Participation of the elderly, women, and minorities in pivotal trials supporting 2011–2013 U.S. Food and Drug Administration approvals

Abstract

BackgroundPivotal trials, the clinical studies that inform U.S. Food and Drug Administration (FDA) approval decisions, provide the foundational evidence supporting the safety and efficacy of novel therapeutics. We determined the representation of the elderly, women, and patients from racial and ethnic minorities in pivotal trials and whether the FDA is making subgroup efficacy analyses among these subpopulations available to the public.MethodsWe conducted a cross-sectional study of novel therapeutics approved by the FDA between 2011 and 2013. Using publicly available FDA documents, we collected information on the demographic characteristics of pivotal trial participants (age ≥65 years, sex [male, female], race [white, black, Asian, other], and ethnicity [Hispanic, non-Hispanic]) and determined the availability of subgroup analyses by age, sex, race, and ethnicity.ResultsWe identified 86 novel therapeutic that were approved by the FDA between 2011 and 2013 for 92 indications on the basis of 206 pivotal trials. The median age of pivotal trial patients was 53.1 years (interquartile range 40.6–60.6), and the mean proportion of patients ≥65 years of age was 28.9 % (95 % CI 23.5–34.4 %). Similar proportions of pivotal trial participants were male (mean 50.3 %, 95 % CI 45.3–55.2 %) and female (mean 49.7 %, 95 % CI 44.7–54.7 %). Most participants were white (mean 79.2 %, 95 % CI 75.9–82.6 %), while the mean proportion of black patients was 7.4 % (95 % CI 5.5–9.3 %), that of Asian patients was 7.4 % (95 % CI 5.2–9.7 %), and that of patients of other races was 5.9 % (95 % CI 4.4–7.5 %). Information about ethnicity was available for only 59.8 % of indications, and where such data were available, the mean proportion of Hispanic participants was 13.3 % (95 % CI 10.3–16.3 %). FDA reviewers performed and made available subgroup efficacy analyses by age, sex, and race for at least one of the pivotal trials used as the basis of approval for over 80 % of indications.ConclusionsAlthough women are equally represented in pivotal trials supporting recent novel therapeutic approvals by the FDA, elderly patients and those from racial and ethnic minorities are underrepresented. FDA reviewers generally perform subgroup efficacy analyses by age, sex, and race and make these subgroup analyses available to the public.

Lipid management in patients with chronic kidney disease

“…However, pressure should be put on regulatory and licensing authorities to demand the inclusion of patients with CKD in these trials in the future. Similar approaches together with several incentives have already improved the recruitment of women, children, elderly people and ethnic minorities into RCTs [280][281][282] .…”

Post‐marketing research and its outcome for novel anticancer agents approved by both the FDA and EMA between 2005 and 2010: A cross‐sectional study

“…Clinical research preceding marketing authorization is highly regulated and has been extensively studied . Although this is an evolving field and despite some differences among regulators, preapproval trials are well known and codified.…”

“…Clinical research preceding marketing authorization is highly regulated [1][2][3] and has been extensively studied. [4][5][6][7][8][9][10] Although this is an evolving field 11,12 and despite some differences among regulators, preapproval trials are well known and codified. However, once a drug has been approved for use, subsequent clinical trials are much less regulated 13 and have not been thoroughly characterized.…”

New and incremental FDA black box warnings from 2008 to 2015

“…The new and major BBW updates in our sample commonly contained serious risks such as death and cardiovascular risk, indicating that important data regarding the most serious safety concerns often emerge in the post-marketing setting after initial drug approval. This dynamic may reflect the limitations of pre-marketing data: given that the majority of pivotal trials used by FDA for approval decisions contain a narrow patient population and limited follow-up period [4,12], and that the near-majority use surrogate endpoints as their primary outcome [13], many risks may not be identified until after a drug is approved and then used in a larger population and with longer follow-up. Further, the majority of new and incremental BBWs were issued for drugs that are typically taken for durations over 2 years, putting patients at risk for potentially fatal and preventable risks for extended time periods.…”