The US Food and Drug Administration wants drugs to be more targeted at the factors that affect patients’ lives in a way that they care about. To achieve this goal, last month the FDA released third guiding document for patient-centered drug development commonly applied to a variety of clinical outcome measures (COA), including patient-reported outcome (PRO), observer-reported outcome (ObsRO), clinician-reported outcome (ClinRO), and measures of outcome-based outcome (PerfO).
- Patient Reported Outcomes (PRO). Reports come directly from the patient. These scores are useful for assessing symptoms (eg, pain intensity, dyspnea), functioning, events, or other aspects of health from the patient’s point of view. Often PROs are collected through questionnaires, but increasingly they are collected using digital health technologies (DHT).
- Observer Reported Results (ObsRO). Reports come from someone other than the patient or health care provider (such as a parent or guardian) who has the opportunity to observe the patient in daily life. These measures are used when patients, such as young children, cannot reliably report themselves or evaluate observable aspects related to patients’ health (eg, signs, events, or behaviors).
- Clinician Reported Results (ClinRO). Reports come from a trained healthcare professional using clinical judgment. This type of measurement is useful when reports of observed signs, behaviors, clinical events, or other manifestations associated with a disease or condition are based on clinical judgment or experience.
- Performance Result (PerfO). These measures are based on standard tasks actively performed by the patient. Examples include the grip strength test or the six-minute walk distance (6MWD).
The Food and Drug Administration recommends that a conceptual model be created to represent how a particular patient’s health status associated with their disease/condition relates to the metrics of interest. An example is below.
The context of how measures are used is also important. Specifically:
- Using a Certificate of Authenticity: Clinical trial objectives and how COA will be used to support COA-based endpoints (e.g. calculating an average COA score after 12 weeks)
- The target audience: Including the definition of the disease or condition; criteria for selecting participants for clinical trials (eg, baseline symptom severity, patient demographics, comorbidities); and anticipated patient experiences or events during the study (eg, that some patients will require assistive devices)
- Research context: Design of the clinical study in which COA will be used, including the type of comparison group and whether individuals providing responses or participating in COA tasks (patients, observers, clinicians, trained assessors) are masked in relation to treatment assignment and/or study visit)
- Timing when the assessment(s) of the certificate of authenticity is carried out269
- Implementation of the certificate of authenticity: Including the place where the certificate of authenticity was collected (for example, hospital, clinic, home); how the certificate of authenticity will be collected (eg DHT, paper form); and by whom (eg, patient, study coordinator, investigator, parent/guardian).
The FDA also provides a roadmap for selecting suitable COAs for use in clinical trials.
Once the roadmap is completed, manufacturers must justify the inclusion of a COA in a clinical trial based on 8 key pieces of evidence.
For more information on the roadmap and specific evidence needed to rationalize the inclusion of a COA in a clinical trial, please see the full FDA guidance. here.