Clinical Outcome Assessment Compendium
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Welcome to the Pilot Phase of the Clinical Outcome Assessment Compendium (COA Compendium) Web Site!
WHAT IS THE PURPOSE OF THE COA COMPENDIUM?
This pilot COA Compendium (PDF) is part of FDA’s efforts to foster patient-focused drug development1. The COA Compendium is intended to facilitate communication and to provide clarity and transparency to drug developers and the research community by collating and summarizing clinical outcome assessment (COA)2 information for many different diseases and conditions into a single resource. It can be used as a starting point when considering how certain clinical outcome assessments might be utilized in clinical trials and will likely be most informative in early drug development.
The COA Compendium is a table that
- Describes how certain clinical outcome assessments have been used in clinical trials to measure the patient’s experience (such as disease-related symptoms) and to support labeling claims.
- Identifies clinical outcome assessments that have been qualified for potential use in multiple drug development programs under the COA type of the Drug Development Tool (DDT) Qualification Program of the Center for Drug Evaluation and Research (CDER).
- Recognizes ongoing qualification projects to encourage community collaboration in the development of clinical outcome assessments for unmet measurement needs.
FDA is seeking public comment and feedback about the pilot COA Compendium through establishment of a docket, as announced on January 13, 2016 in the Federal Register. Comments and recommendations received will be reviewed by the Agency as we consider developing future iterations of the COA Compendium.
WHAT ARE KEY CONSIDERATIONS OF THE COA COMPENDIUM?
- The COA Compendium (PDF) is not a comprehensive list of clinical outcome assessments and is not intended to replace either existing disease-specific guidance or key interactions with FDA concerning drug development (e.g., during pre-IND meetings). Inclusion of a clinical outcome assessment in the COA Compendium is not intended to indicate that the measure is or should be the sole (or primary) determinant of a clinical benefit in a clinical trial.
- 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 the clinical outcome assessment specific to their program, irrespective of whether the disease, condition, indication, claim, or clinical outcome assessment is included in the COA Compendium.
- Some of the clinical outcome assessments listed in the COA Compendium may be protected by proprietary rights, and in some cases, a royalty and fee may be charged by the copyright owners for their authorized use. The inclusion of a clinical outcome assessment in the COA Compendium does not equate to an endorsement by FDA.
HOW ARE CLINICAL OUTCOME ASSESSMENTS SELECTED FOR THE PILOT COA COMPENDIUM?
Clinical outcome assessments for the pilot version of the COA Compendium have been selected from two sources:
- CDER’s DDT COA Qualification Program
- Drug Labeling Approved From 2003 to 2014 (New Molecular Entity (NME) labeling)
The COA Compendium lists clinical outcome assessments that have been qualified,3 as well as those currently in the process of being developed and assessed,4under CDER’s DDT Qualification Program. Qualified clinical outcome assessments are publicly available for clinical trial use and have an associated FDA guidance describing their qualified Context of Use. Clinical outcome assessments that are currently being developed within the qualification program may not yet be publicly available for use but are described in the COA Compendium to encourage collaborative efforts and to be transparent about current efforts to develop clinically relevant measures across a variety of diseases or conditions. Our guidance for industry and FDA Staff—Qualification Process for Drug Development Tools—contains more information about the qualification program.
Drug Labeling Approved From 2003 to 2014 (NME labeling)
The COA Compendium lists clinical outcome assessments from approved drug labeling as described below. Generally, the CLINICAL STUDIES section of labeling summarizes the clinical trials that provide the primary support for the effectiveness of a drug and that may be relevant for clinical decision making while prescribing, including what end points were used in the clinical trials.
In constructing the pilot COA Compendium, FDA reviewed the CLINICAL STUDIES sections of drug labeling for NMEs approved from 2003 to 2014 and any pertinent medical reviews of those NMEs. Clinical outcome assessments that were discussed in labeling (specifically NME labeling from 2003 to 2014) and used as part of primary or secondary endpoints in the controlled clinical trials that provided evidence of efficacy for the approved indication(s) were included in the COA Compendium with a few exceptions, such as when FDA issued guidance recommending the use of different, more recent, or more appropriate clinical outcome assessments for the subject condition. Also, in a few cases, outcome assessments were excluded from the COA Compendium because the assessments were too complex to be amenable to a description in the COA Compendium’s tabular format and currently there were no corresponding guidance references available for additional information.
HOW WILL LISTING LABELED CLINICAL OUTCOME ASSESSMENTS IN THE COA COMPENDIUM COMPLEMENT THE QUALIFICATION PROGRAM?
