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Clinical Outcome Assessment (COA) Compendium Update
Yujin Chung
Parima Ghafoori
Elektra Papadopoulos
CDER, FDA
I

n recent years, FDA has undertaken multiple efforts to better incorporate the patient’s voice in drug development and evaluation through adoption of outcome assessments that measure what matters to patients. One component of these efforts is the Clinical Outcome Assessment (COA) Compendium; its pilot was launched in January 2016. The COA Compendium is designed as a living resource and communication tool to increase FDA transparency and foster patient-focused outcome assessment in drug development.

What is the COA Compendium?

The COA Compendium is a public resource that collates and summarizes, in a tabular format, COA information from approved drug labeling organized by therapeutic area. A COA is a measure used to assess how patients feel, function, or survive. COAs can be based on a report from a patient, a clinician, a non-clinician observer (e.g., caregiver), or can be performance-based (e.g., test of cognition or walking ability).

The COA Compendium covers all COA types including COAs that have been used in clinical trials to measure the patient’s experience (such as disease-related symptoms) and to support labeling claims. The table also identifies COAs that have been qualified for potential use in future drug development programs under CDER’s COA Drug Development Tool (DDT) Qualification Program. The updated COA Compendium includes the following columns:

COLUMNS ELEMENTS DESCRIPTION OF CONTENT
Column 1 Disease/Condition Lists disease or condition
Column 2 Concept Describes the concept that the COA assesses
Column 3 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)
Column 4 COA Context of Use Describes circumstance under which the outcomes of interest and the clinical outcome assessment have been used (i.e., labeled) or have been qualified (for qualified tools under CDER’s DDT Qualification program)
Column 5 Drug Name & Approval Date List the brand and generic name of approved drugs, date of approval for NME/BLA labeling, and the most recent approval date for efficacy supplements.
COLUMN
Column 1
ELEMENT
Disease/Condition
DESCRIPTION OF CONTENT
Lists disease or condition
COLUMN
Column 2
ELEMENT
Concept
DESCRIPTION OF CONTENT
Describes the concept that the COA assesses
COLUMN
Column 3
ELEMENT
COA Tool & Type
DESCRIPTION OF CONTENT
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)
COLUMN
Column 4
ELEMENT
COA Context of Use
DESCRIPTION OF CONTENT
Describes circumstance under which the outcomes of interest and the clinical outcome assessment have been used (i.e., labeled) or have been qualified (for qualified tools under CDER’s DDT Qualification program)
COLUMN
Column 5
ELEMENT
Drug Name & Approval Date
DESCRIPTION OF CONTENT
List the brand and generic name of approved drugs, date of approval for NME/BLA labeling, and the most recent approval date for efficacy supplements.

The pilot COA Compendium included COA information from the following sources: labeling of new molecular entity (NME) drugs and biological license application (BLA) drugs approved from 2003-2014, COA qualification projects currently in development but not yet qualified through the COA DDT Qualification program, and COAs that have been qualified through that program.

Why the COA Compendium?

The COA Compendium is designed to provide a consolidated tabular resource of COAs (e.g., those accepted by FDA in drug labeling) for drug developers and researchers. The COA Compendium is recommended as a starting point and communication tool with FDA clinical review divisions when considering inclusion of a COA(s) in clinical trials to support efficacy endpoints. This resource was developed per the request of relevant and important stakeholders and their desire for increased transparency from the FDA. The initial version was the pilot COA Compendium published for public comment in 2016 with the intention of having room for growth with future improvements and updates.

Many COAs have been in use for many years in drug development and are accepted by the FDA and relevant research communities. Existing instruments that have successfully supported previous regulatory decisions and were included in drug labeling generally would not be excluded from the COA Compendium unless there is a more appropriate replacement, so as not to potentially hinder or stall drug development. It is also important to consider the 2009 Patient Reported Outcomes (PRO) guidance for industry, which is a best practice guidance that describes one approach to PRO development; however, tools developed prior to this guidance or existing tools that may not have all the supportive documentation listed in the guidance may still be useful in drug development and can potentially support labeling claims provided they are well-defined and reliable measures. FDA continues to review all COAs intended for use as pre-specified efficacy endpoints to ensure that they are well-defined, reliable, and can support regulatory decision-making and labeling claims.

Updates to COA Compendium

The upcoming update of the COA Compendium will reflect recommendations made by the public through a public docket following the launch of the pilot COA Compendium in 2016. Additionally, to provide further transparency regarding the origin of each COA listed, the drug’s name and approval date corresponding to the labeling from which the COA was extracted will be included in the updated COA Compendium. Additional information can be found in FDA Clinical and COA Staff reviews, which are publicly available for many of these drugs on the internet in the Drugs@FDA database.

The COA Compendium update will not refer to COAs in development or under review within FDA’s COA DDT Qualification program, because these instruments have not received full FDA review and a positive qualification determination for their proposed context of use. Furthermore, they may not yet be publicly available. Ongoing qualification projects are listed separately on the public COA DDT Qualification website. This reflects the transparency provision of the 21st Century Cures Act enacted in December 2016. Henceforth, the only instruments related to the COA DDT Qualification Program that will be included in the COA Compendium update will be those that have been qualified for the intended context of use and made publicly available.

It is important to recognize that not all COAs used in drug development can undergo formal qualification process review. Qualification is not a requirement for a tool to be deemed well-defined and reliable for its proposed context of use in medical product development.

Although the COA Compendium is not an exhaustive resource, FDA aims to use this document as a communication tool with the public to clarify which COAs have been previously labeled and may serve as a starting point for consideration by drug developers to include as efficacy endpoints in their planned clinical trials. Drug sponsors are strongly encouraged to seek advice from the relevant Office of New Drug (OND) review division early and throughout drug development regarding the selection and implementation of clinical outcome assessments specific to their program. This is irrespective of whether the disease, condition, indication, claim, or clinical outcome assessment is included in the COA Compendium. See All Guidances for Drugs for a repository of guidance documents including disease specific guidances.

Future of the COA Compendium

As part of FDA’s ongoing patient-focused drug development efforts, the COA Compendium is intended to be a “living” resource. Therefore, the COA Compendium will be periodically updated such that information regarding COAs from the most recently approved drugs’ labeling as well as COAs recently qualified will be captured with each update. Because we recognize that continued discussion is needed regarding evolving scientific issues in the selection, development, and implementation of COAs in drug development, we continue to engage with relevant important stakeholders and scientific communities to facilitate modification or development of COAs to fulfill unmet needs in drug development.

Disclaimer: This publication reflects the views of the authors and should not be construed to represent the views, policies, or guidance of the FDA.

References available upon request.