysphoria line appears to be an error, as this CPT code does not relate to penile prostheses in any way.
Most private insurers and other state Medicaid programs consider testicular prosthesis medically necessary for replacement of congenitally absent testes, or testes lost due to disease, injury, or surgery. Some require documentation of detrimental psycho-social sequelae with documentation from a psychiatric evaluation. Breast reconstruction after mastectomy is covered by federal mandate.
According to internet search information, for out-of-pocket payment the total cost of a testicular prosthesis placement surgery is approximately $3,000. Oregon Medicaid reimburses $254, not including the cost of anesthesia, facility fees, etc.
1
Testicular Prosthetics
CPT Code description Current line(s) code 54520 Orchiectomy, simple 94 Undescended testicle (including subcapsular), with 112 Cancer of testis or without testicular 208 Deep open wound, with or without tendon or nerve prosthesis, scrotal or inguinal involvement approach 246 Torsion of testis 259 Cancer of penis and other male genital organs 312 Gender dysphoria/transexualism 327 Functional and mechanical disorders of the genitourinary system including bladder outlet obstruction 329 Cancer of prostate gland 467 Gonadal dysfunction, menopausal management 54522 Orchiectomy, partial 94 Undescended testicle 112 Cancer of testis 246 Torsion of testis 259 Cancer of penis and other male genital organs 581 Benign neoplasm of male genital organs: testis, prostate, epididymis 54530 Orchiectomy, radical, for 112 Cancer of testis tumor; with abdominal 259 Cancer of penis and other male genital organs exploration 329 Cancer of prostate gland 54535 Orchiectomy, radical, for 112 Cancer of testis tumor; with abdominal 259 Cancer of penis and other male genital organs exploration 54660 Insertion of testicular 94 Undescended testicle prosthesis (separate 246 Torsion of testis procedure) 54690 Laparoscopy, surgical; 94 Undescended testicle orchiectomy 112 Cancer of testis 312 Gender dysphoria/transexualism 423 Adrenogenital disorders 467 Gonadal dysfunction, menopausal management
HERC staff recommendations: 1) Add CPT 54660 (Insertion of testicular prosthesis (separate procedure)) to the following lines. This list should cover all cancer and traumatic loss of testicles and return coverage for gender dysphoria as previously intended by the HERC a. 112 CANCER OF TESTIS b. 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT c. 259 CANCER OF PENIS AND OTHER MALE GENITAL ORGANS d. 312 GENDER DYSPHORIA/TRANSEXUALISM 2) Add CPT 54660 to the following lines to match the placement of immediate placement of prosthesis after orchiectomy:
2
Testicular Prosthetics
a. 327 FUNCTIONAL AND MECHANICAL DISORDERS OF THE GENITOURINARY SYSTEM INCLUDING BLADDER OUTLET OBSTRUCTION b. 329 CANCER OF PROSTATE GLAND c. 467 GONADAL DYSFUNCTION, MENOPAUSAL MANAGEMENT
3
Capsulorrhaphy for Recurrent Shoulder Dislocation
Question: Should capsulorrhaphy be a covered procedure for recurrent shoulder dislocation?
Question source: HSD claims reconsideration
Issue: Thermal capsulorrhaphy is a surgical technique which uses thermal energy to treat several types of shoulder instability. The procedure uses heat to shrink and tighten the shoulder capsule, which is the connective tissue around the shoulder joint that helps to keep it stable. Thermal capsular shrinkage was developed as a less invasive way to treat a shoulder that is loose or frequently dislocates. Early short- term results with thermal capsulorrhaphy were encouraging, and the procedure rapidly gained in popularity. However, more recent results with patients over a longer follow-up period have shown a much higher failure rate than was first seen. Also, more complications have been reported (American Academy of Orthopedic Surgeons, http://orthoinfo.aaos.org/topic.cfm?topic=a00034).
HSD has received multiple requests for coverage of capsulorrhaphy for recurrent shoulder dislocation. Currently, any type of capsulorhapthy is only on line 417 DISORDERS OF SHOULDER, INCLUDING SPRAINS/STRAINS GRADE 4 THROUGH 6. Recurrent shoulder dislocation (ICD-10 M24.41) is on line 359 DEFORMITY/CLOSED DISLOCATION OF MAJOR JOINT AND RECURRENT JOINT DISLOCATIONS. The only copsulorrhaphy-like procedure on line 359 is CPT 29806 (Arthroscopy, shoulder, surgical; capsulorrhaphy) which is not the coding used for thermal capsulorrhaphy. A review of the literature did not find other indications for capsulorrhaphy other than for recurrent shoulder dislocation.
Consultation with Dr. Susan Williams indicates that the correct coding for thermal capsulorrhaphy is CPT 29999 (other unlisted procedure, arthroscopy), which is current Ancillary. Additional research found HCPCS S2300 (Arthroscopy, shoulder, surgical; with thermally-induced capsulorrhaphy) as likely a correct code, which is currently on the Services Recommended for Non-Covered Tabled but was not added to the new GN168 at the August 2017 VBBS meeting. CPT 23462-23466 involve other procedures, such as coracoid process transfer or surgery in the glenohumeral joint, and are open procedures.
CPT code Code Description 23462 Capsulorrhaphy, anterior, any type; with coracoid process transfer 23465 Capsulorrhaphy, glenohumeral joint, posterior, with or without bone block 23466 Capsulorrhaphy, glenohumeral joint, any type multi-directional instability 29806 Arthroscopy, shoulder, surgical; capsulorrhaphy HCPCS Arthroscopy, shoulder, surgical; with thermally-induced capsulorrhaphy S2300
Evidence 1) Longo 2015, systematic review of repair of shoulder instability a. N=24 articles comparing patients with open or arthroscopic repair or with conservative treatment of multidirectional instability (MDI) i. N=861 shoulders in 790 patients ii. Median follow up 4.2 years b. The redislocation event occurred in 17 of 226 (7.5%) shoulders with open capsular shift management, in 21 of 268 (7.8%) shoulders with arthroscopic plication management, in 12 of 49 (24.5%) shoulders undergoing arthroscopic thermal shrinkage, and in 11 of 55 (22%) shoulders undergoing arthroscopic laser-assisted capsulorrhaphy.
1
Capsulorrhaphy for Recurrent Shoulder Dislocation
c. Conclusions: Arthroscopic capsular plication and open capsular shift are the best surgical procedures for treatment of MDI after failure of rehabilitative management. Arthroscopic capsular plication shows results comparable to open capsular shift. Level of Evidence: Level IV, systematic review of Level I to IV studies.
Other policies: most major insurers do not cover electrothermal or thermal capsulorrhaphy due to its experimental nature.
HERC staff summary: Thermal or electrothermal capsulorrhaphy has good short-term results but worse long-term outcomes than open surgical repair for recurrent shoulder dislocation—there appears to be a 3 fold increase in redislocation with thermal capsulorrhaphy or other thermal shrinkage techniques compared to open procedures. There are also multiple case reports in the literature of complications from this procedure.
HERC staff recommendations: 1) Add open capsulorrhaphy (CPT 23462-23466) to line 359 DEFORMITY/CLOSED DISLOCATION OF MAJOR JOINT AND RECURRENT JOINT DISLOCATIONS a. Contains recurrent shoulder dislocation diagnoses (ICD-10 M24.41) 2) Remove CPT 23462-23466 (open capsulorrhaphy) from line 417 DISORDERS OF SHOULDER, INCLUDING SPRAINS/STRAINS GRADE 4 THROUGH 6 a. Only used for shoulder dislocation treatment; these diagnoses are not present on line 417 3) Do not add thermal capsulorrhaphy (HCPCS S2300 Arthroscopy, shoulder, surgical; with thermally-induced capsulorrhaphy) to line 359 DEFORMITY/CLOSED DISLOCATION OF MAJOR JOINT AND RECURRENT JOINT DISLOCATIONS a. More effective surgical procedures are available for treatment of recurrent shoulder dislocation 4) Add HCPCS S2300 (Arthroscopy, shoulder, surgical; with thermally-induced capsulorrhaphy) to line 500 Conditions for which certain treatments result in marginal clinical benefit or low cost- effectiveness with an entry in GN168 as shown below
GUIDELINE NOTE 168, TREATMENTS WITH MARGINAL CLINICAL BENEFIT OR LOW COST- EFFECTIVENESS FOR CERTAIN CONDITIONS
The following treatments are prioritized on Line 500 for the conditions listed here:
CONDITION CPT/HCPCS TREATMENT Rationale code Recurrent shoulder S2300 Arthroscopy, shoulder, More effective dislocation or any surgical; with thermally- treatments are available other shoulder induced capsulorrhaphy condition
2
Systematic Review
Multidirectional Instability of the Shoulder: A Systematic Review Umile Giuseppe Longo, M.D., M.Sc., Ph.D., Giacomo Rizzello, M.D., Mattia Loppini, M.D., Joel Locher, M.D., Stefan Buchmann, M.D., Nicola Maffulli, M.D., M.S., Ph.D., and Vincenzo Denaro, M.D.
Purpose: To analyze outcomes of surgical and conservative treatment options for multidirectional instability (MDI). Methods: A systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. A comprehensive search of the PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases using various combinations of the keywords “shoulder,”“multidi- rectional instability,”“dislocation,”“inferior instability,”“capsulorrhaphy,”“capsular plication,”“capsular shift,”“glenoid,” “humeral head,”“surgery,” and “glenohumeral,” over the years 1966 to 2014 was performed. Results: Twenty-four articles describing patients with open capsular shift, arthroscopic treatment, and conservative or combined management in the setting of atraumatic MDI of the shoulder were included. A total of 861 shoulders in 790 patients was included. The median age was 24.3 years, ranging from 9 to 56 years. The dominant side was involved in 269 (58%) of 468 shoulders, whereas the nondominant side was involved in 199 (42%) shoulders. Patients were assessed at a median follow-up period of 4.2 years (ranging from 9 months to 16 years). Fifty-two of 253 (21%) patients undergoing physiotherapy required surgical intervention for MDI management, whereas the overall occurrence of redislocation was seen in 61 of 608 (10%) shoulders undergoing surgical procedures. The redislocation event occurred in 17 of 226 (7.5%) shoulders with open capsular shift management, in 21 of 268 (7.8%) shoulders with arthroscopic plication management, in 12 of 49 (24.5%) shoulders undergoing arthroscopic thermal shrinkage, and in 11 of 55 (22%) shoulders undergoing arthroscopic laser- assisted capsulorrhaphy. Conclusions: Arthroscopic capsular plication and open capsular shift are the best surgical procedures for treatment of MDI after failure of rehabilitative management. Arthroscopic capsular plication shows results comparable to open capsular shift. Level of Evidence: Level IV, systematic review of Level I to IV studies.
See commentary on page 2444
ultidirectional instability (MDI) of the shoulder MDI, making classification of these patients difficult and Mwas initially described by Neer and Foster in leading to considerable variation of an MDI diagnosis. 1980 as instability in 2 or more directions.1 In the The precise incidence of MDI of the glenohumeral joint medical literature, a number of definitions exist for is unknown. In 2008 in Norway, 7% of operations for shoulder instability were caused by MDI.2 Among From the Department of Orthopaedic and Trauma Surgery, Campus Bio- sedentary individuals, the condition is more common in Medico University (U.G.L., G.R., M.L., J.L., V.D.), Rome, Italy; Department of Orthopaedic Sports Medicine, Klinikum rechts der Isar, Technical University young women with poor muscular development. MDI of Munich (S.B.), Munich, Germany; Centre for Sports and Exercise Medicine, often affects athletic or active individuals, even without Barts and The London School of Medicine and Dentistry (N.M.), London, generalized joint laxity, who participate in sports or England; and Department of Musculoskeletal Disorders, University of Salerno work requiring repetitive overhead movements.3 After School of Medicine and Surgery (N.M.), Salerno, Italy. the age of 40 years, the condition is less common The authors report that they have no conflicts of interest in the authorship and publication of this article. because of the natural stiffening of tissues around the Received April 2, 2015; accepted June 5, 2015. shoulder. Address correspondence to Umile Giuseppe Longo, M.D., M.Sc., Ph.D., Since the initial description, research in basic science Department of Orthopaedic and Trauma Surgery, Campus Bio-Medico and clinic evidence have contributed to a better un- University, Via Alvaro del Portillo, 200, 00128 Trigoria, Rome, Italy. derstanding of glenohumeral stability and MDI. E-mail: [email protected] 4 Ó 2015 by the Arthroscopy Association of North America Congenital hyperlaxity, muscular disbalance, and 0749-8063/15311/$36.00 bony and capsulolabral anatomy (labral hypoplasia, 5 http://dx.doi.org/10.1016/j.arthro.2015.06.006 glenoid size) may lead to recurrent dislocation
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 31, No 12 (December), 2015: pp 2431-2443 2431 Transcutaneous Neurostimulators
Question: Should transcutaneous electrical nerve stimulation [TENS], Scrambler therapy, and all similar transcutaneous neurostimulators be added to the new treatments with no clinically important benefit line?
Question source: HSD staff, HERC staff, Jay Richards, DO
Issue: During the initial creation of the Prioritized List in 1999, TENS was considered for the above the line spinal conditions lines and neurologic dysfunction lines but not added. TENS was last reviewed in February, 2010 and found to have no evidence of effectiveness.
From the HOSC February, 2010 minutes TENS Smits introduced a summary document reviewing the evidence for the effectiveness for TENS treatment for chronic and acute pain conditions. The HOSC found lack of evidence of effectiveness. Saha reported on a review of back pain treatments by Chou et al in the 2007 Annals of Internal Medicine, which found no benefit for TENS for acute or chronic back pain. The HOSC members agreed that this service should not be covered due to lack of effectiveness. Smits reported that there were additional CPT/HCPCS codes which were not included in the handout that needed to be added to the Never Covered List if TENS is not to be covered. Recommendations: 1) Delete 64550 (Application of surface (transcutaneous) neurostimulator) from Lines 517, 546 and 616. Recommend adding 64550 (Application of surface (transcutaneous) neurostimulator) to Never Covered List. 2) Delete 97032 from all 57 lines on Prioritized List. Recommend adding 97032 to Never Covered List 3) Recommend adding HCPCS codes A4556-A4558, A4595, A4630, E0720, E0730, E0731 to Never Covered List
Currently, all cutaneous neurostimulator CPT and HCPCS codes are on the Services Recommended for Non-Coverage table. 64550 Application of surface (transcutaneous) neurostimulator 97014 Application of a modality to 1 or more areas; electrical stimulation (unattended) 97032 Application of a modality to 1 or more areas; electrical stimulation (manual), each 15 minutes E0720 Transcutaneous electrical nerve stimulation (tens) device, two lead, localized stimulation E0730 Transcutaneous electrical nerve stimulation (tens) device, four or more leads, for multiple nerve stimulation G0283 Electrical stimulation (unattended), to one or more areas for indication(s) other than wound care, as part of a therapy plan of care
1
Transcutaneous Neurostimulators
GUIDELINE NOTE 56, NON-INTERVENTIONAL TREATMENTS FOR CONDITIONS OF THE BACK AND SPINE includes the following sentence: Transcutaneous electrical nerve stimulation (TENS; CPT 64550, 97014 and 97032) is not included on the Prioritized List for any condition due to lack of evidence of effectiveness.
Federal rule no longer allows absolute exclusion for DME. Therefore the GN56 sentence is in conflict with federal rule.
In May, 2017, a similar technology, Alpha Stim, was reviewed and found to have no evidence of effectiveness. The following entry was added to GN 172:
GUIDELINE NOTE 172, TREATMENTS THAT HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS FOR CERTAIN CONDITIONS The following treatments are prioritized on Line 660, CONDITIONS FOR WHICH CERTAIN TREATMENTS HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS, for the conditions listed here:
CONDITION CPT/HCPCS Code TREATMENT Rational Chronic pain, CPT 64550, Cranial electrical No clinically important anxiety, depression, 97014, 97032 stimulation benefit for chronic pain; insomnia, all other HCPCS E0720, insufficient evidence of indications E0730 effectiveness for all other indications
2
Transcutaneous Neurostimulators
Scrambler Therapy Recently, the HERC has been contacted about Scrambler therapy, which is a similar electrical stimulation device used to treat chronic pain. It is coded with CPT 0278T (Transcutaneous electrical modulation pain reprocessing (e.g, scrambler therapy), each treatment session (includes placement of electrodes)). Scrambler therapy is a noninvasive pain modifying technique that utilizes transcutaneous electrical stimulation of pain fibers with the intent of re- organizing maladaptive signaling pathways. It is used to treat various types of chronic pain.
From Jay Richards, DO: Currently Radiant Pain center in Portland and myself are the only providers in Oregon using this treatment. As a primary care provider in a rural area it has been a huge struggle to provide pain relief options for many of our OHP patients. The population that has been the hardest to treat are those suffering for neuropathic pain. A disproportionately large number of these patients are on chronic narcotics, despite evidence to show this class of medication isn’t indicated. Many also do not get improvement from commonly used medication like gabapentin, the expensive Lyrica and other treatments like physical therapy, chiropractic’s and acupuncture. Promoting exercise in this population is also challenging because the pain is aggravated with movement, which leads to increased sedentary lifestyle. In 2015, I came across a noninvasive, low risk treatment called Scrambler Therapy. It uses electrical impulses delivered through electrodes attached to different dermatomes in areas of normal skin, surrounding the area of neuropathy. The theory is this specialized signal scrambles the burning nerve pain signal delivered by the c-delta pain fibers, which is the hallmark of neuropathy. Over a series of 10 consecutive treatments the burning pain progressively reduces in intensity. After the patient has been without pain for 48 hours the pain is considered to be “in remission”. I met with the device vendor and set up a small demo on a couple of my patients. All of them felt the device helped their pain the first day, but what sold me was one patient with severe diabetic neuropathy returned the following morning asking if he could continue the treatment. Seeing his benefit I decided to proceed with the purchase of the device and start an after-hours pain treatment clinic for community patients with neuropathy. Over the course of 2016 I have seen 26 patients. Of these, 12 were eligible for treatment due to having an appropriate condition and ability to pay a sliding fee, which ranged from pro-bono to $150 per treatment session. All patients had a comprehensive review of their pain and medications. Only those with symptoms of neuropathy and an elevated DN4 score, where able to proceed with treatment.
3
Transcutaneous Neurostimulators
The average pain score for the 12 patients prior to the first treatment was 7/10. Of the 12 treated, 5 did not have sustained pain improvement beyond the full 10 treatment course, despite the average pain level during treatment being reduced to 2/10. Interestingly, and what I find to be the most rewarding, is 7 of the 12 patients who completed the full course of treatment achieved pain scores ranging from 0-2/10, which where sustained from 3 months to over a year after treatment. Several patients were also able to reduce or eliminate their medications. Four patients stopped their narcotic and the fifth one is working to reduce her dependence on oxycodone. Also 2 prescriptions for Lyrica were stopped. All 7 with improved pain have increased their activity level and one is actively seeking a job after 8 years of unemployment due to his diabetic neuropathy. Participating in this treatment and experiencing these patient’s improvement has been very rewarding. My experience treating patients with Scrambler Therapy is this can be a viable option for patients with neuropathy, particularly diabetic and chemotherapy induced neuropathy. It is noninvasive and a very low risk procedure. It does not treat all pain and patients should be screened well before starting treatment. The treatment is also very provider dependent so success depends both on treating the correct type of pain and placing the electrodes in the correct locations. I recognize higher power studies are needed to show better evidence-based practice. Hopefully, over the next couple years we will see randomized trials published from Mayo Clinic and Johns Hopkins, who are currently studying Scrambler Therapy.
Evidence 1) Majithea 2016, systematic review of Scrambler therapy a. Note: no studies identified which were not included in this systematic review b. N=20 studies i. 2 RCTs (N=14 patients in abstract only paper, N=30 patients in published trial), 1 open label RCT (N=52 patients), 11 prospective cohort studies (N=477 patients, 10 in abstract only paper), 5 “clinical practice experience” articles (N=417 patients), 1 retrospective cohort study (N=201 patients) ii. Studies of “varying clinical quality” iii. Studies generally small and short-term, and most lacked a comparator group and were not randomized. c. Results: i. RCTs: one study found no difference between treatment and placebo arms (Campbell 2013, N=14, abstract only), the other found significant improvement in reported pain in active treatment group compared to placebo treated group (Starkweather 2015, N=30)
4
Transcutaneous Neurostimulators
1. The Starkweather study was small and short term and the authors concluded that further research was needed ii. Other articles found significant reduction in pain scores d. Conclusions: The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.
Other policies: Most major insurers do not cover Scrambler therapy
Clinical practice guidelines: none found recommending Scrambler therapy
HERC staff summary: The evidence base regarding the benefits of transcutaneous electrical modulation pain reprocessing (i.e., scrambler therapy) as a treatment for pain from any etiology is extremely limited. Early, pilot studies with small numbers of patients treated for short periods of time are promising, but larger, well conducted, randomized trials are needed. There are no clinical practice guidelines that recommend scrambler therapy and major insurers are not covering this therapy. Based on the limited literature, scrambler therapy appears to be investigational.
5
Transcutaneous Neurostimulators
HERC staff recommendations: 1) Add CPT 64550, 97014 and 97032 and HCPCS E0720, E0730, and G0283 (Transcutaneous electrical nerve stimulation [TENS]; electrical stimulation) to line 660 CONDITIONS FOR WHICH CERTAIN TREATMENTS HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS 2) Add CPT 0278T (Transcutaneous electrical modulation pain reprocessing (e.g, scrambler therapy), each treatment session (includes placement of electrodes)) to line 660 3) Delete the following sentence from GUIDELINE NOTE 56, NON-INTERVENTIONAL TREATMENTS FOR CONDITIONS OF THE BACK AND SPINE Transcutaneous electrical nerve stimulation (TENS; CPT 64550, 97014 and 97032) is not included on the Prioritized List for any condition due to lack of evidence of effectiveness. 4) Modify the entry to GN173 adopted in May, 2017 as shown below
GUIDELINE NOTE 173, TREATMENTS THAT HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS FOR CERTAIN CONDITIONS; UNPROVEN TREATMENTS The following treatments are prioritized on Line 660, CONDITIONS FOR WHICH CERTAIN TREATMENTS HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS, for the conditions listed here:
CONDITION CPT/HCPCS TREATMENT Rational Date of last Code Review All conditions 64550, Transcutaneous No clinically important September, Chronic pain, 97014, electrical nerve benefit (CES) or insufficient 2017 anxiety, 97032, 0278T stimulation [TENS]; evidence of effectiveness depression, E0720, Scrambler therapy; (all other) for chronic pain; insomnia, all other E0730, and Cranial electrical insufficient evidence of indications G0283 stimulation; all similar effectiveness for all other transcutaneous indications electrical neurostimulation therapies
6
Support Care Cancer (2016) 24:2807-2814 Cross Mark DOI 10.1007/s00520-016-3177-3
Scrambler Therapy for the management of chronic pain
1 2 3 4 Neil Majithia f!) ·Thomas J. Smith ·Patrick J. Coyne • Salahadin Abdi • 5 6 7 7 Deirdre R. Pachman • Daniel Lachance • Randy Shelerud • Andrea Cheville • 7 8 5 5 Jeffrey R. Basford ·David Farley ·Carrie O'Neill ·Kathryn J. Ruddy • 9 5 5 Frank Sparadeo ·Andreas Beutler • Charles L Loprinzi
Received: 8 December 2015 I Accepted: 11 March 2016 /Published online: 4 April 2016 © Springer-Verlag Berlin Heidelberg 2016
Abstract case studies and clinical trials were evaluated and reported in Pwpose Chronic pain is a widespread and debilitating condi a descriptive manner. tion, encountered by physicians in a variety of practice set Results To date, 20 reports, of varying scientific quality, have tings. Although many pharmacologic and behavioral strate been published regarding this device; all but one small study, gies exist for the management of this condition, treatment is published only as an abstract, provided results that appear often unsatisfactory. Scrambler Therapy is a novel, non positive. invasive pain modifying technique that utilizes trans Conclusion The positive findings from preliminary studies cutaneous electrical stimulation of pain fibers with the intent with Scrambler Therapy support that this device provides ben of re-organizing maladaptive signaling pathways. This review efit for patients with refractory pain syndromes. Larger, ran was conducted to further evaluate what is known regarding domized studies are required to further evaluate the efficacy of the mechanisms and mechanics of Scrambler Therapy and to this approach. investigate the preliminary data pertaining to the efficacy of this treatment modality. Keywords Scrambler Therapy · Pain · Chronic pain · Methods The PubMed/Medline, SCOPUS, EMBASE, and Chemotherapy-induced peripheral neuropathy Google Scholar databases were searched for all articles pub lished on Scrambler Therapy prior to November 2015. All
Introduction
[8J Charles L Loprinzi Chronic pain is estimated to affect 100 million people in the [email protected] USA alone, resulting in up to $635 billion in medical expenses and lost productivity each year. [I] It predisposes to psychiat Internal Medicine, Mayo Clinic, Rochester, MN, USA ric comorbidity, and its massive impact is highlighted by the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, fact that it is the most common cause oflong-term disability in Baltimore, MD, USA the USA [2]. Medical University of South Carolina, Charleston, SC, USA In simplest terms, pain can be defined as a bodily sensation experienced during genuine, or perceived, tissue injury [3]. In 4 Pain Medicine, MD Anderson Cancer Center, Houston, TX, USA the acute setting, this sensation can serve as a protective role Medical Oncology, Mayo Clinic, 200 First Street SW, by alerting an individual to avoid potentially harmful stimuli Rochester, MN 55905, USA and to protect the body during healing. When pain fails to Neurology, Mayo Clinic, Rochester, MN, USA communicate biologically useful or accurate information, it Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN, is maladaptive and thereby becomes a disease state in its USA own right. It is generally agreed that pain becomes "chronic" West Lynn Family Health Center, West Lynn, OR, USA when it persists beyond the expected period of tissue injury Salve Regina University, Newport, RI, USA and healing. The specific duration of symptoms required to
~Springer Physical Therapy for Interstitial Cystitis
Question: Should physical therapy (PT) be paired with interstitial cystitis?
Question source: HSD claims reconsideration
Issue: HSD has received several requests for physical therapy to treat interstitial cystitis. Interstitial cystitis is also known as bladder pain syndrome (BPS), a type of chronic pain that affects the bladder. Symptoms include feeling the need to urinate urgently, needing to urinate often, and pain with sex. IC/BPS is associated with depression and lower quality of life. Many of those affected also have irritable bowel syndrome and/or fibromyalgia. There is no cure for interstitial cystitis. Treatments that may improve symptoms include lifestyle changes, medications, or procedures. Lifestyle changes may include stopping smoking and reducing stress. Medications may include ibuprofen, pentosan polysulfate, or amitriptyline. Procedures may include bladder distention, nerve stimulation, or surgery. Pelvic floor exercises (Kegels) and long-term antibiotics are not recommended.
