Clinical Outcome Assessment Qualification Program

A clinical outcome assessment (COA) directly or indirectly measures how patients feel or function and can be used to determine whether or not a drug has been demonstrated to provide a treatment benefit. COAs can also measure a safety benefit (e.g., fewer side effects) compared to other treatments. COA qualification is based on a review of the evidence to support the conclusion that the COA is a well-defined and reliable assessment for use in adequate and well-controlled investigations[1].  FDA qualifies a COA as a measure of a specific concept in a specific context of use.

The context of use for a COA qualification includes but is not limited to the following elements:

• Disease definition
• Patient population (e.g., age, disease severity, language, culture)
• Clinical trial design
• Role of the COA within the study objectives (e.g., primary or secondary role)
• Targeted labeling or promotional claims (i.e., proposed claim wording)

COAs considered for qualification include only those intended to support primary or secondary endpoints.  [Note that measures supporting exploratory endpoints or not used to assess the impact of treatment (e.g., for population stratification or for diagnostic purposes) are not eligible for COA qualification at this time.]

A COA is composed of a measure that produces a score plus clearly defined methods and instructions for administration or responding, a standard format for data collection, and well-documented methods for scoring, analysis, and interpretation of results in the targeted patient population.  COAs can measure treatment benefit directly or indirectly.  For COAs that measure treatment benefit indirectly, qualification also includes a review of the evidence that the concept assessed is an adequate replacement for how patients feel or function in daily life.

One of the distinguishing characteristics of COAs is who is doing the reporting of the outcome, i.e., the patient, a clinician, or another observer.  

Patient-reported outcome (PRO) assessment: A measurement based on a report that comes directly from the patient (i.e., study subject) about the status of particular aspects of or events related to a patient’s health condition.  PROs are recorded without amendment or interpretation of the patient’s response by a clinician or other observer. A PRO measurement can be recorded by the patient directly, or recorded by an interviewer provided that the interviewer records exactly the patient’s response.

Observer reported outcome (ObsRO) assessment:  An assessment that is determined by an observer who does not necessarily have a background of professional training that is relevant to the measurement being made, i.e., a parent, teacher or caregiver.  This type of assessment is often used when the patient is unable to self-report (e.g., infants, young children, cognitively incapacitated).  An ObsRO assessment should only be used in the reporting of observable concepts (e.g., signs or behaviors); ObsRO assessments cannot be validly used to directly assess symptoms (e.g., pain) or other unobservable concepts.

Clinician-reported outcome (ClinRO) assessment: An assessment that is determined by an observer with some recognized professional training that is relevant to the measurement being made.  ClinRO assessments cannot be validly used to directly assess symptoms (e.g., pain) or other unobservable concepts.  However, ClinRO assessments may include an evaluation and interpretation of the patient's condition based on clinical judgement.

For COAs, FDA qualification represents a conclusion that within the stated context of use, results of assessment can be relied upon to measure a specific concept and have a specific interpretation and application in drug development and regulatory decision-making and labeling.

[1] 21 CFR 314.126.