Clinical Outcome Assessment (COA): Frequently Asked Questions
1. What is the standard of evidence for COA qualification?
The measurement principles of content validity, reliability, construct validity, and ability to detect change apply to all types of COAs. The PRO guidance, while developed for patient-reported outcomes, provides many recommendations that are applicable to the development of all COAs, including clinician-reported outcome (ClinRO) assessments, observer-reported outcome (ObsRO) assessments, and performance outcome (PerfO) assessments. In addition, we often refer instrument developers to the ISPOR Task Force publications3 on content validity.
The COA Wheel and Spokes (PDF - 1MB) provided here identifies the key components of various stages of instrument development and the points at which qualification may occur.
2. What is FDA’s position on use of modern psychometric methods (e.g., Rasch analysis and Item Response Theory) and qualitative research in an iterative approach in early instrument development to inform and guide thinking about content validity?
FDA recognizes that different approaches to instrument development may be appropriate. FDA will consider different approaches to instrument development than what is described in the FDA PRO guidance.
FDA does not require the use of modern psychometric methods in early instrument development.
3. Is it necessary for an instrument to be qualified in order to use that instrument as the basis for a primary or secondary endpoint in a clinical trial?
No. A tool that is not formally qualified may still be acceptable for use, and should be discussed with the review division within an IND. We recommend discussing outcome assessments and endpoints with the FDA as early as possible.
4. Are drug sponsors (IND/NDA/BLA holders) required to use qualified instruments when they exist?
No. While we believe there are benefits of using a qualified tool, drug sponsors may select any well-defined and reliable tool(s) they believe will be best suited for their clinical trial(s). We encourage drug sponsors to discuss those decisions with the appropriate review division.
5. An instrument has been used to support claims in labeling. Does this mean that tool is qualified?
No. Only tools that have been reviewed through the formal Drug Development Tool (DDT) qualification process, about which a positive qualification decision has been made, are considered qualified. Tools that have not been formally qualified may still be acceptable for use and could support labeling claims.
6. Who participates in a COA Qualification Review Team (QRT)?
The COA QRT is comprised of representatives from across CDER and always includes representatives from the CDER’s Study Endpoints Team, the appropriate review division(s), and the Office of Biostatistics. All consultation and advice as well as final qualification decisions are made jointly with input from all QRT members. Representatives from other Centers within the Agency may also participate in QRT meetings when appropriate.
7. How do FDA and EMA work together on COA qualification?
A confidentiality agreement between the FDA and the EMA enables submitters of DDTs to engage with each agency in parallel. The FDA and EMA may discuss DDT submissions during regular conference calls, or on an ad hoc basis. In addition, FDA and EMA may participate in joint discussions with the submitters. While each agency makes its own qualification decisions and offers its own advice letters to submitters, we try to coordinate to the fullest extent possible.
8. Is the qualification route the only way a drug sponsor can interact with CDER’s Study Endpoints Team?
The Study Endpoints Team works in a consultative basis with the Review Divisions within CDER’s Office of New Drugs as well as with CBER and CDRH. For individual medical product development programs, the Study Endpoints Team is consulted on a case-by-case basis and provides advice to the primary review team, who issues the final comments/agreements to the drug sponsor.
The Study Endpoints Team manages the DDT qualification program and serves as the primary point of contact for the qualification program. As stated above, a drug sponsor may submit an instrument they have developed within their drug development program for CDER review under the DDT qualification program with the understanding that, if qualified, it will be available for public use.
9. What is the relationship between CDER’s and CDRH’s qualification programs?
CDRH has its own qualification process for Medical Device Development Tools, including COAs (include link to guidance). CDRH’s qualification process is similar to but operates independently from CDER’s. We encourage submitters to consider whether their COA may have applicability in medical device studies and, when appropriate, submit for qualification by CDRH.
10. Are there any other means of seeking Agency input on clinical outcome assessments before submission of an IND?
Yes. The Critical Path Innovations Meeting (CPIM) is another route for seeking early Agency input on clinical outcome assessments for a particular context of use outside of a specific drug development program. CPIMs do not result in any formal agreements. For more information, please refer to the CPIMs website: http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm395888.htm
11. When submitters enter the qualification process, they agree that the qualified DDT will be made publicly available. Does this mean that the DDT needs to be free of charge for public use?
No. CDER DDT qualification does not displace any intellectual property, copyrights, or ownership rights. Although qualified COA instruments must be made publicly available, this does not prevent the DDT owner from charging a reasonable fee for its use.
12. Are only newly developed COA instruments eligible for qualification?
No. The FDA will consider COA qualification program letters of intent for both new and existing measures.
13. How many development projects are currently in the COA DDT Qualification program?
Please see the COA current projects.