N30.1 (Interstitial cystitis (Chronic)) is on line 327 FUNCTIONAL AND MECHANICAL DISORDERS OF THE GENITOURINARY SYSTEM INCLUDING BLADDER OUTLET OBSTRUCTION. Various procedures are included on this line, but not physical therapy.
The CPT codes specifically appearing on HSD claims are 97140 (Manual (physical) therapy techniques to 1 or more regions, each 15 minutes) and 97161-97164 (Physical therapy evaluation and re-evaluation), which appear on many lines on the Prioritized List.
Evidence: 1) Pazin 2016, systematic review of treatments for interstitial cystitis a. FitzGerald et al (2012) compared massage therapy with myofascial physiotherapy. Multi-center RCT, N=81 (42 PT vs 39 massage), 10 sixty minute sessions over 12 weeks. They reported that in the massage therapy group, bladder pain and voiding frequency decreased by 25.86 % and 10.48 % respectively, and that in the myofascial physiotherapy group, greater decreases of 37.70 % and 14.70 % respectively were observed. b. No other studies met inclusion criteria
Guidelines: 1) Hanno 2014, American Urological Association guideline on interstitial cystitis: http://www.auanet.org/guidelines/interstitial- cystitis/bladder-pain-syndrome-(2011-amended-2014 (HTML & PDF available) a. First line treatments include education, behavioral modifications, and stress management b. Second line treatments include:
1
Physical Therapy for Interstitial Cystitis
i. Appropriate manual physical therapy techniques (e.g., maneuvers that resolve pelvic, abdominal and/or hip muscular trigger points, lengthen muscle contractures, and release painful scars and other connective tissue restrictions), if appropriately-trained clinicians are available, should be offered to patients who present with pelvic floor tenderness. Pelvic floor strengthening exercises (e.g., Kegel exercises) should be avoided. Clinical Principle Standard (Evidence Strength- Grade A) 1. Based on the Fitzgerald 2012 RCT findings only ii. Noted: Very importantly, there is no evidence that physical therapy aimed at pelvic floor strengthening (such as Kegel exercises) can improve symptoms, and in fact this type of pelvic floor therapy may worsen the condition. iii. Appropriate manual physical therapy techniques include maneuvers that resolve pelvic, abdominal and/or hip muscular trigger points, lengthen muscle contractures, and release painful scars and other connective tissue restrictions. Unfortunately, appropriate physical therapy expertise and experience is not available in all communities. In the absence of appropriate expertise, routine forms of pelvic physical therapy that are primarily aimed at strengthening of the pelvic floor are not recommended. 2) Cox 2016, Canadian Urologic Association guideline on interstitial cystitis/bladder pain syndrome (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5065402/pdf/cuaj-5-6-e136.pdf) a. Physiotherapy and massage (RECOMMENDED for patients with pelvic floor dysfunction, Grade A) i. Many IC/BPS patients have high-tone pelvic floor muscle dysfunction (PFD). Those patients who have tenderness on physical exam might benefit from various physical therapy techniques, including: physiotherapy (± biofeedback); myofascial tender points release; or intravaginal Thiele massage. Various techniques have been described that involve skillful, hands-on maneuvers directed toward relaxation, elongation, stretching, and massaging of tightened muscles. Physical therapists with expertise in pelvic floor muscle relaxation should be involved. Evidence supporting this management option in IC/BPS is more robust, with RCTs and prospective case series reporting moderate or marked improvement of symptoms in 50‒62% of patients and an additional 21% of patients having complete resolution of symptoms in one study.
Other policies: 1) Major insurers cover pelvic physical therapy for interstitial cystitis
HERC staff summary: Based on expert guidelines, physical therapy is recommended for treatment of interstitial cystitis in those patients with tenderness as a primary symptom. This expert recommendation is based mainly on a single RCT. Appropriately trained physical
2
Physical Therapy for Interstitial Cystitis therapists are required as inappropriate PT can be harmful. Many alternative, far more invasive therapies are available on the current line for pairing with interstitial cystitis.
HERC staff recommendations: 1) Add pelvic physical therapy to line 327 FUNCTIONAL AND MECHANICAL DISORDERS OF THE GENITOURINARY SYSTEM INCLUDING BLADDER OUTLET OBSTRUCTION (CPT codes below are included for pelvic PT on the urinary incontinence line and gender dysphoria lines). a. CPT 97140 Manual therapy techniques (e.g., mobilization/manipulation, manual lymphatic drainage, manual traction), one or more regions, each 15 minutes b. CPT 97161-97164 Physical therapy evaluation or reevaluation c. DO NOT include exercise based PT (e.g. Kegels) as such therapy has been shown to be harmful. These CPT codes are on the urinary incontinence and gender dysphoria lines i. CPT 97110 Therapeutic procedure, one or more areas, each 15 minutes; therapeutic exercises to develop strength and endurance, range of motion and flexibility ii. CPT 97530 Therapeutic activities, direct (one on one) patient contact (use of dynamic activities to improve functional performance), each 15 minutes 2) Adopt a new guideline note for line 327 as shown below a. Multiple other diagnoses are included on line 327 which are not appropriate for pairing with pelvic PT
GUIDELINE NOTE XXX PELVIC PHYSICAL THERAPY FOR INTERSTITIAL CYSTITIS Line 327 Pelvic physical therapy (CPT 97140 and 97161-97164) is included on this line only for treatment of interstitial cystitis in patients who present with pelvic floor tenderness. Such pelvic PT is only included on this line when provided by professionals trained and experienced in pelvic floor therapy and as limited in Guideline Note 6 REHABILITATIVE AND HABILITATIVE THERAPIES.
3
Int Urogynecol J (2016) 27:697–708 DOI 10.1007/s00192-015-2815-5
REVIEW ARTICLE
Treatment of bladder pain syndrome and interstitial cystitis: a systematic review
Carolina Pazin1 & Andréia Moreira de Souza Mitidieri1 & Ana Paula Moreira Silva1 & Maria Beatriz Ferreira Gurian1 & Omero Benedicto Poli-Neto1 & Julio Cesar Rosa-e-Silva1
Received: 12 March 2015 /Accepted: 24 July 2015 /Published online: 14 August 2015 # The International Urogynecological Association 2015
Abstract used; therefore, further studies with better methodological Introduction and hypothesis Bladder pain syndrome/ quality are needed. interstitial cystitis (BPS/IC) has various treatments; however, no standardized treatment has been established. The aim was Keywords Bladder pain syndrome . Interstitial cystitis . Drug to analyze different types of treatment of BPS/IC and their treatment . Prospective and clinical trials effectiveness. Methods A literature review with a search strategy for articles related to BPS/IC published between 1990 and 2014 was con- Introduction ducted on MEDLINE, PUBMED, and SCOPUS. Only ran- domized controlled trials in women were included in the meta- Chronic pelvic pain (CPP) is characterized by severe, acyclic analysis, while other experimental studies were used as bases pain in the lower abdomen or pelvis that lasts for at least for a systematic review of the topic. Clinical trial quality was 6 months, which can interfere with daily activities and thus defined according to the Jadad scale. requires medical or surgical treatment [1, 2]. Its etiology is not Results Of 356 articles, 13 were included in the analysis. The clear and often results from a complex interaction among the intervention methods were as follows: instillation of gastrointestinal, urinary, neurological, gynecological, and hyaluronic acid, botulinum toxin A, intravesical lidocaine, musculoskeletal systems, being further influenced by psycho- hyperbaric chamber, massage, physiotherapy, phosphate- logical and sociocultural factors [3]. buffered saline, piroxicam in combination with doxepin, and Some interaction with other organs is possible, such as the others. We did not find any treatment with at least two ran- urinary tract, in which case bladder pain syndrome or intersti- domized controlled trials for meta-analysis. Among the as- tial cystitis (BPS/IC) can develop [4]. IC is more restricted to sessment tools for symptoms of BPS/IC, the most frequently cases with cystoscopic and histological findings typical of the used were the visual analogue scale, voiding record, and the disease (Hunner’sulcers)[5]. The International Society for the O’Leary–Sant questionnaire. Study of BPS (ESSIC) chose to use the name Bbladder pain Conclusion Existing studies were not able to define the best syndrome^ for the clinical picture, with typical findings that approach for the treatment of BPS/IC. The lack of standard- are combined with voiding urgency or frequent voiding asso- ized treatment may be related to the diversity of interventions ciated with CPP. Bladder pain syndrome/interstitial cystitis is a condition that results in discomfort or recurrent abdominal and pelvic pains in the absence of urinary tract infections. The change in * Julio Cesar Rosa-e-Silva symptomatology includes discomfort, increased bladder pres- [email protected] sure, sensitivity and intense pain in the bladder and pelvic areas, increased voiding frequency and urgency, or a combi- 1 Department of Gynecology and Obstetrics, Faculty of Medicine, nation of these symptoms. The pain often worsens during University of São Paulo, Av. Bandeirantes, 3900, Ribeirão Preto, São menstruation and may intensify during intercourse (National Paulo 14049-900, Brazil Institute of Diabetes and Digestive and Kidney Diseases 698 Int Urogynecol J (2016) 27:697–708
[NIDDK]). It also worsens with bladder filling and is relieved Results after bladder emptying [6]. In the United States, an estimated 3.3 to 7.9 million women The results presented in this section are from studies that met older than 18 years have pelvic pain and other symptoms such the inclusion criteria and are shown in Table 1. as a voiding urgency and increased voiding frequency, which Regarding the parameters analyzed by the authors, 11 of are compatible with a diagnosis of BPS/IC [7]. the 134 studies reviewed used the visual analog scale as an The diagnosis and treatment of BPS/IC are challenging evaluation method for pain in women with BPS/IC. Only 2 because of the lack of research; thus, diagnosis is often de- studies did not assess pain [16, 17]. layed [8]. Because of these difficulties, patients are often re- To assess voiding frequency, 5 studies (38.46 %) used the ferred to physicians of various specialties, including family voiding dictionary and 6 (46.15 %) used the O’Leary–Sant physicians, gynecologists, urologists, and pain specialists; this questionnaire; 2 studies (15.38 %) did not assess voiding fre- leaves patients confused with the diagnosis and frustrated [9]. quency at all. Voided volume was evaluated in 7 studies Owing to the divergence of diagnoses, the NIDDK established (53.84 %). criteria to facilitate the inclusion of patients in studies, but The O’Leary–Sant questionnaire assesses IC by using the these criteria do not define BPS/IC [10, 11]. Interstitial Cystitis Symptom Index (ICSI) and the Interstitial Various treatments have been suggested; however, no tra- Cystitis Problem Index and was applied in 8 studies ditional therapy has demonstrated efficacy in relieving symp- (61.53 %), but 1 study assessed only ICSI [18]. toms [12]. Tirumuru et al. [13] conducted a systematic review On the issue of study quality according to the Jadad scale, 5 in 2010 on the use of botulinum toxin in the treatment of studies (38.46 %) had a score of 1; 1 study (15.38 %), 2; 1 painful bladder syndrome and found only 3 randomized con- study (7.69 %), 3; 2 studies (15.38 %), 4; and 4 studies trolled clinical trials and 9 prospective studies, and concluded (30.76 %), 5. These low-quality ratings were because the stud- that more studies are needed. In 2012, Matsuoka et al. [14] ies did not present a control group, placebo, blinding, random- carried out a systematic review and meta-analysis on the sub- ization, or a description of losses or exclusions. ject and revealed a lack of controlled and randomized clinical The results demonstrate diverse interventions and forms of trials. Thus, the aim of this study was to review the various treatment, which are presented in the sections that follow. existing treatments of BPS/IC and their effectiveness.
Types of controlled treatment in women with BPS/IC Materials and methods Bladder hydrodistention A wide literature search for articles regarding treatments for BPS/IC that were published between January 1990 and In the bladder hydrodistention technique, which was devel- May 2014 was conducted on scientific databases, namely oped at least 60 years ago, a catheter is inserted in the urethra MEDLINE, PUBMED, and SCOPUS, following the to the bladder, through which a saline solution and/or drug is PRISMA reporting guidelines for systematic reviews. Only instilled into the bladder. Thereafter, the bladder is emptied, studies on clinical trials, with female patients, and published and the procedure is repeated weekly or every 2 weeks. About in English were considered for inclusion in this study. The 30 % of patients who undergo this procedure experience tem- keywords used were (cystitis, interstitial), (interstitial cystitis), porary pain relief [19]. However, the increase in tension (interstitial cystitis), (painful bladder syndrome), (cystitis, caused by the stretching mechanism damages the afferent chronic interstitial), (chronic interstitial cystitis), (cystitis, nerve fibers located below the bladder mucosa, causing pain chronic interstitial), (interstitial cystitis, chronic), (interstitial reduction [20]. Most studies use bladder hydrodistention as a cystitis, chronic), (chronic interstitial cystitis), and (random or control technique and classify it as a placebo, without any trial). We found 356 studies (Fig. 1). report of an existing mechanical effect. For greater reliability of the search, the authors of 5 of the 18 randomized controlled studies with inadequate methodol- Hyaluronic acid ogy and missing data or methodological description were contacted, but returned no response. Hyaluronic acid is an important natural glycosaminoglycan Among the articles we found in our search, 13 met the (GAG) that is present in the urothelium [21]. In patients with inclusion criteria of our study. To assess the quality of the BPS/IC, the concentration of this acid is decreased and randomized controlled trials, we used the Jadad scale to score urothelial permeability toward potassium compounds is in- studies with grades between 0 and 5 [15]. Studies graded≤2 creased, causing an increase in bladder pain. Hyaluronic acid were classified as poor. This scale assesses features such as inhibits leukocyte chemotactic and phagocytic functions, and randomization, blinding, and description of sample loss. reduces the permeability of the synovial membrane [22]. Int Urogynecol J (2016) 27:697–708 699
Fig. 1 Article selection from the Arcles found: 356 literature search
Excluded arcles: 321 Arcles selected: 35 2 Validaons 3 Meta-analysis 45 Reviews 4 Diagnoscs Arcles excluded: 22 1 Preliminary result 4 insufficient RCT 7 Experimental 18 Uncontrolled Studies 19 Other languages 189 Other subjects 19 Does not report on sex 1 Rheumatoid arthris Arcles included: 5 Comorbidies 13 clinical trials 1 Esophageal reflux 9 Pilot studies 5 Prevalence 1 Repeated 2 Case control 8 Leers to editor
Daha et al. [23] used hydrodistention in combination with Sodium pentosan polysulfate hyaluronic acid with potassium chloride (KCl), in addition to sodium chloride (NaCl), as a treatment of BPS/IC. With the Sodium pentosan polysulfate (SPP) is the only oral use of KCl and NaCl, pain was improved by 62.5 % and medication for BPS/IC approved by the US Food and 71.48 % respectively [23]. Drug Administration. The most widely accepted mech- According to the 2012 data of the Brazilian Ministry anism of action of the drug is the repair of GAG layer of Health, the production of intravesical hyaluronic ac- damage caused by urine [27]. The main drawback of id was stimulated by instillation of chondroitin sulfate, SPP as an oral therapy is that only about 1–3%ofthe a substance that blocks the action of lytic enzymes and drug reaches the bladder, resulting in a long course of stimulates proteoglycan synthesis by inducing increased treatment of approximately 3–6months[28]. La Rock hyaluronic acid levels, thus reconstituting the and Sant [29] suggested that in comparison with oral urothelium. therapy, intravesical SPP therapy promotes direct ab- Nickel et al. [24] conducted an interventional study by sorption of the drug by the bladder. using bladder hydrodistention with 20 mL of saline associated In conjunction with these facts, Bade et al. [30] and Davis with 2 % chondroitin sulfate, and found an improvement in et al. [31] reported treatment groups given intravesical SPP pain and urinary urgency of 47 % and a decrease in voiding (300 mg of SPP in 50 mL of 0.9 % NaCl) and oral SPP frequency by 51.8 % [24]. (200 mg or two capsules of SPP mixed with 30 mL of sa- Shao et al. [25] performed bladder hydrodistention with line+oral SPP) respectively, in addition to a control group. 40 mg of hyaluronic acid and compared it with bladder Bade et al. did not present pain assessment results, but report- hydrodistention alone and with 100 mL of lidocaine with ed an improved urodynamic capacity of 17.25 %. As for 500 U of heparin. None of the treatment groups presented an voiding volume and frequency, the placebo group showed improvement in pain, bladder capacity, or voiding frequency improvements of 17.58 % and 9.09 % respectively, whereas [25]. the treatment group showed no improvement in voiding fre- Hyaluronic acid does not provide immediate relief of quency, but showed a slight increase in voiding volume of symptoms, as some time is required before the onset of regen- 7.75 %. Meanwhile, Davis et al. reported that in the treatment eration of the GAG layer. By contrast, lidocaine (a local an- group, pain was improved by 50 %, and sexual function and esthetic) can reduce sensory ending excitability in the bladder desire improved by 91.66 % and 58.82 % respectively. In the and help with the control and immediate relief of pain and placebo group, improvements in pain, sexual function, and voiding frequency. Lv et al. [26] proposed a therapy that sexual desire were 57.44 %, 80 % and 82.05 % respectively. may provide immediate and sustained relief of symptoms by The two groups of authors presented placebo-controlled stud- combining hyaluronic acid with lidocaine. With the combined ies in which the control groups had satisfactory results in the treatment, voiding frequency was decreased by 67.25 % and treatment of BPS/IC. Thus, SPP therapy did show efficacy pain was decreased by 70.82 % [26]. compared with hydrodistention [30, 31]. 700 Table 1 Results in ascending order by year of randomized controlled trials of bladder pain syndrome/interstitial cystitis (BPS/IC) treatments
Author n Intervention Control Treatment duration Safety Group Assessment Result Jadad method scale score
Bade et al. [30]20n=10 (1 left the proposed treatment), n=10 (50 mL of saline solution) 2× per week for 3 months Not reported Treatment VAS score from 0 to 5 VAS score (no results 1 300 mg of pentosan polysulfate presented) in 50 mL of 0.9 % NaCl Urodynamics Urodynamic capacity (226–265 mL) Cystometry Volume (116–125 mL) Voidingrecord Frequency(18–18 times) Placebo VAS score from 0 to 5 VAS score (no results presented) Urodynamics Urodynamic capacity (202–208 mL) Cystometry Volume (91–107 mL) Voidingrecord Frequency(22–24 times) Peters et al. [33]33n=18 (3 excluded: 1 had an undiagnosed n=15 hydrodistention 1× per week for 6 weeks with Arthralgia Treatment Voiding record Frequency (no improvement) 4 urinary tract infection at baseline, 1 had a 6-month follow-up VAS score 10 (67 %) arthralgia, 1 was obtaining controlled Voided volume Increased substances off protocol), 50 mg of bacillus Calmette–Guérin (BCG) Urgency 7 (47 %) Burning sensation 5 (33 %) Control Voiding record Frequency (no improvement) VAS score 4 (27 %) Voided volume No improvement Urgency 7 (47 %) Burning sensation 2 (13 %) Barbalias et al. [16]36n=24 (1 left the proposed treatment), 10 mg n=12 (4 left the proposed 1× per week for 6 weeks; then Not reported Treatment Voiding record (before Frequency (15–13 times) 2 oxybutynin diluted in 500 mL of saline treatment) 500 mL of saline 1× per month for 3 months and after 6 months) Volume (before and Volume (105–134.6 mL) after 1 week) Placebo Voiding record (before Frequency (14.7–13.75 times) and after 6 months) Volume (before and Volume (109.25–113.37 mL) after 1 week) O’Reilly et al. [17]56n=29 (4 left the proposed treatment), n=27 (3 left the proposed 1× per week for 12 weeks Not reported Treatment O ’Leary–Sant (ICSI) Frequency (88.43–87.93) 4 30 s of transdermal laser on the SP6 treatment), laser sham ICSI (11.79–10) acupuncture point; penetration (points around the O’Leary–Sant (ICPI) ICPI (12.69–10.69) depth, 2 to 3.5 cm acupuncture point) 27:697 (2016) J Urogynecol Int Voided volume (L) Volume (11.84–10.78 mL) Control O’Leary–Sant (ICSI) Frequency (85.33–78.54) ICSI (12.85–11) O’Leary–Sant (ICPI) ICPI (13.70–10.74) Voided volume (L) Volume (12.07–11.04 mL) Smith and 13 Group I: n=5 (1 left the proposed None 1 session of 20 to 30 applications Decreased urinary Group I VAS score VAS score (no results 1 Chancellor [18] treatment) 10 U/mL of Botox stream presented) O’Leary–Sant (ISCI) ISCI (17–5.3) IPCI (15.7–4.5) Group II: n=7; 100 U/mL Dysport Group II Frequency (16–9) – Urodynamics Volume (159–250 mL) 708 n rgnclJ(06 27:697 (2016) J Urogynecol Int Table 1 (continued)
Author n Intervention Control Treatment duration Safety Group Assessment Result Jadad method scale score
Group III: n=1; 200 U of Botox diluted Bladder instillation Group III VAS score VAS score (10–5cm) in 200 mL of saline Daha et al. [23] 48 Group I: n=16 (does not report segment None 1× per week for 10 weeks No adverse events Group I VAS score VAS score: (8–3cm) 1 loss), intravesical injection of 40 mg were observed Group I I VAS score VAS score: (7–2cm) of hyaluronic acid in 2 M KCl Group II: n=32–40 mg of hyaluronic –
acid in 0.9 % NaCl 708 Van Ophoven 21 n=14 (2 excluded: 1 mild oxygen n=7, hyperbaric chamber 1sessionfor90min,6×per Oxygen Treatment VAS score (follow-up VAS score (4.31–3.12 cm) 5 et al. [43] intoxication and 1 left the proposed and face mask with week for 5 weeks intoxication of 3 months) treatment), hyperbaric chamber and a compressed air and O’Leary–Sant (follow- (25.7–19.9) – face mask with 100 % O2 and pressure of 1.3 1.4 atm up of 3 months) Frequency (16.2–15.9 times) 2.4 atm pressure Urodynamics (follow- Volume (127–147 mL) up of 3 months) Placebo VAS score (follow-up VAS score (5.14–5.57 cm) of 3 months) O’Leary–Sant (follow- (27.3–26.7) up of 3 months) Frequency (18.9–20.9 times) Urodynamics (follow- Vol ume ( 119 –118 mL) up of 3 months) Davis et al. [31]41n=21 (there was no loss of segment), n=20, 30 mL of Bladder instillation: 2× per Possible urinary Treatment VAS score from 1 to 9 VAS score (4–2cm) 5 200 mg or 2 capsules of sodium saline+sodium pentosan week for 6 weeks+sodium tract infection O’Leary–Sant (ICSI) ICSI (14–6) pentosan polysulfate mixed with polysulfate oral pentosan polysulfate 2× O’Leary–Sant (ICPI) ICPI (13–6) 30 mL of oral saline+sodium daily (1 h before or 2 h after – pentosan polysulfate meals) for 18 weeks PUF PUF (23 7) SF-36 SF-36 (65–15) VAS score for sexual VAS score for sexual function function (2.4–0.2 cm) Placebo VAS score for sexual VAS score for sexual desire desire (1.7–0.7 cm) VAS score from VAS score (4.7–2cm) 1to9cm O’Leary–Sant (ICSI) ICSI (12–4) O’Leary–Sant (ICPI) ICPI (11.5–4) PUF PUF (21.5–6) SF-36 SF-36 (65–5) VAS score for sexual VAS score for sexual function function (before and (3–0.6 cm) after 4, 6, 12, and 18 weeks) VAS score for sexual VAS score for sexual desire desire (3.9–0.7) Nickel et al. [24]98n=49 (9 excluded: 1 withdrawal of consent, n=49 (8 excluded: 1 withdrawal Single application Angina, rectal Treatment Urgency Urgency (9.5–7.2) 5 5 lack of efficacy, 2 lost to follow-up, of consent, 5 lack of efficacy, bleeding, and Volume Volume (129.8–144.8) 1 other), chondroitin sulfate 2 lost to follow-up, 1 adverse chronic colitis VAS score VAS score (65.0–43.5) effect), hydrodistention O’Leary–Sant (ICSI) Frequency (14.0–12.4) ICSI (12.9–9.7)
O’Leary–Sant (ICPI) ICPI (12.4–7.9) 701 702 Table 1 (continued)
Author n Intervention Control Treatment duration Safety Group Assessment Result Jadad method scale score
Control Urgency Urgency (9–6.7) Volume Volume (163.1–160.6) VAS score VAS score (63.8–46.6) O’Leary–Sant (ICSI) Frequency (15.1–12.3) ICSI (12.8–9.7) O’Leary–Sant (ICPI) ICPI (11.7–8.3) Shao et al. [25]47n=22 (2 left the proposed treatment), n=19 (1 left the proposed 1× per week for 4 weeks, then Not reported Hyaluronic acid Voiding frequency Frequency (19.3–17.5) 1 40 mg of hyaluronic acid treatment), hydrodistention 1× per month for 2 months VAS score VAS score (7.1–6.1) Bladder capacity Capacity (115–116) Heparin Voiding frequency Frequency (19–19.7) n=6, heparin 500 U+100 mL of lidocaine VAS score VAS score (7.2–7.1) Bladder capacity Capacity (107–108) Control Voiding frequency Frequency (18.5–19.7) VAS score VAS score (7.1–7.5) Bladder capacity Capacity (110–104) FitzGerald 81 n=39 (1 dissatisfaction with treatment), None 10 sessions for 60 min No adverse events MTG VAS score VAS score (5.8–4.3 cm) 3 et al. [47] massage therapy group (MTG) for 12 weeks were observed O’Leary–Sant (ICSI) Frequency (12.4–11.1) ICSI (11.4–9.3) O’Leary–Sant (ICPI) ICPI (10.7–8.6) FSFI FSFI (20.7–22.2) SF-12 (physical) SF-12 (physical) (45.4–46.6) SF -12 (mental) SF -12 (mental) (45.8–49.3) FSQ FSQ (28.1–22.4) n=42 (2 left the proposed treatment), FMG VAS score VAS score (6.1–3.8 cm) myofascial physiotherapy group (FMG) O’Leary–Sant (ICSI) Frequency (13.6–11.6 times) ICSI (11.9–8.6) O’Leary–Sant (ICPI) ICPI (10.5–6.9) FSFI FSFI (18.7–20.5) SF-12 (physical) SF-12 (physical; 41.5–45.6) –
SF-12 (mental) SF-12 (mental; 40.1 45) 27:697 (2016) J Urogynecol Int FSQ FSQ (29.8–21.1) Lv et al. [26] 48 Group I: n=16 (1 financial reasons), 40 mg None 1× per week for Not reported Group I (before and Voiding record (before Frequency (7.76–3.07 times) 1 of hyaluronic acid, 10 mL of 2 % 8 weeks; then, 1× per after 12 months) and after 12 months) lidocaine, and 5 mL of 8.4 % month for 4 months VAS score VAS score (7.53–2.76 cm) sodium bicarbonate O’Leary–Sant (ICSI) ICSI (15.2–10.67) O’Leary–Sant (ICPI) ICPI (12.6–8.2) Group II: n=17 (2 intolerance to treatment), Group II (before and Voidingrecord Frequency(7.6–7.8 times) 40 mg of hyaluronic acid and 10 mL of after 12 months) VAS score VAS score (7.6–7.87 cm) 2 % lidocaine+8.4 % sodium bicarbonate O’Leary–Sant (ICSI) ICSI (15–15.4) O ’Leary–Sant (ICPI) ICPI (12.87–12.87) – Group III: n=15, treatment I + II Voiding record Frequency (7.33–2.4 times) 708 Int Urogynecol J (2016) 27:697–708 703
Bacillus Calmette–Guérin vaccine scale score
The bacillus Calmette-Guérin (BCG) vaccine, prepared by
Female Sexual using live bacilli from a strain of bovine tuberculosis bacillus, 2.13 cm) 3.7) 2.9) – – –
7.93) is used against tuberculosis. Bladder instillation of BCG is FSFI 13.7) 13.6) 10.2) – 10.7) – – – – 10.27)
– widely used in the treatment of bladder cancer [32]. Based on these data, Peters et al. [33] performed bladder
Result Jadad instillation of 50 mg of BCG in women with BPS/IC. The study used bladder hydrodistention as the control treatment. In the treatment group, a 67 % improvement in pain was observed, whereas in the control group, a 27 % improvement Sant (ICPI) ICPI (13.8 Sant (ICSI) ICSI (13.6 Sant (ICPI) ICPI (12.33 Sant (ICPI) ICPI (13.8 Sant (ICSI) ICSI (15 Sant (ICSI) ICSI (13.1 – – – – – – in pain was observed. Meanwhile, voiding frequency, voiding Leary Leary Leary Leary Leary Leary ’ ’ ’ ’ ’ ’ urgency, burning sensation, and voided volume did not show VAS score VAS score (3.5 O VAS VAS score (3.8 O O O VAS score VAS score (7.33 method Short (36) Form Health Survey, significant results [33].
