Patient-Reported Outcome Consortium

Overview

Despite a number of available safe and effective therapies to treat asthma, a high proportion of persons with asthma remain symptomatic and at risk for exacerbations. When the Asthma Working Group was formed in 2012, no standard patient-reported outcome (PRO) measure existed that was considered adequate for measuring important patient-experienced aspects of the disease. Such a measure could be used in addition to spirometric assessment of lung function in the development of drugs for the treatment of persistent asthma. The Asthma Working Group developed the Asthma Daytime Symptom Diary (ADSD) and the Asthma Nighttime Symptom Diary (ANSD) to enable the capture of the core symptoms of asthma in adolescents (12 to 17 years old) and adults (18 years and older) for the assessment of clinical benefit in asthma treatment trials. In March 2019, the ADSD and ANSD were qualified by FDA for use in drug development. The Qualification Statement can be found by searching the new CDER & CBER Drug Development Tool Qualification Project Search Database.  Further information about the ADSD and ANSD and how to license them is available at: https://www.c-pathcoas.org.

Publications

• Assessing asthma symptoms in adolescents and adults: qualitative research supporting development of the Asthma Daily Symptom Diary
• Asthma Daytime Symptom Diary (ADSD) and Asthma Nighttime Symptom Diary (ANSD): Measurement Properties of Novel Patient-Reported Symptom Measures
• Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary-Child (PAD-C) and Pediatric Asthma Diary-Observer (PAD-O)

Working Group Sponsors

The following firms provided financial support for Asthma Working Group:

Actelion (now part of Janssen Pharmaceutical Companies of Johnson & Johnson)
Allergan (now AbbVie, Inc.)
Amgen Inc.
AstraZeneca Pharmaceuticals LP
Boehringer Ingelheim Pharmaceuticals Inc.
Genentech, Inc.
GlaxoSmithKline plc
Ironwood Pharmaceuticals, Inc.
Janssen Pharmaceutical Companies of Johnson & Johnson
Merck & Co., Inc.
Novartis Pharmaceutical Corporation
Pfizer Inc.
Sanofi

Overview

There is an acute need for therapeutic interventions that can slow or halt the progression of Alzheimer’s disease (AD), and it is currently believed that intervention is necessary at a very early stage of the disease. Assessment of the impact of subtle cognitive changes in early AD on a patient’s ability to perform the daily activities necessary to remain independent may be a critical tool for measuring effects of potential therapeutic agents being tested in clinical trials. The Cognition Working Group is gathering evidence to support the Virtual Reality Functional Capacity Assessment Tool-Short List Mild Cognitive Impairment (VRFCAT-SL MCI) as a performance outcome (PerfO) measure for assessing the ability to perform instrumental activities of daily living in people with mild cognitive impairment (MCI) due to AD, currently defined as Stage 2 to 3 AD. This measure would be used to support labeling claims of therapies aimed at preventing or delaying the progression of cognitive impairment in persons with AD.

Publications

• Clinically Meaningful Outcomes in Early Alzheimer Disease: A Consortia-Driven Approach to Identifying What Matters to Patients
• Development of a Patient-Reported Outcome Instrument to Assess Complex Activities of Daily Living and Interpersonal Functioning in Persons with Mild Cognitive Impairment: The Qualitative Research Phase
• Patient Self-report for Evaluating Mild Cognitive Impairment and Prodromal Alzheimer’s Disease

Working Group Sponsors

The following firms provided financial support for the Cognition Working Group:

AbbVie, Inc.
AstraZeneca Pharmaceuticals LP
Boehringer Ingelheim Pharmaceuticals, Inc.
Eli Lilly and Company
Eisai
Genentech, Inc.
Merck & Co., Inc.
Novartis Pharmaceutical Corporation
Pfizer Inc.
Regeneron Pharmaceuticals, Inc.
Sanofi

Overview

Chronic heart failure (CHF) is a condition in which the heart is unable to pump enough blood to meet the body’s needs. People with CHF experience signs and symptoms that include, but are not limited to, shortness of breath, fatigue, and swelling. Although a variety of patient-reported outcome (PRO) measures exist that are aimed at assessing symptoms, physical activity/physical capacity, and other aspects of quality of life, they were deemed to be insufficiently targeted at the most important, most proximal and, potentially, most treatable consequences of CHF. In addition, reliable and accurate measurement of specific aspects of functional capacity, such as physical activity in daily life outside of the clinic, could be enhanced by a more objective measurement approach such as by using an activity monitor. The CHF Working Group aims to obtain FDA qualification of two PRO measures—Chronic Heart Failure Symptom Scale (CHF-SS) and Chronic Heart Failure Impact Scale (CHF-IS)—and an activity monitor-based endpoint measure of physical activity for adults with CHF. The goal is to incorporate both patient-reported and activity monitor-derived data into the assessment of clinical benefit in CHF treatment trials.

