National Center for Health Research, February 28, 2020
National Center for Health Research’s Public Comments on FDA’s Office of Minority Health and Health Equity Strategic Priorities; Establishment of a Public Docket; Request for Comments
The National Center for Health Research (NCHR) appreciates the opportunity to provide comments on strategic priorities for the Food and Drug Administration’s (FDA’s) Office of Minority Health and Health Equity to advance health equity. The National Center for Health Research is a nonprofit think tank that conducts, analyzes, and scrutinizes research, policies, and programs on a range of issues related to health and safety. We do not accept funding from companies that make products that are the subject of our work, so we have no conflicts of interest.
Unfortunately, minority populations have historically been disproportionately underrepresented in studies submitted to the FDA, and this under-representation continues to this day. For example, on February 26, an FDA Advisory Committee reviewed TOOKAD, a treatment for prostate cancer that was studied on several hundred patients, but only five of them were not white. Prostate cancer is more likely to be fatal for black men, and yet this lack of diversity was not mentioned as an issue in the FDA PowerPoint presentation to the Advisory Committee. Increased minority representation in clinical trials is needed, and subgroup analyses that specifically determine safety and effectiveness for minority groups are essential.
Our Center published a groundbreaking study indicating that many high-risk medical devices are still tested on patient populations with little diversity and that subgroup analyses are not always conducted.1 Even when subgroup analyses are conducted, the results are often not included on the labeling. We examined demographic profiles and subgroup analysis in 22 high-risk medical devices reviewed by the FDA Advisory Committees from 2014 – 2017. The number of nonwhite patients in pivotal trials ranged from 4 (3%) to 6,788 (17%). However, of the 19 treatment devices, only seven included subgroup analysis for race for effectiveness and three for safety. One of the three in vitro diagnostic devices did not provide subgroup analysis for sensitivity and specificity. Even when analyses were conducted, their conclusions were often discredited by FDA, blamed on chance differences due to small sample size.
Scientists at FDA reviewed the labeling for the 167 new molecular entities approved between 2008 and 2013 and found that approximately 20% had differences in exposure or response across racial or ethnic groups, or both.2
Subgroup analyses submitted to the FDA often compare the safety or effectiveness of a medical product between two different demographic groups. However, this is not the information that patients and healthcare providers need to make an informed choice. Instead, subgroup analyses need to evaluate whether the benefits outweigh the risks of a product for each demographic group. Consider, for example, a new medical product that works significantly better for one group compared to another. This may not be a problem if the benefit outweighs the risk for both groups, but it would be a problem for patients if the product is not safe or effective for one of the demographic groups.
FDA has encouraged sponsors to seek diversity in clinical trials, but when companies have failed to do so – for example, by not including a sufficient number of black patients in a study of diabetes or uterine fibroids, which are more common in black patients – the products were approved anyway. When FDA has demanded that post-market testing include more diverse populations, that has not been enforced. The FDA can do more to encourage appropriate inclusion of minority populations with clear incentives. For example, FDA can refuse to approve a product for all patients if it has not been tested on sufficient numbers of patients in specific minority groups or if it has not been analyzed to determine if the benefits outweigh the risks for specific racial or ethnic groups, as described above.
In conclusion, efforts to improve inclusion of racial and ethnic minority populations in clinical trials needs to include incentives that are more effective than merely asking companies to do so. Greater diversity would, in turn, improve the generalizability of clinical trial results and provide patients and health care professionals with the information necessary to make an informed decision about which products to use for which patients.
Thank you for the opportunity to comment on this important medical and patient issue.
The National Center for Health Research can be reached at firstname.lastname@example.org or at (202) 223-4000.
- Fox-Rawlings SF, Gottschalk L, Doamekpor LA, Zuckerman D. Diversity in Medical Device Clinical Trials: Do We Know What Works for Which Patients? Milbank Quarterly. 2018;96(3):499-529. https://onlinelibrary.wiley.com/doi/abs/10.1111/1468-0009.12344
- Ramamoorthy A, Pacnowski MA, Bull J, Zhang L. Racial/Ethnic Differences in Drug Disposition and Response: Review of Recently-Approved Drugs. Clinical Pharmacology & Therapeutics. 2015;97(3):263-273. https://www.ncbi.nlm.nih.gov/pubmed/25669658