SF-36 Oxybutynin
after 12 months) Oxybutynin is an anticholinergic drug with an antispasmodic Control O Treatment O Group III (before and effect that acts directly on the smooth muscle of the bladder and has local anesthetic action [34]. Barbalias et al. [16] used intravesical instillation of 10 mg
infection of oxybutynin diluted in 500 mL of saline as a treatment for BPS/IC in comparison with a placebo control. The treatment group showed a 13.33 % improvement in voiding frequency pelvic pain and urgency/frequency, and a 28.19 % increase in voided volume [16]. PUF Transdermic laser
This technique has an analgesic action mediated by serotonin
Single application Urinary tract and endogen opioids, and also by the suppression of the amyelinic C fibers in afferent nerve pathways [35]. O’Reilly, et al. [17] applied this technique in an acupunc- ture SP6 area, located 5 cm above the medial malleolus, for 30 s, 2–3.5 cm from the skin surface. He also had a control
interstitial cystitis problem index, group with placebo (sham laser around the SP6 point). He observed that this therapy in the posterior tibial nerve was ICPI data and 5 urinary tract infection), bladder hydrodistention+30 mL of saline =27 (7 excluded: 2 incomplete
n not effective for treating women with BPS/IC.
Botulinum toxin A
Botulinum toxin A is a neurotoxin that can cause an itis symptom index, antinociceptive effect in the afferent nerve pathways of the bladder, decreasing muscle contraction at the injection site [18]. It has recently been introduced as a treatment of hyper- activity of the smooth muscle of the lower urinary tract [18], interstitial cyst with satisfactory results in the detrusor muscle of the bladder ICSI urinary tract infection, 1 withdrawn pre-randomization owing to bladder cancer), hydrodistention+applications of 500 U AboBTXA (Dysport) diluted in 30of mL saline Short (12) Form Health Survey
=26 (8 excluded: 1 incomplete data and 7 [36, 37]. n Intervention Control Treatment duration SafetySmith Group and Chancellor Assessment [18] performed approximately 40 n SF-12 intravesical local needle applications of 100 U of botulinum
38 ]54 toxin A diluted in 20 mL of saline in women with BPS/IC (continued) and reported a 50 % improvement in pain in just one woman
visual analog scale, who used botulinum toxin A with 200 U diluted in 20 mL of Manning et al. [ Function Index, Table 1 Author VAS saline solution. 704 Int Urogynecol J (2016) 27:697–708
Manning et al. [38] used bladder hydrodistention in Other types of treatment for BPS/IC combination with 500 U of botulinum toxin A diluted in 30 mL of saline as a treatment for BPS/IC and applied Electromotive or iontophoresis bladder hydrodistention in combination with 30 mL of saline as the control. They found that the group treated This is the active transport of molecules generated by an elec- with botulinum toxin A showed a small improvement in tric current through an ionic solution. The combination of this ICSI and ICPI scores evaluated by using the O’Leary– electric current with lidocaine causes an increase in the trans- Sant questionnaire [38]. port of the drug to the tissues [48]. Theoretically, this penetra- tion results in greater efficacy of the drug, based on the relative impermeability of the urothelium; therefore, the bladder is an Hyperbaric chamber ideal medium for this application [49]. Rosamilia et al. [50] used the intravesical injection of 2 % NaCl-free lidocaine, The hyperbaric chamber promotes unique conditions in which 1.5 mg of epinephrine, and 16 mg of dexamethasone diluted hemoglobin is fully saturated. A high dose of oxygen promotes in sterile water in combination with pulsed current with an physiological mechanisms that have a clinical effect on ischemic intensity of 30 mA in the lower abdomen. They noted de- diseases [39]. Ischemia occurs in the bladder wall of BPS/IC creases in pain and voiding frequency of 37.5 % and patients [40], and blood flow is impaired mainly in the bladder- 18.06 % respectively [50]. filling phase [41, 42]. Van Ophoven et al. [43] treated BPS/IC patients in a hy- Hyaluronic acid perbaric chamber with a pressure of 2.4 atm and an O2 face ’ mask to maintain the patients oxygen saturation at 100 %; the Porru et al. [51] used 40 mg of hyaluronic acid in combination patients in the control group were subjected to a pressure of with bladder hydrodistention to evaluate the improvement of 1.4 atm of normal air, only enough for the patient to notice the patients with BPS/IC and observed an improvement of pressure, and the face mask was used with compressed air. 29.78 % in pain and 27.27 % in voiding frequency [51]. The treatment group showed a 27.61 % improvement in pain intensity and a 15.74 % increase in voided volume, whereas Hyaluronic acid+chondroitin sulfate the control group did not show significant improvements [43]. Porru et al. [21], Cervigni et al. [52], and Giberti et al.[53] used an intravesical injection of 1.6 % hyaluronic acid and Massage therapy and myofascial physiotherapy 2.0 % chondroitin sulfate as a treatment for BPS/IC, and ob- served a decrease of 35–50.76 % in pain, a decrease of 26– Both massage therapy and myofascial physiotherapy 57.14 % in voiding frequency, and an increase of 24.90–41 % stimulate the normalization of muscle tone through re- in voided volume [21; 52]. The study had many limita- flex and mechanical actions, in addition to an increase tions; however, they reported an improvement in BPS/ in blood circulation, muscle flexibility, and lymphatic IC symptoms [53]. flow [44]. However, in myofascial physiotherapy, pres- sure is applied to the trigger points [45]. Abnormalities known as myofascial trigger points, Sodium pentosan polysulfate defined as taut bands or nodules sensitive to palpation, are believed to contribute significantly to pain in BPS/ Daha et al. [54] evaluated the interleukin-6 levels in the urine IC patients associated with CPP. Whether these muscle after bladder hydrodistention with 300 mg of SPP twice a changes are a consequence of the lower urinary tract or week for 5 weeks. The authors concluded that some patients are a primary disorder that gives rise to secondary uri- with BPS/IC exhibited elevated levels of interleukin-6, which nary symptoms is still unclear [46]. was resolved using GAG replacement therapy [54]. FitzGerald et al. [47] compared massage therapy with myofascial physiotherapy. They reported that in Bacillus Calmette–Guérin the massage therapy group, bladder pain and voiding frequency decreased by 25.86 % and 10.48 % respec- Aghamir et al. [55] used bladder instillation of 120 mg of tively, and that in the myofascial physiotherapy group, BCG once a week for 6 months in women with BPS/IC and greater decreases of 37.70 % and 14.70 % respectively observed that 84 % of the treated women showed improve- were observed [47]. ment in voiding frequency, 23.1 % reported improved urgen- The results of the randomized controlled studies de- cy, 46.2 % reported improvement in pain, and 76.9 % showed scribed in the text are summarized in Table 1. an increase in voiding volume [55]. Int Urogynecol J (2016) 27:697–708 705
Antidepressants and nonsteroidal anti-inflammatory drugs and IL-5, key cytokines in the development of allergic dis- eases, and has already been proven effective in the treatment Combination therapies are effective in treating chronic of allergic diseases [64, 65]. pain [56]. This approach is based on the following Ueda et al. [66], based on the data described earlier, used three assumptions made by Weselmann [57]: different 300 mg of IPD-1151 T orally for 1 year and found that pathological mechanisms may be the cause of chronic owing to the suppression of T cells, the drug can be effective pain in patients with visceral complaints, mainly BPS/ in the treatment of BPS/IC, enhancing bladder capacity by IC; different pathogenic mechanisms may exist and dif- 20 % [66]. ferent treatment strategies may be suggested; and dif- ferent pathogenic mechanisms can coexist in the same Sacral neuromodulation patient, and combination therapies are needed. Wammack et al. [58] proposed a combination therapy for Sacral neuromodulation is an alternative therapy for patients the treatment of BPS/IC by using 40 mg of piroxicam (anti- with voiding dysfunction [67]. The purpose of this treatment inflammatory) and 25 mg of doxepin (antidepressant) for is to inhibit detrusor action by the electrical stimulation of 3 weeks, with an increase of 25 mg of doxepin per week, for somatic afferent sacral nerve fibers via a subcutaneous elec- a total of 75 mg of antidepressant at the end of the third week. trode implanted in the region of the third sacral vertebra (S3). Little improvement was shown with regard to voiding fre- The justification for this treatment is based on the existence of quency, voided volume, and cystometric capacity, but this spinal inhibitory systems, which are able to stop the contrac- highlighted the pain improvement of 48.43 % [58]. tion of the detrusor muscle [68]. Maher et al. [69]introduceda needle into the S3 sacral foramen connected to an electric Botulinum toxin A current. The electrode remained in place for around 10 days, with an observed pain improvement of 75 % in pain and a Shie et al. [59]andLeeandKuo[60] administered ap- reduction in voiding frequency of 34.61 % [69]. proximately 40 local needle intravesical applications with 100 U of botulinum toxin A diluted in 20 mL of saline to Thiele massage women with BPS/IC. The patients presented a 67.68 % improvement in pain, a 35.24 % improvement in voiding Transvaginal massage is applied for spasm relief of the pelvic frequency, and a 29.62 % improvement in voiding volume floor muscles [70]. [59]. The use of botulinum toxin was not effective in the Oyama et al. [71]performed10–15 movements of the mas- women with ulcers [60]. sage twice a week for 5 weeks, with ischemic compression at the points of greatest tension for up to 15 s. The massage was Epigallocatechin gallate applied to the coccygeus, iliococcygeus, pubococcygeus, and obturator internus muscles. Epigallocatechin gallate (EGCG) is a substance found in abundance in green tea that was demonstrated to reduce and prevent the increase in free radicals associated with chronic Conclusion neurodegenerative diseases [61]. Furthermore, EGCG inhibits the growth of cancer cells in the bladder [62]. Through this systematic review, we conclude that various in- Liu et al. [63] were the first to use EGCG in humans and in terventions and treatments can be used for BPS/IC, but only a women with BPS/IC to verify its effect on the proteins in- few clinical trials present a high level of evidence on this volved in oxidative stress and inflammatory responses. Pa- subject. Owing to these factors and to the methodological tients who received bladder instillation of 4 mg/kg of EGCG diversity used by the authors, performing a meta-analysis on diluted in 150 mL of phosphate saline solution presented a the subject was not possible. Therefore, further studies with decrease in bladder pain of 34.61 % and a decrease in voiding higher methodological quality are necessary to analyze the frequency of 26.42 % [63]. diverse range of existing therapies with greater rigor. The studies included presented a great variety of treatments Suplatast tosilate for BPS/IC; however, with different, sometimes insufficient, assessments. Also, the results are confusing or lagged, which Interstitial cystitis may be related to vascular and lymphatic makes it hard to define the best treatment. Nevertheless, an obstruction, genetic, endocrine, and allergic disorders [62]. improvement in symptoms is often observed, and considering Suplatast tosilate (IPD-1151 T) is a new immunoregulatory the patients’ well-being, we consider that the first option for agent that selectively suppresses the production of immuno- BPS/IC treatment is the antidepressants associated with phys- globulin E via suppression of T-helper cells that produce IL-4 iotherapy, as combined therapies are usually more efficient at 706 Int Urogynecol J (2016) 27:697–708 treating chronic pelvic pain. In this case it is a combined ther- interstitial cystitis: a systematic review. Int Urogynecol J 21: – apy with low costs, minimally invasiveness, and reduced side 1285 1300. doi:10.1007/s00192-010-1162-9 14. Matsuoka PK, Haddad JM, Pacetta AM, Baracat EC (2012) effects. The second option, for patients whose symptoms are Intravesical treatment of painful bladder syndrome: a systematic recurrent, is the use of bladder hydrodistention with or without review and meta-analysis. Int Urogynecol J 23:1147–1153. doi: botulinum toxin A. However, this is an invasive procedure, is 10.1007/s00192-012-1686-2 more expensive, and carries greater risks with the same effi- 15. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ, McQuay HJ (1996) Assessing the quality of reports cacy of the first option. of randomized clinical trials: is blinding necessary? Control Clin Trials 17:1–12. doi:10.1016/0197-2456(95)00134-4 Acknowledgements The authors acknowledge the collaboration in the 16. 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Question: How should the intent of the Plastic Surgery ICD-10 review group be clarified regarding coverage of repair of acute peripheral nerve injuries?
Question source: HERC staff; Tracy Muday, OHP medical director
Issue: in 2012, the Plastic Surgery ICD-10 review group proposed the addition of a new line to allow coverage of acute peripheral nerve injuries. At that time, peripheral nerve injuries were included in two lines (one medical, one surgical) which were both below the funding line. The intent of the review group was to allow coverage for repair of acute injuries (initially defined as <8 weeks, later extended to <6 months). The rationale for this change was “If you don’t repair a nerve, you will have a residual defect. If upper extremity is desensate, will significantly impact functionality.”
It was not recognized during this review that many nerve injuries are also included, with appropriate repair CPT codes, on what is now line 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT.
The diagnoses suggested for this new line were S74.00xA-S74.11x (Injury of sciatic nerve, Injury of femoral nerve). Also mentioned in the review materials were S44.00xA-S44.42xA / S54.00xA- S54.22xA / S64.00xA-S64.498A (Injury of ulnar nerve, Injury of median nerve, Injury of radial nerve, Injury of axillary nerve, Injury of musculocutaneous nerve) and S94.00xA-S94.22xA (Injury of lateral plantar nerve, Injury of medial plantar nerve, Injury of deep peroneal nerve). However this series of codes was never adopted for this line, although it appears to be the intent of the review group. The diagnoses were noted to come from the two peripheral enthesopathy lines (now 484 and 503), and were supposed to stay on these lines. These diagnoses do not currently appear on the enthesopathy lines and do not appear to have ever been on those lines. These diagnoses only currently appear on line 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT.
The new line has CPT codes from then line 503 PERIPHERAL ENTHESOPATHIES Treatment: SURGICAL TREATMENT, which contain the vast majority of nerve repair CPT codes.
The guideline proposed by the review group and accepted in modified form by the HERC included references to two lines (now lines 507 PERIPHERAL NERVE DISORDERS Tx MEDICAL TREATMENT and 534 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT). However, the diagnoses included on line 425 ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY do not appear on either of these lines, and never did.
At some point, line 514 PHLEBITIS AND THROMBOPHLEBITIS, SUPERFICIAL was mistakenly added to GN 133. There is no mention in any minutes of this addition and it appears to be in error. Additionally, line 483 BELL'S PALSY, EXPOSURE KERATOCONJUNCTIVITIS also now appears in the guideline, although it does not contain appropriate diagnoses.
1
Acute Peripheral Nerve Injuries
From the ICD-10 Plastic Surgery review group recommendations: Line XXX Condition: ACUTE PERIPHERAL NERVE INJURY Treatment: SURGICAL THERAPY ICD10: S74.00xA-S74.11x CPT codes: CPT codes from line 503
Create a new line with diagnoses from lines 516 PERIPHERAL ENTHESOPATHIES Treatment: MEDICAL THERAPY and line 531 PERIPHERAL ENTHESOPATHIES Treatment: SURGICAL TREATMENT. The new line would be a surgical only line. The diagnoses on this line would stay on the current lines (516 and 531). Rationale: in the acute setting, urgent treatment can prevent lifelong complications and/or disability.
PLACED SENSORY NERVES ON LOWER LINES (535, 557) WITH THE EXCEPTION OF DIGITAL NERVES, WHICH REMAIN ON ACUTE NERVE INJURY LINE
S44.00xA-S44.42xA S54.00xA-S54.22xA S64.00xA-S64.498A Codes S94.00xA-S94.22xA
The following guideline would apply to the new line
GUIDELINE NOTE XXX ACUTE PERIPHERAL NERVE INJURY Line XXX Repair of acute peripheral nerve injuries are included on line XXX (now 425 ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY). Non-surgical medical care of these injuries are covered on line 535 (now 507 PERIPHERAL NERVE DISORDERS Tx MEDICAL Therapy). Chronic nerve injuries are covered on line 557 (now 534 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT).
Note: this guideline was revised during the VBBS/HERC meetings to include a definition of acute nerve injury (originally <8 weeks, revised later to <6 months).
Rescoring recommendations Category 7 Impact on Healthy Life Years 4 Rationale: If you don’t repair a nerve, you will have a residual defect. If upper extremity is desensate, will significantly impact functionality Impact on Pain and Suffering 1 Population effects 0 Vulnerable 0 Tertiary Prevention 1 Effectiveness 3 Need for service 0.90 Net cost 2 Score 324 Line 450 (now 425)
2
Current Prioritized List status:
Line 425 contains the following diagnosis codes: G57.2 (Lesion of femoral nerve) [also on 575,539] S74.0 (Injury of sciatic nerve at hip and thigh level) [also on 208] S74.1 (Injury of femoral nerve at hip and thigh level) [also on 208]
Line 208 contains the following diagnosis codes: S44.00xA-S44.42xA S54.00xA-S54.22xA S64.00xA-S64.498A S94.00xA-S94.22xA
Lines: 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT 425 ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY 483 BELL'S PALSY, EXPOSURE KERATOCONJUNCTIVITIS 507 PERIPHERAL NERVE DISORDERS Tx MEDICAL TREATMENT 514 PHLEBITIS AND THROMBOPHLEBITIS, SUPERFICIAL 534 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT)
GUIDELINE NOTE 133, ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY Lines 425,483,507,514,534 Repair of acute (<6 months) peripheral nerve injuries are included on Line 435. Non-surgical medical care of these injuries are included on Line 483. Chronic nerve injuries are included on Lines 507, 514 and 534.
HERC staff recommendations: 1) Interim modification (effective January 1, 2018) a. Add peripheral nerve injury ICD-10 codes as proposed by the ICD-10 Plastic Surgery review group to lines 512 PERIPHERAL NERVE DISORDERS Tx MEDICAL TREATMENT and 539 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT: i. S44.00xA-S44.42xA / S54.00xA-S54.22xA / S64.00xA-S64.498A (Injury of ulnar nerve, Injury of median nerve, Injury of radial nerve, Injury of axillary nerve, Injury of musculocutaneous nerve) ii. S94.00xA-S94.22xA (Injury of lateral plantar nerve, Injury of medial plantar nerve, Injury of deep peroneal nerve). b. Add additional peripheral nerve injury ICD-10 codes from line 425 to lines 512 PERIPHERAL NERVE DISORDERS Tx MEDICAL TREATMENT and 539 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT i. S74.0 (Injury of sciatic nerve at hip and thigh level) ii. S74.1 (Injury of femoral nerve at hip and thigh level) c. Revise GN133 as shown below. i. The lines referenced are: 1. 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT 2. 425 ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY 3. 512 PERIPHERAL NERVE DISORDERS Tx MEDICAL TREATMENT 4. 539 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT ii. The removed lines are 1. 519 PHLEBITIS AND THROMBOPHLEBITIS, SUPERFICIAL 2. 483 BELL'S PALSY, EXPOSURE KERATOCONJUNCTIVITIS
GUIDELINE NOTE 133, ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY Lines 208,425,483,512,519,539 Repair of acute (<6 months) peripheral nerve injuries are included on Line 208 and 425. Non-surgical medical care of these injuries are included on Line 512 483. Surgical repair of cChronic nerve injuries are included on Lines 512, 519 and 539.
2) Biennial Review 2020 (effective January 1, 2020): a. Delete line 425 ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY i. All diagnoses are already on line 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT other than G57.2 (Lesion of femoral nerve); all appropriate CPT repair codes appear on line 208 ii. Add ICD-10 G57.2 (Lesion of femoral nerve) to line 208 b. Modify GN133 as shown below: i. The lines referenced are:
1. 208 DEEP OPEN WOUND, WITH OR WITHOUT TENDON OR NERVE INVOLVEMENT 2. 425 ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY 3. 483 BELL'S PALSY, EXPOSURE KERATOCONJUNCTIVITIS 4. 507 PERIPHERAL NERVE DISORDERS Tx MEDICAL TREATMENT 5. 514 PHLEBITIS AND THROMBOPHLEBITIS, SUPERFICIAL 6. 534 PERIPHERAL NERVE DISORDERS Tx SURGICAL TREATMENT
GUIDELINE NOTE 133, ACUTE PERIPHERAL MOTOR AND DIGITAL NERVE INJURY Lines 208,507,534 Repair of acute (<6 months) peripheral nerve injuries are included on Line 208 and 425. Non-surgical medical care of these injuries are included on Line 507 483. Surgical repair of cChronic nerve injuries are included on Lines 512, 519 and 534.
Statement of Intent Regarding the Role of the Prioritized List in Coverage
Question: Should a new statement of intent be added to the Prioritized List to explicitly state the intent of the HERC to cover diagnostic and ancillary services and to describe the possibility of exceptions to List prioritization?
Question source: HERC staff, HSD, Oregon Department of Justice (DOJ)
Issue: There is a long term understanding at the HERC, HSD, and among the CCOs regarding the availability of coverage for diagnostic and ancillary services, as well as the presence of the ability to have low priority services covered in certain circumstances (e.g., co-morbidity situations). There is also the generally understood knowledge that a certain condition/pairing may not be covered if a particular patient’s medical situation does not require it (i.e. it is not medical necessary). HERC staff and HSD staff are proposing to explicitly describe this coverage in a new statement of intent. There is no new coverage proposed for this SOI; rather it is an attempt to be transparent to various stakeholders about coverage. Oregon DOJ has reviewed the proposed guideline wording and their comments and requests are reflected in the wording below.
HERC staff recommendation: 1) Adopt a new statement of intent regarding diagnostic and ancillary services, and the exceptions process as shown below a. Note: if significant edits are made to this SOI, the implementation of the SOI may be delayed due to the need for re-review by the Oregon DOJ
STATEMENT OF INTENT XXX, ROLE OF THE PRIORITIZED LIST IN COVERAGE
The Commission makes its prioritization decisions based on the best available published evidence about treatments for each condition. The Prioritized List prioritizes health services according to their importance for the population served and the legislature determines where to place the funding line on the Prioritized List.
The Commission recognizes that a condition and treatment pairing above the funding line does not necessarily mean that the service will be covered by the Oregon Health Plan (OHP). There may be other restrictions that apply, such as the service not being medically necessary or appropriate for an individual member. Likewise, the absence of a treatment and condition pairing above the funding line is not meant to be an absolute exclusion from coverage. Coverage may still be authorized under applicable federal and state laws, and Oregon’s Medicaid State Plan and Waiver for an individual member. For example, OAR 410-141-0480 (Oregon Health Plan Benefit Package of Covered Services) includes services such as, but not limited to, the following:
Diagnostic services, subject to the List’s diagnostic guideline notes when applicable;
1
Statement of Intent Regarding the Role of the Prioritized List in Coverage
Ancillary services (such as hospitalization, durable medical equipment, certain medications and anesthesia) provided for conditions appearing above the funding line, subject to the List’s ancillary guideline notes when applicable; and Services paired with an unfunded condition which is causing or exacerbating a funded condition, the treatments for the funded condition are not working or contraindicated, and treatment of the unfunded condition would improve the outcome of treating the funded condition (the “Comorbidity Rule” OAR 410-141-0480(8)(a through b))
In addition, Oregon’s 1115(a) Waiver includes coverage for services such as, but not limited to: Services on unfunded lines for children ages from birth through 1 Services provided for a condition appearing in the funded region of the List in conjunction with federal requirements for Early and Periodic Screening, Diagnosis and Treatment (EPSDT) and Oregon’s waiver
As a result, the Prioritized List must be used in conjunction with applicable OHP provisions found in federal and state laws, the State Plan and Waiver in coverage determination.
2
Grafts, Flaps, and Pedicles
Question: Should procedure codes for graphs, flaps and pedicles be removed from the Prioritized List and made Ancillary?
Question source: HSD
Issue: HSD has requested consideration of removing graphs, flaps and pedicles CPT codes from Prioritized List lines and making them Ancillary. There are a great variety of codes, and many end up not pairing with a specific surgery. According to HSD, review of graft and flap procedures come up frequently at medical review and making them Ancillary would save time and effort on the part of the review nurses and HSD staff. Graphs and flaps are skin, muscle, bone, fascia, or cartilage sections which are mobilized to close a surgical wound or repair a defect or injury. These tissues can come from adjacent areas of the body or from distant areas. The flaps and grafts proposed for movement are generic and could be used for a variety of surgeries. If these procedures were proposed for a cosmetic surgery, they would deny as such surgeries are below the funding line.
