Clinical Outcome Assessment (Coa) Compendium

CENTER FOR DRUG EVALUATION AND RESEARCH CLINICAL OUTCOME ASSESSMENT (COA) COMPENDIUM

June 2021 www.fda.gov 1

Table of Contents

COA COMPENDIUM DESCRIPTION...... 3 DIVISION OF NEUROLOGY I AND II (DN I AND II)...... 37

OFFICE OF CARDIOLOGY, HEMATOLOGY, ENDOCRINOLOGY, DIVISION OF PSYCHIATRIC (DP)...... 46 AND NEPHROLOGY (OCHEN)...... 5 DIVISION OF ANESTHESIOLOGY, ADDICTION MEDICINE AND PAIN MEDICINE DIVISION OF CARDIOLOGY AND NEPHROLOGY (DCN)...... 5 (DAAP)...... 50

DIVISION OF DIABETES, LIPID DISORDERS AND OBESITY (DDLO)...... 9 OFFICE OF ONCOLOGIC DISEASES (OOD)...... 51

DIVISION OF GENERAL ENDOCRINOLOGY (DGE)...... 9 DIVISION OF ONCOLOGY I (DO I)...... 51

DIVISION OF NON-MALIGNANT HEMATOLOGY (DNH)...... 10 DIVISION OF ONCOLOGY II (DO II)...... 51

OFFICE OF IMMUNOLOGY AND INFLAMMATION (OII)...... 13 DIVISION OF HEMATOLOGIC MALIGNANCIES I (DHM I)...... 53

DIVISION OF DERMATOLOGY AND DENTISTRY (DDD)...... 13 DIVISION OF HEMATOLOGIC MALIGNANCIES II (DHM II)...... 53

DIVISION OF GASTROENTEROLOGY (DG)...... 17 OFFICE OF RARE DISEASES, PEDIATRICS, UROLOGY AND REPRODUCTIVE MEDICINE (ORPURM)...... 58 DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC)...... 21 DIVISION OF RARE DISEASES AND MEDICAL GENETICS (DRDMG)...... 58 DIVISION OF RHEUMATOLOGY AND TRANSPLANT MEDICINE (DRTM).29 DIVISION OF UROLOGY, OBSTETRICS, AND GYNECOLOGY (DUOG)...... 59 OFFICE OF INFECTIOUS DISEASE (OID)...... 33 OFFICE OF SPECIALTY MEDICINE (OSM)...... 63 DIVISION OF ANTI-INFECTIVES (DAI)...... 33 DIVISION OF OPHTHALMOLOGY (DO) ...... 63 DIVISION OF ANTIVIRALS (DAV)...... 36

OFFICE OF NEUROSCIENCE (ON)...... 37

Drug sponsors are strongly encouraged to check the repository of guidance documents for the most current disease specific FDA guidances, which may contain additional information related to COA selection. Visit: https://www.fda.gov/regulatory- information/search-fda-guidance-documents Note: Inclusion of a COA in the COA Compendium does not necessarily indicate that the measure is or should be the primary or sole determinant of effectiveness in a clinical trial nor is it indicative of endpoint positioning (e.g., primary or secondary). Please refer to Compendium’s full disclaimer on COAs and associated guidance document. The inclusion of a clinical outcome assessment in the COA Compendium does not equate to an endorsement by FDA and does not represent agency guidance. CLINICAL OUTCOME ASSESSMENT Compendium 2

Disclaimer

The Clinical Outcome Assessment (COA) Compendium is a communication tool and it is intended to serve as a starting point when considering a COA for use in clinical trials. The inclusion of a COA in the COA Compendium does not equate to an endorsement by FDA and does not represent agency guidance.

Drug sponsors are strongly encouraged to seek advice from the relevant Office of New Drug (OND) review division early in drug development to discuss the selection and implementation of COAs specific to their program. This is irrespective of whether the disease, condition, indication, claim, or COA is included in the COA Compendium.

Limitations of the COA Compendium include, but are not limited to:

• It is not a comprehensive list of COAs and is not intended • It does not include biomarkers with the exception of biomarkers to replace either existing disease-specific guidance or key used in composite endpoints interactions with FDA concerning drug development (e.g., during pre-IND meetings) • It does not include measures of survival with the exception of use in composite endpoints • Inclusion of a COA in the COA Compendium does not necessarily indicate that the measure is or should be the primary or sole • It does not include the endpoint definition of labeled COAs determinant of effectiveness in a clinical trial nor is it indicative of • Some of the COAs listed in the COA Compendium may be protected endpoint positioning (e.g., primary or secondary) by proprietary rights and, in some cases, a royalty and fee may be • The COA Compendium presents information that was available charged by the copyright owners for their authorized use at the time it was compiled and updated; it may not include newer COAs that could be recommended for a drug development program, or more recent scientific and regulatory thinking

COA COMPENDIUM DESCRIPTION

This COA Compendium is part of FDA’s efforts to foster patient-focused drug development. The COA Compendium is intended to facilitate communication and to provide clarity and transparency to drug developers and researchers by collating and summarizing COA information for many different diseases and conditions into a single resource. We suggest using the COA Compendium as a starting point when considering a COA for use in clinical trials.

The COA Compendium is a table that:

• Describes how certain COAs have been used in clinical trials to measure the patient’s experience (such as disease-related symptoms) and to support labeling claims.

• Identifies COAs that have been qualified for potential use in multiple drug development programs under CDER’s Drug Development Tool (DDT) Qualification Program.

This is the second update to the Compendium since the launch of the pilot in January 2016. The update is an extension of the original document and includes COAs from three major sources:

• Labeling of new molecular entity (NME) drugs and biological license application (BLA) drugs approved from July 2017 to June 2019 collected through Drugs@FDA

• Efficacy supplements pertaining to a new indication and/or new population approved from July 2017 to June 2018 collected through Drugs@FDA

• Qualified measures based on CDER’s COA DDT Qualification Program collected through the Qualification Website for Qualified COAs

The COA Compendium is organized by CDER’s OND offices and review divisions. The table alphabetically lists conditions or diseases based on each review division’s therapeutic assignment. The gray shaded rows describe information about a COA DDT qualification project.

COLUMNS ELEMENTS DESCRIPTION OF CONTENT Column 1 Disease/Condition Lists disease or condition Column 2 COA Context of Use Describes circumstance under which the COA has been used (i.e., labeled) or has been qualified (for qualified tools under CDER’s DDT Qualification program) Column 3 Concept Describes the concept that the COA measures Column 4 COA Tool & Type Describes the: • COA as listed in labeling or the qualification statement • COA Type (i.e., a patient-reported outcome, observer-reported outcome, clinician-reported outcome, or performance outcome tool) Tools listed in Column 3 were found in labeling for all drugs listed in Column 5, with the exception of those denoted with a superscript

Column 5 Drug Name & List the brand and generic name of approved drugs, date of approval for NME labeling and the most recent approval date Approval Date for efficacy supplements.

A clinical outcome assessment (COA) is defined as an assessment of a clinical outcome that can be made through report by a clinician, a patient, a non-clinician observer or through a performance-based assessment. The FDA-NIH BEST Glossary defines them as:

Clinician-reported outcome (ClinRO): A measurement based on a report that comes from a trained health-care professional after observation of a patient’s health condition.

Patient-Reported outcome (PRO): A measurement based on a report that comes directly from the patient (i.e., study subject) about the status of a patient’s health condition without amendment or interpretation of the patient’s response by a clinician or anyone else.

Observer-reported outcome (ObsRO): A measurement based on a report of observable signs, events or behaviors related to a patient’s health condition by someone other than the patient or a health professional.

Performance outcome (PerfO): A measurement based on standardized task(s) actively undertaken by a patient according to a set of instructions.

A biomarker is a defined characteristic that is measured as an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention, including therapeutic interventions. Molecular, histologic, radiographic, or physiologic characteristics are types of biomarkers. A biomarker is not an assessment of how an individual feels, functions, or survives.

OFFICE OF CARDIOLOGY, HEMATOLOGY, ENDOCRINOLOGY, AND NEPHROLOGY (OCHEN)

DIVISION OF CARDIOLOGY AND NEPHROLOGY (DCN)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Acute coronary syndrome Adults with ACS • Incidence of cardiovascular Composite: ClinRO 1. Brilinta (ticagrelor) (ACS) death July 20, 2011 • Non-fatal myocardial 2. Effient (prasugrel) infarction July 10, 2009 • Non-fatal stroke Acute myocardial infarction Adults receiving percutane- • All-cause mortality Composite: ClinRO Kengreal (cangrelor) ous coronary intervention • Myocardial infarction June 22, 2015 • Ischemia-driven revascularization • Stent thrombosis Atrial fibrillation (AF) /atrial Adults in sinus rhythm with Hospitalization due to cardio- Composite: ClinRO Multaq (dronedarone HCL) flutter (AFL) a history of paroxysmal or vascular cause or death from July 1, 2009 persistent AF/AFL any cause First symptomatic AF/AFL Composite: ClinRO recurrence Autosomal dominant Adults at risk of rapidly Time to multiple clinical Composite: Jynarque (tolvaptan) polycystic kidney disease progressing ADPKD progression: • Biomarker April 23, 2018 (ADPKD) • Worsening kidney function • ClinRO • Medically significant kidney • ClinRO pain • Biomarker • Worsening hypertension • Worsening albuminuria

DIVISION OF CARDIOLOGY AND NEPHROLOGY (DCN) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Cardiomyopathy Adults with cardiomyopathy • All-cause mortality Composite: ClinRO Vyndaqel (tafamidis of wild type or hereditary • Frequency of meglumine) transthyretin-mediated cardiovascular-related May 3, 2019 amyloidosis hospitalizations

Frequency of cardiovascular- Composite: ClinRO related hospitalizations Functional capacity 6-Minute Walk Test (6MWT): PerfO Health status Kansas City Cardiomyopathy Questionnaire-Overall Sum- mary (KCCQ-OS) score: PRO Chronic coronary artery Adults with a history of • Incidence of cardiovascular Composite: ClinRO Zontivity (vorapaxar) disease atherosclerosis involving death, myocardial May 8, 2014 the coronary, cerebral, or infarction and stroke peripheral vascular systems • Avoidance of hospitalization for unstable angina • Avoidance of coronary revascularization Chronic heart failure (CHF) Limited Context of Use CHF symptoms and their im- PRO Qualified COA pact on physical limitations Kansas City Cardiomyopathy See qualification statement Questionnaire (KCCQ) for additional information Visit “Clinical Outcome Assessment (COA) Qualification Program Qualified Clinical Outcome Assessments” Website for additional information

