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Dhruva SS, Mazure CM, Ross JS, Redberg RF. Inclusion of Demographic-Specific Information in Studies Supporting US Food & Drug Administration Approval of High-Risk Medical Devices. JAMA Intern Med. 2017;177(9):1390–1391. doi:10.1001/jamainternmed.2017.3148
Women, the elderly, and minorities have been underrepresented in clinical trials.1-3 Risks and benefits of medical therapies, however, can vary based on these patient characteristics. The 2012 Food & Drug Administration (FDA) Safety and Innovation Act sought to address this issue by requiring the agency to initiate a plan that increases enrollment and clinical data for these important patient groups. This requirement led to the 2014 FDA Action Plan.4 We characterized enrollment reporting and evaluation of device safety and effectiveness for women, the elderly, and minorities for all 2015 premarket approval (PMA) devices, which undergo the most rigorous FDA review.
For each original PMA device approved in 2015, we abstracted data on the number of patients enrolled according to age, race, and/or ethnicity, and sex for all studies, both nonpivotal and pivotal, from both the Summary of Safety and Effectiveness Data (“Summary”) and device labels. We also determined whether results were analyzed by age, race and/or ethnicity, and sex; and if so, whether any difference in device safety or effectiveness was identified, even if a statistical analysis was not reported. We collected additional details for sex because the FDA issued a specific 1994 directive calling for analysis of gender bias in assessment of PMA devices.5 We used descriptive statistics to analyze the data.
In 2015, 82 studies supported FDA approval of 42 original PMA devices. Of the 82 studies, age was reported for 53 (65%) in FDA Summaries and 41 (50%) in device labels (Table 1); race and/or ethnicity was reported for 42 (51%) and 27 (33%), respectively; and of 77 studies including both men and women, sex composition was reported for 51 (66%) and 38 (49%), respectively. However, there was a discrepancy between the number of people enrolled and the number for which mean age was reported for 17 (32%) of 53 studies. A discrepancy also was found for reporting race and/or ethnicity in 17 (41%) of 41 studies, and for sex composition in 17 (33%) of 51 studies. Seventeen studies (21%) had an upper age limit, ranging from 50 to 85 years.
Analyses examining results by age were performed for 7 (9%) of 82 studies; 1 of these 7 found less device effectiveness in younger patients, while 2 found less effectiveness for older patients (Table 2). Such analyses were performed by race for 3 (4%) of 82 studies; 1 found a device less effective in nonwhite patients. Such analyses were performed by sex for 13 (17%) of 77 studies: 1 found less safety in men; 1 found less safety in women; and 1 found less effectiveness in women.
In device labels, 6 (7%) studies reported results by age, 1 (1%) by race and/or ethnicity, and 12 (16%) by sex.
For studies supporting FDA approval in 2015 of original PMA devices, age and sex of study participants were reported for two-thirds of all studies, and race and/or ethnicity for half. Although the 2014 FDA Action Plan4 calls for examination of results by age, race and/or ethnicity, and sex, such analyses infrequently occur—fewer than 20% of all studies for original PMAs approved in 2015. It is important for all demographic-specific analyses to consider clinical significance.6 However, we could not determine if this was the case because statistical tests or analyses were often unspecified.
With reauthorization of the Medical Device User Fee Amendments due by September 30, 2017, Congress has the opportunity to provide the FDA with the statutory authority to mandate the enrollment of sufficient women, the elderly, and minorities in device trials to proportionately represent the target population for which the high-risk medical device is intended to be used. The FDA could also be authorized to require the conduct of appropriate analyses, with consequences for noncompliance. Such changes would allow clinicians and patients to be better informed about the applicability of trial results to clinical practice.
Corresponding Author: Sanket S. Dhruva, MD, Robert Wood Johnson Foundation Clinical Scholars Program, Yale University School of Medicine, 333 Cedar St, SHM I-456, PO Box 208088, New Haven, CT 06520-8088 (firstname.lastname@example.org).
Accepted for Publication: May 22, 2017.
Correction: This article was corrected on September 5, 2017, to add an omitted affiliation and disclaimer statement.
Published Online: July 24, 2017. doi:10.1001/jamainternmed.2017.3148
Author Contributions: Dr Dhruva had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Dhruva, Mazure, Ross.
Acquisition, analysis, or interpretation of data: Dhruva, Mazure, Ross, Redberg.
Drafting of the manuscript: Dhruva, Mazure.
Critical revision of the manuscript for important intellectual content: Mazure, Ross, Redberg.
Statistical analysis: Dhruva, Redberg.
Supervision: Mazure, Redberg.
Conflict of Interest Disclosures: Dr Ross receives support through Yale University from the Centers of Medicare and Medicaid Services (CMS) to develop and maintain performance measures that are used for public reporting, from Johnson & Johnson to develop methods of clinical trial data sharing, from Medtronic Inc and the FDA to develop methods for postmarket surveillance of medical devices, from the FDA as part of the Centers for Excellence in Regulatory Science and Innovation (CERSI) program, from the Blue Cross Blue Shield Association to better understand medical technology evaluation, and from the Laura and John Arnold Foundation to support the Collaboration on Research Integrity and Transparency (CRIT) at Yale. Dr Dhruva is supported by the Robert Wood Johnson Foundation Clinical Scholars Program and the Department of Veterans Affairs. No other disclosures are reported.
Disclaimer: Dr Ross is Associate Editor of JAMA Internal Medicine, and Dr Redberg is Editor of JAMA Internal Medicine, but neither author was involved in any of the decisions regarding review of the manuscript or its acceptance.
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