Working Group Sponsors

The following firms provided financial and/or in-kind support for the CHF Working Group:

Amgen Inc.
AstraZeneca Pharmaceuticals LP
Bayer AG
Bristol Myers Squibb
Eli Lilly and Company
GlaxoSmithKline plc
Janssen Pharmaceutical Companies of Johnson & Johnson
Merck & Co., Inc.
Regeneron Pharmaceuticals, Inc.

Overview

Depression is a highly prevalent and under-treated condition in the U.S. and worldwide. Despite the availability of safe and effective medications, a high proportion of persons with depression do not achieve remission of symptoms even after switching treatments. Adequate assessment of symptom improvement from a patient’s perspective is imperative for the development of novel therapies. The Depression Working Group developed a new PRO measure — the Symptoms of Major Depressive Disorder Scale (SMDDS). In November 2017, the SMDDS was qualified by FDA for use in drug development to measure symptoms of major depressive disorder. The Qualification Statement can be found by searching the new CDER & CBER Drug Development Tool Qualification Project Search Database. Further information about the SMDDS and how to license it is available at: https://www.c-pathcoas.org.

Publications

• Patient-Centered Research To Support The Development Of The Symptoms Of Major Depressive Disorder Scale (SMDDS): Initial Qualitative Research
• Symptoms of Major Depressive Disorder Scale: Performance of a Novel Patient-Reported Symptom Measure

Working Group Sponsors

The following firms provided financial support for the Depression Working Group:

AbbVie, Inc.
Allergan (now AbbVie, Inc.)
Eli Lilly and Company
Genentech, Inc.
Janssen Pharmaceutical Companies of Johnson & Johnson
Pfizer Inc.
Sunovion Pharmaceuticals Inc.
Takeda

Overview

With FDA qualification of the Symptoms of Major Depressive Disorder Scale (SMDDS), the Depression Working Group embarked on a new qualification initiative that was driven by growing recognition of the need for assessment tools that can measure antidepressant effects within shorter time frames, potentially within hours or days rather than weeks. Trials are being conducted that could benefit from well-defined and reliable PRO measures of faster onset of symptom relief in persons with major depressive disorder (MDD). Although the SMDDS, with its 7-day recall period, will continue to be a relevant outcome measure for MDD treatment trials, this initiative’s goal is to leverage what was learned in its development to create a 24-hour recall version—the Symptoms of Major Depressive Disorder Diary (SMDDD)—and an “at this moment” version—the Symptoms of Major Depressive Disorder Momentary Assessment (SMDDMA).

Working Group Sponsors

The following firms provided financial support for the Depression Working Group 2.0:

AbbVie, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc.
Janssen Pharmaceutical Companies of Johnson & Johnson

Overview

Functional dyspepsia is defined by the absence of any organ, systemic, or metabolic disease likely to explain symptoms thought to originate in the gastroduodenal region. It is estimated that 30% to 40% of the general population experience this condition, which reflects the variability in diagnostic criteria used in clinical studies. The Functional Dyspepsia Working Group has developed a PRO measure, the Functional Dyspepsia Symptom Diary (FDSD), to assess symptoms related to the two functional dyspepsia subtypes: postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). The FDSD was developed for use in clinical trials to assess clinically meaningful relief of FD symptoms and to support labeling claims.

Publications

• Development of a Symptom-Based Patient-Reported Outcome Instrument for Functional Dyspepsia: A Preliminary Conceptual Model and an Evaluation of the Adequacy of Existing Instruments

Working Group Sponsors

The following firms provided financial support for the FD Working Group:

Allergan (now AbbVie, Inc.)
Ironwood Pharmaceuticals, Inc.
Shire (now Takeda)

Overview

Development of therapies to treat irritable bowel syndrome (IBS) depends upon critical communication from the patient about symptoms such as abdominal pain and bloating that cannot be measured any other way. There is an abundance of literature on available outcome measures in IBS, however, the development and testing methods used with these measures may not meet FDA’s regulatory expectations. Hence, the IBS Working Group has developed new PRO measures for each of the three main IBS subtypes: Diary for Irritable Bowel Syndrome Symptoms – Constipation (DIBSS-C) for constipation-predominant IBS, DIBSS-D for diarrhea-predominant IBS, and DIBSS-M for mixed or alternating IBS. These measures will be used to assess primary efficacy endpoints in treatment trials for IBS.