DIVISION OF CARDIOLOGY AND NEPHROLOGY (DCN) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Chronic stable angina Adults with chronic angina Exercise duration Modified Bruce Treadmill Ranexa (ranolazine) Exercise test: PerfO January 27, 2006 Angina attack frequency Diary: PRO Nitroglycerin use Diary: PRO Chronic thromboembolic Adults with CTEPH Exercise capacity 6-Minute Walking Distance Adempas (riociguat) pulmonary hypertension (6MWD): PerfO October 8, 2013 (CTEPH) World Health Organization World Health Organization functional class / lack of functional assessment: deterioration ClinRO Heart failure Adults with chronic heart Composite as first event Composite: ClinRO 1. Corlanor (ivabradine) failure • Cardiovascular death April 15, 2015 • Hospitalization due to 2. Entresto (sacubitril and heart failure valsartan) July 7, 2015 Neurogenic orthostatic Adults with symptomatic Symptom severity (e.g., Orthostatic Hypotension Northera (droxidopa) hypotension neurogenic orthostatic dizziness, lightheadedness, Questionnaire Item (OHQ) #1: February 18, 2014 hypotension feeling faint, and “feeling like PRO you might blackout” Non-valvular atrial Adults with NVAF • Stroke Composite: ClinRO 1. Savaysa (edoxaban) fibrillation (NVAF) • Systemic embolic event January 8, 2015 2. Eliquis (apixaban) December 28, 2012 3. Xarelto (rivaroxaban) November 4, 2011 4. Pradaxa (dabigatran) October 19, 2010

DIVISION OF CARDIOLOGY AND NEPHROLOGY (DCN) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Pulmonary arterial Adults with PAH Exercise capacity 6-Minute Walking Distance 1. Uptravi (selexipag) hypertension (PAH) (6MWD): PerfO2,3,4,5 December 21, 2015 Incidence of death or clinical ClinRO2,3,4,5 2. Opsumit (macitentan) deterioration October 18, 2013 • Incidence of PAH Composite1 3. Adempas (riociguat) • Worsening of PAH • Hospitalization for PAH: October 8, 2013 ClinRO 4. Letairis (ambrisentan) • PAH worsening resulting June 15, 2007 in need for lung 5. Ventavis (iloprost) transplantation or balloon December 29, 2004 atrial septostomy: ClinRO Patients with a history of Adult patients with a history • Incidence of cardiovascular Composite: ClinRO Zontivity (vorapaxar) atherosclerosis of atherosclerosis involving death, myocardial May 8, 2014 the coronary, cerebral, or infarction, and stroke peripheral vascular systems • Avoidance of hospitalization for unstable angina • Avoidance of coronary revascularization Varicose veins Adult patients with spider or Improvement of varicose Digital photographs of the Asclera (polidocanol) reticular varicose veins veins treatment area: ClinRO March 30, 2010 Patient satisfaction with 5-point verbal rating scale: treatment PRO

DIVISION OF DIABETES, LIPID DISORDERS AND OBESITY (DDLO)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Cardiovascular risk Adults with established • Cardiovascular death Composite: ClinRO Repatha (evolocumab) associated with established cardiovascular disease • Myocardial infarction August 27, 2015 cardiovascular disease December 1, 2017 • Stroke • Hospitalization for unstable angina • Coronary revascularization

Cardiovascular risk Adults with type 2 diabetes • Cardiovascular death Composite: ClinRO Victoza (liraglutide) associated with type 2 mellitus (T2DM) and • Non-fatal myocardial January 25, 2010 diabetes mellitus (T2DM) and established cardiovascular infarction August 25, 2017 established cardiovascular disease disease • Non-fatal stroke

Type 2 diabetes mellitus Adults with T2DM Severe hypoglycemia ClinRO Tresiba (insulin degludec) (T2DM) and atherosclerotic and atherosclerotic outcomes September 25, 2015 cardiovascular disease cardiovascular disease March 26, 2018

DIVISION OF GENERAL ENDOCRINOLOGY (DGE)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Human immunodeficiency Adult patients with HIV- Body image Belly appearance distress Egrifta (tesamorelin) virus (HIV)-related related lipodystrophy score: PRO November 10, 2010 lipodystrophy

DIVISION OF NON-MALIGNANT HEMATOLOGY (DNH)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Acquired thrombotic Adults with aTTP, • Recurrence of TTP Composite: ClinRO Cablivi (caplacizumab-yhdp) thrombocytopenic purpura in combination with (exacerbation) February 6, 2019 (aTTP) plasma exchange and • Treatment-emergent major immunosuppressive therapy thromboembolic event • TTP-related death

Hemophilia A Adult and adolescent males Frequency of bleeding ClinRO Hemlibra (emicizumab- (aged 12 to 75 years) with requiring treatment with kxwh) hemophilia A and FVIII coagulation factors November 16, 2017 inhibitors who previously received either episodic (on-demand) or prophylactic treatment with bypassing agents

Adults with hemophilia A Health related quality of life- Haemophilia-specific Quality and FVIII inhibitors who physical health of Life (Haem-A-QoL) previously received either Physical Health Score: PRO episodic (on-demand) or prophylactic treatment with bypassing agents

Iron deficiency anemia Adults with iron deficiency Disease-related fatigue Functional Assessment of Feraheme (ferumoxytol) anemia who have intolerance Chronic Illness Therapy- June 30, 2009 to oral iron or have had Fatigue (FACIT-fatigue): PRO February 2, 2018 unsatisfactory response to oral iron

DIVISION OF NON-MALIGNANT HEMATOLOGY (DNH) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Myelofibrosis (MF) Patients with intermediate MF symptom severity (e.g., Myelofibrosis Symptoms Jakafi (ruxolitinib) or high risk MF, post tiredness, night sweats, Assessment Form (MF-SAF) November 16, 2011 polycythemia-vera itchiness, abdominal diary*: PRO October 10, 2017 MF and post essential discomfort, pain under the thrombocythemia MF who ribs, feeling of fullness, bone are symptomatic or muscle pain) Fatigue-related symptoms PROMIS-Fatigue 7-item and associated impacts on short form (PROMIS-Fatigue daily activities 7b): PRO

Paroxysmal nocturnal Adult patients with PNH Disease-related fatigue Functional Assessment of 1. Soliris (eculizumab) hemoglobinuria (PNH) and hemolysis requiring Chronic Illness Therapy- March 16, 2007 transfusion Fatigue (FACIT-fatigue): PRO 2. Ultomiris (ravulizumab-

2 cwvz) Transfusion avoidance ClinRO December 21, 2018

Primary hemophagocytic Adult and pediatric (newborn Overall response rate ClinRO/Biomarker Gamifant (emapalumab-lzsg) lymphohistocytosis (HLH) and older) patients with November 20, 2018 primary HLH with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy Thrombocytopenia Thrombocytopenia in adult Need for rescue medication ClinRO 1. Doptelet (avatrombopag) patients with chronic liver or procedure May 21, 2018 disease who are scheduled 2. Mulpleta (lusutrombopag) to undergo a procedure July 31, 2018

*MFSAF v4.0 is the currently recommended version instead of v2.0 which was used in the Jakafi approval

DIVISION OF NON-MALIGNANT HEMATOLOGY (DNH) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Venous thromboembolism Prophylaxis of VTE in adult DVT/PE related symptomatic Composite1 1. Bevyxxa (betrixaban) (VTE) patients events: • Biomarker June 23, 2017 • Asymptomatic proximal • ClinRO 2. Savaysa (edoxaban) Deep Vein Thrombosis January 8, 2015 • ClinRO (DVT) (detected by 3. Xarelto (rivaroxaban) ultrasound) • ClinRO July 1, 2011 • Symptomatic proximal or distal DVT • Non-fatal Pulmonary Embolism (PE), or • VTE-related death

DVT/PE related symptomatic Composite: ClinRO2 events: • Recurrent DVT • New non-fatal symptomatic PE • Fatal PE DVT/PE related symptomatic Composite: ClinRO3 events: • Recurrent DVT • Non-fatal PE • Fatal PE

OFFICE OF IMMUNOLOGY AND INFLAMMATION (OII)

DIVISION OF DERMATOLOGY AND DENTISTRY (DDD)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Acne vulgaris Patients 9 years of age and Global assessment of Investigator’s Global Seysara (sarecycline) older with inflammatory the overall severity of the Assessment: ClinRO October 1, 2018 lesions of non-nodular disease (e.g., clear or almost moderate- to-severe acne clear) vulgaris Inflammatory lesion count ClinRO

Actinic keratosis (topical Adult patients with actinic Clearance of actinic ClinRO Picato (ingenol mebutate) therapy) keratosis keratosis lesions January 23, 2012

Adult patients with actinic Levulan kerastick (amino- keratoses of the upper levulinic acid hydrochloride) extremities December 3, 1999 March 6, 2018 Atopic dermatitis Adults with moderate-to- Global assessment of Investigator’s Global Assess- Dupixent (dupilumab) severe atopic dermatitis the overall severity of the ment: ClinRO March 28, 2017 disease (e.g., erythema and April 10, 2018 papulation/infiltration) Extent and severity of the Eczema Area and Severity disease (e.g., thickness, Index (EASI-75): ClinRO scratching and lichenification) Itching intensity Pruritus Numeric Rating Scale (NRS): PRO Atopic dermatitis Patients 2 years of age and Global assessment of Investigator’s Static Global Eucrisa (crisaborole) older with mild-to-moderate the overall severity of the Assessment: ClinRO December 14, 2016 atopic dermatitis disease (e.g., clear or almost clear)

DIVISION OF DERMATOLOGY AND DENTISTRY (DDD) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link External genital and perianal Adult patients with external Clearance of external genital ClinRO Veregen (kunecatechins) warts (topical therapy) genital and perianal warts and perianal warts October 31, 2006

Forehead lines Adults with forehead lines Forehead line severity at Facial Wrinkle Scale with Botox Cosmetic maximum eyebrow elevation Photonumeric Guide: ClinRO (OnabotulinumtoxinA) December 9, 1991 Forehead line severity at Facial Wrinkle Scale with October 2, 2017 maximum eyebrow elevation Photonumeric Guide: PRO

Facial line satisfaction Facial Line Satisfaction Questionnaire: PRO

Glabellar lines Adults with moderate- Glabellar line severity at Glabellar Line Scale (GLS): Jeuveau to-severe glabellar lines maximum frown PRO (prabotulinumtoxinA-xvfs) associated with corrugator February 1, 2019 and/or procerus muscle Glabellar line severity at Glabellar Line Scale (GLS): activity maximum frown ClinRO

Head lice infestation (topical Pediatric and adult patients Absence of live lice ClinRO 1. Natroba (spinosad) therapy) with head lice infestation January 18, 2011 2. Ulesfia 5% Lotion (benzyl alcohol) April 9, 2009

