The FDA wants drugs to be more targeted to the factors that affect patients’ lives in ways they care about.To achieve this goal, last month the FDA issued a Third Guidance Document on Patient-Centered Drug Development Commonly applied to a variety of clinical outcome assessments (COAs), including patient-reported outcomes (PRO), observer-reported outcomes (ObsRO), clinician-reported outcomes (ClinRO), and performance-based outcome (PerfO) measures.
- Patient-Reported Outcomes (PRO). The report comes directly from the patient. These measures can be used to assess symptoms (eg, pain intensity, shortness of breath), function, events, or other aspects of health from the patient’s perspective. PROs are typically collected through questionnaires, but are increasingly collected using digital health technologies (DHT).
- Observer-Reported Outcomes (ObsRO). Reports are from someone other than the patient or a health professional (eg, parent or caregiver) who has the opportunity to observe the patient in their daily lives. These measures are used when patients, such as young children, cannot reliably report or assess for themselves observable aspects (eg, signs, events, or behaviors) that are relevant to the patient’s health.
- Clinician-Reported Outcomes (ClinRO). Reports are from trained healthcare professionals using clinical judgment. This type of measurement is useful when the reporting of observable signs, behaviors, clinical events, or other manifestations associated with a disease or condition benefits from clinical judgment or expertise.
- Performance Outcome (PerfO). These measures are based on standardized tasks undertaken on the patient’s own initiative. Examples include a grip strength test or a six-minute walk distance (6MWD).
FDA recommends creating a conceptual model to represent the relationship between a patient’s specific health experience from a disease/condition and the measure of interest. Below is an example.
The context of how the measure is used is also important. Specifically:
- Using COAs: Clinical trial objectives and how COA will be used to support COA-based endpoints (eg, calculating mean COA score at 12 weeks)
- Target population: Include definitions of the disease or condition; participant selection criteria for clinical trials (eg, baseline symptom severity, patient demographics, comorbidities); and expected patient experiences or events during the trial (eg, some patients requiring assistive devices)
- Research Background: Design of clinical trials using COA, including types of comparison groups and whether those who provided responses or participated in COA tasks (patients, observers, clinicians, trained evaluators) were at treatment assignments and/or study visits)
- timing When to Conduct a COA Assessment 269
- COA implementation: Include where COA is collected (eg, inpatient hospital, clinic, home); how COA is collected (eg, DHT, paper forms); and by whom (eg, patient, study coordinator, investigator, parent/carer).
The FDA also provides a roadmap for selecting fit-for-purpose COAs for clinical trials.
Once the roadmap is followed, manufacturers need to justify the inclusion of COA in clinical trials based on 8 key pieces of evidence.
For more information on the roadmap and the specific evidence needed to reasonably include COA in clinical trials, please see the full FDA guidance here.
