Older adults, Black patients underrepresented in post-marketing studies

Regulatory NewsRegulatory News | 28 April 2021 |  By 

In postmarketing studies of cancer therapies approved by the US Food and Drug Administration (FDA), representation of older adults and Black patients does not appear to be improved compared with premarketing studies, a recent investigation in JAMA Network Open suggests.
In addition, the sex and race of participants were identified less frequently in postmarketing studies than premarketing studies, according to a cross-sectional analysis of 77 premarketing and 56 postmarketing studies of FDA-approved cancer therapies between 2012 and 2016 by Tanvee Varma, BA, of the Yale School of Medicine in New Haven, CT, and colleagues.
“Inadequate demographic representation in premarketing and postmarketing studies calls into question the generalizability of cancer clinical trial results to clinical practice as well as the FDA’s ability to encourage or enforce demographic representation in clinical studies,” Varma and colleagues said.
The authors analyzed the demographic data from premarketing and postmarketing studies from publicly available sources and compared to demographic data of people with cancer drawn from United States Cancer Statistics. They determined which premarketing and postmarketing trials gathered data on sex, age and race/ethnicity; then calculating participation to prevalence ratios (PPR) for the studies as well as by type of cancer. Of 45 therapeutics approved by FDA between 2012 and 2016, 31 were drugs and 14 were biologics, 53.3% had received accelerated approval and 77.8% were granted orphan drug status.
Varma and colleagues found 77 premarketing studies (100%) reported patient gender compared with 42 postmarketing studies (P < .001), and both premarketing and postmarketing studies “adequately represented” women (mean PPR, 1.00). While 62 premarketing studies (80.5%) reported data on the race of participants, 27 postmarketing studies (48.2%) reported this information, the authors said (P < .001). The results showed older adults were underrepresented in premarketing (mean PPR, 0.73) and postmarketing (mean PPR, 0.75) studies. Patients who reported their race as Black were also underrepresented in both premarketing (mean PPR, 0.32) and postmarketing studies (mean PPR, 0.21).
“Ultimately, these findings suggest that the FDA must do more to improve the transparency of clinical trial demographic data and to ensure that women, older adults, and racial/ethnic minority groups are adequately represented in premarketing and postmarketing studies of novel cancer therapeutics,” the authors concluded.
The trial setting matters
In a related editorial, Joseph M. Unger, PhD, MS, of the Fred Hutchinson Cancer Research Center in Seattle, noted that clinical trials in the United States have for decades been “distinctly nonrepresentative” compared with the population of people who would receive the therapy being investigated.
In the case of differences in enrollment of racial and ethnic minority groups for these trials based on an expected patient population, Unger attributed these discrepancies to “different recruitment strategies” between trials sponsored by pharmaceutical companies and those sponsored by the National Cancer Institute (NCI).
“Whereas pharmaceutical companies—whose mission is directly tied to winning approval of new drugs—primarily conduct their trials at large academic centers and, often, at international sites, NCI-sponsored trials are conducted with a concerted outreach to community, minority, and underserved sites, with an emphasis on improving representativeness of minority and rural populations. Perhaps not surprisingly, enrollment representativeness for racial groups in NCI-sponsored trials is often more in line with cancer population rates,” he said.
“Calcified” disparities in postmarketing studies
The findings by Varma et al, he said, have identified a research gap showing these disparities have “calcified” and carry over into the postmarketing study setting. Unger said FDA has taken steps to address this issue, such as holding a workshop on how to increase representation of Black patients in clinical trials for multiple myeloma. Recommendations at this workshop included “prospective targeting of specific treating institutions serving diverse populations and the use of real-world data to augment what is learned from trials to fill gaps in knowledge about patient subpopulations,” Unger said.
“However, the findings from Varma et al suggest that postmarketing studies—even if designed to be more inclusive—still fail to adequately represent the demographic profile of the US cancer population,” Unger noted. “If so, the conduct of postmarketing trials may have limited utility in resolving the lack of data on diverse populations in premarketing trials.”
Regarding inclusion of more older adults in cancer trials, Unger said FDA is examining this issue as well, issuing draft guidance for industry in March. The NCI also held a virtual event in late April on how to engage older adults and have them participate in clinical trials. While it is “it is inevitable that older patients will never account for two-thirds of patients in trials,” Unger said, “recent and continued efforts to reduce unnecessary exclusion criteria are likely to improve the participation rates of older patients in trials.”
Varma and colleagues suggested that FDA require demographic representation in clinical trials that resembles the population that will use a potential therapeutic. Unger called this notion into question: “Although the authors go on to indicate that this could be ensured through the up-front investment of sufficient resources for recruitment, therein lies the rub, as there can be no guarantee that representative enrollment across the intersecting domains of age, sex, race, and ethnicity will necessarily be achieved in a timely fashion, especially given the multidimensional layers of structural, clinical, physician, and patient barriers that exist to trial enrollment,” he said.
Rather, “a prospective strategy that better targets treatment settings with diverse cancer populations will improve demographic and socioeconomic representativeness and limit the potential for harmful delays in the development of new treatments,” Unger said. “At the same time, continued and focused efforts to eliminate structural, clinical, physician, and patient barriers to enrollment are necessary to allow patients of all backgrounds to more easily participate.”
JAMA Network Open Varma et al.
JAMA Network Open Unger JM.


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Tags: clinical, DEI, FDA, trials, US

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