By McKenzie E. Cato* & Allyson B. Mullen –
In May 2015, FDA issued a draft guidance addressing how FDA might consider patient preference information (PPI) in review of premarket approval applications (PMA), humanitarian device exemption (HDE) applications, and de novo requests; the types of data and information to include in a submission; and how to incorporate PPI into a product’s labeling (see our previous post here). On August 24, 2016, FDA finalized this guidance, titled “Patient Preference Information – Voluntary Submission, Review in Premarket Approval Applications, Humanitarian Device Exemption Applications, and De Novo Requests, and Inclusion in Decision Summaries and Device Labeling.”
This guidance is the result of a Patient Preference Initiative launched by FDA in 2013 to engage patients in medical device regulatory processes. Additionally, FDA created the first-ever Patient Engagement Advisory Committee in September 2015, following the release of the draft guidance. The Committee is designed to provide advice to the Commissioner on a variety of patient-related topics regarding medical devices, including patient preference study design, benefit-risk determinations, and device labeling.
The objectives of this guidance are to:
- Encourage the submission of PPI by sponsors or stakeholders and to aid in FDA decision making;
- Outline recommended methods for patient preference studies;
- Provide recommendations for collecting and submitting PPI to FDA; and
- Discuss FDA’s inclusion of PPI in its decision summaries and provide recommendations for the inclusion of PPI in device labeling.
The guidance states that PPI may not be relevant or appropriate for all devices, and clarifies that the guidance “does not change the review standards for PMAs, HDE applications, or de novo requests” and does not “create any extra burden on sponsors of premarket submissions.” The submission of PPI is voluntary. This guidance is meant to provide recommendations relating to the collection of PPI which may be submitted for consideration as part of FDA’s benefit-risk determination.
There are several significant changes and additions incorporated in the final guidance, which are outlined below.
The final guidance distinguishes the different ways patients can provide input to FDA. “Patient input” includes anecdotal comments (e.g., testimony at Advisory Committee meetings), patient opinions expressed publicly (e.g., through social media), qualitative responses to surveys, and quantitative measurements of patient-reported outcomes. “Patient perspectives” include patients’ experiences with a disease or condition and its management. PPI, the subject of this guidance, is a type of patient perspective. The guidance states that PPI is particularly useful when patient decisions are “preference sensitive.” Treatment decisions are “preference sensitive” when (1) there is no clinically superior option for all patients; (2) evidence supporting one treatment option is uncertain or variable; and/or (3) patients’ views about the most important benefits and risks vary within a population or differ from those of healthcare professionals.
The final guidance includes a new section describing how patient input can impact decision making. The guidance explains that patient input can be useful for improving understanding of a disease or condition, defining design inputs to meet patient needs, and assessing the outcomes that are most important to patients. This section references a new appendix and flowchart with suggestions for how sponsors and FDA can incorporate PPI and other patient input into the total product lifecycle (i.e., nonclinical, clinical, and postmarket stages). The appendix includes a lengthy discussion of how PPI can be used in the earliest stages of development (the “discovery and ideation phase”) to inform study design, product development, and ultimately, FDA’s assessment of product benefit versus risk.
The draft guidance did not contemplate the use of PPI in the public decision summaries that FDA posts on its website when it approves a PMA, approves an HDE application, or grants a de novo request; it only discussed the inclusion of PPI in device labeling. The final guidance references the use of PPI in decision summaries throughout the document. The guidance notes that “[i]nclusion of PPI in FDA’s public decision summaries can be helpful to healthcare professionals and patients in making healthcare decisions involving difficult benefit-risk tradeoffs or novel treatments.” This information also has the potential to be useful for sponsors in deciding whether and how to incorporate PPI in their premarket applications.
The draft guidance included, as an appendix, proposed modifications to the “Worksheet for Benefit-Risk Determinations” from FDA’s Benefit-Risk Guidance to incorporate PPI. This guidance was also finalized on August 24. While the proposed modifications in the draft patient preference guidance were not adopted exactly as written, the Worksheet in the final Benefit-Risk Guidance now includes an extensive new section on “patient perspectives,” which has many questions related to PPI.
The final guidance appears to contemplate use of PPI throughout the total product lifecycle from device initiation through approval and beyond. We assume that FDA will begin utilizing the guidance and revised worksheets now that they are finalized. However, it will be assessing devices that were conceived and designed long before initiation of the Patient Preference Initiative. Neither the final guidance nor the worksheet address how much weight FDA will place on PPI during the premarket review process and whether it is possible for PPI to outweigh traditional benefit-risk factors, on which manufacturers may have relied when designing and developing a device years before it is ready for submission to the Agency. That is, if a device undergoing premarket review meets traditional benefit-risk, why would a company need to consider PPI? According to the guidance, submission of PPI is voluntary, and thus, it should add to rather than modify the traditional factors considered in the benefit-risk analysis.
Also, because this guidance is part of a broader initiative by FDA to include patient input in medical device regulatory processes, it will be interesting to see how this initiative incorporates patient preference into other guidance documents or FDA procedures moving forward. For example, for now, PPI has not been contemplated in the 510(k) process, however, FDA could attempt to incorporate it into that review process as well for at least some 510(k)s.
* Law Clerk