Applied Clinical Trials
New agency initiatives aim is to fully reflect the impact of treatment on patients representing a range of ages, ethnic backgrounds, and other demographic features
New drugs and biologics should be developed following strategies that consider the needs and responses of patients representing a range of ages, ethnic backgrounds, and other demographic features. The aim is to fully reflect the impact of treatment on individuals with differing health status and conditions, according to new guidances and initiatives from the regulatory agency.
Most recently, FDA officials advised drugmakers on strategies for including more elderly individuals in development programs for cancer therapies, as an expanding number of older patients accounts for a substantial portion of those likely to need and use new cancer drugs. Trials should include “an adequate representation of the range of patients” that may be exposed to an approved drug to “maximize the generalizability of the trial results,” FDA stated in draft guidance issued March 6. It advises sponsors and institutional review boards on specifics for enrolling patients ages 65-74 and those over 75 in both early and later-stage clinical trials, as well as post-approval studies.1
The agency considers it particularly important to collect information on drug safety, exposure, and response in elderly individuals as part of early-stage development to better inform the design and endpoints of larger later-stage studies. And including information on older adults in labeling can help promote the safe and effective use of these products and better inform treatment decisions in clinical practice. FDA advises sponsors on strategies for consulting with older patients to facilitate enrollment, especially of patients over age 75, and for specifying certain meaningful study endpoints, such as functional status and frailty.
Efforts to expand clinical trial diversity also should consider ways to overcome bias among healthcare professionals, which often limits recruitment of racial and ethnic minorities for clinical trials. A study published in the journal Cancer last month found such bias particularly notable in testing new cancer therapies, where some clinicians and investigators regarded minority patients as less promising study participants.2
FDA documents clinical trial diversity more broadly through its Drug Trials Snapshots transparency initiative, which has tracked data for important new drugs by sex, age, race, and ethnicity since 2015. The latest Summary Report on Drug Trials Snapshots for 2019 presents data on the 46,391 individuals who participated in clinical trials to support the 48 novel drugs and biologics approved last year by the Center for Drug Evaluation and Research (CDER).3 More than 70% of participants in these clinical trials were women and were white, while less than 10% were black or Asian; about one-third were 65 or older.
In many cases, skewed clinical trial participation, not surprisingly, reflects expected uses of a new treatment. Women dominate studies for breast cancer and osteoporosis, while elderly men primarily are enrolled to test new prostate cancer drugs. African Americans participated notably in studies involving sickle cell disease and schizophrenia. These trends continue, as seen in the recent FDA Drug Trials Snapshots posting for Lundbeck’s recently approved Vyepti for migraine. Of the 1,741 patients enrolled at 212 sites in the U.S., Russia, and Europe, 87% were women, 88% were white, 63% were ages 35-64 and only 1% over 65.
Additional information on participants in clinical trials, along with more extensive data on study designs and outcomes, may be found through another FDA transparency initiative that offers researchers access to a CDER compilation of curated data on drug products approved over the last 30 years. The aim is to facilitate data accessibility, transparency, and accuracy of information on approved drugs, starting with those vetted from 1985 through the end of 2019.4 FDA specifies that the dataset is a high-level compilation of existing, publicly available information-and that it may be accessed for research purposes only.
Jill Wechsler is the Washington Correspondent for Applied Clinical Trials