Anesthesia for surgical procedures is currently Ancillary; making grafts and flaps Ancillary would put them in a similar position. These procedures would be covered when done in conjunction with other covered procedures, but not for procedures below the funding line or excluded procedures such as cosmetic procedures.
HSD also requested that wound repair codes be made Ancillary as they frequently are subject to review and might be used for a variety of procedures. However, these codes appear to be specific for parts of the body and are on a limited set of lines which appear appropriate. If there is a surgical non-healing wound, that diagnosis can be coded and should pair. As part of a surgery, wound closure should be bundled with the surgical procedure and not billed separately.
There are flap and graft codes that are not being proposed for removal from their current placement. These codes include: 1) Flaps and grafts with specific procedures as part of the code description. The procedure specified in the code needs to remain on the current line(s). For example: CPT 19364 (Breast reconstruction with free flap) will remain in the breast cancer line 2) Flap or graft codes only used for below the line diagnoses, such as CPT 11762 (Reconstruction of nail bed with graft) 3) Codes that have a guideline attached, such as skin substitute codes 4) Codes on the previous Services Recommended for Non-Coverage table that will appear on lines 500/660 as of 1/1/18, such as hair transplant graft codes 5) Codes with a specific diagnosis in their description or that were likely to be used for only one diagnosis, such as CPT 15840 (Graft for facial nerve paralysis) 6) CPT 12000 and 13000 (wound closure) series were considered, but thought to be part of the overall surgery (bundled) and should not be billed separately.
When there was doubt about the use of a flap or graft for more than a limited number of procedures, it was left on the line(s) were it currently appears. These typically were more specialized grafts such as nerve grafts or tendon grafts.
HERC staff recommendation: 1) Remove the CPT codes in the following table from all lines on the Prioritized List a. Advise HSD to add these codes to the Ancillary Procedures List
1
Grafts, Flaps, and Pedicles
CPT Code Description Current line(s) code 14000- Adjacent tissue transfer or rearrangement, various many 14302 locations and types 15040 Harvest of skin for tissue cultured skin autograft, 100 many sq cm or less 15050 Pinch graft, single or multiple, to cover small ulcer, tip many of digit, or other minimal open area (except on face), up to defect size 2 cm diameter 15100 Split-thickness autograft, trunk, arms, legs; first 100 sq many cm or less, or 1% of body area of infants and children (except 15050) 15101 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof 15110 Epidermal autograft, trunk, arms, legs; first 100 sq cm many or less, or 1% of body area of infants and children 15111 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof 15115 Epidermal autograft, face, scalp, eyelids, mouth, neck, many ears, orbits, genitalia, hands, feet, and/or multiple digits; first 100 sq cm or less, or 1% of body area of infants and children 15116 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof 15120 Split-thickness autograft, face, scalp, eyelids, mouth, many neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; first 100 sq cm or less, or 1% of body area of infants and children (except 15050) 15121 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof 15130 Dermal autograft, trunk, arms, legs; first 100 sq cm or many less, or 1% of body area of infants and children 15131 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof 15135 Dermal autograft, face, scalp, eyelids, mouth, neck, many ears, orbits, genitalia, hands, feet, and/or multiple digits; first 100 sq cm or less, or 1% of body area of infants and children 15136 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof (List separately in addition to code for primary procedure) 15150 Tissue cultured skin autograft, trunk, arms, legs; first many 25 sq cm or less 15151 additional 1 sq cm to 75 sq cm many 15152 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof
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Grafts, Flaps, and Pedicles
CPT Code Description Current line(s) code 15155 Tissue cultured skin autograft, face, scalp, eyelids, many mouth, neck, ears, orbits, genitalia, hands, feet, and/or multiple digits; first 25 sq cm or less 15156 additional 1 sq cm to 75 sq cm many 15157 each additional 100 sq cm, or each additional 1% of many body area of infants and children, or part thereof 15200 Full thickness graft, free, including direct closure of many donor site, trunk; 20 sq cm or less 15201 each additional 20 sq cm, or part thereof many 15220 Full thickness graft, free, including direct closure of many donor site, scalp, arms, and/or legs; 20 sq cm or less 15221 each additional 20 sq cm, or part thereof many 15240 Full thickness graft, free, including direct closure of many donor site, forehead, cheeks, chin, mouth, neck, axillae, genitalia, hands, and/or feet; 20 sq cm or less 15241 each additional 20 sq cm, or part thereof many 15260 Full thickness graft, free, including direct closure of many donor site, nose, ears, eyelids, and/or lips; 20 sq cm or less 15261 each additional 20 sq cm, or part thereof many 15570 Formation of direct or tubed pedicle, with or without many transfer; trunk 15572 scalp, arms, or legs many 15574 forehead, cheeks, chin, mouth, neck, axillae, genitalia, many hands or feet 15576 Formation of direct or tubed pedicle, with or without 208,230,276,379 transfer; eyelids, nose, ears, lips, or intraoral 15600 Delay of flap or sectioning of flap (division and inset); 87,208,230,276,379 at trunk 15610 at scalp, arms or legs 87,208,230,276,379 15620 at forehead, cheeks, chin, neck, axillae, genitalia, 87,160,208,230,276,379 hands, or feet 15630 at eyelids, nose, ears, or lips 208,230,276,379 15650 Transfer, intermediate, of any pedicle flap (eg, 87,208,230,276,379 abdomen to wrist, Walking tube), any location 15731 Transfer, intermediate, of any pedicle flap (eg, 56,208,213,230,276,379 abdomen to wrist, Walking tube), any location 15732 Muscle, myocutaneous, or fasciocutaneous flap; head 42,200,208,230,276,287,300,379 and neck (eg, temporalis, masseter muscle, sternocleidomastoid, levator scapulae) 15734 Muscle, myocutaneous, or fasciocutaneous flap; trunk 168,200,208,230,255,276,287,314, 379 15736 Muscle, myocutaneous, or fasciocutaneous flap; upper 87,200,208,230,276,379 extremity
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Grafts, Flaps, and Pedicles
CPT Code Description Current line(s) code 15738 Muscle, myocutaneous, or fasciocutaneous flap; lower 87,200,208,230,276,379 extremity 15740 Flap; island pedicle requiring identification and 200,208,230,276,379 dissection of an anatomically named axial vessel 15750 Flap; neurovascular pedicle 200,208,230,276,379 15756 Free muscle or myocutaneous flap with microvascular 72,113,200,208,230,276,287,379 anastomosis 15757 Free skin flap with microvascular anastomosis 72,113,208,230,276,287,379 15758 Free fascial flap with microvascular anastomosis 72,113,200,208,230,276,287,379 15760 Graft; composite (eg, full thickness of external ear or 208,230,276,287,379 nasal ala), including primary closure, donor area 15770 Graft; derma-fat-fascia 57,72,181,208,230,276,379 20900 Bone graft, any donor area; minor or small (eg, dowel many or button) 20902 Bone graft, any donor area; major or large 160,441,482,575,582 20920 Fascia lata graft; by stripper 136,160,272,359,525,540 20922 Fascia lata graft; by incision and area exposure, 136,160,272,359,453,525,540 complex or sheet 20924 Tendon graft, from a distance (eg, palmaris, toe 140,164,276,364,392,436,530,545 extensor, plantaris) 20926 Tissue grafts, other (eg, paratenon, fat, dermis) many
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Iliotibial Band Syndrome
Question: Where should iliotibial band syndrome be prioritized and what treatments should be paired with it?
Question source: HSD, OHP medical directors
Issue: Iliotibial band syndrome is inflammation and pain of the iliotibial band, a thick band of fascia on the lateral aspect of the knee, extending from the outside of the pelvis, over the hip and knee, and inserting just below the knee. The band is crucial to stabilizing the knee during running, as it moves from behind the femur to the front of the femur during activity. The continual rubbing of the band over the lateral femoral epicondyle, combined with the repeated flexion and extension of the knee during running may cause the area to become inflamed. The main treatment for IT band syndrome is rest, ice, compression, and NSAIDs. Stretching, massage and physical therapy can also be helpful.
Currently, IT band syndrome is only on line 376 DISRUPTIONS OF THE LIGAMENTS AND TENDONS OF THE ARMS AND LEGS, EXCLUDING THE KNEE, RESULTING IN SIGNIFICANT INJURY/IMPAIRMENT. The ICD- 9 code for IT band syndrome (728.89 Other disorders of muscle, ligament, and fascia) was generic and was only on the equivalent of line 376 as well.
The question raised by several medical directors was whether IT band syndrome was intended to pair with the surgical codes on line 376, or if it should be included on a knee line, such as 430 INTERNAL DERANGEMENT OF KNEE AND LIGAMENTOUS DISRUPTIONS OF THE KNEE, RESULTING IN SIGNIFICANT INJURY/IMPAIRMENT, or the sprains and strains line, line 605 SPRAINS AND STRAINS OF ADJACENT MUSCLES AND JOINTS, MINOR. All three of these lines (line 376, 430 and 605), are subject to GN 98, which limits line 376 to “significant injuries resulting in joint instability or mechanical interference with motion.” IT band syndrome never results in joint instability or mechanical interference. The only therapy that might be required other than a primary care office visit would be physical therapy.
Similar conditions, such as patellofemoral disorders and strains of various ligaments are included on either line 376 or 430 and on line 605. The current placement of IT band syndrome only on line 376 appears to imply that this diagnosis should always be covered, even if it does not meet the criteria in GN98.
Current Prioritized List status: ICD10 M47.3 (Iliotibial band syndrome) is on line 376 DISRUPTIONS OF THE LIGAMENTS AND TENDONS OF THE ARMS AND LEGS, EXCLUDING THE KNEE, RESULTING IN SIGNIFICANT INJURY/IMPAIRMENT
GUIDELINE NOTE 98, SIGNIFICANT INJURIES TO LIGAMENTS AND TENDONS Lines 376,430,605 Significant injuries to ligaments and/or tendons are those that result in clinically demonstrable joint instability or mechanical interference with motion. Significant injuries are covered on Line 376 or Line 430; non-significant injuries are included on Line 605.
HERC staff recommendation: 1) Add ICD10 M47.3 (Iliotibial band syndrome) to line 605 SPRAINS AND STRAINS OF ADJACENT MUSCLES AND JOINTS, MINOR and keep on line 376 DISRUPTIONS OF THE LIGAMENTS AND
1
Iliotibial Band Syndrome
TENDONS OF THE ARMS AND LEGS, EXCLUDING THE KNEE, RESULTING IN SIGNIFICANT INJURY/IMPAIRMENT a. Not actually a knee condition; therefore not appropriate for line 430 b. GN98 will apply to this diagnosis
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Section 7.0 Coverage Guidances Colorectal Cancer Screening Modalities Draft Coverage Guidance for VbBS and HERC Consideration September 28, 2017
Center For Evidence-based Policy Background
• Colorectal cancers start in the colon or the rectum; often grouped together because of their common features • Risk of colorectal cancer increases with age: 90% occur in people aged 50+ • Other risk factors include: – Inflammatory bowel disease – Family history of colorectal cancer – Lack of physical exercise – Diet low in fruits and vegetables, low-fiber diet, obesity – Heavy alcohol consumption – Tobacco use
2 Center For Evidence-based Policy Background
• Most colorectal cancers begin as polyps on the inner lining of the colon or rectum • Colorectal cancer does not always cause symptoms, especially in the early stages • Lifetime risk is 4.7% for men and 4.4% for women • In the U.S., 136,119 people were diagnosed and 51,813 people died from colorectal cancer in 2013 • Death rate has declined for several decades because polyps are being found and removed and treatments have improved
3 Center For Evidence-based Policy Background
• Screening tests can find precancerous polyps (which can be removed during a colonoscopy) and detect colorectal cancer at earlier stages • U.S. Preventive Services Task Force (USPSTF) 2016 guidelines: – Colorectal cancer screening for average-risk adults aged 50 to 75 – Grade A Recommendation – Screening decisions for 76 to 85 years old should be based on individual circumstances, including overall health and screening history – Grade C Recommendation – Did not include recommendations on which screening test to use
4 Center For Evidence-based Policy Scope Statement
• Populations – Adults age 50 and older with average risk of colorectal cancer • Interventions – Computed tomographic colonography – Fecal DNA tests – Serum tests for SEPT9 – Colonoscopy with chromoendoscopy
5 Center For Evidence-based Policy Scope Statement
• Comparators – Colonoscopy – Flexible sigmoidoscopy (with or without fecal occult blood testing) – Fecal occult blood tests – Fecal immunochemical test (FIT) – Other listed interventions
6 Center For Evidence-based Policy Scope Statement
• Critical Outcomes – Colorectal cancer incidence – All-cause mortality – Colorectal cancer morbidity • Important Outcomes – Diagnostic test characteristics – Harms
7 Center For Evidence-based Policy Scope Statement
Key Questions 1. What is the comparative effectiveness of colorectal cancer screening modalities? 2. How does the comparative effectiveness of colorectal cancer screening modalities vary by: a. Age b. Gender c. Race or ethnicity d. Patient adherence/acceptance of test e. Screening interval 3. What are the harms of colorectal cancer screening?
8 Center For Evidence-based Policy Scope Statement
Contextual Questions 1. What are the optimal screening intervals for each modality? 2. What is the comparative effectiveness of offering various colorectal cancer screening modalities in underscreened populations?
9 Center For Evidence-based Policy Screening Modalities: Comparators
• Colonoscopy is the most common colorectal cancer screening test – Rectum and entire colon are examined using a flexible lighted tube with a lens for viewing and a tool for removing tissue – Air or carbon dioxide is pumped in to expand the colon – Thorough cleansing of the colon is necessary, and most patients are sedated for the procedure – Frequency: every 10 years
10 Center For Evidence-based Policy Screening Modalities: Comparators
• Flexible sigmoidoscopy is similar procedure to colonoscopy – Only the rectum and sigmoid colon are examined – Lower colon must be cleared of stool – Patients are usually not sedated – Use of flexible sigmoidoscopy is decreasing in the US – Frequency: every 5 years
11 Center For Evidence-based Policy Screening Modalities: Comparators
• Fecal immunochemical test (FIT) – Patient collects stool sample – Uses antibodies to detect human hemoglobin protein – Frequency: every year • Guaiac-based fecal occult blood testing (gFOBT) – Patient collects stool sample – Test detects heme, a component of hemoglobin, indicating the presence of blood that might derive from polyps or cancers – Frequency: every year
12 Center For Evidence-based Policy Evidence Summary
• Lack of direct evidence comparing the effectiveness of colorectal cancer screening tests • Only gFOBT and flexible sigmoidoscopy have been shown to decrease colorectal cancer incidence and colorectal cancer- specific mortality in RCTs • There is sparse information on the differential effectiveness of various screening strategies among subgroups • Experts in colorectal cancer screening and the USPSTF have emphasized the importance of high-quality screening programs regardless of the test selected
13 Center For Evidence-based Policy CT Colonography
Intervention Description • CT colonography (virtual colonoscopy) uses a CT scan of the colon and rectum to show polyps and other abnormalities • Thorough cleansing of the colon is necessary, and the procedure does not require sedation • Air or carbon dioxide is pumped into the colon to expand it for better viewing of the colon’s lining • When polyps or other abnormal growths are found during the CT colonography, a standard colonoscopy is usually performed to remove them • Frequency: every 5 years
14 Center For Evidence-based Policy CT Colonography
Evidence Sources • Lin et al., 2016 • Good-quality systematic review for USPSTF • Included 9 prospective diagnostic accuracy studies of CT colonography with 6,497 participants • Included 15 studies that reported on the harms of screening CT colonography
15 Center For Evidence-based Policy CT Colonography
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate All-cause mortality Insufficient data (Critical outcome)
Colorectal cancer incidence Insufficient data (Critical outcome)
Colorectal cancer morbidity Insufficient data (Critical outcome)
16 Center For Evidence-based Policy CT Colonography
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate Diagnostic test Sensitivity for adenomas >10 mm 67% to 94% characteristics Specificity for adenomas >10 mm 96% to 98% (Important outcome) Sensitivity for adenomas >6 mm 73% to 98% Specificity for adenomas >6 mm 89% to 91%
●●◌◌ (Low confidence based on seven prospective studies done with cathartic bowel preparation, comparing CT colonography to colonoscopy, N=5,328)
17 Center For Evidence-based Policy CT Colonography
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate Harms Little to no risk of serious adverse events (Important outcome) ●●◌◌ (Low confidence based on 11 studies, N=10,272) Ionizing radiation exposure of 1 to 7 mSv ●●◌◌ (Low confidence based on 7 studies, N not stated) Extracolonic findings occur in 27% to 69% of examinations (not all represent harm) ●●◌◌ (Low confidence based on 21 studies, N=38,293)
18 Center For Evidence-based Policy CT Colonography
Guidelines • USPSTF: – Risks and benefits of different screening methods vary, and thus no recommendations were made on which screening methods to use • Scottish Intercollegiate Guidelines Network: – No evidence to support CT colonography • National Comprehensive Cancer Network: – Evidence was not sufficient to provide recommendations about CT colonography • These guidelines did not include a recommendation on CT colonography – American College of Physicians – Canadian Task Force on Preventive Health Care
19 Center For Evidence-based Policy CT Colonography
Payer Policies • Washington Medicaid – Does not cover CT colonography • Medicare – No Medicare National Coverage Determination – 5 Medicare Local Coverage Determinations for CT colonography and none provide coverage
20 Center For Evidence-based Policy CT Colonography
Payer Policies • Private Payers – Aetna and Cigna cover CT colonography – Moda and Regence cover CT colonography only when the patient is unable to undergo conventional colonoscopy for medical reasons, such as • Chronic anticoagulation therapy • Sedation risk • Conventional colonoscopy was incomplete because of colonic stenosis, obstruction, or other significant anatomical abnormality
21 Center For Evidence-based Policy CT Colonography
Resource allocation CT colonography is less costly than colonoscopy, but more costly than some of the other screening options (e.g., FIT). To the extent that offering CT colonography improves adherence to screening recommendations, population screening costs might be higher than predicted in comparison to colonoscopy (if more testing is performed). The recommended testing frequency for CT colonography (5 years) potentially doubles utilization as compared with colonoscopy (10 years). Diagnostic work-up of extracolonic findings could also be a factor in increased expenditures related to use of CT colonography. Any savings related to reduced cancer costs would come many years after the screening.
22 Center For Evidence-based Policy CT Colonography
Values and preferences Some individuals might view CT colonography as less invasive and less costly than colonoscopy, leading to higher preference for CT colonography, and this is especially the case if bowel preparation is not utilized for CT colonography. However, several factors would generally limit preference for CT colonography, including radiation exposure, detection of non-significant extracolonic findings requiring work-up, and lower testing accuracy compared to colonoscopy even when bowel preparation is performed. Other considerations Colonoscopy is necessary for removal of any polyps detected by screening CT colonography, whereas polyp removal can generally be performed at the time of an initial colonoscopy.
23 Center For Evidence-based Policy CT Colonography
Balance of benefits and harms No population outcome benefit (critical outcome) has been identified utilizing CT colonography. Sensitivity and specificity for detection of colon adenomas is lower than for colonoscopy (low confidence level). CT colonography is generally safe, but potential harms include radiation exposure and detection of extracolonic findings of no clinical significance.
24 Center For Evidence-based Policy CT Colonography
Rationale The available evidence suggests that screening CT colonography is less sensitive and less specific than colonoscopy in detection of colon adenomas, and diagnostic accuracy is reduced when cathartic bowel preparation is not performed. There is no evidence directly comparing CT colonography with other colorectal cancer screening tests. Although some might prefer the less invasive nature of this imaging study as compared with colonoscopy, there are no strong preferences that would favor CT colonography (when used with appropriate cathartic bowel preparation), nor strong resource allocation benefits. However, there are individuals in the screening population who are unable to undergo colonoscopy for medical or anatomical reasons, and coverage of CT colonography for those individuals seems reasonable, given the limitations of other available screening options.
25 Center For Evidence-based Policy CT Colonography
DRAFT Coverage Guidance CT colonography for colorectal cancer screening is recommended for coverage only when the patient is unable to undergo an indicated screening colonoscopy for medical reasons (for example, sedation risk), or when screening colonoscopy was incomplete because of colonic stenosis, obstruction, or other significant anatomical abnormality (weak recommendation). CT colonography is recommended for coverage only when cathartic bowel preparation is included (weak recommendation).
26 Center For Evidence-based Policy Multitarget Stool DNA
Intervention Description • The only multitarget stool DNA test approved by the U.S. Food and Drug Administration (FDA) is Cologuard® • This test detects small amounts of blood in the stool and nine DNA biomarkers in three genes that have been found in colorectal cancer and precancerous advanced adenomas • The DNA is from cells in the lining of the colon and rectum that are collected in the stool as it passes • Frequency: every 1 to 3 years (suggested by manufacturer)
27 Center For Evidence-based Policy Multitarget Stool DNA
Evidence Sources • Lin et al., 2016 • Good-quality systematic review for USPSTF • Included one large prospective diagnostic accuracy study of FIT plus mt-sDNA testing
28 Center For Evidence-based Policy Multitarget Stool DNA
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate All-cause mortality Insufficient data (Critical outcome)
Colorectal cancer incidence Insufficient data (Critical outcome)
Colorectal cancer morbidity Insufficient data (Critical outcome)
29 Center For Evidence-based Policy Multitarget Stool DNA
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate Diagnostic test Sensitivity for colorectal cancer 92% (95% CI 84% to 97%) characteristics Specificity for colorectal cancer 84% (95% CI 84% to 85%) (Important Sensitivity for advanced adenomas 42% (95% CI 39% to 46%) outcome) Specificity for advanced adenomas 87% (95% CI 86% to 87%) ●●◌◌ (Low confidence based on 1 prospective diagnostic accuracy study comparing mt-sDNA and colonoscopy, N = 9,989) Harms Insufficient data (Important outcome)
30 Center For Evidence-based Policy Multitarget Stool DNA
Guidelines • USPSTF: – Risks and benefits of different screening methods vary, and thus no recommendations were made on which screening methods to use • National Comprehensive Cancer Network: – Recommend against fecal DNA testing • These guidelines did not include a recommendation on multitarget stool DNA tests – Scottish Intercollegiate Guidelines Network – American College of Physicians – Canadian Task Force on Preventive Health Care
31 Center For Evidence-based Policy Multitarget Stool DNA
Payer Policies • Washington Medicaid – Does not cover fecal DNA testing • Medicare – National Coverage Determination covers Cologuard® every three years • Private Payers – Aetna, Cigna, Moda, and Regence cover Cologuard®, the fecal DNA test, usually every three years
32 Center For Evidence-based Policy Multitarget Stool DNA
Resource allocation An individual multitarget stool DNA test is less costly than an individual colonoscopy, but more expensive than other screening options (e.g., FIT). Mt-sDNA tests need to be performed more frequently than colonoscopy, although the optimal interval is not known. Improved adherence to screening recommendations with mt-sDNA might tend to increase population screening costs. Positive mt-sDNA tests require evaluation by colonoscopy, additionally increasing resource utilization. If additional cancers were to be detected because of higher screening rates, any savings related to reduced cancer costs would come many years after the screening.
33 Center For Evidence-based Policy Multitarget Stool DNA
Values and preferences Many individuals in the screened population would prefer mt-sDNA as a non- invasive test that does not involve cathartic bowel preparation, radiation exposure, or other evident harms. However, others would prefer to avoid the collection and shipping of a stool specimen (as compared with having a blood draw, for example).
Other considerations Offering mt-sDNA testing may improve screening adherence in the subpopulation that is non-adherent to the recommendation for screening colonoscopy. The optimal frequency for CRC screening utilizing mt-sDNA has not been established (yearly vs. every three years).
34 Center For Evidence-based Policy Multitarget Stool DNA
Balance of benefits and harms Evidence is insufficient to establish any population screening benefit utilizing mt-sDNA. Sensitivity for detection of advanced colon adenomas is quite limited. No harms are evident with this testing modality, other than the risk of underdiagnosis of precancerous adenomas.
35 Center For Evidence-based Policy Multitarget Stool DNA
Rationale The available evidence for multitarget stool DNA testing is limited to diagnostic test characteristics, which includes high sensitivity for detection of colorectal cancer but relatively poor sensitivity for detection of adenomas. Specificity for colorectal cancer is relatively low, which is likely to increase the need for additional work-up with related cost and anxiety. Preferences weigh in favor of mt-sDNA as a noninvasive and safe testing strategy, but insufficient evidence of population benefit and the limited adenoma detection rate do not provide justification for the additional expenditures required for mt- sDNA coverage. The recommendation for noncoverage is weak, as further research may better establish a positive role or strategy of use for this modality.
36 Center For Evidence-based Policy Multitarget Stool DNA
DRAFT Coverage Guidance Multitarget stool DNA testing for colorectal cancer screening (also known as Cologuard®, mt-sDNA, or FIT-DNA) is not recommended for coverage (weak recommendation).
37 Center For Evidence-based Policy Methylated SEPT9
Intervention Description • In April 2016, the FDA approved the first blood-based test that detects the presence of SEPT9 • Colorectal polyps and tumors can release cells and DNA into the bloodstream, including the altered gene SEPT9 • Appropriate frequency for screening has not been established
38 Center For Evidence-based Policy Methylated SEPT9
Evidence Sources • Yan et al., 2016 • Fair-quality systematic review and meta-analysis of the diagnostic operating characteristics of the mSEPT9 test • Most of the studies were case-control designs • Only one prospective accuracy study in an asymptomatic screening population • Authors observed several sources of serious bias in the included studies
39 Center For Evidence-based Policy Methylated SEPT9
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate All-cause mortality Insufficient data (Critical outcome)
Colorectal cancer incidence Insufficient data (Critical outcome)
Colorectal cancer morbidity Insufficient data (Critical outcome)
40 Center For Evidence-based Policy Methylated SEPT9
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate Diagnostic test Sensitivity for colorectal cancer 48% characteristics Specificity for colorectal cancer 91% (Important outcome) ●◌◌◌ (Very low confidence based on 1 study, N=6,874)
Harms Insufficient data (Important outcome)
41 Center For Evidence-based Policy Methylated SEPT9
Guidelines • USPSTF: – mSEPT9 not included in table of interventions because of limited evidence evaluating its use • These guidelines did not include a recommendation on mSEPT9 tests – National Comprehensive Cancer Network – Scottish Intercollegiate Guidelines Network – American College of Physicians – Canadian Task Force on Preventive Health Care
42 Center For Evidence-based Policy Methylated SEPT9
Payer Policies • Washington Medicaid – No coverage policy identified • Medicare – No National or Local Coverage Determinations were found • Private Payers – Aetna and Cigna do not cover mSEPT9 – mSEPT9 is not listed in Moda’s policy on Colorectal Cancer Screening and Related Ancillary Services – No coverage policy identified for Regence
43 Center For Evidence-based Policy Methylated SEPT9
Resource allocation A recommended screening frequency utilizing mSEPT9 has not been established, making it difficult to estimate population screening costs. Improvement in adherence to screening recommendations with this blood test might increase screening costs. Positive mSEPT9 tests require colonoscopy for confirmation.
