03/08/2022

The Food and Drug Administration (FDA) released a guidance “Principles for Selecting, Developing, Modifying and Adapting Patient-Reported Outcome Instruments for Use in Medical Device Clinical Evaluation” in January 2022. This and a related guidance, “Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims” from December 2009 are part of an initiative by the Center for Devices and Radiological Health (CDRH) to incorporate the use of patient-reported outcomes (PROs) in evaluating medical devices. The guidance does not replace the Patient-Focused Drug Development (PFDD) guidance series.

Background:

What is a Patient Reported Outcome (PRO)?

A PRO is a clinical outcome assessment reported directly by the study participant. When electronic, it is commonly referred to as ePRO. PRO collect safety and effectiveness information that compliments other data sources. Examples of PRO include diaries and apps that collect symptoms data. They are particularly helpful in collecting information that is not very observable, but the participant is aware of, such as pain or quality of life. PRO are qualified tools under the MDDT program, meaning that there is scientific evidence to back the collected data as valid and reliable. This decision allows sponsors to use PRO data as part of the determination of safety and/or effectiveness of medical devices. Information from PRO can also provide evidence for benefit-risk assessments and device labeling.

Summary of the Guidance:

The following are best practices for use of PRO:

The key consideration a PRO is fit-for-purpose for the context of use (COU) is that the population where the validity evidence is gathered should be similar to the intended population in the protocol.
PRO should measure outcomes that are important to patients who have the condition the medical device treats, where possible. Since additional data is needed to support endpoints, it is also acceptable to use PRO to collect data important to the clinical trial.
PRO should be easily understood by the participants using them to aid in the collection of their informed responses.
The intended use of the PRO in the clinical trial should be well defined in the protocol and statistical analysis plan (SAP). This includes validity evidence.
Existing PRO can be used for the COU as is or modified as needed, which may reduce burden over developing new PRO. Any modifications should be documented. The PRO should demonstrate it is relevant and reliable for the COU.
Real word evidence outside clinical trials can be used as validity evidence for PRO to reduce burden on sponsors.
If validity evidence is generated in a clinical trial, the data collected via the PRO can be used for validation, but not safety and/or effectiveness. Data from future trials using that PRO can then be used to support safety and/or effectiveness.
Stakeholders are encouraged to collaborate in developing or modifying PRO used for regulatory submissions. This can lead to reduced bias and increased confidence in results FDA receives.

Sponsors are encouraged to submit PRO for qualification under the Medical Device Development Tools (MDDT) Program. Validated PRO that are collaboratively developed could provide greater quality, less biased data on outcomes that are important to patients who have the condition being studied. This guidance is the next step in supporting sponsors to fulfill the patient centric approach to investigational product development.