Herpes Zoster Phenotype Algorithm Pseudo Code Group Health and University of Washington

March 7, 2013

Contacts: David Carrell ([email protected], 206-287-2705) Eric Baldwin ([email protected])

BACKGROUND

Herpes zoster, also known as zoster or shingles, is caused by a virus called varicella zoster virus (VZV). Initial infection with the virus causes chickenpox. After chickenpox resolves the virus continues to reside in certain nerve cells. It may remain latent for many years. It may re-activate any time, up to years later, and cause shingles. Shingles is a painful skin rash. How the virus remains latent in the body is not well understood. For additional information see Wikipedia (http://en.wikipedia.org/wiki/Herpes_zoster).

ALGORITHM and COVARIATES

This algorithm and covariates require the following types of information: • Patient demographics • Enrollment/encounter history • Diagnosis codes (ICD) • Procedure codes (CPT and/or ICD) • Medications • Nursing home admissions Some covariates are ever/never measures and others are repeated measures requiring associated dates.

CASES

Cases are identified by first applying inclusion criteria, then excluding from this set any subjects meeting any of the exclusion criteria. Inclusion criteria include a minimum enrollment history to increase the probability that a subject’s status with respect to herpes zoster infection is known by the health care system. This is especially important for controls, but the criterion is applied to cases as well to enhance comparability across the two groups. An index date is required for each case.

Zoster_definition.doc Page 1 of 11 Case inclusion criteria: Potential cases must meet all of the following inclusion criteria: I-1 Is at least 40 years of age at time of assessment. I-2 Has at least one diagnosis code for herpes zoster (ICD 053.xx) or varicella zoster (ICD 052.xx) on or after the 40th birthday. I-2-a Exclude from any such diagnosis codes those occurring on the same calendar date as a herpes vaccination. This reduces the chance of false positives caused when a zoster/varicella diagnosis code is recorded for an encounter where an uninfected person with no history of infection receives a zoster vaccination. Group Health used CPT procedures codes to identify vaccinations (defined in section COVARIATES, below). You may use additional site- specific information to identify vaccinations as appropriate for your site. I-3 Has ≥5 years of continuous enrollment (or encounter) history since age 35. Note: Implementations of “continuous enrollment” may vary by institution. Continuous enrollment is defined at Group Health as a period of enrollment in a Group Health-administered insurance or integrated health care plan for at least 5 years, allowing interruptions or gaps in coverage of up to three months. Gaps of this size are allowed because they typically represent administrative data inconsistencies rather than actual interruptions in access to care. Sites may implement continuous enrollment in whatever manner they deem to be consistent with continuous enrollment, including use of more granular rules. For example, Mayo Clinic’s continuous enrollment rules incorporate patient age and gender into the calculation. This is sensible because younger men receiving regular care at Mayo Clinic tend to have fewer encounters than women of the same age or older men. Case exclusion criteria: Exclude from the set of potential cases subjects with any of the following: E-1 Has diagnosis codes on 2+ separate calendar days for HIV infection (ICD 042.xx–044.xx). E-2 Has any diagnosis codes for cancer of the blood or bone marrow (ICD 200.xx– 208.xx) during the 365-day period prior to the index date (index date is defined below). Note: Optionally, ICD diagnosis data may be supplemented with diagnosis data available locally from cancer registries, such as the Surveillance Epidemiology and End Results (SEER) registry. E-3 Has any cancer chemotherapy infusion (see Appendix A) during the 180-day period prior to the index date (index date is defined below)..

Zoster_definition.doc Page 2 of 11 Index date for cases: The index date for cases is provided as subject age in years at the subject’s index date. The index date is defined as the date of the first valid herpes zoster or varicella zoster diagnosis on or after the subject’s 40th birthday.

CONTROLS

Controls are identified by first applying inclusion criteria, then excluding from this set any subjects who meet any of several exclusion criteria. Index dates are not defined for controls. Controls inclusion criteria: Potential controls must meet all of the following inclusion criteria: I-1 Is at least 40 years of age at time of assessment. I-2 Has ≥5 years of continuous enrollment/contact since age 35. Note: “Continuous enrollment/contact” is implemented in an integrated group practice (HMO) setting as a period of continuous enrollment ignoring gaps of up to 90 days (which tend to reflect administrative data lags rather than actual interruptions in access to care). In fee-for-service or non-integrated care settings, continuous enrollment is implemented as consecutive 18-month periods with at least one encounter per period. Encounters may be rolled up to the calendar date for purposes of establishing encounters during an 18-month period. Controls exclusion criteria: Exclude from the set of potential controls subjects with any of the following: E-1 Has diagnosis codes on ≥2 separate calendar days for HIV infection (ICD: 042.xx–044.xx). E-2 Has any diagnosis codes ever for herpes zoster (ICD: 053.xx) or varicella zoster (ICD: 052.xx). No index date for controls: There is no index date for controls.

Zoster_definition.doc Page 3 of 11 FLOW DIAGRAM

This is a schematic representation of the phenotype definition logic described above.