In December 2020, the DIBSS-C was qualified by FDA to support symptom-based efficacy endpoints in clinical trials for products intended to treat constipation-predominant IBS (IBS-C) in adults. The Qualification Statement can be found by searching the new CDER & CBER Drug Development Tool Qualification Project Search Database.  Further information about the DIBSS-C and how to license it is available at: https://c-pathcoas.org.

Publications

• Development of the Diary for Irritable Bowel Syndrome Symptoms to Assess Treatment Benefit in Clinical Trials: Foundational Qualitative Research
• Psychometric Analysis of the Abdominal Score From the Diary for Irritable Bowel Syndrome Symptoms-Constipation Using Phase IIb Clinical Trial Data

Working Group Sponsors

The following firms provided financial support for the IBS Working Group:

Allergan (now AbbVie, Inc.)
Ironwood Pharmaceuticals, Inc.
Takeda

Overview

Although clinician-reported disability and relapse are the mainstay of efficacy endpoints for multiple sclerosis (MS) trials, a measurement gap exists in the assessment of patient-reported MS-related symptoms and functional impact. Direct self-reports from persons with MS regarding symptom experience and daily functioning could provide a valuable complement to disability-and-relapse-related endpoints. In addition, incorporating MS patients’ voices into the evaluation of new medical products is consistent with the increasing emphasis on patient-centered outcomes research and FDA’s patient-focused drug development initiative. The MS Working Group aims to generate evidence to support standardized PRO measures to assess fatigue and physical function that will meet the requirements for FDA qualification. The current focus of the MS Working Group is the qualification of the PROMIS® Short Form v1.0—Fatigue-Multiple Sclerosis 8a (PROMIS FatigueMS—8a) and the PROMISnq Short Form v2.0 – Physical Function – Multiple Sclerosis 15a (PROMISnq PFMS—15a) as endpoint measures in MS clinical trials.

Working Group Sponsors

The following firms provided financial and in-kind support for the MS Working Group:

AbbVie, Inc.
Actelion (now part of Janssen Pharmaceutical Companies of Johnson & Johnson)
EMD Serono, an affiliate of Merck KGaA Germany
Genentech, Inc.
Novartis Pharmaceutical Corporation
Sanofi

Overview

Myelofibrosis is a rare bone marrow cancer that impairs the body’s ability to produce normal blood cells. As a result, excessive scarring (fibrosis) forms in the bone marrow and a cardinal sign is an enlarged spleen (splenomegaly). People with myelofibrosis may suffer from symptoms that include fatigue, abdominal discomfort, bone pain, night sweats, itching, and early satiety. Multiple versions of symptom assessment questionnaires have been used in myelofibrosis drug development programs. The Myelofibrosis Working Group created a single harmonized, consensus-defined symptom assessment questionnaire, the Myelofibrosis Symptom Assessment Form (MFSAF v4.0) based on available empirical evidence. It can be used as an endpoint measure in myelofibrosis treatment trials to assess clinical benefit. Further information about the MFSAF v4.0 and how to license it is available at: https://www.c-pathcoas.org.

Publications

• Development of a Harmonized Patient-Reported Outcome Questionnaire to Assess Myelofibrosis Symptoms in Clinical Trials

Working Group Sponsors

The following firms provided financial support for the Myelofibrosis Working Group:

CTI BioPharma
Janssen Pharmaceutical Companies of Johnson & Johnson

Overview

Lung cancer is the most common cancer worldwide and non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Substantial unmet medical need exists in this patient population, and the survival advantage of different treatment regimens has, historically, been small. Thus, detection of therapeutic impact that can palliate potentially debilitating symptoms is critical. The NSCLC Working Group has developed a patient-reported symptom measure— the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ)— for use in supporting labeling claims of clinical benefit. In April 2018, the NSCLC-SAQ was qualified by FDA for use in drug development to measure overall symptom severity in adults with advanced non-small cell lung cancer. The Qualification Statement can be found by searching the new CDER & CBER Drug Development Tool Qualification Project Search Database. Further information about the NSCLC-SAQ and how to license it is available at: https://www.c-pathcoas.org.

