Patients Know Best: FDA Releases Draft Guidance on Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations

There is little or no debate that patients are the experts on their own diseases.  The FDA has promoted this concept for years and on September 24, 2019, the Center for Devices and Radiological Health (CDRH) and the Center for Biologics Evaluation and Research (CBER) issued a draft guidance document Patient Engagement in the Design and Conduct of Medical Device Clinical Investigations (“Guidance”). In developing this draft guidance, FDA considered discussions from its October 11-12, 2017 Patient Engagement Advisory Committee (PEAC) meeting and the pursuant public docket. This meeting sought feedback from targeted questions about patient engagement and its potential impact on medical device clinical investigations.  The questions included:

• What opportunities and barriers (perceived or real) might patients and patient groups experience when attempting to collaborate with industry on the design of clinical trials?
• In general, what aspects of the trial design contribute to enrollment and participant retention challenges?

The meeting summary stated, “Studies have shown patient engagement at the design stage led to increased study enrollment rates, improved retention, and the addition of relevant patient outcomes.”

The draft guidance defines “patient engagement” as intentional, meaningful interactions with patients that provide for mutual learning and effective collaborations. In developing this draft guidance, FDA intended to:

1. Help sponsors understand how patient engagement can be used to gather perspective, experience, and other relevant information from patient advisors to improve the design and conduct of medical device clinical investigations;
2. Highlight the benefits of early engagement with patient advisors;
3. Clarify which patient engagement activities are or are not under FDA purview; and
4. Address questions and misconceptions about collecting and submitting patient engagement information to FDA.

FDA is careful to delineate those it considers patients, study/research participants, and patient advisors:

• Patients – individuals with or at risk of a specific disease or health condition, whether or not they currently receive therapy to prevent or treat that disease/condition;
• Study/research participants – individuals who are or become a participant in research; and
• Patient advisors – individuals who have experience living with a disease or condition and can serve in advisory or consultative capacity to improve clinical investigation design and conduct, but who are not study/research participants themselves.

FDA believes medical device clinical investigations designed with early input from patient advisors (including those who may have participated in previous clinical investigations of the same disease/condition or similar device-type or who were screened for but ultimately did not meet or choose to participate in a clinical study, healthy individuals who may be potential non-therapeutic device users, or caregivers of patients) could lead to quicker study/research participant recruitment, enrollment and study completion, improved study/research participant commitment and compliance, less protocol revisions, streamlined data collection, and more relevant data on outcomes that are important to patients. Patient advisors who are well-versed about clinical investigations, the various approaches to managing the subject disease/condition and how a device may work may feel more empowered to voice their perspective in engagement activities. They may provide recommendations on how a study is designed and conducted and improve patient experience during the investigation and the relevance, quality, and impact of patient results.

Some patient engagement activities that may lead to improvements of the design and conduct of clinical investigations include input on how to improve the informed consent to improve patient understanding of information, flexible options for follow-up visits and data collection techniques, discussions with patient advisors on which potential endpoints are clinical meaningful, and work with patient advisors to understand their perception of benefit-risk tradeoffs.

Effective patient engagement can mitigate common challenges during the course of clinical investigations such as study/research participant enrollment and retention (including lengthy follow-ups and frequent visits) and how to broaden inclusion of the people living with the disease/condition to participate in the clinical investigation. If left unaddressed, these challenges can contribute to increased time and cost to sponsors, increased risk to participants, and delays in access to medical devices. Therefore, patient advisors should be engaged during the early phases of the clinical investigation such as during the development of the clinical protocol and informed consent. For sponsors interested in receiving FDA feedback on patient engagement strategies and plans, FDA encourages submitting an information meeting request.

It should be noted that because patient advisors tend to operate in a consultative or advisory capacity, FDA does not generally consider patient engagement activities with patient advisors to constitute research or an activity subject to FDA’s regulations. On the other hand, interactions between study/research participants and investigators are generally in the context of a clinical investigation subject to FDA’s regulations.

This guidance continues to build on other Agency efforts to engage with patients. CDRH launched its Patient Preference Initiative in September 2013 to assess patient valuations of benefit and risk related to specific devices to help inform product review. In 2012, as part of PDUFA V, the Center for Drug Evaluation and Research (CDER) established its Patient Focused Drug Development meetings program and held 26 meetings with patient groups from various diseases to hear directly from patients. Currently, the FDA supports Externally-Led Patient Focused Drug Development meetings sponsored by patient advocacy organizations.

As a part of CDRH’s ongoing efforts to encourage patient engagement in clinical studies, CDRH developed the Patient Reported Outcome (PRO) Compendium as a part of its 2016-2017 strategic priorities and ultimately issued a report on the Value and Use of PROs in Assessing Effects of Medical Devices (link). The PRO Compendium lists some, but not all, of the PROs that can be used and reported in medical device pre-market clinical studies submitted to CDRH (link). The purpose of the PRO Compendium is to serve as case examples for sponsors in particular disease-areas on PROs that have successfully been used in approved or cleared device submissions. CDRH continues to encourage sponsors interested in using a PRO in a clinical study to engage with them early through a pre-submissions meeting.

We are hopeful that this draft guidance will continue to encourage patient engagement at every phase of device development and improve efficiency and quality in the design and conduct of clinical investigations which in turn will lead to earlier patient access to medical devices.

*Not admitted to the Bar. Work supervised by the Firm pending Bar admission.