DIVISION OF DERMATOLOGY AND DENTISTRY (DDD) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Interdigital tinea pedis, tinea Pediatric and/or adult • Clearance of signs and Composite1 1. Luzu cream 1% cruris, tinea corporis (topical patients with interdigital symptoms (e.g., erythema, • ClinRO & PRO (luliconazole) therapy) tinea pedis, tinea cruris, and/ scaling, and pruritus) November 14, 2013 or tinea corporis • Laboratory measure: February 20, 2018 • Mycological cure (fungal Biomarker(s) culture and potassium Note: pruritus symptoms 2. Ertaczo (sertaconazole hydroxide (KOH) tests) are assessed based on nitrate cream 2%) patient-reported outcome December 10, 2003 Clearance of signs and PRO2 & ClinRO2 symptoms (e.g., erythema, scaling, and pruritus)

Onychomycosis (topical Adults patients with Composite Composite 1. Kerydin (Tavaborole) therapy) onychomycosis • Clinical evidence of the • ClinRO July 7, 2014 disease (absence of signs/ • Laboratory measures: 2. Jublia (efinaconazole) symptoms) Biomarker(s) June 6, 2014 • Mycological cure (fungal culture and potassium hydroxide (KOH) tests) Pemphigus vulgaris Adults with pemphigus Complete remission: ClinRO Rituxan (rituximab) vulgaris • Complete epithelialization November 26, 1997 and absence of new and/or June 7, 2018 established lesions • Discontinuation of prednisone therapy

DIVISION OF DERMATOLOGY AND DENTISTRY (DDD) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Plaque psoriasis Adults with moderate-to- Extent and severity of Psoriasis Area and Severity 1. Siliq (brodalumab) severe plaque psoriasis affected body surface area Index (PASI): ClinRO1,2,3,4,5,6,7 February 15, 2017 (e.g., induration, erythema, 2. Taltz (ixekizumab) and scaling) March 22, 2016 Global assessment of the Physician’s Global 3. Cosentyx (secukinumab) overall severity of the Assessment: ClinRO1,2,3,4,5,6,7 January 21, 2015 disease (e.g., plaque thick- January 23, 2018 ness/induration, erythema, 4. Tremfya (guselkumab) and scaling) July 13, 2017 Symptoms of plaque Psoriasis Symptom Inventory 5. Ilumya (tildrakizumab- psoriasis (PSI): PRO1 asmn) March 20, 2018 Itching severity Itch numeric Rating Scale: 2 6. Skyrizi (risankizumab- PRO rzaa) April 23, 2019 Patient-reported symptoms Psoriasis Symptom Diary: PRO3 7. Cimzia (certolizumab pegol) Symptoms of psoriasis (itch, Psoriasis Symptoms and April 22, 2008 pain, stinging, burning and Signs Diary (PSSD): PRO4 May 24, 2018 skin tightness) Global assessment of Scalp specific Investigator’s the overall severity of the Global Assessment Scale: disease of the scalp ClinRO4

Signs and symptoms related Psoriasis Symptom Scale to pain, redness, itching and (PSS): PRO6 burning Global assessment of Investigator Global the overall severity of the Assessment scalp only disease of the scalp score: ClinRO3

DIVISION OF DERMATOLOGY AND DENTISTRY (DDD) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Plaque psoriasis Patients 12 years or older Extent and severity of Psoriasis Area and Severity Stelara (ustekinumab) with plaque psoriasis affected body surface area Index (PASI): ClinRO October 13, 2017 (e.g., induration, erythema, and scaling) Global assessment of Physician's Global the overall severity of the Assessment: ClinRO disease (e.g., induration, erythema and scaling) Submental fat Adults with moderate-to- Improvement in submental Composite Kybella (deoxycholic acid) severe convexity or fullness convexity or fullness • Clinician-Reported April 29, 2015 associated with submental Submental Fat Rating fatvere convexity or fullness ScaleFat Rating Scale (CR-SMFRS): ClinRO • Patient-Reported Submental Fat Rating Scale (PR-SMFRS): PRO

Visual and emotional impact Six-question survey: PRO of submental fat

DIVISION OF GASTROENTEROLOGY (DG)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Bowel prep Adults scheduled for elective Successful (excellent ClinRO Prepopik (citric acid; colonoscopy or good) bowel prep magnesium oxide; sodium (visualization of mucosa and picosulfate) minimal need for additional July 16, 2012 suctioning or washing)

DIVISION OF GASTROENTEROLOGY (DG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Carcinoid syndrome diarrhea Adults with carcinoid Frequency of bowel Diary: PRO Xermelo (telotristat ethyl) syndrome diarrhea movement February 28, 2017 Abdominal pain

Flushing

Carcinoid syndrome diarrhea Adults with carcinoid Use of rescue therapy Diary: PRO Somatuline Depot syndrome diarrhea (lanreotide) Frequency of diarrhea and August 30, 2007 flushing symptoms September 15, 2017 Chronic idiopathic Adults with CIC Frequency of complete Diary: PRO1,2,4 1. Trulance (plecanatide) constipation (CIC) spontaneous bowel January 19, 2017 movements (CSBM) 2. Linzess (linaclotide) Frequency of spontaneous Diary: PRO1,2,3 August 30, 2012 bowel movements (SBM) 3. Amitiza (lubiprostone) January 31, 2006 Straining—amount of time Diary: PRO1 pushing or physical effort to 4. Motegrity (prucalopride) pass stool December 14, 2018 Stool consistency Bristol Stool Form Scale (BSFS): PRO1,2 Signs and symptoms Numeric rating scale related to constipation assessing signs and (e.g., abdominal pain, stool symptoms: PRO2,3 consistency, severity of straining) Crohn’s disease (CD) Adults with CD • Signs and symptoms of the Composite: 1. Cimzia (certolizumab disease • PRO & ClinRO pegol) April 22, 2008 • Disease activity • Biomarkers 2. Entyvio (vedolizumab) May 20, 2014

DIVISION OF GASTROENTEROLOGY (DG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Diary for irritable bowel Adults (18 years or older) • Bowel movement (BM)- PRO Qualified COA syndrome symptoms — with IBS-C related symptoms (i.e., Diary for Irritable Bowel constipation (DIBSS-C) BM frequency, stool Syndrome Symptoms- consistency, incomplete Constipation (DIBSS-C) BMs, and straining) Visit “Clinical Outcome • Abdominal symptoms (i.e., Assessment (COA) abdominal pain, abdominal Qualification Program discomfort, and bloating) Qualified Clinical Outcome Assessments” Website for additional information

Irritable bowel syndrome Adults with IBS-C Frequency of complete Diary: PRO 1. Linzess (linaclotide) with constipation (IBS-C) spontaneous bowel August 30, 2012 movements (CSBM) 2. Trulance (plecanatide) January 19, 2017 Abdominal pain intensity 11-point abdominal pain January 24, 2018 numeric rating scale: PRO

Irritable bowel syndrome Adults with IBS-D Abdominal pain intensity and Composite Viberzi (eluxadoline) with diarrhea (IBS-D) stool consistency • Diary: PRO May 27, 2015 • Bristol Stool Scale (BSS): PRO 11-point abdominal pain numeric rating scale: PRO

DIVISION OF GASTROENTEROLOGY (DG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Nausea and vomiting Adults with delayed nausea Absence of vomiting, retch- Diary: PRO1,2 1. Aloxi (palonosetron associated with and vomiting associated with ing or nausea and no use of hydrochloride) chemotherapy emetogenic chemotherapy2 rescue medication2 July 25, 2003 2. Varubi (rolapitant) Adults at risk for nausea and Absence of emetic episodes September 1, 2015 vomiting associated with and no use of rescue emetogenic chemotherapy1 medication1

Nausea and vomiting Adults with acute and de- Complete Response: Diary: PRO Akynzeo (fosnetupitant and associated with layed nausea and vomiting • Emetic episodes palonosetron) chemotherapy associated with initial and April 19, 2018 repeat courses of highly • Use of rescue medication emetogenic chemotherapy Non-infectious diarrhea Adults with noninfectious Stool consistency Bristol Stool Form Scale: Mytesi (crofelemer) diarrhea, HIV related PRO December 31, 2012

Frequency of the watery Patient diary: PRO bowel movement Opioid induced constipation Adults with opioid induced Frequency of spontaneous Diary: PRO1,2 1. Amitiza (lubiprostone) constipation bowel movements without January 31, 2006 laxative use April 19, 2013 Frequency of complete Diary: PRO2 2. Symproic (naldemedine) spontaneous bowel March 23, 2017 movement Opioid induced ileus, Adults with opioid induced Resolution of opioid induced Diary: PRO Entereg (alvimopan) postoperative ileus, postoperative ileus, both the upper and May 20, 2008 lower gastrointestinal tract (i.e., toleration of solid food and first bowel movement)

DIVISION OF GASTROENTEROLOGY (DG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Pancreas divisum undergo- Adults with pancreas divisum Cannulation of the minor ClinRO Chirhostim (secretin ing endoscopic retrograde undergoing ERCP duct of the pancreas synthetic human) cholangiopancreatography April 9, 2004 (ERCP)

Ulcerative colitis Adults with moderate to Disease activity and severity Endoscopy: ClinRO 1. Entyvio (vedolizumab) severely active UC May 20, 2014 Signs and symptoms of UC Diary: PRO 2. Xeljanz (tofacitinib) (blood and stool frequency) November 6, 2012 May 30, 2018

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Allergic rhinitis Pediatric and adult patients Nasal symptoms severity 4-point categorical nasal Omnaris (ciclesonine) with allergic rhinitis (e.g., runny nose, nasal symptom severity scale: PRO October 20, 2006 itching, sneezing, and nasal congestion)

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Asthma Limited context of use Severity of asthma PRO Qualified COA symptoms Asthma Daytime Symptom See qualification statement Diary (ADSD) and Asthma for additional information Nighttime Symptom Diary (ANSD) Visit “Clinical Outcome Assessment (COA) Qualification Program Qualified Clinical Outcome Assessments” Website for additional information

Asthma Patients 6 years of age and Signs and symptoms of Asthma Control Spiriva Respimat (tiotropium older for the maintenance asthma and adequacy of Questionnaire (ACQ-7) bromide) treatment of asthma asthma control • Asthma symptoms: PRO February 15, 2017 Health Related Quality of life Asthma Quality of Life Questionnaire (AQLQ): PRO Signs and symptoms of Composite: Asthma asthma and measure of exacerbation asthma exacerbation • Peak Expiratory Flow (PEF): Biomarker • Asthma symptoms: PRO

Asthma Patients with asthma 6 to Functional problems Pediatric Asthma Quality of Symbicort (budesonide/ less than 12 years of age related to asthma (physical, Life Questionnaire (PAQLQ): formoterol) emotional and social) PRO January 27, 2017

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Asthma Adults with severe asthma Functional problems related Asthma Quality of life Cinqair (reslizumab) with an esoinophilic to asthma questionnaire (AQLQ): PRO March 23, 2016 phenotype for add on maintenance treatment Adequacy of and change in Asthma Control asthma control Questionnaire (ACQ-7): PRO