44 Center For Evidence-based Policy Methylated SEPT9
Values and preferences Values and preferences would greatly favor the convenience and simplicity of blood testing, as opposed to stool sample testing or colonoscopy. However, many individuals in the screening population would favor methods with better accuracy or more established testing protocols. Other considerations None
45 Center For Evidence-based Policy Methylated SEPT9
Balance of benefits and harms Currently available evidence is insufficient to establish any population benefit with use of mSEPT9 for colorectal cancer screening. Harms of this testing modality have not been established, but there is possible risk of colorectal cancer underdiagnosis if this test is used for population screening, given the limited sensitivity in cancer detection.
46 Center For Evidence-based Policy Methylated SEPT9
Rationale We have very low confidence in the evidence regarding test characteristics of mSEPT9, and the single study of accuracy in an asymptomatic screening population reported sensitivity well below other testing methods. Although many would prefer the convenience and simplicity of a blood test, current evidence is insufficient to recommend coverage. The noncoverage recommendation is weak because further research may support population screening benefits with mSEPT9.
47 Center For Evidence-based Policy Methylated SEPT9
DRAFT Coverage Guidance Methylated SEPT9 testing (mSEPT9) for colorectal cancer screening is not recommended for coverage (weak recommendation).
48 Center For Evidence-based Policy Chromoscopy
Intervention Description • Standard colonoscopy with the addition of dye sprayed onto the surface of the colon to make polyps more visible • Some polyps, especially smaller, flat lesions, can be difficult to detect using a standard colonoscopy • Frequency: every 10 years
49 Center For Evidence-based Policy Chromoscopy
Evidence Sources • Brown et al., 2016 • High-quality Cochrane systematic review • Included 7 randomized trials (n=2,727) of chromoscopy compared to standard or high-definition colonoscopy • Some studies included populations with above-average risk of colorectal cancer
50 Center For Evidence-based Policy Chromoscopy
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate All-cause mortality Insufficient data (Critical outcome)
Colorectal cancer incidence Insufficient data (Critical outcome)
Colorectal cancer morbidity Insufficient data (Critical outcome)
51 Center For Evidence-based Policy Chromoscopy
Evidence Review Estimate of Effect for Outcome/ Outcomes Confidence in Estimate Diagnostic test characteristics Increases total number of neoplastic lesions detected (Important outcome) (MD 0.33, 95% CI 0.25 to 0.41) Increases total number of participants with at least one neoplastic lesion identified (OR 1.53, 95% CI 1.31 to 1.79), Increases number of participants with a diminutive neoplastic lesion identified (OR 1.51, 95% CI 1.19 to 1.92) Increases number of participants with 3 or more adenomas identified (OR 4.63, 95% CI 1.99 to 10.80) ●●◌◌ (Low confidence based on 7 studies, N=2,727)
52 Center For Evidence-based Policy Chromoscopy
Evidence Review
Estimate of Effect for Outcome/ Outcomes Confidence in Estimate Harms Insufficient data (Important outcome)
53 Center For Evidence-based Policy Chromoscopy
Guidelines • USPSTF: – Risks and benefits of different screening methods vary, and thus no recommendations were made on which screening methods to use • These guidelines did not include a recommendation on chromoscopy – National Comprehensive Cancer Network – Scottish Intercollegiate Guidelines Network – American College of Physicians – Canadian Task Force on Preventive Health Care
54 Center For Evidence-based Policy Chromoscopy
Payer Policies • Washington Medicaid – No coverage policy identified • Medicare – No National or Local Coverage Determinations were found • Private payers – Aetna, Cigna, and Regence do not cover chromoscopy – Chromoscopy is not listed in Moda’s policy on Colorectal Cancer Screening and Related Ancillary Services
55 Center For Evidence-based Policy Chromoscopy
Resource allocation Dye enhancement would presumably add minimal cost to colonoscopy. Additional lesion detection would add to expenditures for biopsies and follow-up. Diagnosis of colorectal cancer at an earlier stage, however, could later result in treatment cost savings that offset initial expenditures. Values and preferences Values and preferences would weigh in favor of a screening method that improves the colon adenoma detection rate. However, chromoscopy has all of the drawbacks associated with standard colonoscopy as a screening test.
56 Center For Evidence-based Policy Chromoscopy
Other considerations None Balance of benefits and harms Colon polyp detection is improved with chromoscopy, but currently available evidence is insufficient to establish any population benefit with use of chromoscopy for colorectal cancer screening. Harms have not been established, but risks of chromoscopy would be similar to standard colonoscopy, plus the risks of any adverse reactions to the dye.
57 Center For Evidence-based Policy Chromoscopy
Rationale There is low-quality evidence that chromoscopy improves polyp detection compared to standard colonoscopy, but its role in primary colorectal cancer screening for average-risk individuals has not been established. Population outcomes have not been demonstrated that might justify additional expenditures for dye enhancement, and there are no strong values or preferences supporting chromoscopy coverage. Our recommendation for noncoverage is weak because further evidence of population screening benefits may develop over time.
58 Center For Evidence-based Policy Chromoscopy
DRAFT Coverage Guidance Chromoscopy (dye-enhanced colonoscopy) for colorectal cancer screening is not recommended for coverage (weak recommendation).
59 Center For Evidence-based Policy DRAFT Coverage Guidance
Based on contextual evidence and USPSTF recommendations, HERC makes the following additional recommendations: Colorectal cancer screening for average-risk adults aged 50 to 75 is recommended for coverage (weak recommendation), as follows: • Colonoscopy every 10 years • Flexible sigmoidoscopy every 5 years • Fecal immunochemical test (FIT) every year • Guaiac-based fecal occult blood test (gFOBT) every year
60 Center For Evidence-based Policy DRAFT Coverage Guidance
Colorectal cancer screening for average-risk adults aged 76 to 85 is recommended for coverage only for those who (1) are healthy enough to undergo treatment if colorectal cancer is detected, and (2) do not have comorbid conditions that would significantly limit their life expectancy (weak recommendation). Colorectal cancer screening modalities are recommended for coverage as components of a comprehensive screening program that emphasizes individual patient choice, shared decision- making, and effectiveness (strong recommendation).
61 Center For Evidence-based Policy
Health Evidence Review Commission (HERC) Coverage Guidance: Colorectal Cancer Screening Modalities DRAFT for VbBS/HERC meeting materials 9/28/2017
HERC Coverage Guidance CT colonography for colorectal cancer screening is not recommended for coverage (weak recommendation). Multitarget stool DNA testing for colorectal cancer screening (also known as Cologuard®, mt-sDNA, or FIT-DNA) is not recommended for coverage (weak recommendation). Methylated SEPT9 testing (mSEPT9) for colorectal cancer screening is not recommended for coverage (weak recommendation). Chromoscopy (dye-enhanced colonoscopy) for colorectal cancer screening is not recommended for coverage (weak recommendation). Based on contextual evidence and USPSTF recommendations, HERC makes the following additional recommendations: Colorectal cancer screening for average-risk adults aged 50 to 75 is recommended for coverage (weak recommendation), using one of the following screening programs: Colonoscopy every 10 years Flexible sigmoidoscopy every 5 years Fecal immunochemical test (FIT) every year Guaiac-based fecal occult blood test (gFOBT) every year Colorectal cancer screening for average-risk adults aged 76 to 85 is recommended for coverage only for those who (1) are healthy enough to undergo treatment if colorectal cancer is detected, and (2) do not have comorbid conditions that would significantly limit their life expectancy (weak recommendation).
Note: Definitions for strength of recommendation are in Appendix A. GRADE Informed Framework Element Description.
Table of Contents
HERC Coverage Guidance ...... 1 Rationale for development of coverage guidances and multisector intervention reports ...... 4 GRADE-Informed Framework ...... 5 Should computed tomographic colonography be recommended for coverage for colorectal cancer screening? ...... 5 Should multitarget stool DNA (Cologuard®) testing be recommended for coverage for colorectal cancer screening? ...... 7 Should methylated SEPT9 (mSEPT9) testing be recommended for coverage for colorectal cancer screening? ...... 9 Should chromoscopy be recommended for coverage for colorectal cancer screening? ...... 11 Clinical Background ...... 13 Indications ...... 13 Technology Description ...... 15 Evidence Review ...... 16 Lin et al., 2016 ...... 16 Knudsen et al., 2016...... 18 Yan et al., 2016 ...... 18 Brown et al., 2016 ...... 18 Contextual Questions ...... 19 Evidence Summary ...... 20 Other Decision Factors ...... 21 Policy Landscape ...... 22 Payer Coverage Policies ...... 22 Professional Society Guidelines ...... 22 Quality Measures ...... 23 References ...... 24 Evidence Sources ...... 24 Other Citations ...... 24 Appendix A. GRADE-Informed Framework Element Descriptions ...... 26 Appendix B. GRADE Evidence Profile ...... 28 Appendix C. Methods ...... 32 Scope Statement ...... 32 Search Strategy ...... 32
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Appendix D. Applicable Codes ...... 34
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Rationale for development of coverage guidances and multisector intervention reports Coverage guidances are developed to inform coverage recommendations for public and private health plans in Oregon as plan administrators seek to improve patient experience of care, population health, and the cost-effectiveness of health care. In the era of public and private sector health system transformation, reaching these goals requires a focus on maximizing the benefits and minimizing the harms and costs of health interventions. Multisector intervention reports will be developed to address these population-based health interventions or other types of interventions that occur outside of the typical clinical setting. HERC uses the following principles in selecting topics for its reports to guide public and private payers:
Represents a significant burden of disease or health problem Represents important uncertainty with regard to effectiveness or harms Represents important variation or controversy in implementation or practice Represents high costs or significant economic impact Topic is of high public interest HERC bases its reports on a review of the best available research applicable to the intervention(s) in question. For coverage guidances, which focus on clinical interventions and modes of care, evidence is evaluated using an adaptation of the GRADE methodology. For more information on coverage guidance methodology, see Appendix A. Multisector interventions can be effective ways to prevent, treat, or manage disease at a population level. In some cases, HERC has reviewed evidence and identified effective interventions, but has not made formal coverage recommendations when these policies are implemented in settings other than traditional health care delivery systems because effectiveness may be dependent on the environment in which the intervention is implemented.
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GRADE-Informed Framework HERC develops recommendations by using the concepts of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. GRADE is a transparent and structured process for developing and presenting evidence and for performing the steps involved in developing recommendations. The table below lists the elements that determine the strength of a recommendation. HERC reviews the evidence and makes an assessment of each element, which in turn is used to develop the recommendations presented in the coverage guidance box. Estimates of effect are derived from the evidence presented in this document. Assessments of confidence are from the published systematic reviews and meta-analyses, where available and judged to be reliable. In some cases, no systematic reviews or meta-analyses encompass the most current literature. In those cases, HERC may describe the additional evidence or alter the assessments of confidence in light of all available information. Such assessments are informed by clinical epidemiologists from the Center for Evidence-based Policy. Unless otherwise noted, estimated resource allocation, values and preferences, and other considerations are assessments of HERC.
Should computed tomographic colonography be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Values and Other Outcomes Resource Allocation Confidence in Estimate Preferences Considerations All-cause Insufficient data CT colonography is less costly than Some individuals Colonoscopy is mortality colonoscopy, but more costly than might view CT necessary for (Critical outcome) some of the other screening colonography as less removal of any Colorectal cancer Insufficient data options (e.g., FIT). invasive and less polyps detected by costly than screening CT incidence To the extent that offering CT colonoscopy, colonography, (Critical outcome) colonography improves adherence Colorectal cancer Insufficient data leading to higher whereas polyp to screening recommendations, morbidity preference for CT removal can population screening costs might (Critical outcome) colonography, and generally be be higher than predicted in Diagnostic test Sensitivity for adenomas >10 mm 67% this is especially the performed at the comparison to colonoscopy (if more characteristics to 94% case if bowel time of an initial testing is performed). (Important Specificity for adenomas >10 mm 96% preparation is not colonoscopy. outcome) to 98% utilized for CT
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Should computed tomographic colonography be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Values and Other Outcomes Resource Allocation Confidence in Estimate Preferences Considerations Sensitivity for adenomas >6 mm 73% The recommended testing colonography. to 98% frequency for CT colonography (5 However, several Specificity for adenomas > 6 mm 89% years) potentially doubles factors would to 91% utilization as compared with generally limit colonoscopy (10 years). preference for CT ●●◌◌ (Low confidence based on colonography, seven prospective studies done with Diagnostic work-up of extracolonic including radiation cathartic bowel preparation, findings could also be a factor in exposure, detection comparing CT colonography to increased expenditures related to of non-significant colonoscopy N = 5,328) use of CT colonography. Harms Little to no risk of serious adverse extracolonic findings Any savings related to reduced (Important events requiring work-up, outcome) ●●◌◌ (Low confidence based on 11 cancer costs would come many and lower testing studies, N = 10,272) years after the screening. accuracy compared to colonoscopy even Ionizing radiation exposure of 1 to 7 when bowel mSv preparation is ●●◌◌ (Low confidence based on 7 performed. studies, N not stated)
Extracolonic findings occur in 27% to 69% of examinations (not all represent harm) ●●◌◌ (Low confidence based on 21 studies, N = 38,293)
Balance of benefits and harms: No population outcome benefit (critical outcome) has been identified utilizing CT colonography. Sensitivity and specificity for detection of colon adenomas is lower than for colonoscopy (low confidence level). CT colonography is generally safe, but potential harms include radiation exposure and detection of extracolonic findings of no clinical significance.
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Should computed tomographic colonography be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Values and Other Outcomes Resource Allocation Confidence in Estimate Preferences Considerations Rationale: The available evidence suggests that screening CT colonography is less sensitive and less specific than colonoscopy in detection of colon adenomas, and diagnostic accuracy is reduced when cathartic bowel preparation is not performed. There is no evidence directly comparing CT colonography with other colorectal cancer screening tests. Although some might prefer the less invasive nature of this imaging study as compared with colonoscopy, there are no strong preferences that would favor CT colonography (when used with appropriate cathartic bowel preparation), nor strong resource allocation benefits. Our decision for non-coverage is based on the availability of alternatives to screening colonoscopy that are less costly and have fewer potential harms than CT colonography (e.g., FIT testing), which can be utilized by those who are unable or unwilling to undergo colonoscopy. In addition, we are concerned that coverage of less accurate testing modalities like CT colonography could erode utilization of the screening method that has the best sensitivity and specificity for colorectal cancer detection (colonoscopy). Recommendation: CT colonography for colorectal cancer screening is not recommended for coverage (weak recommendation).
Should multitarget stool DNA (Cologuard®) testing be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Values and Other Outcomes Resource Allocation Confidence in Estimate Preferences Considerations All-cause Insufficient data An individual multitarget stool DNA Many individuals in Offering mt-sDNA mortality test is less costly than an individual the screened testing may (Critical outcome) colonoscopy, but more expensive population would improve screening Colorectal cancer Insufficient data than other screening options (e.g., prefer mt-sDNA as a adherence in the incidence FIT). non-invasive test subpopulation that that does not is non-adherent to (Critical outcome) Mt-sDNA tests need to be Colorectal cancer Insufficient data involve cathartic the performed more frequently than morbidity bowel preparation, recommendation (Critical outcome)
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Should multitarget stool DNA (Cologuard®) testing be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Values and Other Outcomes Resource Allocation Confidence in Estimate Preferences Considerations Diagnostic test Sensitivity for colorectal cancer 92% colonoscopy, although the optimal radiation exposure, for screening characteristics (95% CI 84% to 97%) interval is not known. or other evident colonoscopy. (Important Specificity for colorectal cancer 84% Improved adherence to screening harms. However, The optimal outcome) (95% CI 84% to 85%) recommendations with mt-sDNA others would prefer frequency for CRC might tend to increase population to avoid the screening utilizing Sensitivity for advanced adenomas screening costs. Positive mt-sDNA collection and 42% (95% CI 39% to 46%) mt-sDNA has not tests require evaluation by shipping of a stool Specificity for advanced adenomas been established colonoscopy, additionally specimen (as 87% (95% CI 86% to 87%) (yearly vs. every increasing resource utilization. compared with three years). having a blood ●●◌◌ (Low confidence based on 1 If additional cancers were to be draw, for example). prospective diagnostic accuracy study detected because of higher comparing mt-sDNA, and colonoscopy screening rates, any savings related N = 9,989) to reduced cancer costs would Harms Insufficient data come many years after the (Important screening. outcome)
Balance of benefits and harms: Evidence is insufficient to establish any population screening benefit utilizing mt-sDNA. Sensitivity for detection of advanced colon adenomas is quite limited. No harms are evident with this testing modality, other than the risk of underdiagnosis of precancerous adenomas. Rationale: The available evidence for multitarget stool DNA testing is limited to diagnostic test characteristics, which includes high sensitivity for detection of colorectal cancer but relatively poor sensitivity for detection of adenomas. Specificity for colorectal cancer is relatively low, which is likely to increase the need for additional work-up with related cost and anxiety. Preferences weigh in favor of mt-sDNA as a noninvasive and safe testing strategy, but insufficient evidence of population benefit and the limited adenoma detection rate do not provide justification for the additional expenditures required for mt-sDNA coverage. The recommendation for noncoverage is weak, as further research may better establish a positive role or strategy of use for this modality.
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Should multitarget stool DNA (Cologuard®) testing be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Values and Other Outcomes Resource Allocation Confidence in Estimate Preferences Considerations Recommendation: Multitarget stool DNA testing (also known as Cologuard®, mt-sDNA, or FIT-DNA) for colorectal cancer screening is not recommended for coverage (weak recommendation).
Should methylated SEPT9 (mSEPT9) testing be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Other Outcomes Resource Allocation Values and Preferences Confidence in Estimate Considerations All-cause Insufficient data A recommended screening Values and preferences mortality frequency utilizing mSEPT9 would greatly favor the (Critical outcome) has not been established, convenience and Colorectal cancer Insufficient data making it difficult to simplicity of blood incidence estimate population testing, as opposed to (Critical outcome) screening costs. stool sample testing or Colorectal cancer Insufficient data Improvement in adherence colonoscopy. However, morbidity to screening many individuals in the (Critical outcome) recommendations with this screening population Diagnostic test Sensitivity for colorectal cancer 48% characteristics Specificity for colorectal cancer 91% blood test might increase would favor methods (Important ●◌◌◌ (Very low confidence based on 1 screening costs. Positive with better accuracy or outcome) study, N=6,874) mSEPT9 tests require more established Harms Insufficient data colonoscopy for testing protocols. (Important confirmation. outcome)
Balance of benefits and harms: Currently available evidence is insufficient to establish any population benefit with use of mSEPT9 for colorectal cancer screening. Harms of this testing modality have not been established, but there is possible risk of colorectal cancer underdiagnosis if this test is used for population screening, given the limited sensitivity in cancer detection.
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Should methylated SEPT9 (mSEPT9) testing be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Other Outcomes Resource Allocation Values and Preferences Confidence in Estimate Considerations Rationale: We have very low confidence in the evidence regarding test characteristics of mSEPT9, and the single study of accuracy in an asymptomatic screening population reported sensitivity well below other testing methods. Although many would prefer the convenience and simplicity of a blood test, current evidence is insufficient to recommend coverage. The noncoverage recommendation is weak because further research may support population screening benefits with mSEPT9. Recommendation: Methylated SEPT9 testing (mSEPT9) for colorectal cancer screening is not recommended for coverage (weak recommendation).
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Should chromoscopy be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Other Outcomes Resource Allocation Values and Preferences Confidence in Estimate Considerations All-cause mortality Insufficient data Dye enhancement would Values and preferences (Critical outcome) presumably add minimal would weigh in favor of a cost to colonoscopy. screening method that Colorectal cancer Insufficient data Additional lesion detection improves the colon incidence would add to expenditures adenoma detection rate. (Critical outcome) for biopsies and follow-up. However, chromoscopy Colorectal cancer Insufficient data Diagnosis of colorectal has all of the drawbacks morbidity cancer at an earlier stage, associated with standard (Critical outcome) however, could later result colonoscopy as a Diagnostic test Increases total number of neoplastic in treatment cost savings screening test. characteristics lesions detected that offset initial (Important (MD 0.33, 95% CI 0.25 to 0.41) expenditures. outcome) Increases total number of participants with at least one neoplastic lesion identified (OR 1.53, 95% CI 1.31 to 1.79),
Increases number of participants with a diminutive neoplastic lesion identified (OR 1.51, 95% CI 1.19 to 1.92)
Increases number of participants with three or more adenomas identified (OR 4.63, 95% CI 1.99 to 10.80)
●●◌◌ (Low confidence based on 7 studies, N=2,727) Harms Insufficient data (Important outcome)
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Should chromoscopy be recommended for coverage for colorectal cancer screening? Estimate of Effect for Outcome/ Other Outcomes Resource Allocation Values and Preferences Confidence in Estimate Considerations Balance of benefits and harms: Colon polyp detection is improved with chromoscopy, but currently available evidence is insufficient to establish any population benefit with use of chromoscopy for colorectal cancer screening. Harms have not been established, but risks of chromoscopy would be similar to standard colonoscopy, plus the risks of any adverse reactions to the dye. Rationale: There is low-quality evidence that chromoscopy improves polyp detection compared to standard colonoscopy, but its role in primary colorectal cancer screening for average-risk individuals has not been established. Population outcomes have not been demonstrated that might justify additional expenditures for dye enhancement, and there are no strong values or preferences supporting chromoscopy coverage. Our recommendation for noncoverage is weak because further evidence of population screening benefits may develop over time. Recommendation: Chromoscopy (dye-enhanced colonoscopy) for colorectal cancer screening is not recommended for coverage (weak recommendation). Note: GRADE-informed framework elements are described in Appendix A. A GRADE Evidence Profile is in Appendix B.
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Clinical Background Colorectal cancers start in the colon or the rectum and are often grouped together because of their common features. The risk of colorectal cancer increases with age; 90% of cases occur in people 50 years or older. Other risk factors include having inflammatory bowel disease, a family history of colorectal cancer, or genetic syndromes such as familial adenomatous polyposis or hereditary non- polyposis colorectal cancer (Lynch syndrome). Lifestyle factors that can increase the risk of colorectal cancer include lack of physical exercise, a diet low in fruits and vegetables, a low-fiber diet, obesity, heavy alcohol consumption, and tobacco use (Centers for Disease Control and Prevention [CDC], 2016). Most colorectal cancers begin as polyps on the inner lining of the colon or rectum. A polyp can change into cancer over several years, however, not all polyps become cancer. Colorectal cancer does not always cause symptoms, especially in the early stages (American Cancer Society [ACS], 2017). The lifetime risk of developing colorectal cancer is 4.7% for men and 4.4% for women (ACS, 2017). In 2013 in the U.S., 136,119 people were diagnosed with colorectal cancer and 51,813 people died from colorectal cancer (CDC, 2016). The death rate from colorectal cancer has been declining for several decades because colorectal polyps are being found more often by screening and then removed, and treatments for colorectal cancer have improved (ACS, 2017). Colorectal cancer screening tests can find precancerous polyps so that they can be removed before turning into cancer. Screening tests can also detect colorectal cancer at earlier stages, when treatment is more effective (CDC, 2016). Screening tests for colorectal cancer include colonoscopy, computed tomography (CT) colonography, flexible sigmoidoscopy, fecal occult blood tests (FOBT), fecal immunochemical tests (FIT), fecal DNA tests (Cologuard®), methylated SEPT9 (mSEPT9) DNA test (Epi proColon®), and double-contrast barium enema. Indications The U.S. Preventive Services Task Force (USPSTF) 2016 guidelines recommend colorectal cancer screening for average-risk adults aged 50 to 75. This is a Grade A Recommendation, defined as follows: “The USPSTF recommends the service. There is high certainty that the net benefit is substantial.” The USPSTF guidelines state that screening decisions for adults aged 76 to 85 years old should be based on individual circumstances, including the person’s overall health and screening history. Adults in this age group who have never been screened for colorectal cancer are more likely to benefit. Screening would be most appropriate among adults who 1) are healthy enough to undergo treatment if colorectal cancer is detected and 2) do not have comorbid conditions that would significantly limit their life expectancy. This is a Grade C Recommendation, defined as follows: “The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.” The USPSTF did not include recommendations on which screening test to use, but the following table was included as part of its 2016 Final Recommendation Statement on Colorectal Cancer Screening (USPSTF, 2016).