Publications

• Qualitative Development and Content Validity of the Non–small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ), A Patient-reported Outcome Instrument
• Non–Small Cell Lung Cancer Symptom Assessment Questionnaire: Psychometric Performance and Regulatory Qualification of a Novel Patient-Reported Symptom Measure
• Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ): Measurement Properties and Estimated Clinically Meaningful Thresholds From a Phase 3 Study
• Patient-Reported Outcomes In Cancer Drug Development And US Regulatory Review: Perspectives From Industry, The Food And Drug Administration, And The Patient
• Recommendations For Incorporating Patient-Reported Outcomes Into Clinical Comparative Effectiveness Research In Adult Oncology

Working Group Sponsors

The following firms provided financial support for the NSCLC Working Group:

AbbVie, Inc.
AstraZeneca Pharmaceuticals LP
Boehringer Ingelheim Pharmaceuticals, Inc.
Bristol Myers Squibb
Eli Lilly and Company
EMD Serono, an affiliate of Merck KGaA Germany
Genentech, Inc.
GlaxoSmithKline plc
Janssen Pharmaceutical Companies of Johnson & Johnson
Merck & Co., Inc.
Novartis Pharmaceutical Corporation

Overview

Although asthma is the most common chronic disease in children, there are no standardized and generally accepted COAs for use in pediatric clinical trials of asthma therapy to support labeling claims. Since younger children may not be able to reliably self-report their symptom experience, pediatric asthma trials can involve the collection of patient-reported symptoms from older children and observer- (e.g., parent, caregiver) reported outcomes (i.e., observable asthma-related signs) for younger children. The Pediatric Asthma Working Group aims to obtain FDA qualification of the Pediatric Asthma Diary-Observer (PAD-O) for parents/caregivers of children four through 11 years old and the Pediatric Asthma Diary-Child (PAD-C) for self-report by children eight through 11 years old. These measures are intended to inform efficacy endpoints in pediatric asthma treatment trials.

Publications

• Assessing asthma symptoms in children: qualitative research supporting the development of the Pediatric Asthma Diary-Child (PAD-C) and Pediatric Asthma Diary-Observer (PAD-O)
• Practical Considerations for the Use of Clinical Outcome Assessments (COAs) in Pediatric Clinical Research: Examples From Pediatric Gastroenterology

Working Group Sponsors

The following firms provided financial support for the Pediatric Asthma Working Group:

AstraZeneca Pharmaceuticals LP
GlaxoSmithKline plc
Novartis Pharmaceutical Corporation

Overview

Rheumatoid Arthritis (RA) affects about 1% of the population in Western countries and is characterized by painful inflammation of the joints that leads to physical disability. The objective of the RA Working Group is to generate evidence to support a PRO measure that will support the evaluation of clinical benefit in treatment trials for persons with mild to severe RA, with the intention to support claims in product labeling. Current RA clinical trial endpoints don’t reflect all concepts deemed important to persons with RA, including fatigue. The current focus of the RA Working Group is the qualification of the PROMIS® Fatigue Short Form 10a as an endpoint measure of fatigue severity in RA clinical trials.

Working Group Sponsors

The following firms provided financial support for the RA Working Group:

AbbVie, Inc.
Boehringer Ingelheim Pharmaceuticals, Inc.
Eli Lilly and Company
EMD Serono, an affiliate of Merck KGaA Germany
GlaxoSmithKline plc
Novo Nordisk
Takeda
UCB Pharma Ltd.

Overview

Lung cancer is the most common cancer worldwide, and small cell lung cancer (SCLC) is the most aggressive form. About 15% of all lung cancer cases are SCLC; the two stages of SCLC are limited (cancer that is only in the chest and can be treated with radiation therapy) and extensive (cancer that has spread outside the area that can be covered by radiation). As most current therapies for limited and extensive stage SCLC are not curative and survival rates remain low, any new therapy should demonstrate meaningful relief from distressing disease-related symptoms.

While reliable and responsive patient-reported outcome (PRO) measures exist for the assessment of lung cancer symptoms, we know of none that were developed specifically for SCLC nor that have met the current regulatory expectations for supporting an FDA-approved labeling claim. With FDA qualification of the Non-Small Cell Lung Cancer Symptom Assessment Questionnaire (NSCLC-SAQ) in April 2018, the SCLC Working Group was convened to work toward FDA qualification of a patient-reported measure of SCLC symptom severity for use in assessing clinical benefit in SCLC treatment trials among both limited and extensive stage patient populations.

Working Group Sponsors

The following firms provided financial support for the SCLC Working Group:

Amgen Inc.
AstraZeneca Pharmaceuticals LP
Boehringer Ingelheim Pharmaceuticals, Inc.
Bristol Myers Squibb
Eli Lilly and Company
EMD Serono, an affiliate of Merck KGaA Germany
Genentech, Inc.
GlaxoSmithKline plc
Janssen Pharmaceutical Companies of Johnson & Johnson
Jazz Pharmaceuticals
Merck & Co., Inc.
Novartis Pharmaceutical Corporation