Asthma exacerbation Composite: ClinRO • Use or increase in the use of a systemic corticosteroid • Asthma-related emergency treatment or asthma-related hospitalization Asthma Patients with severe asthma Asthma exacerbation Composite: ClinRO1,2 1. Nucala (mepolizumab) aged 12 years and older, • Use of oral/systemic November 4, 2015 and with an eosinophilic steroids 2. Fasenra (benralizumab) phenotype as an add-on November 14, 2017 maintenance treatment • Increase in the use of oral/ systemic corticosteroids2 • Hospitalization • Emergency department visits Asthma control Asthma Control Questionnaire-5 (ACQ-5): PRO1 Asthma Control Questionnaire-6 (ACQ-6): PRO2

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Asthma (continued) Functional problems related Standardized Asthma to asthma Quality of Life Questionnaire for 12 years and Older (AQLQ(S)+12): PRO2

Symptoms frequency and St. Georges Respiratory severity, physical activity Questionnaire (SGRQ): PRO1 limitations, and impact on daily life Reduction in oral ClinRO2 corticosteroid use Asthma Pediatric and adult patients Frequency and severity of Diary: PRO Xolair (omalizumab) with asthma asthma exacerbation June 20, 2003

Lung function FEV1: Biomarker

Improvement in asthma Asthma symptoms score: symptoms severity PRO

Asthma Patients with asthma 12 Asthma exacerbation Composite: ClinRO 1. Symbicort (budesonide/ years of age and older • Use of systemic formoterol) corticosteroids January 27, 2017 December 20, 2017 • Hospitalization 2. Dulera (mometasone and • Emergency department formoterol) visits June 22, 2010 December 20, 2017 Asthma Patients aged 5 years to 11 Use of rescue medication Diary: PRO and/or ObsRO as Arnuity Ellipta (fluticasone years old appropriate furoate) August 20, 2014 May 17, 2018

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Chronic obstructive Limited context of use Respiratory symptoms of PRO Qualified COA pulmonary disease (COPD) See qualification statement stable COPD Evaluating Respiratory for additional information Symptoms in Chronic Obstructive Pulmonary Disease (E-RS: COPD) Visit “Clinical Outcome Assessment (COA) Qualification Program Qualified Clinical Outcome Assessments” Website for additional information Chronic obstructive Adult patients with COPD Symptoms frequency and St. George’s Respiratory 1. Breo Ellipta (fluticasone pulmonary disease (COPD) severity, physical activity Questionnaire: PRO2,4,6 furoate and vilanterol limitations, and impact on St. George’s Respiratory trifenatate) daily life Questionnaire for COPD May 10, 2013 patients (SGRQ-C): PRO5 2. Arcapta Neohaler (indacaterol maleate) • Symptoms of exacerbation Composite of pulmonary 1,3,5,6 July 1, 2011 • Therapeutic intervention exacerbations: ClinRO 3. Daliresp (roflumilast) • Hospitalization February 28, 2011 • Death3,5 August 31, 2017 4. Yupelri (revefenacin) 5 Reduction in rescue Diary: PRO November 9, 2018 medication use 5. Trelegy Ellipta (fluticasone, meclidinium, and vilanterol) September 18, 2017 April 24, 2018 6. Symbicort (budesonide/ formoterol) January 27, 2017 September 11, 2017

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Cystic fibrosis Patients age 12 years and Respiratory symptoms Cystic Fibrosis Questionnaire 1. Orkambi (lumacaftor/ older with cystic fibrosis (CF) (cough, sputum production, —Revised (CFQ-R) ivacaftor) difficulty breathing) Respiratory Domain: PRO July 2, 2015 Sino-pulmonary signs and Pulmonary exacerbation: 2. Symdeko (tezacaftor/ symptoms of exacerbation ClinRO ivacaftor) February 12, 2018 Cystic fibrosis Pediatric and adult patients Respiratory symptoms Cystic Fibrosis Questionnaire Kalydeco (ivacaftor) with cystic fibrosis severity —Revised respiratory January 31, 2012 domain (CFQ-R): PRO May 17, 2017 July 31, 2017 Sino-pulmonary signs and Pulmonary exacerbation: symptoms of exacerbation ClinRO

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Eosinophilic granulomatosis Adult patients with Remission Birmingham Vasculitis Nucala (mepolizumab) with polyangiitis (EGPA) eosinophilic granulomatosis Activity Score (BVAS): ClinRO November 4, 2015 with polyangiitis (EGPA) December 12, 2017 Oral corticosteroid use: ClinRO Time to first relapse: Composite (Worsening): • Vasculitis activity • Birmingham Vasculitis • Asthma control Activity Score (BVAS): ClinRO • Sino-nasal symptoms • Asthma Control • Corticosteroid use Questionnaire-6 ACQ-6: • Immunosuppressive PRO therapy • Diary: PRO • Hospitalization • ClinRO • ClinRO • ClinRO Reduction of oral ClinRO corticosteroid use Asthma control Asthma Control Questionnaire-6 (ACQ-6): PRO

DIVISION OF PULMONOLOGY, ALLERGY AND CRITICAL CARE (DPACC) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Hereditary angioedema Pediatric and adult patients Signs and symptoms severity 100mm visual analog scale 1. Firazyr (icatibant acetate) (HAE) with HAE (e.g., skin swelling, skin pain, or evaluating each sign/ August 25, 2011 1 abdominal pain) symptom severity: PRO 2. Kalbitor (ecallantide) 4-point categorical scale December 1, 2009 (Mean Symptom Complex Severity score): PRO2

Improvement of each Categorical scale evaluating anatomic site of attack treatment improvement (Treatment Outcome Score): PRO2

Hereditary angioedema Prophylaxis for patients age HAE attacks ClinRO Takhzyro (lanadelumab-flyo) (HAE) 12 years and older to prevent August 23, 2018 HAE

Idiopathic pulmonary fibrosis Adult patients with idiopathic IPF exacerbation (defined as Composite Ofev (nintedanib) (IPF) pulmonary fibrosis worsening or development • ClinRO and Biomarker October 15, 2014 of dyspnea and imaging abnormalities) Respiratory distress Premature infants at high Prevention of RDS in Incidence of RDS and RDS *Surfaxin (lucinactant) syndrome (RDS) risk for RDS premature infants at high related mortality: ClinRO March 6, 2012 risk for RDS

*Surfaxin is no longer marketed but the clinical outcome assessment is still considered acceptable.

DIVISION OF RHEUMATOLOGY AND TRANSPLANT MEDICINE (DRTM)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Ankylosing spondylitis Adult patients with Signs and symptoms of Composite: Assessment 1. Simponi (golimumab) ankylosing spondylitis ankylosing spondylitis (e.g., in Ankylosing Spondylitis April 24, 2009 1,2 pain, inflammation) (ASAS): PRO 2. Simponi Aria (golimumab) • VAS pain scale July 18, 2013 • Bath Ankylosing October 20, 2017 Spondylitis Functional Index • Bath Ankylosing Spondylitis Disease Activity Index • Patient global assessment

Bath Ankylosing Spondylitis Disease Activity Index: PRO2 Bath Ankylosing Spondylitis Metrology Index: ClinRO2 General health status Short Form (SF-36): PRO2

Health-related quality of life Ankylosing Spondylitis Quality of Life questionnaire (ASQoL): PRO2 Cryopyrin-associated Pediatric and adult patients Signs and symptoms severity Severity rating of each 1. Ilaris (canakinumab) periodic syndromes (CAPS) with CAPS (e.g., rash, fatigue, joint pain, symptom on a 0-10-point June 17, 2009 feeling of fever/chills, eye scale with half point 2. Arcalyst (rilonacept) redness/pain) increments on the Daily February 27, 2008 Health Assessment Form: PRO2

Physician global assessment Physician’s global rating of disease activity and skin using a categorical rating disease assessment scale: ClinRO1

DIVISION OF RHEUMATOLOGY AND TRANSPLANT MEDICINE (DRTM) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Kidney transplantation Patients with kidney Composite Composite Nulojix (beletacept) (prophylaxis of organ transplant • Incidence of biopsy-proven • ClinRO June 15, 2011 rejection) acute rejection • ClinRO • Death • Biomarker • Graft loss • Patient loss to follow up • Patient loss to follow up

Psoriatic arthritis (PsA) Adults with active PsA • Improvement in number of American College of 1. Orencia (abatacept) tender and swollen joints Rheumatology (ACR) core June 30, 2017 • Pain intensity set of outcome measures: 2. Otezla (apremilast) [ClinRO, PRO and March 21, 2014 • Patient’s global Biomarker]1,2,3,4,5,6 assessment of disease 3. Simponi (golimumab) activity April 24, 2009 • Physician’s global 4. Simponi Aria (golimumab) assessment of disease July 18, 2013 activity October 20, 2017 • Disability 5. Xeljanz (tofacitinib) • Physical functioning November 6, 2012 December 14, 2017 • Laboratory measure (Biomarker(s)) (e.g., 6. Taltz (ixekizumab) sedimentation rate) March 22, 2016 December 1, 2017 Physical function Health Assessment Questionnaire Disability Index (HAQ-DI): PRO1,2,3,4,5,6 General health status Short Form (SF-36): PRO4,5,6

Improvement in enthesitis Leeds Enthesitis Index: ClinRO4

DIVISION OF RHEUMATOLOGY AND TRANSPLANT MEDICINE (DRTM) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Rheumatoid arthritis (RA) Adult patients with RA • Improvement in number of Composite 1. Kevzara (sarilumab) tender and swollen joints • American College of May 22, 2017 • Pain intensity Rheumatology (ACR) core 2. Simponi Aria (golimumab) • Patient’s global set of outcome measures: July 18, 2013 [ClinRO, PRO, and assessment of disease 1,2,3,4,5,6 3. Xeljanz (tofacitinib) activity Biomarker(s)] November 6, 2012 • Physician’s global 4. Actemra (tocilizumab) assessment of disease January 8, 2010 activity 5. Orencia (abatacept) • Disability December 23, 2005 • Physical functioning 6. Olumiant (baricitinib) • Laboratory measure May 31, 2018 (Biomarker(s)) (e.g., sedimentation rate)

• Number of tender joints Composite: • Number of swollen joints Disease Activity Score (DAS)-28: [ClinRO, PRO and • Patient global assessment Biomarker(s)]6 of disease activity • Laboratory measure (Biomarker(s)) (e.g., sedimentation rate)

Physical function Health Assessment Questionnaire Disability Index (HAQ-DI): PRO1,2,3,4,5,6 General health status Short Form (SF-36): PRO1,5,6

DIVISION OF RHEUMATOLOGY AND TRANSPLANT MEDICINE (DRTM) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Systemic lupus Patients with systemic lupus Signs and symptoms and Composite Benlysta (belimumab) erythematosus erythematosus disease activity severity • Systemic Lupus March 9, 2011 Erythematosus Disease July 20, 2017 Global impression Activity Index: ClinRO • British Isles Lupus Activity Group: ClinRO • Clinician’s Global Assessment: ClinRO