ALL SUBJECTS

N Age ≥40?

Y

N ≥5 yrs enrl?

Y

N ≤1 HIV dx?

Y

N ≥1 Zoster dx?

Y

N Blood/bone ca?

Y

N Chemothrpy?

Y

CONTROLS CASES EXCLUDE

Zoster_definition.doc Page 4 of 11 APPENDIX A Procedure Codes for Cancer Chemotherapy Procedure codes for identifying administration of cancer chemotherapies are drawn from the following sources. • International Classification of Diseases (ICD) • National Uniform Billing Committee Official UB-04 Data Specifications (UB-04) • Medicare G-Codes (G) • Current Procedural Terminology (CPT) • Healthcare Common Procedure Coding System (CPT_HCPCS) Note that the chemotherapeutic infusion codes listed in Table A below are sufficient to capture cancer chemotherapy events. Chemotheraputic agents (captured, e.g., by CPT J-codes) provide additional information about the medication being infused, but because some medications are indicated for non-cancer treatments, a code for a therapeutic agent alone is insufficient to identify cancer chemotherapy. We thus rely exclusively on the infusion code to capture the events of interest.

Table A: Cancer Chemotherapy Infusion Codes Source Code Brief Description ICD 00.10 Implant chemo agent UB-04 331 Rad therapeutic chemo in UB-04 332 Rad therapeutic chemo or UB-04 335 Rad therapeutic chemo iv G 4621B 10 quart chemotherapy wa CPT 61517 Implt brain chemotx add-on code CPT 96400 Chemotherapy, sc/im che CPT 96401 Chemo, anti-neopl, sq/im CPT 96402 Chemo hormon antineopl s CPT 96405 Chemo intralesional, up CPT 96406 Chemo intralesional over CPT 96408 Chemotherapy, push techn CPT 96409 Chemo, iv push, sngl dru CPT 96410 Chemotherapy,infusion me CPT 96411 Chemo, iv push, addl dru CPT 96412 Chemo, infuse method add CPT 96413 Chemo, iv infusion, 1 hr CPT 96414 Chemo, infuse method add CPT 96415 Chemo, iv infusion, addl CPT 96416 Chemo prolong infuse w/p CPT 96417 Chemo iv infus each addl CPT 96420 Chemo, ia, push tecnique CPT 96422 Chemo ia infusion up to CPT 96423 Chemo ia infuse each add

Zoster_definition.doc Page 5 of 11 Table A: Cancer Chemotherapy Infusion Codes Source Code Brief Description CPT 96425 Chemotherapy,infusion me CPT 96440 Chemotherapy, intracavit CPT 96445 Chemotherapy, intracavit CPT 96450 Chemotherapy, into cns CPT 96500 Chemo injection chemo CPT 96501 Chemo injection chemo CPT 96504 Chemo injection chemo CPT 96505 Chemo injection chemo CPT 96508 Chemo injection chemo CPT 96509 Chemo injection chemo CPT 96510 Chemo injection chemo CPT 96511 Chemo injection chemo CPT 96512 Chemo injection chemo CPT 96524 Chemo injection chemo CPT 96526 Chemo injection chemo CPT 96535 Chemo injection chemo CPT 96538 Chemo injection chemo CPT 96540 Chemo injection chemo CPT 96542 Chemotherapy injection CPT 96545 Provide chemotherapy age CPT 96549 Chemotherapy, unspecifie CPT 96910 Photochemotherapy with u CPT 96912 Photochemotherapy with u CPT 96913 Photochemotherapy, uv-a ICD 99.25 Inject/infusion of cancer chemo CPT 99555 Home infuse, chemotherap CPT_HCPCS C8953 Chemotx adm, IV push CPT_HCPCS C8954 Chemotx adm, IV inf up to 1h CPT_HCPCS C8955 Chemotx adm, IV inf, addl hr CPT_HCPCS G0355 Chemo adminisrate subcut/IM CPT_HCPCS G0359 Chemotherapy IV one hr initi CPT_HCPCS G0360 Each additional hr 1-8 hrs CPT_HCPCS G0361 Prolong chemo infuse>8hrs pu CPT_HCPCS G8371 Chemother not rec stg3 colon CPT_HCPCS G8372 Chemother rec stg3 colon ca CPT_HCPCS G8373 Chemo plan documen prior che CPT_HCPCS G8374 Chemo plan not doc prior che CPT_HCPCS G9021 Chemo assess nausea vomit L1 CPT_HCPCS G9022 Chemo assess nausea vomit L2 CPT_HCPCS G9023 Chemo assess nausea vomit L3 CPT_HCPCS G9024 Chemo assess nausea vomit L4 CPT_HCPCS G9025 Chemo assessment pain level1 CPT_HCPCS G9026 Chemo assessment pain level2 CPT_HCPCS G9027 Chemo assessment pain level3 CPT_HCPCS G9028 Chemo assessment pain level4 CPT_HCPCS G9029 Chemo assess for fatigue L1