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Table 1. Characteristics of Colorectal Cancer Screening Strategiesa Screening Frequencyb Evidence of Efficacy Other Considerations Method Stool-Based Tests gFOBT Every year RCTs with mortality end Does not require bowel points: preparation, anesthesia, or High-sensitivity versions transportation to and from the (e.g., Hemoccult SENSA) screening examination (test is have superior test performed at home) performance characteristics than older tests (e.g., Hemoccult II) FITc Every year Test characteristic studies: Does not require bowel Improved accuracy preparation, anesthesia, or compared with gFOBT transportation to and from the screening examination (test is Can be done with a single performed at home) specimen FIT-DNA Every 1 or 3 Test characteristic studies: There is insufficient evidence about d years Specificity is lower than for appropriate longitudinal follow-up FIT, resulting in more of abnormal findings after a false-positive results, more negative diagnostic colonoscopy; diagnostic colonoscopies, may potentially lead to overly and more associated intensive surveillance due to adverse events per provider and patient concerns over screening test the genetic component of the test Improved sensitivity compared with FIT per single screening test Direct Visualization Tests Colonoscopyc Every 10 years Prospective cohort study Requires less frequent screening with mortality end point Screening and diagnostic follow-up of positive results can be performed during the same examination CT Every 5 years Test characteristic studies There is insufficient evidence about e colonography the potential harms of associated extracolonic findings, which are
common
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Screening Frequencyb Evidence of Efficacy Other Considerations Method Flexible Every 5 years RCTs with mortality end Test availability has declined in the sigmoidoscopy points: United States Modeling suggests it provides less benefit than when combined with FIT or compared with other strategies Flexible Flexible RCT with mortality end Test availability has declined in the sigmoidoscopy sigmoidoscopy point (subgroup analysis) United States with FITc every 10 years Potentially attractive option for plus FIT every patients who want endoscopic year screening but want to limit exposure to colonoscopy
Abbreviations: FIT=fecal immunochemical test; FIT-DNA=multitargeted stool DNA test; gFOBT=guaiac-based fecal occult blood test; RCT=randomized clinical trial. a Although a serology test to detect methylated SEPT9 DNA was included in the systematic evidence review, this screening method currently has limited evidence evaluating its use (a single published test characteristic study met inclusion criteria, which found it had a sensitivity to detect colorectal cancer of <50%). It is therefore not included in this table. b Applies to persons with negative findings (including hyperplastic polyps) and is not intended for persons in surveillance programs. Evidence of efficacy is not informative of screening frequency, with the exception of gFOBT and flexible sigmoidoscopy alone. c Strategy yields comparable life-years gained (i.e., the life-years gained with the noncolonoscopy strategies were within 90% of those gained with the colonoscopy strategy) and an efficient balance of benefits and harms in CISNET modeling. d Suggested by manufacturer. e Strategy yields comparable life-years gained (i.e., the life-years gained with the noncolonoscopy strategies were within 90% of those gained with the colonoscopy strategy) and an efficient balance of benefits and harms in CISNET modeling when lifetime number of colonoscopies is used as the proxy measure for the burden of screening, but not if lifetime number of cathartic bowel preparations is used as the proxy measure. Source: USPSTF (2016)
Technology Description The interventions included in this coverage guidance are CT colonography, fecal DNA testing, serum testing for SEPT9, and colonoscopy with chromoscopy (chromoendoscopy). These interventions are described below (National Cancer Institute, 2016). CT colonography, sometimes referred to as virtual colonoscopy, uses a CT scanner to produce a series of pictures of the colon and the rectum that can show polyps and other abnormalities. A thorough cleansing of the colon is necessary before this test, and the procedure does not require sedation. Air or carbon dioxide is pumped into the colon to expand it for better viewing of the colon’s lining. If polyps or
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other abnormal growths are found during the CT colonography, a standard colonoscopy is usually performed to remove them. The only fecal DNA test approved by the U.S. Food and Drug Administration (FDA) is Cologuard®. This test can detect small amounts of blood in the stool and nine DNA biomarkers in three genes that have been found in colorectal cancer and precancerous advanced adenomas. The DNA is from cells in the lining of the colon and rectum that are collected in the stool as it passes. Colorectal polyps and tumors can release cells and DNA into the bloodstream, including the altered gene called SEPT9. In April 2016, the FDA approved the first blood-based test to screen for colorectal cancer, which detects the presence of SEPT9. Some polyps, especially smaller, flat lesions, can be difficult to detect using a standard colonoscopy. In colonoscopy with chromoscopy, a dye is sprayed onto the surface of the colon to make polyps more visible. Along with the interventions above, the comparators considered in this coverage guidance are colonoscopy, flexible sigmoidoscopy, and FOBT, including FIT. Colonoscopy is the most common colorectal cancer screening test, in which the rectum and entire colon are examined using a flexible lighted tube with a lens for viewing and a tool for removing tissue. A colonoscope is inserted through the anus into the rectum and colon as air or carbon dioxide is pumped in to expand the colon. Polyps and abnormal growths can be removed during the procedure. A thorough cleansing of the colon is necessary, and most patients are sedated during the test. A flexible sigmoidoscopy is a similar procedure in which the rectum and only the sigmoid colon are examined. This procedure also uses a flexible lighted tube with a lens for viewing and a tool for removing tissue and air or carbon dioxide is pumped in to expand the colon. The lower colon must be cleared of stool before sigmoidoscopy, and patients are usually not sedated for this procedure. FOBT can detect small amounts of blood in feces that might derive from polyps and colorectal cancers. Currently, two types of FOBT are approved by the FDA, guaiac FOBT and FIT. Guaiac FOBT uses a chemical to detect heme, a component of hemoglobin. FIT uses antibodies to detect human hemoglobin protein. Evidence Review Lin et al., 2016 This is a good-quality systematic review of colorectal cancer screening tests that was done to inform the United States Preventive Services Task Force recommendations for colorectal cancer screening. The review summarizes evidence on the clinical effectiveness, diagnostic operating characteristics, and harms of colonoscopy, flexible sigmoidoscopy, fecal occult blood testing (FOBT), fecal immunohistochemical testing (FIT), FIT plus stool DNA, and CT colonography. Although they are beyond the scope of this coverage guidance, the conclusions regarding the effectiveness and harms of colonoscopy, flexible sigmoidoscopy, FOBT, and FIT are presented here for comparison. No colorectal cancer screening test has been shown to reduce all-cause mortality. There were no screening trials involving colonoscopy, although the authors did identify one prospective cohort study that they did not further summarize because of methodological limitations. Based on four pragmatic trials (n=458,002) with 11 to 12 years of follow-up, sigmoidoscopy was associated with a
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reduction in colorectal cancer-specific mortality when compared to no screening (incidence rate ratio 0.73, 95% CI 0.66 to 0.82). In one trial, the combination of sigmoidoscopy and FIT reduced the risk of colorectal cancer mortality more than sigmoidoscopy alone (hazard ratio 0.62, 95% CI 0.42 to 0.90). Based on five pragmatic trials with 11 to 30 years of follow-up, biennial screening with guaiac-based FOBT reduced the risk of colorectal cancer-specific mortality when compared to no screening (relative risk [RR] 0.78, 95% CI 0.65 to 0.93 at 30 years). One trial suggested that annual screening was associated with greater improvements in colorectal cancer-specific mortality at 30 years (RR 0.68, 95% CI 0.56 to 0.82). In their analysis of FIT testing, the authors focused on currently available assays with more than one diagnostic accuracy study; the sensitivity and specificity of FIT for colorectal cancer ranged from 73% to 88% and 90% to 96% respectively. The sensitivity of FIT for detecting advanced adenomas was limited and ranged from 22% to 40%, but with high specificity (range 91% to 97%). The systematic review conducted by Lin et al. (2016) found no studies examining clinical outcomes for screening with CT colonography or FIT plus multitarget stool DNA (mt-sDNA) testing. Lin et al. (2016) found nine prospective diagnostic accuracy studies of CT colonography that included 6,497 participants. The reference standard for all of these studies was colonoscopy. Lin et al. (2016) rated the overall evidence quality as fair to good. Seven of the studies performed CT colonography after a cathartic bowel preparation and two were done without bowel preparation. In the studies of CT colonography done after bowel preparation, the sensitivity and specificity for the detection of adenomas >10 mm ranged from 67% to 94% and 96% to 98%, respectively. For detecting adenomas >6 mm, the sensitivity and specificity for CT colonography with bowel preparation ranged from 73% to 98% and 89% to 91%, respectively. Lin et al. (2016) observed that the two studies of CT colonography without bowel preparation found lower sensitivity to detect smaller adenomas (58% in one study and 75% in the other). Lin et al. (2016) identified several limitations to the included studies, most importantly that they were not designed to evaluate the diagnostic performance of CT colonography for cancer detection. Additionally, Lin et al. (2016) noted that the included studies were mainly single-center and relied on a small number of experienced radiologists to interpret the results. Lin et al. (2016) identified one large prospective diagnostic accuracy study of FIT plus mt-sDNA testing in an asymptomatic screening population. In this study, 9,989 patients had FIT alone and FIT plus mt-sDNA testing performed, and the results were compared to a reference standard of colonoscopy. Lin et al. (2016) rated the study as fair quality. For FIT plus mt-sDNA, sensitivity for colorectal cancer was 92% (95% CI 84% to 97%) and specificity was 84% (95% CI 84% to 85%). For detection of advanced adenomas, the sensitivity FIT plus mt-sDNA was 42% (95% CI 39% to 46%) and specificity was 87% (95% CI 86% to 87%). Compared to FIT alone, FIT plus mt-sDNA increased the sensitivity while decreasing specificity. Lin et al. (2016) noted that 6% of FIT plus mt-sDNA tests could not be performed because of inadequate specimens. Lin et al. (2016) identified one small (n=661) study of the diagnostic accuracy of FIT plus mt- sDNA in a screening population of Alaskan Natives; although the results were similar to the larger study, the authors cautioned that the smaller study was not adequately powered to identify differences in cancer detection. Lin et al. (2016) identified 15 studies that reported on the harms of screening CT colonography. In general, serious adverse events were rare. The estimated ionizing radiation exposure for a single CT colonography ranged from 1 to 7 miliSieverts. Extracolonic findings were common during CT
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colonography, occurring in 27% to 69% of examinations; 5% to 37% of examinations had extracolonic findings requiring additional diagnostic evaluation. The likelihood of extracolonic findings increased with advancing age. Overall, Lin et al. (2016) assessed the evidence quality as fair because of concerns about sparse reporting in average-risk screening populations, reporting bias, and uncertainty about the net benefits or harms of extracolonic findings. The authors did not report on nor summarize harms from studies of FIT plus mt-sDNA testing. Knudsen et al., 2016 This is a comparative modeling study conducted on behalf of the USPSTF to assess the balance between screening burdens and life-years gained for different screening strategies initiated at different ages. Three previously validated models were used in the analysis. Notably, all of the models assumed perfect adherence to the various screening strategies and the authors stated that there is “limited empirical evidence on test-specific adherence over multiple rounds of screening” (p. 2606). Based on the simulations performed across the three models, the authors ultimately concluded that screening between the ages of 50 and 74 years with colonoscopy every 10 years, annual FIT, sigmoidoscopy every 10 years with annual FIT, or CT colonography every five years all result in a similar number of life-years gained with comparable screening burdens. It should be noted that in all three models, FIT plus mt- sDNA testing was a dominated strategy (i.e., it produced fewer life-years than other strategies) when performed every three or five years, and was deemed less efficient than alternative screening strategies when it was performed yearly. Yan et al., 2016 This is a fair-quality systematic review and meta-analysis of the diagnostic operating characteristics of the mSEPT9 test for colorectal cancer diagnosis. Most of the studies were case-control designs, and the authors observed several sources of serious bias in the included studies, ranging from unblinded performance of index tests to non-prespecified thresholds to define positive tests. In the overall analysis, the pooled sensitivity of mSEPT9 for the diagnosis of colorectal cancer was 66% (95% CI 61% to 77%) and the specificity was 91% (95% CI 90% to 91%); both pooled estimates showed high levels of heterogeneity (I2 values of 88% and 91%, respectively). Aside from the methodological flaws of the included studies, the major limitation of this review was that only one of the included studies was a prospective accuracy study performed in an asymptomatic screening population; in that study the sensitivity of mSEPT9 was 48% and specificity was 91%. Brown et al., 2016 This is a high-quality Cochrane systematic review of seven randomized trials (n=2,727) of chromoscopy compared to standard or high-definition colonoscopy. Two of the trials were analyzed separately because the design of these studies involved standard colonoscopy followed by repeat colonoscopy or colonoscopy with chromoscopy. Only one study explicitly enrolled only patients at average risk of developing polyps, and the other studies might have included above-average-risk populations (although studies of patients with inflammatory bowel disease or polyposis syndromes were specifically excluded). The authors assessed the overall risk of bias in the studies as unclear, although all studies had high risk of bias because of lack of blinding. The variability in the use of high-definition colonoscopy as the comparator and lack of standardized examination durations between the arms could have introduced bias. The authors of the review applied GRADE methods to their assessments. Overall, there was low-
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quality evidence that chromoscopy increased the average number of neoplastic lesions found per patient (polyps or cancers) (mean difference 0.33, 95% CI 0.25 to 0.41), the total number of participants with at least one neoplastic lesion identified (OR 1.53, 95% CI 1.31 to 1.79), the number of participants with a diminutive neoplastic lesion identified (OR 1.51, 95% CI 1.19 to 1.92), and the number of participants with three or more adenomas identified (OR 4.63, 95% CI 1.99 to 10.80). None of the included studies reported on adverse events related to administration of the chromoscopy dye. The authors concluded that there is low-quality evidence that chromoscopy increases the detection of polyps compared to conventional colonoscopy. Contextual Questions Lieberman et al., 2016 This is a review and commentary on the recently updated USPSTF recommendations for colorectal cancer screening in average-risk individuals. The authors provided a comprehensive summary of the merits of various screening strategies and summarized several professional society guidelines. This review is included here to emphasize the authors’ conclusions that no evidence supports the superiority of one screening program over another, and that attention to quality and adherence within a given screening program is required. Prince et al., 2017 This is a cross-sectional study describing the use of an mt-sDNA test among 393 Medicare beneficiaries who were non-adherent to recommended screening colonoscopy in a single multi-specialty practice in Texas. One of the authors is employed by and owns stock in the manufacturer of the mt-sDNA test Cologuard® and the source of funding for the study was not disclosed. During a one-year period, providers ordered mt-sDNA studies for 393 patients (average age of 70 years, 64% women) who had not been adherent to recommendations for screening colonoscopy. The mt-sDNA test was completed by 347 patients (88% adherence). Among the 347 completed mt-sDNA tests, 296 (85%) were negative and 51 (15%) were positive. Forty-nine of the patients with a positive mt-sDNA test underwent colonoscopy, which disclosed colon cancer in four patients (8%), advanced adenomas in 29 patients (43%), and non- advanced adenomas in 15 patients (31%); the remaining colonoscopies were negative. The authors concluded that offering mt-sDNA testing improves screening adherence in a population non-adherent to the recommendation for screening colonoscopy. Stoop et al., 2012 This is a randomized controlled trial comparing invitation to screening colonoscopy to invitation to CT colonography with a non-cathartic bowel preparation within a colorectal cancer screening program in the Netherlands. People between 50 and 75 years in the general population were randomly allocated to screening colonoscopy (n=5,924) or CT colonography (n=2,920). All invitees were followed through the national cancer registry for colorectal cancer incidence and mortality. Overall, 34% of the CT colonography group attended screening compared to 22% of the colonoscopy group (RR 1.56, 95% CI 1.46 to 1.68). The improved screening attendance with CT colonography was observed across age, gender, and socioeconomic subgroups. Although the diagnostic yield for advanced neoplasia was higher in the colonoscopy group (8.7 per 100 screened) compared to the CT colonography group (6.1 per 100 screened), the diagnostic yield of the two strategies for detection of advanced adenomas was similar when considering invitations to screening (1.9 per 100 invitations to screening colonoscopy vs. 2.1 per
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100 invitations to screening CT colonography, RR 0.91, 95% CI 0.66 to 2.03). The authors concluded that CT colonography with a non-cathartic bowel preparation could increase screening adherence with a similar diagnostic yield per invitee. Domingo & Brown, 2017 This is a systematic review of the effectiveness of patient navigation interventions to improve colorectal cancer screening adherence in federally qualified health centers. Among the eight studies included, most targeted African American or Latino populations. Although the effects of offering multiple colorectal cancer screening options was not addressed, the authors found that navigation interventions were likely to improve screening adherence and that one common function of navigators was to help convey a patient’s preference regarding the type of screening test. Duffy et al., 2016 This is a rapid review of interventions to improve participation in cancer screening programs generally. The effects of offering multiple colorectal cancer screening options was not addressed, but the authors observed that more acceptable screening tests improve the likelihood of screening adherence for colorectal and cervical cancer. Specifically, the authors identified two studies showing higher participation rates with FIT compared to colonoscopy or FOBT, and one study that found a “small increase” in participation with capsule colonoscopy compared to conventional colonoscopy. Evidence Summary There is a lack of direct evidence comparing the effectiveness of various colorectal cancer screening tests. Only guaiac FOBT and flexible sigmoidoscopy have been shown to decrease colorectal cancer incidence and colorectal cancer mortality in randomized controlled trials. Colonoscopy is associated with reductions in colorectal cancer incidence and mortality (particularly for cancers of the proximal colon) in observational trials. FIT testing has higher sensitivity than guaiac FOBT, and the addition of mt-sDNA to FIT testing likely further increases the single-test sensitivity of FIT but reduces specificity. The sensitivity and specificity of CT colonography for colorectal cancer detection is unknown, but the reported sensitivity of CT colonography for detecting adenomas of various sizes ranges from 67% to 98% when it is performed with a cathartic bowel preparation. Based on these results and the Knudsen et al. (2016) modeling study, all of the tests described above are endorsed by the USPSTF for colorectal cancer screening in adults between the ages of 50 and 75. The accuracy of mSEPT9 testing in an asymptomatic screening population has only been examined in one study, and the reported sensitivity is well below that of the tests discussed above. There is low-quality evidence that chromoscopy improves polyp detection compared to standard colonoscopy, but its role in primary colorectal cancer screening for average-risk individuals has not been well established. There is sparse information on the differential effectiveness of various screening strategies among subgroups. Limited evidence from a small cross-sectional study suggests that offering mt-sDNA testing to patients who have been non-adherent to recommendations for colonoscopy leads to high rates (>85%) of screening participation. Evidence from a single RCT in the Netherlands suggests that invitation to CT colonography with non-cathartic bowel preparation results in greater screening participation
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compared to invitation to colonoscopy. Otherwise, no direct evidence was found showing that offering multiple options for colorectal cancer screening improves screening adherence. Experts in colorectal cancer screening and the USPSTF have emphasized the importance of high-quality screening programs regardless of the test selected. For colorectal cancer screening programs to be successful in reducing mortality, they need to involve more than the screening method in isolation. The USPSTF considers screening to be a cascade of activities that must occur in concert, cohesively, and in an organized way for benefits to be realized, from the point of the initial screening examination (including related interventions or services that are required for successful administration of the screening test, such as bowel preparation or sedation with endoscopy) to the timely receipt of any necessary diagnostic follow-up and treatment (USPSTF, p. 2570). Other Decision Factors Resource Allocation Costs for screening colonoscopy vary widely depending on the setting in which the colonoscopy is performed, the type of anesthesia or sedation used, and removal of any polyps found. Costs for sigmoidoscopy are lower because it can be performed in an office setting, but it is not widely available in the United States. Adding chromoscopy to colonoscopy would add the cost of the dye and potentially some costs related to complications arising from the use of the dye. All of the noninvasive techniques (CT colonography, FIT, mt-sDNA and FOBT) require follow-up colonoscopy when positive. Offering the fecal tests could result in higher screening rates, which would potentially increase the costs of a screening program unless they result in fewer colonoscopies because of the lack of a requirement for cathartic bowel preparation. FIT and FOBT cost a small fraction of the other modalities. All the noninvasive modalities are recommended more frequently than colonoscopy. Values and Preferences Values and preferences clearly favor colorectal cancer screening tests, which are the most accurate in detection of precancerous polyps and most accurate in detection of cancers at early stages, when cancer treatment is most effective and most likely to be curative. Colonoscopy is currently considered the screening test with the highest sensitivity and specificity, the “gold standard” for colorectal cancer detection. However, there are major drawbacks related to the use of colonoscopy for population screening, including the relatively high cost and invasive nature of the procedure. Those factors limit adherence to population screening recommendations, and thus reflect the limitation of preferences for colonoscopy. Testing strategies that have lower accuracy, but also lower cost and better ease of use, would result in significantly variable values and preferences, depending on the relative merits of these three factors. However, there is clear value in improved adherence to screening recommendations that might come with use of these alternatives. There is also value in offering colorectal cancer screening strategies that emphasize individual choice and shared decision making about test type because such strategies are likely to improve adherence to screening recommendations.
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Policy Landscape Payer Coverage Policies Medicaid The Washington Medicaid program does not cover CT colonography for colon cancer screening, as outlined in a Findings and Coverage Decision from 2008. Washington Medicaid does not cover fecal DNA testing for colorectal cancer. No coverage policies were identified for SEPT9 serum testing and chromoscopy. Medicare There are five Medicare Local Coverage Determinations for CT colonography and none provide coverage for this procedure when used for colon cancer screening. No Medicare National Coverage Determinations were found for CT colonography. A Medicare National Coverage Determination provides coverage for Cologuard® every three years for beneficiaries 50 to 85 years old who have an average risk for developing colorectal cancer and have no signs or symptoms of colorectal disease. No Local or National Cover Determinations were found for fecal DNA testing, serum tests for SEPT9, and chromoscopy. Private Payers Coverage policies were searched for Aetna, Cigna, Moda, and Regence. Aetna and Cigna generally cover CT colonography for screening purposes for average-risk people 50 years and older. CT colonography for screening purposes is covered by Moda and Regence only when the patient is unable to undergo conventional colonoscopy for medical reasons, such as chronic anticoagulation therapy or sedation risk, or conventional colonoscopy was incomplete because of colonic stenosis, obstruction, or other significant anatomical abnormality. Aetna, Cigna, and Regence cover Cologuard®, the fecal DNA test, usually every three years. Fecal DNA testing was not listed in Moda’s policy on Colorectal Cancer Screening and Related Ancillary Services. Serum SEPT9 tests to detect colorectal cancer are not covered by Aetna and Cigna. The SEPT9 test was not listed in Moda’s policy on Colorectal Cancer Screening and Related Ancillary Services, and no coverage policy was found for Regence. Aetna, Cigna, and Regence consider chromoscopy for colorectal cancer screening to be experimental or investigational, and chromoscopy is not listed in Moda’s policy on Colorectal Cancer Screening and Related Ancillary Services. Professional Society Guidelines Recommendations from five guidelines that address colorectal cancer screening are outlined below. None of these guidelines made an affirmative recommendation for use of CT colonography, fecal DNA tests, serum SEPT9 tests, or chromoscopy to screen average-risk patients. The USPSTF (2016) recommends screening for colorectal cancer from age 50 until age 75 for average- risk patients. For adults aged 76 to 85, the screening decision should be individualized, taking into account the patient’s overall health and screening history. The guidelines found that the risks and
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benefits of different screening methods vary, and thus did not make recommendations on which screening methods to use. The guidelines from the Scottish Intercollegiate Guidelines Network (2016) found no evidence to support CT colonography as a primary screening modality. These guidelines also did not recommend consideration of fecal DNA tests, serum tests for SEPT9, or chromoscopy for average-risk patients. The guidelines from the National Comprehensive Cancer Network (Provenzale et al., 2015) found that evidence was not sufficient to provide recommendations about the use of CT colonography for colorectal cancer screening. The guidelines recommend against fecal DNA testing as a primary screening modality. Serum SEPT9 tests and chromoscopy were not addressed in the guidelines. Guidelines from the American College of Physicians (Wilt et al., 2015) recommend that colorectal cancer screening in average-risk adults start at the age of 50. These guidelines did not recommend the use of CT colonography, fecal DNA tests, serum SEPT9 tests, or chromoscopy. The Canadian Task Force on Preventive Health Care guidelines (Bacchus, 2016) recommend colorectal cancer screening of adults ages 50 to 74 and not screening adults age 75 and older. Because no RCTs were identified on the mortality benefits of screening, no recommendations were made for CT colonography, fecal DNA tests, serologic tests (e.g., SEPT9), or chromoscopy. Quality Measures The National Quality Measures Clearinghouse was searched for measures related to colorectal cancer screening for average-risk adults. The most recent colorectal cancer screening measure from the National Committee for Quality Assurance was developed in 2016, “Percentage of members 50 to 75 years of age who had appropriate screening for colorectal cancer.” The definition of appropriate screening for colorectal cancer includes CT colonography and FIT-DNA tests, and does not include serum SEPT9 tests or chromoscopy.
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References Evidence Sources Brown, S. R., Baraza, W., Din, S., & Riley, S. (2016). Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum. Cochrane Database of Systematic Reviews, 4, Cd006439. doi: 10.1002/14651858.CD006439.pub4 Domingo, J. B., & Braun, K. L. (2017). Characteristics of effective colorectal cancer screening navigation programs in federally qualified health centers: A systematic review. Journal of Health Care for the Poor and Underserved, 28(1), 108-126. doi: 10.1353/hpu.2017.0013 Duffy, S. W., Myles, J. P., Maroni, R., & Mohammad, A. (2016). Rapid review of evaluation of interventions to improve participation in cancer screening services. Journal of Medical Screening. doi: 10.1177/0969141316664757 Knudsen, A. B., Zauber, A. G., Rutter, C. M., Naber, S. K., Doria-Rose, V. P., Pabiniak, C., . . . Kuntz, K. M. (2016). Estimation of benefits, burden, and harms of colorectal cancer screening strategies: Modeling study for the US Preventive Services Task Force. JAMA, 315(23), 2595-2609. doi: 10.1001/jama.2016.6828 Lieberman, D., Ladabaum, U., Cruz-Correa, M., Ginsburg, C., Inadomi, J. M., Kim, L. S., . . . Wender, R. C. (2016). Screening for colorectal cancer and evolving issues for physicians and patients: A review. JAMA, 316(20), 2135-2145. doi: 10.1001/jama.2016.17418 Lin, J. S., Piper, M. A., Perdue, L. A., Rutter, C. M., Webber, E. M., O'Connor, E., . . . Whitlock, E. P. (2016). Screening for colorectal cancer: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA, 315(23), 2576-2594. doi: 10.1001/jama.2016.3332 Prince, M., Lester, L., Chiniwala, R., & Berger, B. (2017). Multitarget stool DNA tests increases colorectal cancer screening among previously noncompliant Medicare patients. World Journal of Gastroenterology, 23(3), 464-471. doi: 10.3748/wjg.v23.i3.464 Stoop, E. M., de Haan, M. C., de Wijkerslooth, T. R., Bossuyt, P. M., van Ballegooijen, M., Nio, C. Y., . . . Dekker, E. (2012). Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: A randomised controlled trial. Lancet Oncology, 13(1), 55-64. doi: 10.1016/s1470-2045(11)70283-2 Yan, S., Liu, Z., Yu, S., & Bao, Y. (2016). Diagnostic value of methylated septin9 for colorectal cancer screening: A meta-analysis. Medical Science Monitor, 22, 3409-3418. doi: 10.12659/MSM.900590 Other Citations American Cancer Society. (2017). Colorectal cancer? Retrieved from https://www.cancer.org/cancer/colon-rectal-cancer.html Bacchus, C. M., Dunfield, L., Gorber, S. C., Holmes, N. M., Birtwhistle, R., Dickinson, J. A., . . . Tonelli, M. (2016). Recommendations on screening for colorectal cancer in primary care. Canadian Medical Association Journal, 188(5), 340-348. doi: 10.1503/cmaj.151125
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Centers for Disease Control and Prevention. (2016). Colorectal (colon) cancer. Retrieved from https://www.cdc.gov/cancer/colorectal/index.htm National Cancer Institute. (2016). Tests to detect colorectal cancer and polyps. Retrieved from https://www.cancer.gov/types/colorectal/screening-fact-sheet#q2 Scottish Intercollegiate Guidelines Network. (2016). Diagnosis and management of colorectal cancer. Retrieved from http://www.sign.ac.uk/guidelines/fulltext/126/ Provenzale, D., Jasperson, K., Ahnen, D. J., Aslanian, H., Bray, T., Cannon, J. A., . . . Darlow, S. (2015). Colorectal cancer screening, version 1.2015. Journal of the National Comprehensive Cancer Network, 13(8), 959-968; quiz 968. Wilt, T. J., Harris, R. P., & Qaseem, A. (2015). Screening for cancer: Advice for high-value care from the American College of Physicians. Annals of Internal Medicine, 162(10), 718-725. doi: 10.7326/m14-2326 U.S. Preventive Services Task Force. (2016). Screening for colorectal cancer: US Preventive Services Task Force Recommendation Statement. JAMA, 315(23), 2564-2575. doi: 10.1001/jama.2016.5989
Coverage guidance is prepared by the Health Evidence Review Commission (HERC), HERC staff, and subcommittee members. The evidence summary is prepared by the Center for Evidence-based Policy at Oregon Health & Science University (the Center). This document is intended to guide public and private purchasers in Oregon in making informed decisions about health care services. The Center is not engaged in rendering any clinical, legal, business or other professional advice. The statements in this document do not represent official policy positions of the Center. Researchers involved in preparing this document have no affiliations or financial involvement that conflict with material presented in this document.