The inclusion of labeled clinical outcome assessments in the COA Compendium is not intended to minimize the value of the CDER’s DDT Qualification Program in the collaborative development of clinical outcome assessments, especially in response to unmet measurement needs. COA qualification is a regulatory conclusion that a specific clinical outcome assessment can be relied upon to have a specific interpretation and application in drug and regulatory review. Once a clinical outcome assessment has been qualified, developers and CDER reviewers can feel confident using it within the qualified Context of Use and not have to reconfirm its utility.5 Because it is not feasible (due to the time and resources necessary for qualification) or necessary to qualify all clinical outcome assessments, the inclusion of labeled clinical outcome assessments in the COA Compendium may serve as an additional method of identifying clinical outcome assessments that may be appropriate for clinical trials to support labeling claims.
WHAT DOES THE PILOT COA COMPENDIUM LOOK LIKE?
The pilot COA Compendium (PDF) is a table organized by CDER’s OND offices and review division assignments (e.g., the Division of Cardiovascular and Renal Products within the Office of Drug Evaluation I). The table alphabetically lists conditions or diseases based on each review division’s therapeutic assignment. The table rows are color coded—specifically, the shaded rows describe information relating to a COA qualification project, whereas unshaded rows describe information relating to clinical outcome assessment from previous labeling.
The COA Compendium includes the following six columns:
|COLUMNS||ELEMENTS||DESCRIPTION OF CONTENT|
|Column 1||Disease/Condition||Lists disease or condition and any relevant FDA disease-specific guidance.|
|Column 2||Indication and/or Claim(s) Description||Lists key elements of indication and/or claim (either labeled or qualified). For ongoing COA qualification projects, targeted labeling or promotional claim(s) may not be yet known and may be described as “to be determined.”
*Inclusion of a clinical outcome assessment in the COA Compendium is not intended to indicate that the measure is or should be the sole (or primary) determinant of a clinical benefit in a particular clinical trial.
|Column 3||Outcome of Interest||Describes an outcome of interest that was assessed (labeled) or could be assessed (in our qualification program) by clinical outcome assessment(s) displayed in Column 4.|
|Column 4||COA (COA Type)6||
|Column 5||COA Context of Use||Describes circumstances under which the outcomes of interest and the clinical outcome assessment have been used (i.e., labeled) or are targeted for use (i.e., they have been qualified or are part of an ongoing qualification).|
|Column 6||COA Qualification Information||Lists ongoing and completed clinical outcome assessment qualification project information, if applicable.|
WHAT ARE THE LIMITATIONS OF THE COA COMPENDIUM?
- The COA Compendium is not a comprehensive list of all medical conditions or clinical outcome assessments that could potentially support labeling claims.
- It should be underscored that the current pilot version of the COA Compendium is limited in scope—that is, it is primarily based on the retrospective review of NME labeling approved from 2003 to 2014 and excludes all efficacy supplements.
- Clinical outcome assessments not included in the COA Compendium should also be considered during drug development, as appropriate, especially those supported by data, literature, and good measurement principles.
- The COA Compendium is not a replacement for interactions with appropriate FDA review divisions nor does it supersede existing disease-specific guidance. For example:
- The COA Compendium omits critical aspects of how a listed clinical outcome assessment could be implemented in a clinical trial (e.g., clinical trial design).
- Inclusion of a clinical outcome assessment in the COA Compendium is not intended to indicate that the measure is or should be the sole determinant of a clinical benefit in a clinical trial. Other assessments, such as overall survival, may be critical drivers of establishing efficacy or clinical benefit.
- End point hierarchy and selection of key outcome assessments are always specific to the context of a drug candidate in a therapeutic area and should be discussed with the appropriate review division prior to initiating clinical trials.
1The term drug, as used here, refers to both human drugs and biological products.
2Clinical outcome assessments (COAs) measure a patient’s symptoms, overall mental state, or the effects of a disease or condition on how the patient functions. Clinical outcome assessments include patient-reported outcomes, clinician-reported outcomes, observer-reported outcomes and performance outcomes.
3COA qualification is based on a review of the evidence to support the conclusion that the COA is a well-defined and reliable assessment of a targeted concept(s) in a specified context of use in adequate and well-controlled investigations. See Qualification Process for Drug Development Tools guidance and discussion below for more information.
4FDA has received permission from submitters of COAs that have not been qualified but are in the qualification program to post project information for COA development. Additional information about COA qualification and ongoing COA qualification projects can be found on our “Clinical Outcome Assessment Qualification Program” Web page.
6 Note: Other outcomes such as biomarkers or survival may be listed if they were part of an overall composite assessment that included a COA.