Zoster_definition.doc Page 6 of 11 Table A: Cancer Chemotherapy Infusion Codes Source Code Brief Description CPT_HCPCS G9030 Chemo assess for fatigue L2 CPT_HCPCS G9031 Chemo assess for fatigue L3 CPT_HCPCS G9032 Chemo assess for fatigue L4 CPT_HCPCS Q0081 Infusion ther other than che CPT_HCPCS Q0083 Chemo by other than infusion CPT_HCPCS Q0084 Chemotherapy by infusion CPT_HCPCS Q0085 Chemo by both infusion and o CPT_HCPCS S5019 Chemotherapy admin supplies CPT_HCPCS S5020 Chemotherapy admin supplies CPT_HCPCS S9329 HIT chemo per diem CPT_HCPCS S9330 HIT cont chem diem CPT_HCPCS S9331 HIT intermit chemo diem

Zoster_definition.doc Page 7 of 11 APPENDIX B Antiviral Medications Antiviral medications are collected as covariates for this phenotype. Qualifying medications are listed in Table B. These antiviral medications are sometimes used to treat herpes zoster (which we want to capture) and sometimes used to treat other conditions (which we want to ignore). We use a minimum dosage rule to determine when a medication is most likely being used to treat herpes zoster. Our rule requires that the total dose prescribed over a 28-day period exceed the minimum specified in Table B). Note that minimum dose varies by medication.

Table B: Antiviral Medications Drug name Route Minimum total dose in any 28-day period Acyclovir Oral ≥ 24,000 mg Famcyclovir Oral ≥ 10,500 mg Valcyclovir Oral ≥ 21,000 mg

Zoster_definition.doc Page 8 of 11 APPENDIX C Transplant Medications Tranaplant medications are collected as covariates for this phenotype. Qualifying medications are listed in the following table. Table C: Transplant Medications Drug name Route Dose Cellcept Any Any Tacrolimus Any Any Cyclosporine Any Any Azathioprine Any Any Munoloc Any Any Mycophenylate mofetil Any Any Tacrolimus Any Any fk-506 Any Any fk5 Any Any k506 Any Any Tacarolimus Any Any Tacrolimus hydrate Any Any Fujimycin Any Any Lcp-tacro Any Any Prograf Any Any Protopic Any Any Cyclosporine Any Any Ciclosporin Any Any Cyclosporin Any Any Cyclosporin A Any Any Gengraf Any Any Neoral Any Any Restasis Any Any Restasis Any Any Sandimmune Any Any Sangcya Any Any Azothioprine Any Any Azathioprin Any Any Azathioprine sodium Any Any Azatioprin Any Any Azamun Any Any Azanin Any Any Azasan Any Any Ccucol Any Any Imuran Any Any Imurek Any Any Imurel Any Any Muran Any Any

Zoster_definition.doc Page 9 of 11 APPENDIX D Steroid Medications Steroid medication names are listed in the table below. For this list of medications, include any that meet the following inclusion and exclusion criteria:

Steroid inclusion criteria (satisfy at least one criterion): 1. Route is intravenous (IV), intramuscular injection (IM), or by mouth (PO). 2. Route is not intranasal and a dose measured in milligrams

Steroid exclusion criteria: 1. Dose is not measured in percentage terms (e.g., does not include the “%” in the dose or strength field; this exclusion is designed to exclude topical steroids) 2. Route is intranasal and dose measured in milligrams

Table D: Steriod Medications Drug name Route Dose Cortisone See above See above Cortisone Acetate See above See above Hydrocortisone See above See above Hydrocortisone Sodium Phosphate See above See above Hydrocortisone Sodium Succinate See above See above Hydrocortisone Acetate See above See above Hydrocortisone Cypionate See above See above Prednisone See above See above Prednisolone See above See above Prednisolone Sodium Phosphate See above See above Methylprednisolone See above See above Methylprednisolone See above See above Methylprednisolone Sodium Succinate See above See above Methylprednisolone Acetate See above See above Triamcinolone See above See above Triamcinolone Acetonide See above See above Triamcinolone Diacetate See above See above Triamcinolone Hexacetonide See above See above Dexamethasone See above See above Dexamethasone Acetate See above See above Dexamethasone Sodium Phosphate See above See above Betamethasone See above See above Betamethasone Sodium Phosphate See above See above Betamethasone Acetate See above See above

Zoster_definition.doc Page 10 of 11 APPENDIX E Anti Tumor Necrosis Factor (Anti-TNF) Medications Anti tumor necrosis factor (Anti-TNF) medication names are listed in the table below.

Table E: Anti Tumor Necrosis Factor (Anti-TNF) Medications Drug name Route Dose Infliximab Any Any Remicade Any Any Adalimumab Any Any Humira Any Any Certolizumab Any Any Cimzia Any Any Golimumab Any Any Simponi Any Any Etanercept Any Any Enbrel Any Any

Zoster_definition.doc Page 11 of 11