Dear Commissioner Hahn:
FasterCures appreciates the opportunity to provide comments to the Food and Drug Adminstration’s (FDA’s) request for comments on the reauthorization of the Medical Device User Fee Act (MDUFA). We applaud the significant progress previous MDUFA commitments have supported, including advances inintegrating patient perspectives into device development and review, advancing the use of real world evidence to enhance device development, and exploring innovative paradigms for regulating new tools for digital health. We look forward to contributing to the next round of action to ensure patients have access to new devices in a timely manner and we build a stronger, patient-centered medical device ecosystem for all.
FasterCures, a center of the Milken Institute, is driven by a singular goal: to save lives by speeding scientific advancements to all patients. With an independent voice, FasterCures is working to build a system that is effective, efficient, and driven by a clear vision: working with our partners to build a patient-centric system where science is accelerated, unnecessary barriers are overcome, and lifesaving and life-enhancing treatments get to those who need them as rapidly as possible.
FasterCures’ comments below focus on three priority areas:
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Increasing Diversity in Clinical Trials and Patient Engagement;
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Ensuring the Promise of Digital Health is Realized; and
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Enhancing Transparency and Continuing Progress Driven by COVID-19.
Increasing Diversity in Clinical Trials and Patient Engagement
Notwithstanding the attention paid to diversity in the last decade, a critical need still exists to increase enrollment of underrepresented populations, including racial and ethnic minorities, in clinical trials for high-risk medical devices. With meaningful subgroup analyses for both safety and effectiveness conducted and reported, patients can better understand whether a device is right for them, and can make better informed decisions for their care as specific information on relevant outcomes and risks are known.
But meaningful subgroup analyses require sufficient numbers of trial participants within racial and ethnic minority groups, as well as age and gender groups. And the value of this data only accrues to patients when these analyses are conducted and reported. A 2018 study looking at pivot trials for the 22 devices publicly reviewed at an FDA Advisory Committee meeting between 2014 and 2017 found that “[o]nly 3 (14%) of the devices provided subgroup analyses for both effectiveness and safety or both sensitivity and selectivity for gender, race, and age. However, 55% of the devices reported both of those subgroup analyses for at least 1 of the 3 subgroups. Whether analyses were reported or not, the number of patients in most subgroups was too small to draw meaningful conclusions. Subgroup analyses were more likely to be reported to the FDA's Advisory Committees than in the FDA's public reviews or labeling.”
We appreciate FDA’s initiatives on clinical trial diversity including its guidances on “Collection of Race and Ethnicity Data in Clinical Trials”, and “Evaluation and Reporting of Age-, Race-, and Ethnicity-Specific Data in Medical Device Clinical Studies” which discussed considering relevant age, race, ethnicity, and associated covariates when designing clinical trials, recommended analyses of study subgroup data, and outlined the Agency’s expectations for reporting.
More can be done to increase diversity in device trials, and we recommend FDA build on these efforts and consider ways to further define agency expectations, share best practices and tools–both across the agency and externally--, and drive the development of innovative approaches, including the use of mobile technologies, to increase racial and ethnic diversity in clinical trials, as appropriate. This may include:
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Public meetings and guidance specific to best practices, successful approaches to increasing racial and ethnic diversity, and lessons learned
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Pilots and/or grants, including to non-traditional grantees (e.g., community based organizations), for innovative approaches for outreach and education, enrollment, and retention for clinical trials for racial and ethnic minority populations
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Expected early consultation with the agency to discuss a sponsor’s diversity plan (and patient engagement plan to inform the diversity plan)
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A repository of publicly available tools on FDA’s website as a resource for stakeholders and/or other ways to share information learned from pilots and successful (and unsuccessful) approaches
This premise of increasing diversity applies equally to patient engagement, where it is essential to have as diverse and representative a voice as possible, defined by the aim of the engagement. In addition to hearing from a diverse set of patients–from different ages, racial and ethnic groups, genders, disease severity, or stage of disease – it is important for the agency to solicit and incorporate into its decision-making patient input from diverse sources and collection methods.
We applaud FDA’s significant work on advancing the development and use of patient preference information, including holding a September 2020 public meeting on Using Patient Preference Information in Medical Device Regulatory Decisions: Benefit-Risk and Beyond, and patient reported outcomes, including issuing a recent draft guidance on Principles for Selecting, Developing, Modifying, and Adapting Patient-Reported Outcome Instruments for Use in Medical Device Evaluation. We encourage the agency to continue to (and encourage sponsors to) proactively look to sources of patient input beyond these tools. Patient input comes in many forms, including discussions held in focus groups or public hearings, health data generated by patient use of digital apps and remote tools, patient registries, natural history studies, and others. Patient input from these and other sources and methods can allow a more robust and full-rounded understanding of patients’ experiences, preferences, desires, and needs, and can capture input from a more diverse set of patients.
We also ask FDA to consider how the agency can ensure patients, industry, and the broader public understand the impact of patient engagement and the use of patient input in device development and regulatory decision - making. It is important to patients and patient organizations to understand the impact of their efforts, so that limited resources can be directed to impactful initiatives and funneled away from work that cannot or does not get used. Whether this information makes it into a product label or into a product approval review summary, FDA should consider creating a publicly available set of examples as a resource for patients, manufacturers, and other stakeholders, and other ways to share inf ormation on what and how different types of patient input was used in device development and regulatory decision - making.