Suggested citation: Obley, A., Mosbaek, C., King, V., & Shaffer, W. (2017). Coverage guidance: Colorectal cancer screening modalities. Portland, OR: Center for Evidence-based Policy, Oregon Health & Science University.
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Appendix A. GRADE-Informed Framework Element Descriptions
Element Description Balance of benefits The larger the difference between the desirable and undesirable effects, the higher the and harms likelihood that a strong recommendation is warranted. An estimate that is not statistically significant or has a confidence interval crossing a predetermined clinical decision threshold will be downgraded. Quality of evidence The higher the quality of evidence, the higher the likelihood that a strong recommendation is warranted Resource allocation The higher the costs of an intervention—that is, the greater the resources consumed in the absence of likely cost offsets—the lower the likelihood that a strong recommendation is warranted Values and The more values and preferences vary, or the greater the uncertainty in values and preferences preferences, the higher the likelihood that a weak recommendation is warranted Other considerations Other considerations include issues about the implementation and operationalization of the technology or intervention in health systems and practices within Oregon.
Strong recommendation In Favor: The subcommittee concludes that the desirable effects of adherence to a recommendation outweigh the undesirable effects, considering the balance of benefits and harms, resource allocation, values and preferences and other factors. Against: The subcommittee concludes that the undesirable effects of adherence to a recommendation outweigh the desirable effects, considering the balance of benefits and harms, resource allocation, values and preferences and other factors. Weak recommendation In Favor: The subcommittee concludes that the desirable effects of adherence to a recommendation probably outweigh the undesirable effects, considering the balance of benefits and harms, resource allocation, values and preferences and other factors., but further research or additional information could lead to a different conclusion. Against: The subcommittee concludes that the undesirable effects of adherence to a recommendation probably outweigh the desirable effects, considering the balance of benefits and harms, cost and resource allocation, and values and preferences, but further research or additional information could lead to a different conclusion. Confidence in estimate rating across studies for the intervention/outcome Assessment of confidence in estimate includes factors such as risk of bias, precision, directness, consistency and publication bias. High: The subcommittee is very confident that the true effect lies close to that of the estimate of the effect. Typical sets of studies are RCTs with few or no limitations and the estimate of effect is likely stable.
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Moderate: The subcommittee is moderately confident in the estimate of effect: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Typical sets of studies are RCTs with some limitations or well-performed nonrandomized studies with additional strengths that guard against potential bias and have large estimates of effects. Low: The subcommittee’s confidence in the estimate of effect is limited: The true effect may be substantially different from the estimate of the effect. Typical sets of studies are RCTs with serious limitations or nonrandomized studies without special strengths. Very low: The subcommittee has very little confidence in the estimate of effect: The true effect is likely to be substantially different from the estimate of effect. Typical sets of studies are nonrandomized studies with serious limitations or inconsistent results across studies.
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Appendix B. GRADE Evidence Profile
Quality Assessment (Confidence in Estimate of Effect) Computed Tomographic Colonography Other No. of Studies Study Design(s) Risk of Bias Inconsistency Indirectness Imprecision Factors Quality All-cause mortality Insufficient data Colorectal cancer incidence Insufficient data Colorectal cancer morbidity Insufficient data Diagnostic test characteristics 5 Diagnostic Low to Not serious Not serious Serious Low accuracy moderate ●●◌◌ Harms Serious adverse Observational Low to Not serious Not serious Not serious Low events moderate ●●◌◌ 11 Ionizing radiation 7 Extra-colonic findings 21
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Quality Assessment (Confidence in Estimate of Effect) Multitarget Stool DNA Testing Other No. of Studies Study Design(s) Risk of Bias Inconsistency Indirectness Imprecision Factors Quality All-cause mortality Insufficient data Colorectal cancer incidence Insufficient data Colorectal cancer morbidity Insufficient data Diagnostic test characteristics 1 Diagnostic accuracy Low Not estimable Not serious Not serious Single Low study ●●◌◌ Harms Insufficient data
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Quality Assessment (Confidence in Estimate of Effect) MethylatedMethylated Septin9 SEPT9 No. of Study Other Studies Design(s) Risk of Bias Inconsistency Indirectness Imprecision Factors Quality All-cause mortality Insufficient data Colorectal cancer incidence Insufficient data Colorectal cancer morbidity Insufficient data Diagnostic test characteristics 1 Diagnostic Moderate Not estimable Not serious Not estimable Very low accuracy ●◌◌◌ Harms Insufficient data
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Quality Assessment (Confidence in Estimate of Effect) Chromoscopy No. of Study Other Studies Design(s) Risk of Bias Inconsistency Indirectness Imprecision Factors Quality All-cause mortality Insufficient data Colorectal cancer incidence Insufficient data Colorectal cancer morbidity Insufficient data Diagnostic test characteristics 7 RCTs Unclear Serious Not serious Not serious Low ●●◌◌ Harms Insufficient data
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Appendix C. Methods Scope Statement Populations Adults age 50 and older with average risk of colorectal cancer Population scoping notes: Excludes high risk, such as first-degree relative with colorectal cancer, known predisposing mutations (AFP, HNPCC), or inflammatory bowel disease Interventions Computed tomographic colonography, fecal DNA testing, serum test for SEPT9, colonoscopy with chromoendoscopy Intervention exclusions: Double-contrast barium enema, camera pill Comparators Colonoscopy, flexible sigmoidoscopy (with or without fecal occult blood testing), fecal occult blood testing, FIT testing, other listed interventions Outcomes Critical: Colorectal cancer incidence, all-cause mortality, colorectal cancer morbidity Important: Diagnostic test characteristics, harms Considered but not selected for the GRADE table: Quality of life Key Questions KQ1: What is the comparative effectiveness of colorectal cancer screening modalities? KQ2: How does the comparative effectiveness of colorectal cancer screening modalities vary by: a. Age b. Gender c. Race or ethnicity d. Patient adherence/acceptance of test e. Screening interval KQ3: What are the harms of colorectal cancer screening? Contextual Questions CQ1: What are the optimal screening intervals for each modality? CQ2: What is the comparative effectiveness of offering various colorectal cancer screening modalities in underscreened populations?
Search Strategy A full search of the core sources was conducted to identify systematic reviews, meta-analyses, and technology assessments that met the criteria for the scope described above. Searches of core sources were limited to citations published after 2012.
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The core sources searched included: Agency for Healthcare Research and Quality (AHRQ) Blue Cross/Blue Shield Center for Clinical Effectiveness Canadian Agency for Drugs and Technologies in Health (CADTH) Cochrane Library (Wiley Online Library) Institute for Clinical and Economic Review (ICER) Medicaid Evidence-based Decisions Project (MED) National Institute for Health and Care Excellence (NICE) Tufts Cost-effectiveness Analysis Registry Veterans Administration Evidence-based Synthesis Program (ESP) Washington State Health Technology Assessment Program
A MEDLINE® search was also conducted to identify systematic reviews, meta-analyses, and technology assessments, using the search terms for colorectal cancer and screening. The search was limited to publications in English published since 2012. In addition, a MEDLINE® search was conducted for randomized controlled trials published after the search dates of the most recent systematic review selected for each intervention. Searches for clinical practice guidelines were limited to those published since 2012. A search for relevant clinical practice guidelines was also conducted using MEDLINE® and the following sources: Australian Government National Health and Medical Research Council (NHMRC) Canadian Agency for Drugs and Technologies in Health (CADTH) Centers for Disease Control and Prevention (CDC) – Community Preventive Services National Guidelines Clearinghouse National Institute for Health and Care Excellence (NICE) Scottish Intercollegiate Guidelines Network (SIGN) United States Preventive Services Task Force (USPSTF) Veterans Administration/Department of Defense (VA/DOD) Clinical Practice Guidelines Inclusion/Exclusion Criteria Studies were excluded if they were not published in English, did not address the scope statement, or were study designs other than systematic reviews, meta-analyses, technology assessments, randomized controlled trials, or clinical practice guidelines.
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Appendix D. Applicable Codes
CODES DESCRIPTION CPT Codes Colonoscopy, flexible; with ablation of tumor(s), polyp(s), or other lesion(s) (includes pre- and post- 44388 dilation and guide wire passage, when performed) Colonoscopy, flexible; with endoscopic stent placement (includes pre- and post-dilation and guide 44389 wire passage, when performed) Colonoscopy, flexible; with transendoscopic ultrasound guided intramural or transmural fine needle 44392 aspiration/biopsy(s), includes endoscopic ultrasound examination limited to the rectum, sigmoid, descending, transverse, or ascending colon and cecum, and adjacent structures Colonoscopy, flexible; with decompression (for pathologic distention) (e.g., volvulus, megacolon), 44393 including placement of decompression tube, when performed Colonoscopy through stoma; with removal of tumor(s), polyp(s), or other lesion(s) by snare 44394 technique 44401-8 Colonoscopy through stoma 45399 Unlisted procedure, colon Sigmoidoscopy, flexible; diagnostic, including collection of specimen(s) by brushing or washing, when 45330 performed (separate procedure) 45331 Sigmoidoscopy, flexible; with biopsy, single or multiple 45333 Sigmoidoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by hot biopsy forceps 45338 Sigmoidoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique Colonoscopy, flexible; diagnostic, including collection of specimen(s) by brushing or washing, when 45378 performed (separate procedure) 45380 Colonoscopy, flexible; with biopsy, single or multiple 45384 Colonoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by hot biopsy forceps 45385 Colonoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique 74263 Computed tomographic (CT) colonography, screening, including image postprocessing 74270 Radiologic examination, colon; contrast (e.g., barium) enema, with or without KUB 81327 SEPT9 (Septin9) (e.g., colorectal cancer) methylation analysis Oncology (colorectal) screening, quantitative real-time target and signal amplification of 10 DNA 81528 markers (KRAS mutations, promoter methylation of NDRG4 and BMP3) and fecal hemoglobin, utilizing stool, algorithm reported as a positive or negative result 81479 Unlisted molecular pathology procedure (for SEPT9) Blood, occult, by peroxidase activity (e.g., guaiac), qualitative; feces, consecutive collected specimens 82270 with single determination, for colorectal neoplasm screening (i.e., patient was provided 3 cards or single triple card for consecutive collection) Blood, occult, by fecal hemoglobin determination by immunoassay, qualitative, feces, 1-3 82274 simultaneous determinations HCPCS Level II Codes S0601 Screening proctoscopy S3890 Surface electromyography (emg) S0285 Colonoscopy consultation performed prior to a screening colonoscopy procedure G0104 Colorectal cancer screening; flexible sigmoidoscopy G0105 Colorectal cancer screening; colonoscopy on individual at high risk G0106 Colorectal cancer screening; alternative to g0104, screening sigmoidoscopy, barium enema G0120 Colorectal cancer screening; alternative to g0105, screening colonoscopy, barium enema. G0121 Colorectal cancer screening; colonoscopy on individual not meeting criteria for high risk G0122 Colorectal cancer screening; barium enema Note: Inclusion on this list does not guarantee coverage.
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Question: How should the draft Coverage Guidance Colorectal Cancer Screening Modalities be applied to the Prioritized List?
Question source: HERC Staff, HTAS
Issue: The HTAS approved the following draft “box language”:
HERC Coverage Guidance CT colonography for colorectal cancer screening is not recommended for coverage (weak recommendation).
Multitarget stool DNA testing for colorectal cancer screening (also known as Cologuard®, mt-sDNA, or FIT-DNA) is not recommended for coverage (weak recommendation).
Methylated SEPT9 testing (mSEPT9) for colorectal cancer screening is not recommended for coverage (weak recommendation).
Chromoscopy (dye-enhanced colonoscopy) for colorectal cancer screening is not recommended for coverage (weak recommendation).
Based on contextual evidence and USPSTF recommendations, HERC makes the following additional recommendations: Colorectal cancer screening for average-risk adults aged 50 to 75 is recommended for coverage (weak recommendation), using one of the following screening programs: • Colonoscopy every 10 years • Flexible sigmoidoscopy every 5 years • Fecal immunochemical test (FIT) every year • Guaiac-based fecal occult blood test (gFOBT) every year Colorectal cancer screening for average-risk adults aged 76 to 85 is recommended for coverage only for those who (1) are healthy enough to undergo treatment if colorectal cancer is detected, and (2) do not have comorbid conditions that would significantly limit their life expectancy (weak recommendation).
Rationale for Recommendations The U.S. Preventive Services Task Force (USPSTF) 2016 guidelines recommend colorectal cancer screening for average-risk adults aged 50 to 75. This is a Grade A Recommendation, defined as follows: “The USPSTF recommends the service. There is high certainty that the net benefit is substantial.” The USPSTF guidelines state that screening decisions for adults aged 76 to 85 years old should be based on individual circumstances, including the person’s overall health and screening history. Adults in this age group who have never been screened for colorectal cancer are more likely to benefit. Screening would be most appropriate among adults who 1) are healthy enough to undergo treatment if colorectal
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Coverage Guidance: Colorectal Cancer Screening Modalities
cancer is detected and 2) do not have comorbid conditions that would significantly limit their life expectancy. This is a Grade C Recommendation, defined as follows: “The USPSTF recommends selectively offering or providing this service to individual patients based on professional judgment and patient preferences. There is at least moderate certainty that the net benefit is small.” The USPSTF did not include recommendations on which screening test to use, but a table summarizing characteristics of colorectal screening strategies was included as part of its 2016 Final Recommendation Statement on Colorectal Cancer Screening.
Health Technology Assessment Subcommittee conclusions are as follows: No population outcome benefit has been identified utilizing CT colonography. Sensitivity and specificity for detection of colon adenomas is lower than for colonoscopy, and diagnostic accuracy is reduced when cathartic bowel prep is not performed. CT colonography is generally safe, but potential harms include radiation exposure and detection of extracolonic findings of no clinical significance. Although some might prefer the less invasive nature of this imaging study as compared with colonoscopy, there are no strong preferences that would favor CT colonography (when used with appropriate cathartic bowel preparation), nor strong resource allocation benefits. Alternatives to screening colonoscopy are available that are less costly and have fewer potential harms than CT colonography (e.g., FIT testing), which can be utilized by those who are unable or unwilling to undergo colonoscopy. Coverage of less accurate testing modalities like CT colonography could erode utilization of the screening method that has the best sensitivity and specificity for colorectal cancer detection (colonoscopy).
Evidence is insufficient to establish any population screening benefit utilizing multi-target stool DNA testing (FIT-DNA). Sensitivity for detection of advanced colon adenomas is quite limited. Specificity for colorectal cancer is relatively low, which is likely to increase the need for additional work-up, with related cost and anxiety. No harms are evident with this testing modality, other than the risk of underdiagnosis of precancerous adenomas. Preferences weigh in favor of mt-sDNA as a noninvasive and safe testing strategy, but insufficient evidence of population benefit and the limited adenoma detection rate do not provide justification for the additional expenditures required for mt-sDNA coverage.
Although many would prefer the convenience and simplicity of a blood test, current evidence is insufficient to establish any population benefit with use of mSEPT9 for colorectal cancer screening, and the single study of accuracy in an asymptomatic screening population reported sensitivity well below other testing methods. There is possible risk of colorectal cancer underdiagnosis if this test is used for population screening, given the limited sensitivity in cancer detection. As is also the case with screening CT colonography and multi-target stool DNA, a positive mSEPT9 blood test would still require colonoscopy for more definitive diagnosis and treatment.
There is low-quality evidence that chromoscopy (dye-enhanced colonoscopy) improves polyp detection compared to standard colonoscopy, but its role in primary colorectal cancer screening for average-risk individuals has not been established. Population outcomes have not been demonstrated that might justify additional expenditures for dye enhancement, and there are no strong values or preferences supporting chromoscopy coverage.
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Current Prioritized List Status: Codes See spreadsheet
Current Prioritized List Guideline: GUIDELINE NOTE 106, PREVENTIVE SERVICES Lines 3,625 Included on Line 3 are the following preventive services: 1. US Preventive Services Task Force (USPSTF) “A” and “B” Recommendations in effect and issued prior to January 1, 2016. http://www.uspreventiveservicestaskforce.org/Page/Name/uspstf-a-and-b- recommendations/ a. USPSTF “D” recommendations are not included on this line or any other line of the Prioritized List. 2. American Academy of Pediatrics (AAP) Bright Futures Guidelines: http://brightfutures.aap.org. Periodicity schedule available at http://www.aap.org/en- us/professional-resources/practice-support/Periodicity/Periodicity%20Schedule_FINAL.pdf. a. Screening for lead levels is defined as blood lead level testing and is indicated for Medicaid populations at 12 and 24 months. In addition, blood lead level screening of any child between ages 24 and 72 months with no record of a previous blood lead screening test is indicated. 3. Health Resources and Services Administration (HRSA) Women’s Preventive Services - Required Health Plan Coverage Guidelines as retrieved from http://www.hrsa.gov/womensguidelines/ on 1/1/2017. 4. Immunizations as recommended by the Advisory Committee on Immunization Practices (ACIP): http://www.cdc.gov/vaccines/schedules/hcp/index.html
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Coverage Guidance: Colorectal Cancer Screening Modalities
HERC Staff Recommendations: 1) Add the following CPT codes to line 3 PREVENTION SERVICES WITH EVIDENCE OF EFFECTIVENESS a. 44392 (Colonoscopy through stoma; with removal of tumor(s), polyp(s), or other lesion(s) by hot biopsy forceps) b. 44394 (Colonoscopy through stoma; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique) c. 45333 (Sigmoidoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by hot biopsy forceps) d. 45338 (Sigmoidoscopy, flexible; with removal of tumor(s), polyp(s), or other lesion(s) by snare technique) 2) Add the following HCPCS codes to line 3 PREVENTION SERVICES WITH EVIDENCE OF EFFECTIVENESS and advise HSD to remove from the Ancillary List a. G0104 (Colorectal cancer screening; flexible sigmoidoscopy) b. G0105 (Colorectal cancer screening; colonoscopy on individual at high risk) c. G0106 (Colorectal cancer screening; alternative to g0104, screening sigmoidoscopy, barium enema) d. G0120 (Colorectal cancer screening; alternative to g0105, screening colonoscopy, barium enema) e. G0121 (Colorectal cancer screening; colonoscopy on individual not meeting criteria for high risk) f. G0122 (Colorectal cancer screening; barium enema) 3) Revise Guideline Note 106, as follows:
GUIDELINE NOTE 106, PREVENTIVE SERVICES Lines 3,625 Included on Line 3 are the following preventive services: 1. US Preventive Services Task Force (USPSTF) “A” and “B” Recommendations in effect and issued prior to January 1, 2016. http://www.uspreventiveservicestaskforce.org/Page/Name/uspstf-a-and-b-recommendations/ a. USPSTF “D” recommendations are not included on this line or any other line of the Prioritized List. 2. American Academy of Pediatrics (AAP) Bright Futures Guidelines: http://brightfutures.aap.org. Periodicity schedule available at http://www.aap.org/en-us/professional-resources/practice- support/Periodicity/Periodicity%20Schedule_FINAL.pdf. a. Screening for lead levels is defined as blood lead level testing and is indicated for Medicaid populations at 12 and 24 months. In addition, blood lead level screening of any child between ages 24 and 72 months with no record of a previous blood lead screening test is indicated. 3. Health Resources and Services Administration (HRSA) Women’s Preventive Services - Required Health Plan Coverage Guidelines as retrieved from http://www.hrsa.gov/womensguidelines/ on 1/1/2017. 4. Immunizations as recommended by the Advisory Committee on Immunization Practices (ACIP): http://www.cdc.gov/vaccines/schedules/hcp/index.html
Colorectal cancer screening is included on Line 3 for average-risk adults aged 50 to 75, using one of the following screening programs:
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Coverage Guidance: Colorectal Cancer Screening Modalities
• Colonoscopy every 10 years • Flexible sigmoidoscopy every 5 years • Fecal immunochemical test (FIT) every year • Guaiac-based fecal occult blood test (gFOBT) every year
Colorectal cancer screening for average-risk adults aged 76 to 85 is covered only for those who (1) are healthy enough to undergo treatment if colorectal cancer is detected, and (2) do not have comorbid conditions that would significantly limit their life expectancy.
The development of this guideline note was informed by a HERC coverage guidance. See [link]
4) Add CPT 74263 (Computed tomographic (CT) colonography, screening, including image postprocessing), 81528 (Oncology (colorectal) screening, quantitative real-time target and signal amplification of 10 DNA markers (KRAS mutations, promoter methylation of NDRG4 and BMP3) and fecal hemoglobin, utilizing stool, algorithm reported as a positive or negative result), and 81327 (SEPT9 (Septin9) (eg, colorectal cancer) methylation analysis) to line 500 and add an entry to GN168 as shown below a. Note: 74263, 81528 and 81327 were all previously on the Services Recommended for Non-Coverage b. NOTE: as screening is not a treatment, the word “treatment” is suggested to change to “intervention” in the guideline note. A similar change is suggested for GUIDELINE NOTE 169, TREATMENTS INTERVENTIONS THAT HAVE NO CLINICALLY IMPORTANT BENEFIT OR HAVE HARMS THAT OUTWEIGH BENEFITS FOR CERTAIN CONDITIONS; UNPROVEN TREATMENTS INTERVENTIONS GUIDELINE NOTE 168, TREATMENTS INTERVENTIONS WITH MARGINAL CLINICAL BENEFIT OR LOW COST-EFFECTIVENESS FOR CERTAIN CONDITIONS
The following treatments are prioritized on Line 500 for the conditions listed here: CONDITION CPT/HCPCS TREATMENT Rationale Date of Last Review/Link code INTERVENTION to Meeting Minutes Colorectal cancer 74263, 81528, Screening CT Colonography Insufficient evidence for use September, 2017 screening 81327 FIT-DNA (Cologuard) in population screening mSEPT9
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Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: Colonoscopy through stoma; diagnostic, including Colonoscopy- 44388 collection of specimen(s) by brushing or washing, Diagnostic procedures Y Y No change Stoma when performed (separate procedure) Colonoscopy through stoma; with biopsy, single or Colonoscopy- 44389 Diagnostic procedures Y Y No change multiple Stoma 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage Colonoscopy through stoma; with removal of 101 Congenital anomalies of digestive Colonoscopy- 44392 tumor(s), polyp(s), or other lesion(s) by hot biopsy system and abdominal wall excluding N Y Add to line 3 Stoma forceps necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage Colonoscopy through stoma; with removal of 101 Congenital anomalies of digestive Colonoscopy- 44394 tumor(s), polyp(s), or other lesion(s) by snare system and abdominal wall excluding Y Y Add to line 3 Stoma technique necrosis; chronic intestinal pseudo- obstruction
1 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system No change (would allow for 45399 Unlisted procedure, colon Chromoscopy Ancillary procedures N N Chromoscopy unless edits are set up) Sigmoidoscopy, flexible; diagnostic, including 45330 collection of specimen(s) by brushing or washing, Sigmoidoscopy Diagnostic procedures Y y No change when performed (separate procedure) Sigmoidoscopy, flexible; with biopsy, single or 45331 Sigmoidoscopy Diagnostic procedures Y Y No change multiple
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI Sigmoidoscopy, flexible; with removal of foreign 45332 Sigmoidoscopy tract with risk of perforation or obstruction N N No change body(s) 518 Foreign body in gastrointestinal tract without risk of perforation or obstruction
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage
2 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 101 Congenital anomalies of digestive Sigmoidoscopy, flexible; with removal of tumor(s), 45333 Sigmoidoscopy system and abdominal wall excluding Y y Add to line 3 polyp(s), or other lesion(s) by hot biopsy forceps necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine 56 Ulcers, gastritis, duodenitis, and GI hemorrhage 101 Congenital anomalies of digestive system and abdominal wall excluding necrosis; chronic intestinal pseudo- obstruction Sigmoidoscopy, flexible; with control of bleeding, 157 Cancer of colon, rectum, small intestine 45334 Sigmoidoscopy N N No change any method and anus 166 Anal, rectal and colonic polyps 185 Diverticulitis of colon 227 Ruptured viscus 472 Thrombosed and complicated hemorrhoids 618 Uncomplicated hemorrhoids 636 Benign neoplasms of digestive system 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine
3
Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage 101 Congenital anomalies of digestive system and abdominal wall excluding Sigmoidoscopy, flexible; with directed submucosal 45335 Sigmoidoscopy necrosis; chronic intestinal pseudo- N N Add to line 3 injection(s), any substance obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 185 Diverticulitis of colon 472 Thrombosed and complicated hemorrhoids 618 Uncomplicated hemorrhoids 636 Benign neoplasms of digestive system
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 101 Congenital anomalies of digestive system and abdominal wall excluding Sigmoidoscopy, flexible; with removal of tumor(s), 45338 Sigmoidoscopy necrosis; chronic intestinal pseudo- Y Y Add to line 3 polyp(s), or other lesion(s) by snare technique obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system
4 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage Sigmoidoscopy, flexible; with ablation of tumor(s), 101 Congenital anomalies of digestive 45346 polyp(s), or other lesion(s) (includes pre- and post- Sigmoidoscopy system and abdominal wall excluding Y N No change dilation and guide wire passage, when performed) necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system
Colonoscopy, flexible; diagnostic, including 45378 collection of specimen(s) by brushing or washing, Colonoscopy Diagnostic procedures Y Y No change when performed (separate procedure)
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI Colonoscopy, flexible; with removal of foreign tract with risk of perforation or obstruction 45379 Colonoscopy N y No change body(s) 518 Foreign body in gastrointestinal tract without risk of perforation or obstruction
45380 Colonoscopy, flexible; with biopsy, single or multiple Colonoscopy Diagnostic procedures Y No change 29 Regional enteritis, idiopathic proctocolitis, ulceration ... 41 Intussception, volvulus, intestinal obstruction, hazardou...