Time to first severe flare Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) Flare Index (SFI): ClinRO

Prednisone reduction

OFFICE OF INFECTIOUS DISEASE (OID)

DIVISION OF ANTI-INFECTIVES (DAI)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Acute bacterial exacerba- Limited Context of Use Symptoms of ABECB- PRO Qualified COA tion of chronic bronchitis in See qualification statement COPD (breathlessness, Exacerbations of Chronic patients with COPD (ABECB- for additional information cough and sputum, chest Pulmonary Disease Tool COPD) symptoms, difficulty bringing (EXACT) up sputum, tired or weak, sleep disturbance, scared or Visit “Clinical Outcome worried) Assessment (COA) Qualification Program Qualified Clinical Outcome Assessments” Website for additional information Acute bacterial skin and skin Adults with acute bacterial Reduction in lesion size ClinRO Nuzyra (omadacycline) structure infections (ABSSSI) skin and skin structure October 2, 2018 infections (ABSSSI) Resolution of infection Acute otitis externa Patients 6 months of Resolution of signs and ClinRO Otiprio (ciprofloxacin) age and older with Acute symptoms of acute otitis December 10, 2015 Otitis Externa due to externa (tenderness, March 2, 2018 Pseudomonas aeruginosa erythema, edema, and and Staphylococcus aureus otorrhea)

Bacterial vaginosis Adult women with bacterial Clinical Response: Composite Solosec (secnidazole) vaginosis • normal vaginal discharge • ClinRO and Biomarker September 15, 2017 • negative whiff test • clue cells <20% Clostridioides difficile Adult patients with Sustained clinical response ClinRO Zinplava (bezlotoxumab) infection Clostridioides difficile post initial treatment October 21, 2016

DIVISION OF ANTI-INFECTIVES (DAI) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Clostridioides difficile- Adult patients with Improvement in diarrhea ClinRO Dificid (fidaxomicin) associated diarrhea Clostridioides difficile or other symptoms (e.g., May 27, 2011 unformed stool count)

Sustained clinical response ClinRO post initial treatment Community-acquired bacte- Adults with community- Survival with improvement ClinRO Nuzyra (omadacycline) rial pneumonia (CABP) acquired bacterial in at least two of four October 2, 2018 pneumonia (CABP) symptoms without deterioration in any of the symptoms (cough, sputum production, chest pain, dyspnea)

Complicated intra-abdominal Adults with complicated Complete resolution or ClinRO Xerava (eravacycline) Infections (cIAI) intra-abdominal infections significant improvement of August 27, 2018 proven or strongly suspected signs or symptoms of the to be caused by susceptible index infection bacteria Complicated urinary tract Adults with complicated Clinical Cure: Composite: 1. Vabomere (meropenem Infections (cUTI) urinary tract infections (cUTI) • Resolution or improvement • ClinRO and Biomarker and vaborbactam) including pyelonephritis of the symptoms of cUTI August 29, 2017 caused by designated present at trial entry (and 2. Zemdri (plazomicin) susceptible bacteria no new symptoms) June 25, 2018

Microbiological Eradication

Cystic fibrosis (CF) Patients with CF age 7 years Changes in respiratory CF Questionnaire—Revised Cayston (aztreonam) and above symptoms (cough, wheezing, (CFQ-R) respiratory domain: February 22, 2010 sputum production) PRO

DIVISION OF ANTI-INFECTIVES (DAI) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Fascioliasis Patients 6 years of age and Absence of Fasciola eggs in Biomarker Egaten (triclabendazole) older with fascioliasis the stool February 13, 2019 Resolution of signs and ClinRO symptoms Hospital-acquired Bacterial Adults with HABP/VABP All-cause mortality ClinRO Avycaz (ceftazidime and Pneumonia and Ventila- avibactam) tor-associated Bacterial Resolution or significant February 25, 2015 Pneumonia (HABP/VABP) improvement in signs and February 1, 2018 symptoms associated with pneumonia

Impetigo Adult and pediatric patients Absence or improvement of ClinRO 1. Altabax (retapamulin) with impetigo treated lesions April 12, 2007 2. Xepi (ozenoxacin) December 11, 2017

Leishmaniasis (cutaneous, Adolescents and adult Resolution of edema, ClinRO Impavido (miltefosine) mucosal and visceral) patients with cutaneous erythema, infiltration March 19, 2014 leishmaniasis and erosion and/or epithelialization of lesions

No enlargement of lesions or no appearance of new lesions Clearance of the parasites Laboratory Measure: Biomarker

DIVISION OF ANTI-INFECTIVES (DAI) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Malaria (Plasmodium vivax) Patients aged 16 years and Prevention of relapse: Composite Krintafel (tafenoquine) older receiving appropriate • Initial parasite clearance ClinRO and Biomarker July 20, 2018 antimalarial therapy for acute P. vivax infection • No additional anti-malarial medication use • Confirmed parasite-free at 6-month final assessment Travelers’ diarrhea Adults with travelers' Clinical response based on PRO 1. Xifaxan (rifaximin) diarrhea caused by time to last unformed stool May 25, 2004 noninvasive strains of E. coli Resolution of symptoms 2. Aemcolo (rifamycin November 16, 2018

DIVISION OF ANTIVIRALS (DAV)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Acute uncomplicated Treatment of acute Symptoms of Influenza: Diary: PRO Xofluza (baloxavir marboxil) influenza uncomplicated influenza (cough, sore throat, nasal October 24, 2018 congestion, headache, feverishness, myalgia and fatigue) Acute uncomplicated Treatment of acute Symptoms of Influenza: Diary: PRO Rapivab (peramivir) influenza uncomplicated influenza in (cough, sore throat, nasal December 19, 2014 adult patients congestion, headache, September 20, 2017 feverishness, myalgia and fatigue) Treatment of acute Signs and symptoms of Diary: PRO or ObsRO, as uncomplicated influenza in Influenza appropriate pediatric patients

OFFICE OF NEUROSCIENCE (ON)

DIVISION OF NEUROLOGY I AND II (DN I AND II)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Alzheimer’s disease (AD) Adult patients with moderate Day-to-day function Modified Alzheimer’s Namenda (memantine to severe AD Disease Cooperative Study— hydrochloride) Activities of Daily Living: October 16, 2003 ClinRO

Cognitive function Severe Impairment Battery (SIB): PerfO

Global impression Clinical Global Impression of change: ClinRO Amyotrophic lateral sclerosis Adults with ALS Functional disability ALS Functional Rating Scale- Radicava (edaravone (ALS) revised (ALSFRS-R): ClinRO injection) May 5, 2017

Blepharospasm Adults with blepharospasm Signs and symptoms of Jankovic Rating Scale (JRS)- Xeomin blepharospasm severity domain: ClinRO (incobotulinumtoxinA) July 30, 2010 Cervical dystonia Adults with cervical dystonia • Severity of dystonia Toronto Western Spasmodic 1. Xeomin • Disability Torticollis Rating Scale (incobotulinumtoxinA) (TWSTRS) (composite of July 30, 2010 • Pain ClinRO and PRO) 2. Dysport (abobotulinumtoxinA) April 29, 2009

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Duchenne muscular Children (5 years and up) and Muscle strength Medical Research Council 1. Emflaza (deflazacort) dystrophy (DMD) adults with DMD (MRC) 11-point scale: ClinRO1 February 9, 2017 2. Exondys 51 (eteplirsen) Physical function speed Timed functional tests: September 19, 2016 PerfO1 Walking distance 6 Minute Walk Test (6MWT): PerfO2 Generalized myasthenia Adults with generalized Impact on daily function Myasthenia Gravis-Specific Soliris (eculizumab) gravis (gMG) myasthenia gravis Activities of Daily Living (MG- March 16, 2007 ADL): PRO October 23, 2017

Muscle weakness Quantitative Myasthenia Gravis (QMG) Score: Multicomponent ClinRO/ PerfO/Biomarker Huntington’s chorea Adults with chorea Chorea Total chorea score item of Austedo (deutetrabenazine) associated with HD the Unified Huntington’s April 3, 2017 Disease Rating Scale (UHDRS): ClinRO Global impression Patient-rated Global Impression: PRO Global impression Physician-rated Clinical Global Impression: ClinRO Huntington’s disease (HD) Adults with chorea Chorea Total chorea score item of Xenazine (tetrabenazine) associated with HD the Unified Huntington’s August 15, 2008 Disease Rating Scale (UHDRS): ClinRO Global impression Clinical Global Impression: ClinRO

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Lambert-Eaton myasthenic Adults with Lambert-Eaton Muscle weakness Quantitative Myasthenia Firdapse (amifampridine syndrome (LEMS) myasthenic syndrome Gravis (QMG) Score: phosphate) (LEMS) Multicomponent ClinRO/ November 28, 2018 PerfO/Biomarker

Global impression of Subject Global Impression: the effects of the study PRO treatment on physical well- being Global impression of Clinical Global Impression of improvement Improvement: ClinRO

Migraine headache Adults and adolescents (12 Migraine frequency Diary: PRO 1. Trokendi XR (topiramate) years and up) with migraine August 16, 2013 headaches April 5, 2017 2. Qudexy XR (topiramate) March 11, 2014 March 29, 2017 Adults with migraine Migraine frequency Diary: PRO Aimovig (erenumab-aooe) headaches May 17, 2018

Impact of migraine on Migraine Physical Function everyday activities (EA) and Impact Diary (MPFID): PRO physical impairment (PI) Migraine headache (episodic) Adults with a history of Migraine frequency Diary: PRO 1. Ajovy (fremanezumab- episodic migraines vfrm) September 14, 2018 2. Emgality (galcanezumab- gnlm) September 27, 2018

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Migraine headache (chronic) Adults with a history of • Migraine frequency Diary: PRO 1. Ajovy (fremanezumab- chronic migraines • Headache frequency vfrm) September 14, 2018 Impact of migraine on daily Migraine-Specific Quality of 2. Emgality (galcanezumab- activities Life Questionnaire version gnlm) 2.1 (MSQv2.1) Role Function- September 27, 2018 Restrictive domain: PRO2

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Multiple sclerosis (MS) Adults with primary Physical disability Expanded Disability Status Ocrevus (ocrelizumab) progressive forms of MS Scale (EDSS): ClinRO March 28, 2017 Walking speed Timed 25-foot walk: PerfO

Patients 10 to less than 18 Relapse frequency ClinRO Gilenya (fingolimod years of age with relapsing- hydrochloride) remitting multiple sclerosis September 21, 2010 May 11, 2018 Adults with relapsing Physical Disability Expanded Disability Status Mayzent (siponimod fumaric forms of MS to include Scale (EDSS) score: ClinRO acid) clinically isolated syndrome, March 26, 2019 relapsing-remitting disease, Relapse frequency ClinRO and active secondary progressive disease Walking Speed 25-foot walk test: PerfO

