Help Industry With Clinical Trial Design

Clinical Outcome Assessments

Clinical outcome assessments (COAs) include any assessment that may be influenced by human choices, judgment, or motivation. Since many rare diseases do not have clear biomarkers that can measure the effectiveness and benefits of a therapy, choosing or developing the right COA tool can mean the difference between achieving FDA approval and denial. Providing Sponsors with information from registries, natural history studies, and patient preference studies can ensure the COA that is developed or chosen measures benefits reliably and reflects the desires of the patient population. 

  • There are 4 types of COAs:
    • Patient-reported outcomes (PRO) are used when the benefit of interest can only be observed or felt by the patient, for example symptom severity or effect on overall feelings of well being. 
    • Clinician-reported outcomes (ClinRO) are used when the benefit of interest can be observed by a clinician and requires clinical interpretation or judgement.
    • Observer-reported outcomes (ObsRO) are used when the benefit of interest can only be observed outside the clinical setting and the patient is not able to self-report.
    • Performance outcomes (PerfO) are used if the benefit of interest requires observation of a patient’s function while performing a set of defined tasks in the clinical setting.
  • Clinical studies may use a combination of COAs and may also use clinical biomarkers.
  • Sponsors may use or modify established COAs or develop new ones.
  • The FDA Clinical Outcome Assessment (COA) Qualification Program works with requesters to develop well defined and reliable COAs that integrate the patient voice into therapy development with endpoints that are meaningful to patients and responsive to treatment.
  • Timing of different COAs usage may be determined in part by natural history studies.
  • Some of the assessment time points may be able to be performed remotely, while others may need to be performed at participating centers. The burden of travel experienced by the target participant population may influence these decisions.
  • Learn more about COAs using the following resources:
    • Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims (2009) is an FDA Guidance for Industry that reviews methods used by the Food and Drug Administration to evaluate PRO instruments for claims in labeling of the therapy. 
    • Clinical Outcome Assessment Compendium (updated periodically) is part of FDA’s efforts to foster patient-focused therapy development. The Compendium is a table that describes available COAs and how they can be used in clinical trials. This table can be used to identify if there is a COA available for clinical trials for a specific condition.
    • The Science of Clinical Outcome Assessment (COA) in Medical Product Development – An Intensive Online Educational Series   (2018 launch) is an online course offered by the University of Maryland School of Pharmacy to introduce COA fundamentals for those working in the area of therapy development. Learning goals include understanding the different types of clinical outcome measures and their appropriate use. You will also learn how to apply the principles of the FDA Roadmap to Patient-Focused Outcome Measurement and COA Framework to assess measurement strategies.
    • Amyotrophic Lateral Sclerosis (ALS): Developing Drugs for Treatment Guidance for Industry (2019) is an FDA Guidance for Industry that although specific to ALS, includes information about COAs that is applicable to many rare diseases.