5
Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 56 Ulcers, gastritis, duodenitis, and GI hemorrhage 101 Congenital anomalies of digestive system and abdominal wa... Colonoscopy, flexible; with directed submucosal 45381 Colonoscopy 157 Cancer of colon, rectum, small intestine Y Y Add to line 3 injection(s), any substance and anus 166 Anal, rectal and colonic polyps 185 Diverticulitis of colon 472 Thrombosed and complicated hemorrhoids 618 Uncomplicated hemorrhoids 636 Benign neoplasms of digestive system 3 Prevention services with evidence of effectiveness 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage Colonoscopy, flexible; with removal of tumor(s), 45384 Colonoscopy 101 Congenital anomalies of digestive Y Y No change polyp(s), or other lesion(s) by hot biopsy forceps system and abdominal wall excluding necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system 3 Prevention services with evidence of effectiveness
6
Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 101 Congenital anomalies of digestive Colonoscopy, flexible; with removal of tumor(s), 45385 Colonoscopy system and abdominal wall excluding Y No change polyp(s), or other lesion(s) by snare technique necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction Colonoscopy, flexible; with transendoscopic balloon 101 Congenital anomalies of digestive 45386 Colonoscopy N N No change dilation system and abdominal wall excluding necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 636 Benign neoplasms of digestive system
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction
7
Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 56 Ulcers, gastritis, duodenitis, and GI hemorrhage Colonoscopy, flexible; with ablation of tumor(s), 101 Congenital anomalies of digestive 45388 polyp(s), or other lesion(s) (includes pre- and post- Colonoscopy system and abdominal wall excluding Y N No change dilation and guide wire passage, when performed) necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction Colonoscopy, flexible; with endoscopic stent 101 Congenital anomalies of digestive 45389 placement (includes pre- and post-dilation and guide Colonoscopy N N No change system and abdominal wall excluding wire passage, when performed) necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 636 Benign neoplasms of digestive system Colonoscopy, flexible; with endoscopic mucosal 44390 Colonoscopy Diagnostic procedures N N No change resection Colonoscopy, flexible; with endoscopic ultrasound examination limited to the rectum, sigmoid, Services Recommended for Noncoverage 44391 Colonoscopy N N No change descending, transverse, or ascending colon and File cecum, and adjacent structures
8 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: Colonoscopy, flexible; with transendoscopic ultrasound guided intramural or transmural fine needle aspiration/biopsy(s), includes endoscopic Services Recommended for Noncoverage 44392 Colonoscopy Y Y No change ultrasound examination limited to the rectum, File sigmoid, descending, transverse, or ascending colon and cecum, and adjacent structures
41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI Colonoscopy, flexible; with decompression (for tract with risk of perforation or obstruction pathologic distention) (eg, volvulus, megacolon), 44393 Colonoscopy N Y No change including placement of decompression tube, when 101 Congenital anomalies of digestive performed system and abdominal wall excluding necrosis; chronic intestinal pseudo- obstruction 472 Thrombosed and complicated Colonoscopy, flexible; with band ligation(s) (eg, 44398 Colonoscopy hemorrhoids N Y No change hemorrhoids) 618 Uncomplicated hemorrhoids Computed tomographic (CT) colonography, CT 74263 Services Recommended for Noncoverage Y Y Add to line 500 screening, including image postprocessing Colonography Radiologic examination, colon; contrast (eg, barium) 74270 Barium enema Diagnostic procedures N N No change enema, with or without KUB SEPT9 (Septin9) (eg, colorectal cancer) methylation 81327 9-Sep Services Recommended for Noncoverage N N Add to line 500 analysis Oncology (colorectal) screening, quantitative real- time target and signal amplification of 10 DNA markers (KRAS mutations, promoter methylation of 81528 Fecal DNA Services Recommended for Noncoverage Y N Add to line 500 NDRG4 and BMP3) and fecal hemoglobin, utilizing stool, algorithm reported as a positive or negative result
9 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: Blood, occult, by peroxidase activity (eg, guaiac), qualitative; feces, consecutive collected specimens 82270 with single determination, for colorectal neoplasm FOBT, FIT Diagnostic procedures Y Y No change screening (ie, patient was provided 3 cards or single triple card for consecutive collection) Blood, occult, by fecal hemoglobin determination by 82274 immunoassay, qualitative, feces, 1-3 simultaneous FOBT, FIT Diagnostic procedures Y Y No change determinations 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage N Colonoscopy through stoma; with ablation of 101 Congenital anomalies of digestive (becaus tumor(s), polyp(s), or other lesion(s) (includes pre- Colonoscopy- 44401 system and abdominal wall excluding e of N No change and post-dilation and guide wire passage, when Stoma necrosis; chronic intestinal pseudo- ablation performed) obstruction ?) 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 636 Benign neoplasms of digestive system 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction Colonoscopy through stoma; with endoscopic stent
10 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: Colonoscopy through stoma; with endoscopic stent Colonoscopy- 101 Congenital anomalies of digestive 44402 placement (including pre- and post-dilation and N N No change Stoma system and abdominal wall excluding guide wire passage, when performed) necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 636 Benign neoplasms of digestive system Colonoscopy through stoma; with endoscopic Colonoscopy- 44403 Diagnostic procedures N N No change mucosal resection Stoma 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction 56 Ulcers, gastritis, duodenitis, and GI hemorrhage Colonoscopy through stoma; with directed Colonoscopy- 101 Congenital anomalies of digestive 44404 N N Add to line 3 submucosal injection(s), any substance Stoma system and abdominal wall excluding necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 166 Anal, rectal and colonic polyps 185 Diverticulitis of colon 636 Benign neoplasms of digestive system 29 Regional enteritis, idiopathic proctocolitis, ulceration of intestine
11
Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: 41 Intussception, volvulus, intestinal obstruction, hazardous foreign body in GI tract with risk of perforation or obstruction Colonoscopy through stoma; with transendoscopic Colonoscopy- 101 Congenital anomalies of digestive 44405 N N No change balloon dilation Stoma system and abdominal wall excluding necrosis; chronic intestinal pseudo- obstruction 157 Cancer of colon, rectum, small intestine and anus 636 Benign neoplasms of digestive system Colonoscopy through stoma; with endoscopic ultrasound examination, limited to the sigmoid, Colonoscopy- 44406 Diagnostic procedures N N No change descending, transverse, or ascending colon and Stoma cecum and adjacent structures Colonoscopy through stoma; with transendoscopic ultrasound guided intramural or transmural fine needle aspiration/biopsy(s), includes endoscopic Colonoscopy- 44407 Diagnostic procedures N N No change ultrasound examination limited to the sigmoid, Stoma descending, transverse, or ascending colon and cecum and adjacent structures
46 INTUSSCEPTION, VOLVULUS, INTESTINAL OBSTRUCTION, HAZARDOUS FOREIGN BODY Colonoscopy through stoma; with decompression IN GI TRACT WITH RISK OF PERFORATION (for pathologic distention) (eg, volvulus, megacolon), Colonoscopy- OR OBSTRUCTION 44408 N N No change including placement of decompression tube, when Stoma 105 CONGENITAL ANOMALIES OF DIGESTIVE performed SYSTEM AND ABDOMINAL WALL EXCLUDING NECROSIS; CHRONIC INTESTINAL PSEUDO-OBSTRUCTION
12 Colonoscopy Codes
United Gastro Recommended Code Code Description Type Placement HC Assn changes: Colonoscopy consultation performed prior to a 3 Prevention services with evidence of S0285 Consult Y N No change screening colonoscopy procedure effectiveness Add to line 3 G0104 Colorectal cancer screening; flexible sigmoidoscopy Sigmoidoscopy Ancillary procedures Y Y Remove from ancillary list Add to line 3 Colorectal cancer screening; colonoscopy on Colonoscopy- G0105 Ancillary procedures Y Y Remove from individual at high risk High risk ancillary list Add to line 3 Colorectal cancer screening; alternative to g0104, Sigmoidoscopy, G0106 Ancillary procedures Y Y Remove from screening sigmoidoscopy, barium enema barium enema ancillary list Screening Add to line 3 Colorectal cancer screening; alternative to g0105, G0120 colonoscopy, Ancillary procedures Y Y Remove from screening colonoscopy, barium enema. barium enema ancillary list Add to line 3 Colorectal cancer screening; colonoscopy on G0121 Colonoscopy Ancillary procedures Y Y Remove from individual not meeting criteria for high risk ancillary list Add to line 3 G0122 Colorectal cancer screening; barium enema Barium enema Ancillary procedures Y Y Remove from ancillary list Colorectal cancer screening; fecal occult blood test, G0328 FOBT Diagnostic procedures Y Y No change immunoassay, 1-3 simultaneous Colonoscopy consultation performed prior to a 3 Prevention services with evidence of S0285 Consultation Y N (new) No change screening colonoscopy procedure effectiveness
13
HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments
Table of Contents Discussion Table ...... Error! Bookmark not defined. Commenters...... 1 Public Comments ...... 1 References Provided by Commenters ...... 10
Commenters Identification Stakeholder A Patrick Hope, on behalf of the Medical Imaging and Technology Alliance (MITA) [Submitted July 24, 2017] B Judy Yee, MD, FACR, on behalf of the American College of Radiology [Submitted July 25, 2017]
Public Comments ID/# Comment Disposition A1 As the premier trade association representing the manufacturers of medical imaging equipment and Thank you for your comments. radiopharmaceuticals, the Medical Imaging & Technology Alliance (MITA) is submitting the following comments on the Draft Oregon Health Evidence Review Commission (HERC) Coverage Guidance on colorectal cancer screening (CRC). MITA strongly urges the Oregon HERC to reconsider its draft policy and instead recommend computed tomography colonography (CTC) as a screening service for CRC. CRC is the second most common cancer diagnosed in United States and the third leading cause of cancer death even though it has a roughly 90% 5-year survival rate when detected early.1 Unfortunately, as indicated in a May 2015 report from the Centers for Disease Control and
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition Prevention (CDC), CRC screening is dramatically underutilized.2 For this reason, we support the coverage of CTC. CTC consists of low-dose standard abdomen and pelvis computed tomography (CT) imaging combined with display protocols to optimally visualize the colon.3-13 Since its introduction into clinical practice around the year 2000, CTC has been implemented by over 1,000 radiology facilities in the US as well as a large number of global practices. Some 2000 scientific studies on CTC have been published worldwide since its inception, providing evidence for its value. In the draft coverage guidance posted on June 23, 2017, the Oregon HERC recommends against CTC as a screening service for CRC. This recommendation comes despite the fact that roughly half of the target population is still not being screened.14 And as the recent USPSTF recommendation notes, the best test is the one that gets done.15 MITA is deeply disappointed that the HERC has chosen not to recommend coverage of computed tomography colonography given that: (1) CTC performs at least as well as other widely available CRC screening exams; (2) CTC is less invasive and more patient-friendly than other traditional CRC screening exams; (3) CTC detects pre-cancerous lesions which are missed by blood tests; (4) The harms of CTC are grossly overstated and not supported by evidence; (5) The best test is the one that gets done.
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments A2 1. CTC performs at least as well as other widely available CRC screening exams The USPSTF evidence review and recommendations were considered by the In June 2016, the United States Preventive Services Task Force (USPSTF) endorsed screening for CRC, subcommittee during its deliberations. awarding it an “A” grade and identifying a number of valid exams, including CTC, under the principle that the best test is the one that gets done.16 The available studies on the operating characteristics of CT colonography (CTC) Further, the USPSTF has recognized that CTC is at least as sensitive as optical colonoscopy (OC) in were included in the review by Lin et al. identifying colorectal cancers and large adenomas.17 CTC has significantly higher sensitivity and These studies described the performance of specificity in identifying precursor polyps compared to stool based tests.18 CTC for the detection of adenomas, not for 19 CTC is inherently better at visualizing colonic anatomy than OC. CTC imaging visualizes all segments colorectal cancer per se. The range of of the colon and produces highly diagnostic 2D and 3D volumetric images that can be manipulated, reported sensitivity and specificity of CTC magnified, enhanced, and viewed from multiple angles on dedicated workstation computers to (compared to optical colonoscopy [OC]) are ensure that all colonic detail is visualized. The power of modern CT computers allows for a 3D virtual reported in the coverage guidance. “fly through” of the entire colon in both retrograde and antegrade fashion. Since both supine and The study by Pooler et al. does not provide prone scans are captured in a CTC exam, there are multiple independent projections of the colonic definitive evidence that CTC has an intrinsic anatomy to confidently rule in or rule out the presence of pathology. advantage over OC. It represents a single- Traditional OC, by contrast, has a more limited, unidirectional, and restricted telescopic field of view center experience using 12 experienced that can fail to visualize some lesions that are on the proximal sides of haustral folds, the inner radiologists (who also served as adjudicators aspect of hepatic and splenic flexures, and the distal rectum. These blind spots were noted in early of false-negative OC and false-positive CTC). seminal papers comparing CTC to OC when lesions were identified on CTC exams that then could not OC findings were concordant for 90% of the 20,21 be visualized by follow up optical colonoscopic investigation. The miss rate for OC has been polyps identified on CTC that were followed 22 23 24 reported to be as high as 6%, and the miss rate for adenomas larger than 1 cm is 12% to 17%. up. For the 10% (n=181) of CTC-identified 25 This intrinsic advantage of CTC was recently elucidated further by Pooler and colleagues. lesions that were not confirmed at initial OC, 66 were deemed CTC false-positives on an initial second review of the CTC. Of the remaining 115 findings, 37 had no additional follow-up available. Of the remaining 78 polyps, 16 had a second CTC and 62 underwent a second OC. Of the 16 polyps
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition undergoing a second CTC, 11 were confirmed as false-positive CTC findings and 5 were adjudicated as false-negative OC findings. At the second OC, 36 CTC findings were confirmed as false-positive and 26 yielded 26 findings (of which 9 were advanced adenomas). Ultimately, out of 1,781 polyps identified at CTC, there were only 9 advanced adenomas eventually identified that were not identified at initial OC. Among polyps identified on CTC that were not identified on the initial OC, the likelihood of a false-positive CTC was about four times that of a false-negative OC. It should be noted that in this study, the period between the index CTC and initial OC and the follow-up studies could be as long as 3 years. Additionally, up to 10% of the endoscopies may have been performed by practitioners who were not classified as “experienced gastroenterologists.” Lastly, there was no information on distal clinical outcomes for patients. A3 2. CTC is less invasive and more patient-friendly than other traditional CRC screening exams The differences between the procedures for CTC and OC are noted. The meta-analytic In general, CTC is a significantly less invasive and more patient-friendly procedure than traditional estimates for the rates of perforation (4 per OC. Optical colonoscopy carries a far greater risk of perforation, bleeding, and infection than CTC. 10,000) or bleeding (8 per 10,000) with
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition Unlike colonoscopy in which a colonoscope is inserted into the colon, CTC is minimally invasive, endoscopy were included in the review by Lin requiring only mild colonic insufflation. et al. Further, CTC patients do not receive anesthesia, thereby eliminating the risks inherent to sedation When cathartic bowel preparation is utilized and eliminating the need for an escort to drive the patient home. Patient exams are completed in for CTC, diagnostic accuracy improves, but 10-15 minutes, and the patient can immediately return to normal daily activities. This simple, the CTC procedure is less “patient-friendly.” accurate, and patient-friendly test comports well with classic characteristics of what a good screening exam should be. This is particularly relevant in patients who—for anatomic or other reasons—cannot tolerate insertion of a colonoscope, and helps to characterize the difference in “penetration”. When a patient’s colon is penetrated by a colonoscope, there is serious risk of infection; whereas when there is “penetration” during a CTC procedure, it amounts to a small amount of air escaping from the colon into the peritoneal cavity. A recent study found that 16.3 per 1000 outpatient colonoscopies among Medicare beneficiaries resulted in unplanned hospital visits after the procedure.26 A4 3. CTC detects pre-cancerous lesions which are missed by blood tests The limited sensitivity of serum-based tests for CRC screening was noted in the coverage Although their use has grown in popularity, blood tests for CRC screening only detect tumor markers guidance. when they are circulating in the blood at a more advanced stage of cancer, whereas CTC finds clinically relevant pre-cancerous polyps. Early detection of polyps enables the excision, via polypectomy, of clinically relevant lesions (i.e. polyps which are of a size and shape known to put a patient at risk of colon cancer, before they become cancer). Using a polyp size threshold for referral to treatment, CTC avoids unnecessary polypectomy in patients who do have polyps which might have been excised during colonoscopy but unnecessarily so. 4. The harms of CTC are grossly overstated and not supported by evidence In its assessment, HERC failed to fairly and accurately assess Note: Public comment is limited to 1,000 words, so this submission was truncated at 1,000 words.
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition B1 The American College of Radiology (ACR)1 has a long history of advocating for quality in colorectal Thank you for your comments. cancer screening, and of encouraging patients and their health care providers to utilize proven screening methods to save lives. Therefore, the ACR strongly urges the Health Evidence Review Commission (HERC) to move Computed Tomography (CT) colonography forward as a recommended screening test for colorectal cancer (CRC) in addition to the other strategies for CRC screening included in the United States Preventive Services Task Force (USPSTF) recommendation statement. Provided below are comprehensive comments and robust evidence to support CTC as a recommended colorectal cancer screening test. CRC is the second most common cancer diagnosed in United States and the third leading cause of cancer death even though it has a 90% cure rate with early detection. Over 140,000 Americans are diagnosed with colorectal cancer (CRC) every year, and nearly 50,000 men and women die due to late detection.2 Less than half of adults 50 years of age and older are compliant with recommended screening in the United States3 with the existing USPSTF recommended screening options. Providing patients with additional effective screening tools for CRC will promote early detection and will save thousands of lives as well as help close the gap in CRC screening rates between whites and minority populations.3,4 The time is now for CT colonography to be recognized as an approved screening test.5 CTC is endorsed by the American Cancer Society, the U.S. Multi-Society Task Force, and the ACR as a recommended test for CRC screening. The positive recommendation by the USPSTF will help with broader dissemination and education of CTC to the public and ultimately improve CRC screening adherence. We urge the HERC to support and recommend coverage for CRC screening including CTC as a screening option, increase CRC screening rates, and save thousands of lives. B2 The ACR is disappointed in the methodology used by the HERC to generate this draft, as these types HERC and its subcommittees do not develop of errors were foreseen and outlined by the Institute of Medicine (IOM) in their document “Clinical clinical practice guidelines. The committee Practice Guidelines We Can Trust.”6 Similarly, the HERC document does not reflect the transparency adheres to rules and regulations outlined in and accountability protections afforded by the Administrative Procedures Act and the Federal Oregon statutes and administrative rules. Advisory Committee Act. The HERC has failed to be transparent in its evaluation of the evidence and Public comments, both oral and written, Comments received 6/23/2017 to 7/25/2017 Page 6 Center for Evidence-based Policy
HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition in the processes used to make the draft recommendations. The HERC guidance does not include a have been solicited at each stage in the clear description of the commission’s clinical expertise, their potential biases, and where consensus process, which is transparently described on was apparent or lacking in their deliberations. There should be a systematic process for responding the HERC website. HERC is not subject to the and noting all external review comments and this should be more public and clear. referenced federal laws. B3 HERC has inappropriately applied the Grading of Recommendations, Assessment, Development, and Based on the prespecified critical and Evaluation (GRADE) system. The ACR disagrees with the HERC assertion that CTC, colonoscopy, and important outcomes, the subcommittee all of the CRC screening modalities are delineated as “weak recommendation”. Enclosed are the believed that there was not overwhelming GRADE analysis Part 3 and Part 4. Please note that the National CTC study follows Table 2, for the evidence of benefit, and indeed there was assessment of evidence. For recommendations, a strong recommendation means that there is uncertainty about the clinical outcomes overwhelming benefit with little risk. The Berrington de Gonzalez study has strong data that meets associated with the use of CTC screening. this definition and addresses risk/benefit. Given the overwhelming data, CTC screening meets the Additionally, in the GRADE evidence-to- definition for a strong recommendation. decision framework, factors beyond the evidence, particularly those related to We disagree with the HERC Coverage Guidance and weak GRADE assessment of CTC and other CRC variability in values and preferences or screening modalities. We urge the HERC to review the comments herein and reconsider its guidance resource allocation concerns, can justify to better reflect the current and complete evidence available for CTC and colorectal cancer weak recommendations even in the screening. presence of strong evidence. A detailed review of evidence and analysis of the Task Force is provided below. The subcommittee acknowledges the I. Evidence on the impact of screening with CT colonography on cancer incidence/cancer detection common understanding of the polyp- rather than cancer prevention carcinoma sequence. However, there Target lesion of colorectal polyp remains no direct evidence that screening strategies with improved performance for It is well established that the polyp-carcinoma sequence is responsible for a large number of the detection of polyps result in greater colorectal cancers. Both adenomatous and serrated polyps can transform to cancer in a series of clinical benefits compared to other screening genetic changes, typically over many years.7,8 Unlike breast or lung cancer, screening for colon strategies. Additionally, although polyp cancer has a tremendous opportunity to actually prevent cancer development by removal of these detection rates were not specifically selected by the committee as a critical or important
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition lesions prior to malignant transformation as opposed to simply engaging in early cancer detection to outcome, information regarding the test improve outcomes. performance characteristics for the identification of polyps was provided to the The insistence on ignoring the potentially large benefits of primary prevention and concentrating subcommittee when available. simply on early detection of cancer is puzzling and is a disservice to all individuals requiring screening. On a societal perspective, it is likely that the additional benefits of precursor polyp removal will outweigh the harms occurred. On an individual level, the difference of never having cancer due to screening versus having cancer but detected and treated early is undebatable for that person. Although a screening strategy such as one based on FOBT or FIT to detect early cancers would likely show cancer mortality reduction as predicted from prior prospective randomized trials, the wealth of data regarding adenomatous and serrated precursor polyps gives high scientific confidence that additional benefit would exist for those screening exams capable of their detection. Based on this, optical colonoscopy studies have emphasized the detection of polyps, similar to studies of CT colonography. Current studies of mortality reduction Evidence of colorectal cancer incidence and mortality reduction currently exists largely from four randomized control trials of flexible sigmoidoscopy9-12 and three guaiac FOBT tests.13-15 Guaiac FIT studies have largely used the surrogate measure of validation with guaiac FOBT, with no randomized control studies done. Currently there are also no data of randomized control trials of optical colonoscopy, but several trials are currently underway. Several colonoscopy trials have shown a mortality benefit in prospective trials16-18 and case-control/cohort studies. 19-25 Overall these studies do show wide support of the benefit by various screening interventions in reducing colorectal cancer-specific mortality. CT colonography studies have used the surrogate measure of polyp detection validated with optical colonoscopy. In light of the convincing science already established, further confirmation of mortality reduction using CT Colonography is not indicated or necessary—as the target lesions are the same (precursor adenomas and localized cancers).
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments ID/# Comment Disposition Note: Public comment is limited to 1,000 words, so this submission was truncated at 1,000 words.
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HERC Coverage Guidance: Colorectal Cancer Screening Modalities Disposition of Public Comments
References Provided by Commenters ID/# References A 1. http://www.cancer.org/cancer/colonandrectumcancer/detailedguide/colorectal-cancer-survival-rates 2. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6417a4.htm?s_cid=mm6417a4_w 3. Chang KJ, Heisler MA, Mahesh M, Baird GL, Mayo-Smith WW. CT colonography at low tube potential: using iterative reconstruction to decrease noise. Clin Radiol. 2015;70(9):981-988. 4. Lambert L, Danes J, Jahoda J, Masek M, Lisy J, Ourednicek P. Submilisievert ultralow-dose CT colonography using iterative reconstruction technique: a feasibility study. Acta Radiol. 2015; 56(5):517-525. 5. http://jamanetwork.com/journals/jama/fullarticle/2529486 6. Lambert L, Ourednicek P, Jahoda J, Lambertova A, Danes J. Model-based vs hybrid iterative reconstruction technique in ultralow-dose submillisievert CT colonography.Br J Radiol. 2015; Apr;88 (1048) :20140667. 7. Lubner MG, Pickhardt PJ, Kim DH, Tang J, del Rio AM, Chen GH. Prospective evaluation of prior image constrained compressed sensing (PICCS) algorithm in abdominal CT: a comparison of reduced dose with standard dose imaging. Abdom Imaging. 8. Lubner MG, Pooler BD, Kitchin DR, et al. Sub-milliSievert (sub-mSv) CT colonography: a prospective comparison of image quality and polyp conspicuity at reduced-dose versus standard-dose imaging. Eur Radiol. 2015;25(7):2089-2102. 9. Millerd PJ, Paden RG, Lund JT, et al. Reducing the radiation dose for computed tomography colonography using model-based iterative reconstruction. Abdom Imaging. 2015;40 (5):1183-1189. 10. Nagata K, Fujiwara M, Kanazawa H, et al. Evaluation of dose reduction and image quality in CT colonography: comparison oflow-dose CT with iterative reconstruction and routine-dose CT with filtered back projection. Eur Radiol. 2015;25(1):221-229. 11. Shen H, Liang D, Luo M, et al. Pilot study on image quality and radiation dose of CT colonography with adaptive iterative dose reduction three-dimensional. PloS one. 2015;10(1):e0117116. 12. Shin CI, Kim SH, Lee ES, et al. Ultra-low peak voltage CT colonography: effect of iterative reconstruction algorithms onperformance of radiologists who use anthropomorphic colonic phantoms. Radiology. 2014;273(3):759-771. 13. Yamamura S, Oda S, Imuta M, et al. Reducing the Radiation Dose for CT Colonography: Effect of Low Tube Voltage and Iterative Reconstruction. Acad Radiol. 2015 Apr 11. pii: S1076-6332(15)00130-0. doi: 10.1016/j.acra.2015.03.009. [Epub ahead of print]. 14. https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html 15. http://jamanetwork.com/journals/jama/fullarticle/2529486 16. http://jamanetwork.com/journals/jama/fullarticle/2529486 17. ibid
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