NCHR Comments on FDA Updates to the Breakthrough Devices Program to Reduce Disparities in Health Care

December 20, 2022

We are pleased to have the opportunity to share our views with the Food and Drug Administration (FDA) on their Select Updates for the Breakthrough Devices Program Guidance: Reducing Disparities in Health and Health Care.

The National Center for Health Research (NCHR) is a nonprofit think tank that conducts, analyzes, and scrutinizes research on a range of health issues, with particular focus on which prevention strategies and treatments are most effective for which patients and consumers. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.

NCHR agrees with FDA’s goal to reduce disparities in health and health care.  However, we disagree with the guidance because of the enormous loophole it represents. Altering the eligibility criteria for the breakthrough pathway to include certain devices that have the “potential” to benefit certain populations is too vague. Potential is in the eye of the beholder, and promising medical products with “potential” often fail in Phase III trials and confirmatory trials.  Making unproven devices more available to vulnerable populations could worsen disparities for some subpopulations. Instead, we strongly suggest the following strategies:

  1. Improve the standards of evidence required to authorize Breakthrough medical devices prior to focusing on equity issues.

According to the FDA’s own analysis, the agency gave “Breakthrough” designation to 728 devices as of late September, with 56 of these devices receiving marketing authorization.1 However, research indicates that most devices that were authorized provided limited clinical evidence, with some completely lacking effectiveness data.2 Applications for devices that submitted clinical evidence often relied on the use of surrogate endpoints to demonstrate safety and effectiveness. Almost half the postmarket studies to confirm their intended benefit were not conducted within a decade of being authorized.3 The goal of postmarket studies is to gather additional evidence regarding safety or effectiveness; many do reveal safety concerns that were unanticipated or greater than expected, or reveal a lack of clinical effectiveness. Making these devices more available to vulnerable populations would put them at greater risk than would the standard of care.

The National Center for Health Research conducted research based on FDA databases which found that most implants are cleared through the 510(k) process.  Most do not submit clinical trial data to the FDA and do not include scientific evidence of safety or effectiveness in the summary information provided to the FDA that the agency makes public.4 Devices submitted through the Breakthrough designation are held to even lower scientific standards. Without solid scientific evidence that a Breakthrough device has benefits that outweigh the risks, it would be unethical to increase their availability to already vulnerable populations. FDA’s guidance should include requirements for more rigorous premarket clinical study evidence, both in terms of the device’s overall clinical performance and demonstration of how it could reduce health disparities.

In addition to improving premarket standards, this guidance should be targeted to improve postmarket studies by: 1) establishing time frames for completing post-market studies; 2) ensuring diversity of patients and providing subgroup analyses in postmarket studies; 3) requiring that a post-approval study begin enrollment prior to authorization; and 4) rescinding authorization if the company fails to comply. FDA should explicitly state that Breakthrough status may be rescinded if devices fail to meet expectations, as is discussed in the agency’s  guidance entitled “Considerations for Rescinding Breakthrough Therapy Designation”.5

Basing FDA approval or authorization on a product’s potential to advance equity rather than evidence of beneficial outcomes for vulnerable populations is not appropriate for FDA decisionmaking. As was shown in FDA’s effort to rescind approval for Makena, companies that do not include people of color in their studies too often will try to use statements about racial inequities to justify keeping an unproven product on the market.  In the case of Makena, evidence from observational studies and a post-approval study failed to confirm clinical benefit for any racial group.6 FDA should follow in the footsteps of the Makena Advisory Committee, which rejected the disingenuous claim that their product would reduce health disparities and instead voted 14-1 to recommend rescinding approval of Makena.

  1. Reduce the barriers that prevent access to Breakthrough devices after authorization

The FDA justifies the revised guidance to the Breakthrough device program as promoting equity in access, yet they fail to address the potential harm to patients who rely on the financial stability of Medicare. The Centers for Medicare & Medicaid Services (CMS) projected that covering the first 14 Breakthrough devices would increase Medicare spending by $2.04 billion between 2022

and 2025.7 The concern that devices without verified clinical benefits would significantly increase national health expenditures helped persuade CMS to repeal proposed regulations that would have automatically granted 4 years of Medicare coverage to FDA-authorized Breakthrough devices.8 Such an increase in spending would result in greater costs to patients in the form of Medicare premiums and co-pays for treatment. Despite good intentions, without very careful oversight, the Breakthrough pathway is likely to be subject to financial gamesmanship that will increase rather than decrease barriers to care. It is essential that the FDA consider the implications for CMS beneficiaries before they reduce or expand their standards for evidence for any medical products, including Breakthrough devices.8

We are concerned that the draft guidance states that Breakthrough devices could be considered to improve access “if there is information supporting its use in diverse settings such that a patient population with limited or no available options may have improved adherence to a prescribed medical regimen.” This language is problematic because it ignores the safety and effectiveness of the device and because the FDA has no control over the price of any devices. In most cases, new medical products cost much more than experts expected, and much more than the standard of care.