Ensuring the Promise of Digital Health Tools is Realized
The explosion of digital health tools is revolutionizing the healthcare industry. In order to harness the collective power of these tools, stay ahead of trends and innovation, and ensure the promise of digital health is safely realized for patients, FDA must lead the way. As such, we support additional resources for the agency to achieve this goal and continue to build its expertise and capacity to understand and review these tools.
FasterCures is encouraged by the creation of the FDA’s Digital Health Center of Excellence as a way to coordinate and streamline the understanding of, use, and review of digital health tools, and we greatl y appreciate the agency offering numerous opportunities for external stakeholders to hear about, discuss, and comment on the development of the Center . Below we touch on a few of the Center’s current a reas of focus.
First, with respect to artificial intelligence and machine learning, we encourage the agency to take a proactive approach to understanding and minimizing bias in these tools. We applaud the agency for bringing this topic to the Patient Engagement Advisory Committee recently 7 , and discussing the issue of training and validation data representing a sufficiently diverse set of patients, including demographic considerations, race and ethnicity, and age. We encourage FDA to continue to advan ce this work and meaningfully engage patients throughout its development so that all of regulated AI/machine learning innovations can perform their best in all populations for which the intervention is intended.
Second, FasterCures believes that clarity and transparency is critical for wearable and patient - generated data, and arguably for all digital health. Specifically, given the newness of these technologies and the overlap or similarities to wellness tools, patients and other stakeholders need to unde rstand exactly what is “digital health”, which wearables are regulated and which are not, what is the difference between a wellness tool and a medical device, how is their data protected and what data is actionable and/or used and for what purposes. Creati ng specific public - facing definitions and explanations to these questions and more can go a long way in building trust and reducing misunderstandings about these tools. Again, meaningful engagement with a diverse group of patients is critical to identifyin g needs and communicating effectively with patients, other stakeholders, and the public at large.
And finally, digital tools hold great promise to build a more nuanced and robust understanding of each patient’s experience through their use in clinical st udies and as real world evidence, as well as reduce the clinical trial burden that can allow harder - to - reach volunteers to participate and complete clinical trial s . We support FDA’s work to advance the understanding and use of fit - for - purpose real world ev idence in the regulatory context, and ensure that clinical studies minimize the burden to participants, allow for greater patient - generated data, and increase opportunities for a more diverse participant pool to join and complete clinical trials. In additi on, we encourage the Agency to explore the potential of using mobile health technologies to return study progress information and study results.
Enhancing Transparency and Continuing Progress Driven by COVID-19
In our current landscape, transparency, trust, and understanding how medical products are approved is more critical than ever. We appreciate that FDA publicly relea ses some information on how they make their decisions, and we encourage the agency to consid e r ways to increase transparency through a dditional disclosures that release valuable information while protecting company confidential information and patient privacy . Enhanced transparency can benefit the medical device ecosystem and patients specifically by minimizing costly replication of effort, reducing regulatory uncertainty, and enhancing patient engagement and public trust.
We recommend FDA create a position/group in the Commissioner’s Office that can initiate, lead, and oversee the ag ency’s transparency initiatives. In addition to ensuring that disclosed information is in a useable and understandable format for each audience, including patients and researchers, this group would be responsible for a consistent process of:
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identifying potential transparency initiatives that may benefit the public and other stakeholders, including efforts to harmonize disclosures across regulatory markets;
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consulting with relevant stakeholders, including patients, to investigate the feasibility an d impact of these initiatives;
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running pilots of chosen initiatives and assessing impact/benefit; and
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ending, modifying, or installing as permanent programs these pilots, and communicating these decisions to the public.
We also encourage FDA t o consider additional transparency initiatives, such as ensuring decision summaries for all medical devices include a robust discussion of FDA’s decision - making, d isclosing to the pu blic how patient input is used by FDA and what other (non - sponsor submitte d) sources were used to understand the patient experience , and s haring with the public lessons learne d and best practice s , including related to approaches for patient engagement and increasing diversity in clinical trials.
Additionally, FasterCures recognizes that the devastating COVID - 19 pandemic offers some lessons that we would like to see continued after the pandemic subsides. We have witnessed unprecedented collaboration between the agency and industry, including non - traditional manufacturers, between diverse industry players, and among many stakeholders and across sectors. The urgency of the pandemic has led to a focus on what is critically important, and we would like to see the agency work to ensure that, as appropriate, these workflows, proc edures, and forward - thinking flexibilities continue past the pandemic so that patients using future devices can benefit. For example , reducing the time to draft and release guidance documents can lead to these materials having more real - time impact and al ign with the quick, iterativ e development processes of medical devices.
And finally, the increased awareness and use of remote healthcare and the tools to make that happen seen during the pandemic have given us more opportunity to learn about and coll ect more patient generated data. We would like to see this progress continued so that patient - generated data can help paint a clearer picture of patient experience and be incorporated into more healthcare decision - making.
Conclusion
We appreciate FDA’s consideration of these suggestions, and look forward to working w ith the agency throughout this MDUF A reauthorization. We are happy to discuss any of these areas in greater detail at any time. To do so, please contact me at [email protected] or by phone at 202 - 406 - 0811.
Sincerely,
Brenda Huneycutt, PhD, JD, MPH
Director, FasterCures