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U.S. Department of Health and Human Services


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Clinical Outcome Assessment (COA): Frequently Asked Questions


  1. What is a COA?
    A COA is any assessment that may be influenced by human choices, judgment, or motivation and may provide either direct or indirect evidence of treatment benefit. The four types of COAs are patient-reported outcome (PRO) measures, clinician-reported outcome (ClinRO) measures, observer-reported outcome (ObsRO) measures, and performance outcome measures. 
  2. What is the difference between a COA and a biomarker?
    A biomarker is a patient characteristic that is measured as an indicator of biologic processes; normal, pathogenic, or response to a therapeutic intervention. Unlike biomarkers that rely completely on an automated process or algorithm, COAs depend on the implementation, interpretation, and reporting from a patient, a clinician, or an observer. Patient characteristics can be measured by COAs, which may be significantly influenced by rater judgment or patient motivation and effort (e.g., a measure of a patient’s voluntary performance of the 6-minute walk test).
  3. What is COA qualification?
    Qualification is a regulatory conclusion that within the stated COU, the results of assessment with a COA can be relied upon to have a specific interpretation and application in drug development and regulatory decision-making. COAs considered for qualification are limited to those that are ultimately intended for use as primary or secondary endpoints in clinical trials.

    The COU describes the way the COA is to be used and the purpose of the use. A complete COU statement should describe fully the circumstances under which the COA is qualified and the boundaries within which the available data adequately support use of the COA (See Roadmap (PDF - 463KB) and Wheel and Spokes Diagram (PDF - 1MB)).

    The COU could include use as an exploratory endpoint, or effectiveness endpoint to support claims (i.e., primary, co-primary, or secondary endpoint) A COA may be qualified as an exploratory endpoint when there is sufficient evidence and documentation that the content of the COA is appropriate and there has been cross-sectional evaluation of construct validity and score reliability. Once the longitudinal measurement properties and an understanding of interpretation during longitudinal treatment trials are established, then the COA may be qualified for use as an effectiveness endpoint for regulatory purposes.

  4. 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 publications on content validity.

    The development process for COAs in the qualification process follows the same good measurement principles for development of an instrument submitted as part of an IND, NDA, or BLA. 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.