Adults with relapsing forms Relapse frequency ClinRO 1. Ocrevus (ocrelizumab) of MS March 28, 2017 Physical disability Expanded Disability Status 2. Zinbryta (daclizumab) Scale (EDSS): ClinRO May 27, 2016 3. Tecfidera (dimethyl fumarate) March 27, 2013 4. Aubagio (teriflunomide) September 12, 2012 5. Gilenya (fingolimod) September 21, 2010

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Multiple sclerosis (MS) Adults with MS Walking speed Timed 25-foot walk: PerfO Ampyra (dalfampridine) January 22, 2010 Ambulatory disability 12-item Multiple Sclerosis Walking Scale: PRO Parkinson’s disease (PD) Adults with PD experiencing Signs and symptoms of Diary: PRO Xadago (safinamide) “off” episodes dyskinesia March 21, 2017 Motor function Uniform Parkinson’s Disease Rating Scale (UPDRS) Part III (motor examination): ClinRO Parkinson’s disease (PD) Adults with PD Motor findings Uniform Parkinson’s Disease 1. Neupro (rotigotine) (Early Stage) Rating Scale (UPDRS) Part III May 9, 2007 (motor examination): ClinRO 2. Azilect (rasagiline mesylate) Activities of daily living Unified Parkinson’s Disease May 16, 2006 Rating Scale (UPDRS)—Part II: ClinRO Parkinson’s disease (PD) Adults with PD “Off” time Patient diary: PRO 1. Azilect (rasagiline (Advanced stage) Unified Parkinson’s Disease mesylate) May 16, 2006 Motor findings Unified Parkinson’s Disease 2. Apokyn (apomorphine HCl) Rating Scale (UPDRS)—Part April 20, 2004 III: ClinRO1,2 Activities of daily living Unified Parkinson’s Disease Rating Scale (UPDRS)—Part II: ClinRO1

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Polyneuropathy of hereditary Adults with polyneuropathy Neuropathy impairment modified Neuropathy 1. Onpattro (patisiran transthyretin-mediated of hereditary transthyretin- Impairment Score +7 sodium) amyloidosis mediated amyloidosis (mNIS+7): Multicomponent August 10, 2018 ClinRO/Biomarker 2. Tegsedi (inotersen sodium) October 5, 2018 Patient experience of Norfolk Quality of Life- neuropathy in the following Diabetic Neuropathy total domains: score (QoL-DN): PRO Physical functioning/large fiber neuropathy, activities of daily living, symptoms, small fiber neuropathy, and autonomic neuropathy Restless legs syndrome Adults with moderate to Sensory and motor symptom International Restless Legs Horizant (gabapentin (RLS) severe primary RLS severity and impacts on Syndrome (RLS) Rating enacarbil) sleep, daytime tiredness or Scale: PRO April 6, 2011 sleepiness, activities of daily living, and mood associated with RLS Global impression-RLS Clinical Global Impression: symptoms ClinRO

Seizure disorder Adults and pediatrics 6 years Seizure frequency Diary: PRO and/or ObsRO as Trokendi XR (topiramate) and up with partial onset or appropriate August 16, 2013 primary generalized tonic- April 5, 2017 clonic seizures

Adults and pediatrics 15 Briviact (brivaracetam) years and up with partial February 18, 2016 onset or primary generalized tonic-clonic seizures

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Seizure disorder: Dravet Patients 2–18 years of age Convulsive seizure frequency Diary: PRO and/or ObsRO as Epidiolex (cannabidiol) syndrome with Dravet syndrome (all countable atonic, tonic, appropriate June 25, 2018 clonic, and tonic-clonic seizures)

Seizure disorder: Dravet Patients 3 years of age Generalized clonic or tonic- Diary: PRO and/or ObsRO as Diacomit (stiripentol) syndrome and older with seizures clonic seizure frequency appropriate August 20, 2018 associated with Dravet Seizure frequency syndrome taking clobazam

Seizure disorder: Infantile Pediatric (1 month-2 years) Electroencephalogram Video/electroencephalogram Sabril (vigabatrin) spasm patients with infantile (EEG)—cessation of (EEG): ClinRO August 21, 2009 spasms hypsarrhythmia

Complete cessation of Diary: ObsRO seizures

Seizure disorder: Lennox- Patients 2 years of age and • Drop seizure frequency Diary: PRO and/or ObsRO as Epidiolex (cannabidiol) Gastaut syndrome (LGS) older with LGS (atonic, tonic, or tonic- appropriate June 25, 2018 clonic) • Total seizure frequency (drop and non-drop seizures) Global impression of change Subject/Caregiver Global Impression of Change: PRO and/or ObsRO as appropriate Seizure disorder: Lennox- Pediatric (2 years and up) Seizure frequency Diary: PRO and/or ObsRO as 1. Onfi (clobazam) Gastaut Syndrome (LGS) and adult patients with LGS appropriate October 21, 2011 2. Banzel (rufinamide) November 14, 2008

DIVISION OF NEUROLOGY I AND II (DN I AND II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Seizure disorder: Partial Pediatric patients 4 years Seizure frequency Diary: PRO and/or ObsRO as Lyrica (pregabalin) onset seizures to less than 17 years of age appropriate January 4, 2010 with partial onset seizures May 3, 2018 with or without secondary generalization

Seizure disorder: Refractory Pediatric (2 years and up) Seizure frequency Diary: PRO and/or ObsRO as Sabril (vigabatrin) Complex Partial Seizures and adult patients with appropriate August 21, 2009 refractory complex partial seizures

Spasticity Adults with spasticity and Muscle tone Modified Ashworth Scale Dysport pediatric patients (2 years (MAS): ClinRO (abobotulinumtoxinA) and up) with lower limb April 29, 2009 spasticity June 14, 2017

Spinal muscular atrophy Adults and pediatric patients Motor development Section 2 of Hammersmith Spinraza (nusinersen) (SMA) with SMA Infant Neurologic Exam December 23, 2016 (HINE-motor milestones): ClinRO

Motor skills Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND): ClinRO Spinal muscular atrophy Pediatric patients with later- Motor function Hammersmith Functional Spinraza (nusinersen) (SMA) — later onset onset SMA Motor Scale — Expanded December 23, 2016 (HFMSE): ClinRO May 14, 2018

DIVISION OF PSYCHIATRY (DP)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Attention deficit hyperactivity Patients with ADHD Severity of ADHD for patients ADHD Rating Scale (ADHD- 1. Mydayis (mixed salts of a disorder (ADHD) 13 to 55 years old RS): ClinRO1,2 single-entity amphetamine product) Severity of ADHD in pediatric Connor’s Parent Rating June 20, 2017 patients (13 to 17 years old) Scale: ObsRO2 2. Vyvanse (lisdexamfetamine Attentional symptoms Permanent Product Measure dimesylate) measurement in ADHD of Performance (PERMP): February 23, 2007 PerfO1 Deportment (behavior) in Swanson, Kotkin, Angler, ADHD M-Flynn, and Pelham (SKAMP) Deportment Scores: ClinRO2

Bipolar disorder (manic or Adults with manic or mixed Manic symptoms Young Mania Rating Scale 1. Vraylar (cariprazine) mixed) episodes associated with (YMRS): ClinRO1,2 September 17, 2015 bipolar 1 disorder Global clinical impression of Clinical Global Impression- 2. Saphris (asenapine) bipolar disorder severity Bipolar Severity of Illness August 13, 2009 score: ClinRO1,2

Bipolar disorder (depressive) Patients 10 years of age and Major depressive symptoms Montgomery-Åsberg Latuda (lurasidone older with bipolar 1 disorder (adult) Depression Rating Scale hydrochloride) (MADRS) version 10: ClinRO October 28, 2010 January 27, 2017 Global clinical impression of Clinical Global Impression- March 5, 2018 bipolar disorder severity Bipolar-Severity of Illness Scale: ClinRO Major depressive symptoms Children’s Depression Rating (pediatric) Scale, Revised (CDRS-R): ClinRO

DIVISION OF PSYCHIATRY (DP) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Bipolar disorder (manic or Adults with manic or mixed Recurrence of mood episode ClinRO Abilify Maintena Kit mixed) episodes associated with (aripiprazole) bipolar 1 disorder February 28, 2013 July 27, 2017 Excessive daytime Adults with narcolepsy or Daytime sleepiness PRO Sunosi (solriamfetol) sleepiness associated with obstructive sleep apnea March 20, 2019 narcolepsy or obstructive Wakefulness Maintenance of Wakefulness sleep apnea (OSA) Test (MWT): PerfO Global impression of change Patient Global Impression of of symptom severity Change: PRO Insomnia Adults with insomnia Sleep latency (sleep onset) Diary: PRO1,2,3 1. Belsomra (suvorexant) characterized by difficulty August 13, 2014 with sleep onset and/or 2. Rozerem (ramelteon) maintenance Wake time after sleep onset Polysomnography: July 22, 2005 1,3 [WASO] (sleep maintenance) Biomarker 3. Lunesta (eszopiclone) December 15, 2004 Major depressive disorder Adults with MDD Major depressive symptoms Montgomery-Åsberg 1. Rexulti (brexpiprazole) (MDD) Depression Rating Scale July 10, 2015 (MADRS) version 10: 1,2,3 2. Trintellix (vortioxetine) ClinRO September 30, 2013 Major depressive symptoms Hamilton Depression Rating 3. Viibryd (vilazodone Scale 24 items or 17 items: hydrochloride) ClinRO2,4,5 January 21, 2011 4. Pristiq (desvenlafaxine succinate) February 29, 2008 5. Cymbalta (duloxetine hydrochloride) August 3, 2004

DIVISION OF PSYCHIATRY (DP) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Major depressive disorder Adults with MDD Processing speed Digit Symbol Substitution Trintellix (vortioxetine (MDD) Test (DSST): PerfO hydrobromide) September 30, 2013 May 2, 2018

Major depressive disorder Limited Context of Use Major depressive symptoms PRO Qualified COA: (MDD) See qualification statement Symptoms of Major for additional information Depressive Disorder Scale (SMDDS) Visit “Clinical Outcome Assessment (COA) Qualification Program Qualified Clinical Outcome Assessments” Website for additional information

Non-24-hour sleep-wake Adults with non-24-hour Nighttime sleep time and Diary: PRO Hetlioz (tasimelteon) disorder sleep wake disorder daytime nap time January 31, 2014

Parkinson’s disease (PD) Adults with hallucinations Severity of hallucinations PD adapted Scale for the Nuplazid (pimavanserin) psychosis and delusions associated and delusions Assessment of Positive April 29, 2016 with PD psychosis Symptoms (SAPS-PD) hallucinations and delusions: ClinRO Postpartum depression Adults with postpartum Major depressive symptoms Hamilton Depression Rating Zulresso (brexanolone) (PPD) depression Scale (HAM-D): ClinRO March 19, 2019

DIVISION OF PSYCHIATRY (DP) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Schizophrenia Adults with schizophrenia Severity of schizophrenia Positive and Negative 1. Aristada (aripiprazole symptoms Syndrome Scale (PANSS): lauroxil) ClinRO1,2,3,4,5,6 October 5, 2015 2. Vraylar (cariprazine) September 17,2015 Positive symptoms of Brief Psychiatric Rating November 9, 2017 psychosis Scale derived (BPRSd): ClinRO3,5 3. Latuda (lurasidone hydrochloride) October 28, 2010 Global clinical impression of Clinical Global Impression- January 27, 2017* severity Severity: ClinRO2,3 4. Saphris (asenapine) August 13, 2009 Personal and social Personal and Social 5. Fanapt (iloperidone) functioning Performance (PSP) scale: May 6, 2009 ClinRO6 6. Invega (paliperidone) December 19, 2006 Relapse of psychosis ClinRO2,7 7. Invega Sustenna (paliperidone palmitate) December 20, 2017 Tardive dyskinesia Adults with TD Involuntary movements Abnormal Involuntary 1. Ingrezza (valbenazine) associated with TD Movement Scale (AIMS): April 11, 2017 ClinRO 2. Austedo (deutetrabenazine) August 30, 2017

*Latuda (efficacy supplement) is approved for adults and adolescents (13 to 17 years) with schizophrenia.

