By James E. Valentine* & Josephine M. Torrente –
During FDA’s April 1, 2015 public workshop on clinical outcome assessments (COAs), in a presentation on the future of COA development and utilization in drug development programs, officials from CDER’s Study Endpoints and Labeling Development (SEALD) staff announced the development of a compendium of COA tools. A clinical outcome assessment (COA) measures patients’ symptoms, overall mental state, or the effects of a disease or condition on how the patients function. There are four types of COA measures:
- Patient-reported outcome (PRO) measures
- Clinician-reported outcome (ClinRO) measures
- Observer-reported outcome (ObsRO) measures
- Performance outcome (PerfO) measures
The Compendium’s Two Stages of Development
The COA compendium will be developed in two stages. In Stage 1, or the pilot stage, the compendium will consist of (1) qualified tools, (2) ongoing qualification programs, and (3) previously labeled COAs (from new molecular entity labeling approved 2003 and later). The compendium would be published a table that can be accessed through the FDA website, organized by therapeutic area and disease/condition.
The measurement tools that will be in the Stage 1 compendium consist of those that have arisen under FDA’s two current pathways for review and use of COAs in drug development. The first is the traditional way, which is within an individual drug development program under an IND. These tools, when found acceptable in the course of drug development, can result in labeling claims. The second pathway for use of COAs is through a relatively new process, the Drug Development Tool (DDT) qualification program, which is a formal way to qualify instruments outside of an individual drug development program. These “qualified” COAs are published in the Federal Register and are available publically for use in drug development programs. To date, there is only one qualified clinical outcome assessment, a PRO that is published here.
Stage 2 would expand the compendium, but exactly what information would be included has not been determined. Future expansion may include an expanded scope (e.g., COAs from efficacy supplements), as well as identify gaps in available measurements tools (e.g., concepts highlighted as important in Patient-Focused Drug Development meetings but for which no tool exists).
Goals of the Compendium & Next Steps
Because it is unrealistic to qualify all COAs, CDER hopes creating a public list of COAs used to support labeling claims would be useful to increase their development and use in drug development programs. The compendium would essentially serve as a list of “potentially acceptable endpoints” that could support labeling claims, as well as encourage development COAs more generally. However, the compendium would not include detail on endpoints so that sponsors will still need to discuss with FDA the selection and design of endpoints in clinical trials.
CDER announced it plans to publish a Federal Register Notice in September 2015 in order to gather comments on the proposed compendium (and associated guidance to describe the compendium), with the roll-out of Stage 1 of the compendium following the notice-and-comment period.
Note: This public workshop on COAs was held to satisfy FDA’s Advancing Development of Patient-Reported Outcomes (PROs) and Other Endpoint Assessment Tools commitment in PDUFA V which, in part, committed FDA to “hold a public meeting to discuss FDA’s qualification standards for drug development tools, new measurement theory, and implications for multi-national trials.”
*Admitted only in Maryland. Work supervised by the Firm while D.C. application pending.