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What is the Clinical Outcome Assessment Qualification Process?

May 13, 2016 | Jacquie Powell, PhD, Clinical Research Scientist II | Regulatory Affairs, Drug Development Consulting

Clinical Outcome Assessments (COAs) can be qualified through the COA Qualification Program, one of the Drug Development Tools (DDT) Qualification Programs developed by the Center for Drug Evaluation and Research (CDER) at the FDA.

In a previous post, we discussed that COAs currently under development, as well as those relied upon in recent drug approvals, have been included in the pilot COA compendium. In this post, we will discuss the COA Qualification Program – stay tuned for an upcoming post on the Biomarker Qualification Program, as well.

Outside of the DDT Qualification Program, COAs are generated on a case‑by‑case basis and knowledge of their use is only made available to the public when the investigational drugs they are used to evaluate receive market approval. As you’ll see, an integral part of the COA Qualification Program is its emphasis on transparency.

This blog post describes 6 general steps one should follow in order to develop a COA and get it qualified by FDA.

Step #1: Lay the groundwork

As a starting point, a COA developer needs to identify 2 important things, with future labeling claims in mind.

  • Targeted concept of interest (COI) – What can be measured and how does it relate to clinical improvement? To identify a COI and effectively conceptualize what can be considered a treatment benefit, it is important to understand the natural history of the disease or condition and the subpopulations of patients afflicted. The COI is what a COA measures.
  • Targeted context of use (COU) – What is appropriate for patients? What is feasible for healthcare providers? To identify a reasonable COU it is important to have an understanding of how patient subpopulations interact with the healthcare environment. The COU is who the COA is measured in.

In the process of considering the COI and COU, the drug‑development team may come across a suitable pre‑existing COA (many of which are now searchable through the pilot COA compendium). Otherwise, it may be necessary to begin the COA development process de novo.

Step #2: Create the COA

This is the creative part of the COA development process! With a strong understanding of both the disease state and the patients of interest, this is the time to create a tool that measures treatment benefit.

The process used to develop (or modify) a COA invariably differs by creator but should involve deciding on the most appropriate reporter (patients, clinicians, or others, as described in a previous post) and defining the optimal scoring system, appropriate units of delineation, and associated descriptors. This process may or may not involve consultation with key opinion leaders.

By the end of this stage, COAs should be fully developed instruments with scoring rules designed to measure treatment benefit.

Steps #3-4: Test COA validity using a cross-sectional evaluation and submit to CDER

Once a COA has been developed it can then be tested for validity in a cross section of stable patients, where relative disease severity has already been established. If the COA is capable of detecting differences in this type of patient population, COA developers can consider submitting their COA to CDER for qualification.

CDER approval at this stage allows for COA use in exploratory studies and warrants mention in the publically‑available COA compendium as an exploratory endpoint. COAs at this stage of development are still considered under investigation and are not automatically approved to be used as (or in support of) primary or secondary endpoint measures of effectiveness.


Steps #5-6: Examine COA with a longitudinal evaluation and make final submission to CDER

By continuing to use the COA as an exploratory variable, its validity should continue to be examined over time (longitudinally) in a well-defined patient population. Once the measurement properties of the COA are evaluated over time, its usefulness as a measure of clinical improvement can be better delineated.

At this point, CDER will perform a second review to consider the suitability of the COA as a primary or secondary measure of effectiveness. If the COA is favorably reviewed, its status will be updated in the COA compendium and a guidance will be issued. Success!!

Here is a recap of the 6 main steps in the COA qualification process:
Things to consider

All drug sponsors are strongly encouraged by the FDA to consult with the relevant Office of New Drug (OND) review division early in the drug‑development process to discuss the selection, use, or design of a COA. Also, given the significant amount of time and effort involved in creating and validating a COA, some COAs may be protected under proprietary rights and a royalty fee may be required for their use.

Keep in mind that a favorable review of a COA for one drug‑development program does not ensure its suitability for use in another drug‑development program; the COA must be used in a similar COU in order to be deemed appropriate.

Let us know what you think

Are you thinking of developing a COA to use in your clinical development program? IMPACT has experienced regulatory affairs professionals ready to consult with you. If you would like to discuss your specific needs, please contact us or give IMPACT a call today at (919) 899-9248.

Sharing image courtesy of pakorn from

Category: Regulatory Affairs, Drug Development Consulting
Keywords: Clinical outcomes assessment, COA, FDA, Drug Development Tools Qualification Programs, CDER

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