DIVISION OF ANESTHESIOLOGY, ADDICTION MEDICINE AND PAIN MEDICINE (DAAP)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Alcoholism Adult patients who are Attaining and maintaining Composite Campral (acamprosate alcohol-dependent abstinence or low risk • Diary: PRO calcium) drinking (e.g., frequency July 29, 2004 of alcohol consumption, • Laboratory confirmation: quantity of alcohol Biomarker consumed, and laboratory measure) Opioid withdrawal Adult patients with opioid Opioid withdrawal symptoms Short Opiate Withdrawal Lucemyra (lofexidine) withdrawal symptoms Scale of Gossop (SOWS- May 16, 2018 to facilitate opioid Gossop) total score: PRO discontinuation Pain (acute) Patients with acute pain Pain intensity Numerical pain rating scale Nucynta (tapentadol or visual analog scale: PRO hydrochloride) November 20, 2008 Pain (chronic) Patients with chronic pain Pain intensity Numerical pain rating scale Prialt (ziconotide acetate or visual analog scale: PRO intrathecal infusion) December 28, 2004 Pain (neuropathic) Patients with neuropathic Pain intensity Numerical pain rating scale 1. Qutenza (capsaicin 8% patch) pain or visual analog scale: PRO November 16, 2009 2. Lyrica (pregabalin) December 30, 2004 Postsurgical local analgesia Adults who require Pain intensity Numerical pain rating scale Exparel (bupivacaine liposome) postsurgical local and or visual analog scale: PRO October 28, 2011 regional analgesia April 6, 2018 Smoking cessation Current smokers Abstinence Composite Chantix (varenicline tartrate) • Patient-reported May 10, 2006 abstinence: PRO • Laboratory measure: Biomarker

OFFICE OF ONCOLOGIC DISEASES (OOD)

DIVISION OF ONCOLOGY I (DO I)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Prostate cancer Adult patients with Pain intensity Brief Pain Inventory Item Zytiga (abiraterone acetate) (Metastatic castration- metastatic castration- #3—Short Form: PRO April 28, 2011 resistant) resistant prostate cancer Prostate cancer Patients with non-metastatic Symptomatic progression Composite: ClinRO Erleada (apalutamide) (Non-metastatic castration- castration-resistant prostate February 14, 2018 resistant) cancer

DIVISION OF ONCOLOGY II (DO II)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Metastatic non-small cell Adults with NSCLC whose Delay in time to development European Organization for Zykadia (ceritinib) lung cancer (NSCLC) tumors are anaplastic or worsening of shortness of Research and Treatment May 26, 2017 lymphoma kinase (ALK)- breath of Cancer, Quality of Life positive Questionnaire (EORTC QLQ C-30 / LC13): PRO

DIVISION OF ONCOLOGY II (DO II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Non-small cell lung cancer Limited Context of Use Overall severity of the PRO Qualified COA: (NSCLC) See qualification statement following NSCLC symptoms: Non-Small Cell Lung Cancer for additional information cough, pain, dyspnea, Symptom Assessment fatigue, and appetite Questionnaire (NSCLC-SAQ) Visit “Clinical Outcome Assessment (COA) Qualification Program Qualified Clinical Outcome Assessments” Website for additional information

Recurrent glioblastoma Adults with recurrent Discontinuation of ClinRO Avastin (bevacizumab) glioblastoma corticosteroid use February 26, 2004 December 5, 2017

TSC-associated partial-onset Adult and pediatric patients Seizure frequency Diary: PRO or ObsRO, as Afinitor Disperz (everolimus) seizures aged 2 years and older with appropriate August 29, 2012 TSC-associated partial-onset April 10, 2018 seizures

DIVISION OF HEMATOLOGIC MALIGNANCIES I (DHM I)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Acute myeloid leukemia Adult patients with relapsed Transfusion dependence ClinRO/Biomarker Idhifa (enasidenib) (AML) or refractory AML and an August 17, 2017 IDH2 mutation Adult patients with relapsed Transfusion dependence ClinRO/Biomarker Tibsovo (ivosidenib) or refractory AML and an July 20, 2018 IDH1 mutation Adult patients with relapsed Transfusion dependence ClinRO/Biomarker Xospata (gilteritinib) or refractory AML with a November 28, 2018 FLT3 mutation Blastic plasmacytoid Patients aged 2 years Complete response or ClinRO/Biomarker Elzonris (tagraxofusp-erzs) dendritic cell neoplasm and older with blastic clinical Complete Response December 21, 2018 (BPDCN) plasmacytoid dendritic cell (CR/CRc) neoplasm (BPDCN)

DIVISION OF HEMATOLOGIC MALIGNANCIES II (DHM II)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Chronic graft versus host Adults with cGVHD after Patient-reported symptom Lee Symptom Scale Total Imbruvica (ibrutinib) disease (cGVHD) failure of one or more lines bother Score: PRO November 13, 2013 of systemic therapy August 2, 2017 Overall response rate Modified 2005 National Institute of Health (NIH) Consensus Panel Response Criteria: ClinRO/PRO/ Biomarker

DIVISION OF HEMATOLOGIC MALIGNANCIES II (DHM II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Chronic lymphocytic Adult patients with CLL Composite Composite Treanda (bendamustine leukemia • Incidence of palpable • ClinRO hydrochloride) March 20, 2008 hepatosplenomegaly • ClinRO • Size of lymph nodes; • Laboratory measures: incidence of lymph nodes Biomarker(s) with nodularity • B symptoms evaluation (night sweats, fever, unexplained weight loss) • Laboratory measures (lymphocytes, neutrophils, platelets, histology)

Chronic lymphocytic Adults with relapsed Overall response rate 2008 International Workshop Copiktra (duvelisib) leukemia (CLL)/Small or refractory chronic for Chronic Lymphocytic September 24, 2018 lymphocytic leukemia (SLL) lymphocytic leukemia Leukemia (IWCLL) guidelines (CLL) or small lymphocytic or 2007 International lymphoma (SLL) after at Working Group (IWG) Revised least two prior therapies Response Criteria for Malignant Lymphoma with modification for treatment- related lymphocytosis: ClinRO/Biomarker

Adults with chronic Overall response rate 2008 International Venclexta (venetoclax) lymphocytic leukemia Workshop for Chronic April 11, 2016 (CLL) or small lymphocytic Lymphocytic Leukemia June 8, 2018 lymphoma (SLL), with or (IWCLL) guidelines: ClinRO/ without 17p deletion, who Biomarker have received at least one prior therapy

DIVISION OF HEMATOLOGIC MALIGNANCIES II (DHM II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Cutaneous T-cell lymphoma Adult patients with CTCL Skin involvement Severity Weighted Assess- Zolinza (vorinostat) (CTCL) ment Tool (SWAT) in addition October 6, 2006 to other outcomes (e.g., response duration, time to progression, time to objec- tive response): ClinRO

Physician’s global assessing 7-Point Physician’s Global improvement or worsening in Assessment scale: overall disease ClinRO

Follicular lymphoma (FL) Adults with relapsed Overall response rate 2007 International Working 1. Aliqopa (copanlisib) follicular lymphoma (FL) who Group Revised Response September 14, 2017 have received at least two Criteria for Malignant 2. Copiktra (duvelisib) prior systemic therapies Lymphoma: ClinRO/ September 24, 2018 Biomarker

Mucositis Adult patients with Incidence and severity of oral World Health Organization Kepivance (palifermin) hematologic malignancies mucositis (e.g., soreness/ Oral Mucositis Scale: ClinRO December 15, 2004 receiving myelotoxic therapy erythema, ulcers, oral intake requiring hematopoietic tolerability) stem cell support

Multiple myeloma Prevention of skeletal- Skeletal-related events: ClinRO Xgeva (denosumab) related events in patients • Pathologic fracture June 1, 2010 with multiple myeloma January 4, 2018 and in patients with bone • Radiation therapy to bone metastases from solid • Surgery to bone tumors • Spinal cord compression

DIVISION OF HEMATOLOGIC MALIGNANCIES II (DHM II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Mycosis fungoides (MF) or Adults with relapsed or Overall response rate Composite: Poteligeo (mogamulizumab- Sézary syndrome refractory mycosis fungoides based on global composite • ClinRO kpkc) or Sézary syndrome after response criteria: August 8, 2018 • ClinRO at least one prior systemic • modified Severity Weighted therapy Assessment Tool (mSWAT) • Biomarker • Skin photographs • Biomarker • Central flow cytometry • Computed tomography Mycosis fungoides (MF) Adults with CD30-expressing Global response: Composite: Adcetris (brentuximab mycosis fungoides requiring • Skin evaluations per • ClinRO vedotin) systemic therapy August 19, 2011 modified severity-weighted • Biomarker assessment tool (mSWAT) November 9, 2017 • Biomarker • Nodal and visceral radiographic assessment • Detection of circulating Sézary cells Primary cutaneous Adults with pcALCL Global response: Composite: Adcetris (brentuximab anaplastic large cell requiring systemic therapy • Skin evaluations per • ClinRO vedotin) lymphoma (pcALCL) August 19, 2011 modified severity-weighted • Biomarker assessment tool (mSWAT) November 9, 2017 • Nodal and visceral radiographic assessment Primary mediastinal large Adults with relapsed or Overall response rate 2007 International Working Keytruda (pembrolizumab) B-Cell lymphoma refractory PMBCL Group Revised Response September 4, 2014 Criteria for Malignant June 19, 2018 Lymphoma: ClinRO/ Biomarker

