FDA Commissioner Stephen Hahn referenced the differences in how COVID-19 is affecting various populations in the U.S. to highlight the need for greater diversity in clinical trials as the agency released its final guidance “Enhancing the diversity of clinical trial populations – eligibility criteria, enrollment practices and trial designs” Nov. 9.
The disparities in how different populations are being impacted by the pandemic “illustrates why we must encourage developers of any medical product such as treatments or vaccines for COVID-19 – as well as medical products more broadly – to endeavor to include diverse populations to understand their risks or benefits across all groups,” Hahn said.
Issued in draft form last year before the coronavirus emerged, the guidance advises sponsors on increasing enrollment of underrepresented populations in their trials by taking steps to broaden the eligibility criteria through inclusive trial practices, trial designs and methodological approaches.
The guidance addresses the need for diversity when it comes to demographic characteristics such as sex, race, ethnicity, age and residency, as well as non-demographic characteristics including organ dysfunction, co-morbid conditions, rare diseases, disabilities and weight.
“To further promote and protect public health, it is important that people who are in clinical trials represent the populations most likely to use the potential medical product,” Hahn said.
The guidance recognizes that there are justifiable medical reasons for excluding certain patients from early trials. However, “as data on excretory and metabolic pathways and drug-drug interactions become available during the drug development program, allowing appropriate dose adjustments, there should be fewer exclusions related to concomitant medications or co-morbidities,” according to the guidance. “Similarly, as the safety experience with a product increases, eligibility criteria should be broadened to include more medically complex participants; any remaining exclusions should be justified.”
The guidance also cautions against using commonly accepted eligibility criteria across trials that exclude certain populations from trial participation without strong clinical or scientific justification.
The FDA has been pushing for greater trial diversity for several years. But despite those efforts, “challenges to participation in clinical trials remain, and certain groups continue to be underrepresented in many clinical trials,” according to the guidance.
A report released Nov. 9 by the FDA’s Center for Drug Evaluation and Research showed that trial inclusion varies by location. For instance, of the 102,596 U.S. participants in trials from 2015 to 2019, 56% were women, 16% were Black or African American, 2% were Asian and 21% were 65 years and older.
However, the report, which summarized CDER’s drug snapshots for the five-year period, found that of the 190,170 participants in trials in the rest of the world, 49% were women, 2% were Black or African American, 16% were Asian and 37% were 65 years and older.
Final analysis: hydroxychloroquine offers no benefit
The U.S. NIH turned the final page Nov. 9 on its halted clinical trial evaluating the safety and effectiveness of hydroxychloroquine in treating adults with COVID-19, formally concluding that the malaria drug provides no clinical benefit to hospitalized patients.
The final data and analysis of the ORCHID trial affirmed preliminary evidence that led a data and safety monitoring board to recommend stopping the trial in June. At the time, 479 of the expected 510 patients had been enrolled.
“Having a rigorously designed clinical trial that captured patient-centered, clinically meaningful outcomes was critical to reaching the unequivocal conclusions about the use of hydroxychloroquine in COVID-19. … We hope this clear result will help practitioners make informed treatment decisions and researchers continue their efforts pursuing other possible safe and effective treatments for patients suffering with this disease,” said James Kiley, director of the Division of Lung Diseases at the NIH’s National Heart, Lung, and Blood Institute.
The data and analysis were published online Nov. 9 in the Journal of the American Medical Association.
FDA finalizes PDUFA VI fee guidance
Three years after Congress passed PDUFA VI as part of the 2017 FDA Reauthorization Act, the FDA has finalized its guidance explaining the statute’s new fee structure for fiscal 2018-2022 prescription drug user fees.
The guidance describes the types of user fees authorized by PDUFA VI, the process for submitting payments, the consequences for failing to pay application fees or prescription drug program fees, and the process for requesting a reconsideration of a user fee assessment. It also describes how the FDA determines which products are subject to a fee and discusses certain changes to the agency’s policies under PDUFA VI.