Importance to FDA

FDA increasingly looks to patients to understand how patients describe their health status, because patients are the experts in living with their disease or condition. Input from patients or their caregivers about what is important can then be used to select or develop tools to measure what matters most to patients. Clinical outcome assessments (COAs) may capture outcomes that are important to patients, such as how they feel or function or how long they survive. They play a central role in ensuring that what matters to patients is factored into regulatory decision-making. The 21st Century Cures Act (Cures Act, Public Law 114-225), defines clinical outcome assessment as ‘‘(A) a measurement of a patient’s symptoms, overall mental state, or the effects of a disease or condition on how the patient functions; and (B) includes a patient-reported outcome.”

There are different types of COAs. While each COA should focus on the patient, they provide a different perspective on a patient's health status.

• Patient-reported outcomes (PROs): measures of a patient’s health status as reported directly from the patient without added interpretation by a healthcare worker or anyone else, such as a pain scale.
• Clinician-reported outcomes: reports coming from a trained healthcare professional regarding their interpretation of signs or behaviors that can be observed related to a patient's disease or condition.
• Observer-reported outcomes: assessments of observable signs, events, or behaviors related to a patient's health condition as reported by individuals who observe the patient in daily life, like parents or caregivers.
• Performance outcome assessments: measurements collected when a patient is asked to complete a well-defined, repeatable, and standardized task, such as reading an eye chart or performing a walking test.

Strengthening FDA’s ability to use patient-focused methodology to inform regulatory decision-making is specified in FDA user fee agreements for medical product development and the Cures Act. FDA increased knowledge and experience by performing research that informs the development and refinement of COA measures to support regulatory decision-making.

Examples

FDA advances the development of COAs, including PROs, through the following:

• Implementing a pilot grant research program supporting the development of publicly available core data sets of COAs and their related endpoints for specific disease indications, including PRO measures for migraine, and observer-reported outcome measures for acute pain in infants and young children. The program also supports the development of a core set of COAs (potentially including both performance outcome measures and PRO measures) to assess the full range of physical function severity with potential generalizability across a range of conditions.
• Working with academia to evaluate whether previously developed PRO measures perform differently in people living with heart failure from different demographic groups (such as racial and ethnic groups, gender groups, children, and literacy levels). FDA is exploring how these instruments may be modified to adequately capture symptoms in diverse patient groups. These PRO measures could be used to inform pre-market approvals and postmarket surveillance efforts.
• Collaborating with professional organizations to develop novel PRO measures that measure symptoms patients may experience following placement of artificial lenses. Collecting this information in a structured way is useful for clinical studies on artificial implantable lenses.
• Supporting the study of severe mental illness and suicidal ideation and behavior by supplementing existing FDA Sentinel System data with PRO measures. PRO measures are collected through validated depression, anxiety, alcohol use, and drug use surveys used in mental health specialty and primary care clinics. The PRO measures are used to develop models to predict suicidal behaviors for use in future observational research and trials.