  1. Equity should be considered throughout device development

 Many devices are approved despite the lack of diversity in clinical trials. A study of high-risk devices by the National Center for Health Research found that due to lack of patient diversity and publicly available data, clinicians and patients often cannot determine which devices are safe and effective for specific demographic groups.9 In that study, of the 22 medical devices recently reviewed through the PMA pathway, 4 were based on 2 pivotal trials and the rest were based on a single pivotal trial. None of the studies were reported to be powered to support statistical evaluation of subgroups. When subgroup analyses were conducted, they were considered exploratory, and the numbers of people of color were usually too small to draw any conclusions.  For example, the number of nonwhite patients in pivotal trials for treatment devices and IVDs ranged from 4 (3%) to 280 (17%). Only 37% of the treatment device trials included subgroup analysis by race or ethnicity for effectiveness, and only 21% included analysis for safety.

All of the devices were tested primarily on adults. Age ranges and means were available for 19 (86%) devices for at least 1 pivotal trial. The oldest patients ranged from 45 to 95 years old; although most devices were indicated for all adults and included at least 1 patient who was at least 65 years old, most did not specify how many patients were over 65. Two devices were approved for all adults even though the oldest patients in their studies were 67 or younger.  Only 37% of the studies provided subgroup analysis of safety based on age.

If we do not consider diversity in medical device testing, patients’ lives can be at risk.  One wellestablished example is pulse oximeters, which have been found to be less accurate for individuals with darker skin pigmentation and as the level of oxygenation decreases. “Clinically, this means sicker patients are less likely to get an accurate reading from a pulse oximeter and are, therefore, less likely to get appropriate care.”10 To avoid devices that contribute to health disparities, FDA should establish requirements for Breakthrough devices that ensure diversity and subgroup analyses. To reduce health disparities, the FDA should include the FDA’s Office of Minority Health and Health Equity in the decision-making of Breakthrough devices.

In summary, we strongly urge the FDA to establish explicit, stricter scientific standards when awarding Breakthrough designations, and require subgroup analyses, in order to improve the likelihood that the devices have benefits that outweigh the risks for all patients included in the indication. It is only after that occurs that the agency should consider other steps to promote equity in the development of medical devices as well as in access to the safest and most effective medical devices.

  1. U.S. Food and Drug Administration. (2022). Breakthrough devices program. (2022). https://www.fda.gov/medicaldevices/how–study–and–marketyour–device/breakthrough–devices–program.
  2. Johnston, J., Dhruva, S., Ross J., Rathi V. (2020). Early experience with the FDA’s Breakthrough devices program. Nature Biotechnology.;38:933-938. https://www.nature.com/articles/s41587–020–0636–7.
  3. Kadakia, et al. (2022) Select Updates for the Breakthrough Devices Program Guidance: Reducing Disparities in Health and Healthcare. https://www.regulations.gov/comment/FDA–2022–D–1061–0006
  4. Zuckerman, D., Brown, P., & Das, A. (2014). Lack of publicly available scientific evidence on the safety and effectiveness of implanted medical devices. JAMA internal medicine, 174(11), 1781–1787. https://doi.org/10.1001/jamainternmed.2014.4193
  5. U.S. Food and Drug Administration (2022). Considerations for Rescinding Breakthrough Therapy Designation. https://www.fda.gov/regulatory–information/search–fda–guidance–documents/considerations–rescindingbreakthrough–therapy–designation
  6. Calendar, E. (2022) NCHR testifies for FDA Advisory Committee about withdrawing approval for drug to prevent preterm birth. https://www.center4research.org/nchr–testifies–for–fda–advisory–committee–about–withdrawal–ofapproval–for–preterm–labor–drug/
  7. The Federal Register. (2021). Medicare program; Medicare coverage of innovative technology (MCIT) and definition of “reasonable and necessary”. https://www.federalregister.gov/documents/2021/11/15/202124916/medicare–program–medicare–coverage–of–innovative–technology–mcit–and–definitionof–reasonable–and.    8 Centers for Medicare & Medicaid Services. CMS repeals MCIT/R&N rule; will consider other coverage pathways to enhance access to innovative medical devices. November 12, 2021. Accessed November 11, 2022. https://www.cms.gov/newsroom/press–releases/cmsrepeals–mcitrn–rule–will–consider–other–coverage–pathwaysenhance–access–innovativemedical.
  8. Fleisher LA, Blum JD. A vision of Medicare coverage for new and emerging technologies—a consistent process to foster innovation and promote value. JAMA Internal Medicine. 2022. https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2797447.
  9. Fox-Rawlings SR, Gottschalk LB, Doamekpor LA, and Zuckerman D. Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients?. Milbank Q. 2018;96(3):499-529. doi:10.1111/14680009.12344
  10. National Center for Research. NCHR urges FDA to require more diversity in trials to improve accuracy of pulse ox devices. center4research.org https://www.center4research.org/pulse–ox–inaccurate–on–pigmented–skin/ December 2, 2022.