DIVISION OF HEMATOLOGIC MALIGNANCIES II (DHM II) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Systemic mastocytosis Adult patients with systemic Assessment of complete 2013 International Working Rydapt (midostaurin) mastocytosis associated with remission (CR) response Group—Myeloproliferative April 28, 2017 hematological neoplasm Neoplasms Research and Treatment—European Competence Network on Mastocytosis (IWG-MRT- ECNM): ClinRO

OFFICE OF RARE DISEASES, PEDIATRICS, UROLOGY AND REPRODUCTIVE MEDICINE (ORPURM)

DIVISION OF RARE DISEASES AND MEDICAL GENETICS (DRDMG)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Hypophosphatasia (HPP) Patients with perinatal/ Assessment of gait Modified Performance Strensiq (asfotase alfa) infantile and juvenile-onset Oriented Mobility October 23, 2015 HPP Assessment-Gait (MPOMA-G): PerfO Walking distance 6 Minute Walk Test (6MWT): PerfO

Assess skeletal burden in Radiographic Global HPP Impression of Change (RGI-C): ClinRO

Mucopolysaccharidosis I Pediatric and/or adult Walking distance 6 Minute Walk Test (6MWT): Aldurazyme (laronidase) (MPS I) (Hurler and Hurler- patients with MPS I PerfO April 30, 2003 Scheie forms of MPS I) Mucopolysaccharidosis II Pediatric and/or adult Walking distance 6 Minute Walk Test (6MWT): Elaprase (idursulfase) (MPS II) (Hunter syndrome) patients with MPS II PerfO July 24, 2006

Mucopolysaccharidosis Pediatric and/or adult Walking distance 6 Minute Walk Test (6MWT): Vimizim (elosulfase) IVA (MPS IVA) (Morquio A patients with MPS IVA PerfO February 14, 2014 syndrome) Stair-climbing capacity 3 Minute Stair Climb Test: PerfO

Mucopolysaccharidosis VI Pediatric and/or adult Walking distance 12-Minute Walk Test: PerfO Naglazyme (galsulfase) (MPS VI) (MaroteauxLamy patients with MPS VI May 31, 2005 syndrome) Stair-climbing capacity 3-Minute Stair Climb Test: PerfO

DIVISION OF RARE DISEASES AND MEDICAL GENETICS (DRDMG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Mucopolysaccharidosis VII Pediatric and/or adult Walking distance 6 Minute Walk Test (6MWT): Mepsevii (vestronidase alfa) (MPS VII, Sly syndrome) patients with MPS VII PerfO November 15, 2017

Neuronal ceroid Symptomatic pediatric Measure of motor related CLN2 Clinical Rating Scale Brineura (cerlinponase alfa) lipofuscinosis type 2 (CLN2) patients 3 years of age and functioning/mobility (motor domain): ClinRO April 27, 2017 older with late infantile CLN2

Pompe disease, late-onset Patients with Pompe Walking distance 6-Minute Walk Test: PerfO Lumizyme (alglucosidase disease, late-onset alfa) May 24, 2010

Urea cycle disorder (UCD) Patients 2 months to less Composite Composite: Ravicti (glycerol than 2 years with UCD • Signs and symptoms of • ClinRO phenybutyrate) April 28, 2017 hyperammonemia • Biomarker • Venous ammonia value

DIVISION OF UROLOGY, OBSTETRICS, AND GYNECOLOGY (DUOG)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Benign prostatic hyperplasia Adults with BPH BPH symptoms severity International prostate 1. Rapaflo (silodocin) (BPH) (irritative and obstructive symptom score (IPSS): PRO October 8, 2008 symptoms) 2. Uroxatral (alfuzosin hydrochloride) June 12, 2003

DIVISION OF UROLOGY, OBSTETRICS, AND GYNECOLOGY (DUOG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Contraception Prevention of pregnancy Pregnancy rate ClinRO1,2 1. Annovera (segesterone in female patients with acetate and ethinyl reproductive potential estradiol) August 10, 2018 Return to fertility Diary: PRO1 2. Liletta (levonorgestrel) February 26, 2015 October 15, 2018 Endometriosis Females with moderate-to- Dysmenorrhea pain Endometriosis Daily Pain Orilissa (elagolix) severe pain associated with Impact Scale: PRO July 23, 2018 endometriosis Non-menstrual pelvic pain

Dyspareunia

Worst endometriosis pain Numerical pain rating scale: PRO Erectile dysfunction Adult men diagnosed with Erectile function Erectile function domain of 1. Stendra (avanafil) erectile dysfunction the International Index of April 27, 2012 Erectile Function (IIEF): PRO 2. Cialis (tadalafil) November 21, 2003 Attainment and maintenance Sexual Encounter Profile of erection (SEP) diary: PRO 3. Levitra (vardenafil hydrochloride) August 19, 2003

DIVISION OF UROLOGY, OBSTETRICS, AND GYNECOLOGY (DUOG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Hypoactive sexual desire Adult premenopausal women Sexual satisfaction Satisfying sexual events 1. Addyi (flibanserin) disorder (Female) with acquired, generalized (SSEs): PRO1 August 18, 2015 hypoactive sexual desire 2. Vyleesi (bremelanotide) disorder Female Sexual Encounter Profile-Revised (FSEP-R) June 21, 2019 Question 10 Satisfying Sexual Event (SSE): PRO2 Sexual desire Sexual desire from e-Diary: PRO1 Female Sexual Function Index Desire Domain (FSFI Questions 1 & 2): PRO1,2

Sexually-related distress Female Sexual Distress Scale—Revised (FSDS-R): PRO1 Female Sexual Distress Scale — Desire/Arousal/ Orgasm Question 13 (FSDS- DAO Q13): PRO2 Nocturia Adults with nocturnal Nocturia episodes Nocturic episodes: PRO Noctiva (desmopressin polyuria who waken at least acetate) 2 times per night to void Nighttime urination bother Impact of Nighttime March 3, 2017 Urination (INTU) questionnaire: PRO

DIVISION OF UROLOGY, OBSTETRICS, AND GYNECOLOGY (DUOG) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Overactive bladder Patients with overactive Incontinence episodes, Voiding diary: PRO 1. Myrbetriq (mirabegron) bladder with symptoms of urinary frequency and June 28, 2012 urge urinary incontinence, urinary void volume April 27, 2018 urgency, and urinary 2. Toviaz (fesoterodine) frequency October 31, 2008 3. Enablex (darifenacin hydrobromide) December 22, 2004 4. Vesicare (solifenacin succinate) November 19, 2004

Vasomotor symptoms (VMS) Postmenopausal women Frequency of VMS (hot Diary: PRO Duavee (conjugated with moderate-to-severe flashes/flushes) estrogens/bazedoxifene) VMS due to menopause Severity of VMS (hot flashes/ Daily severity score: PRO October 3, 2013 flushes) Vulvar and vaginal atrophy Postmenopausal women Symptoms of vulvar and Diary: PRO Osphena (ospemifene) (VVA) with moderate-to-severe vaginal atrophy (e.g., vaginal February 26, 2013 symptoms of VVA due to dryness, dyspareunia, menopause vaginal irritation/itching)

OFFICE OF SPECIALTY MEDICINE (OSM)

DIVISION OF OPHTHALMOLOGY (DO)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Allergic conjunctivitis (itching Pediatric and adult patients Ocular itching severity 5-point itching severity 1. Lastacaft (alcaftadine) associated with allergic with itching associated with numerical rating scale with July 28, 2010 conjunctivitis) allergic conjunctivitis half unit increments: PRO 2. Bepreve (bepotastine besilate) September 8, 2009 3. Elestat (epinastine) October 16, 2003

Bacterial conjunctivitis Pediatric and adult patients Clinical resolution based on ClinRO Besivance with bacterial conjunctivitis absence of all three clinical (besifloxacin hydrochloride) along with other key signs (e.g., ocular discharge, May 28, 2009 efficacy measures (e.g., bulbar conjunctival injection, microbiology) and palpebral conjunctival injection) Microbiological eradication Laboratory measure: Biomarker Cataract surgery or Patients undergoing ocular Absence of post-surgical Visual analog scale (VAS): Omidria (phenylephrine intraocular lens replacement surgery ocular pain/discomfort PRO and ketorolac intraocular solution) Intraoperative miosis Pupil diameter: ClinRO May 30, 2014 December 8, 2017

Diabetic retinopathy (DR) Adults with diabetic Severity of retinopathy Early Treatment Diabetic Lucentis (ranibizumab) retinopathy Retinopathy Study Diabetic April 15, 2017 Retinopathy Severity Scores (ETDRS-DRSS): ClinRO

DIVISION OF OPHTHALMOLOGY (DO) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Dry eye disease (DED) Adults with eye dryness Symptoms of DED: Extent of Eye Dryness Score (EDS) Xiidra (lifitegrast ophthalmic eye dryness rated by a Visual Analogue solution) Scale (VAS): PRO July 11, 2016

Signs of DED Inferior fluorescein corneal staining score (ICSS): ClinRO

Myopic choroidal Adults with high myopia and Best Corrected Visual Acuity BCVA Assessment: PerfO Lucentis (ranibizumab) neovascularization (mCNV) choroidal neovascularization (BCVA) January 5, 2017 Neovascular (wet) Adults with age-related Best Corrected Visual Acuity BCVA assessment: PerfO 1. Eylea (aflibercept) age-related macular macular degeneration (BCVA) November 18, 2011 degeneration 2. Macugen (pegaptanib) sodium) September 17, 2004 3. Lucentis (ranibizumab) June 30, 2006

Neurotrophic keratitis Patients with neurotrophic Absence of staining of the ClinRO Oxervate (cenegermin-bkbj) keratitis corneal lesion August 22, 2018

Ocular inflammation and Adults undergoing ocular Absence of post-surgical Slit lamp evaluation and 1. Durezol (difluprednate) pain associated with ocular surgery ocular inflammation anterior chamber cell/flare June 23, 2008 surgery grade score: ClinRO 2. Nevanac (nepafenac) August 19, 2005 Absence of post-surgical Visual Analog Scale (VAS) ocular pain/discomfort and/or 6-point numeric pain rating scale: PRO Ophthalmic surgery aid Patients undergoing Anterior lens capsule Biomicroscopy: ClinRO VisionBlue (trypan blue) ophthalmic surgical staining December 16, 2004 procedures

DIVISION OF OPHTHALMOLOGY (DO) (CONTINUED)

Drug Name/Approval Date/ Disease/Condition COA Context of Use Concept COA Tool & Type Qualification Link Vitreomacular adhesion Adults with symptomatic Nonsurgical vitreomacular Biomicroscopy using 4-point Jetrea (ocriplasmin) vitreomacular adhesion adhesion resolution scale: ClinRO October 17, 2012

Best Corrected Visual Acuity BCVA assessment: PerfO (BCVA)

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