In August, the FDA issued the final guidance document on Evaluation of Sex-Specific Data in Medical Device Clinical Studies. The intention of this guidance document is to improve the quality and consistency of available data regarding device performance in both sexes for devices that require clinical information in support of a marketing submission or post-approval/post-market surveillance submissions. The primary limitation on devices involves devices that are sex-specific; for instance, urology devices that are designed to be single-sex only.
For medical devices, certain medical products elicit different responses in women as compared to men. This has been illustrated for ventricular assist devices (VADs), cardiac resynchronization therapy defibrillators (CRT-D), and metal-on-metal hip replacements. Reasons for these differences include intrinsic factors, such as genetics or hormones, or extrinsic factors, such as diet or environment. The lack of available data is attributed to various reasons described in a previous IMARC blog that discussed the 2011 draft guidance document.
The overall objectives of the final guidance document are to:
- Encourage consideration of sex and associated covariates during study design stage,
- Provide recommendations for study design and conduct to encourage enrollment of each sex,
- Outline recommended sex-specific statistical analyses of study data with framework for considering sex-specific data when interpreting overall study outcomes, and
- Specify expectations for reporting sex-specific information in summaries and labeling for approved or cleared devices.
The document provides details on achieving appropriate enrollment, designing studies and data interpretation, and reporting information in applications and public documents. A key takeaway is this guidance document applies to new or ongoing studies, completed studies, and post-market studies. Also included in the guidance document is a detailed decision framework for statistical analyses.
Specifically for enrollment, these factors are most easily considered during study design and conduct; this includes the incorporation of information into the risk analysis section of the investigational plan. Recommended strategies include revising the enrollment criteria, examining alternative communication strategies, planning for a continued access study, involving community or local health care practitioners, and exploring flexibility in follow-up visit scheduling that may include provision for child care or elder care services. In addition, general conduct best practices are described for avoiding or minimizing subjects lost-to-follow up.
While the focus of this guidance document is sex-specific differences, other demographic variables also may affect device performance. Some recommendations provided in the guidance may also be used to promote enrollment and data analysis with demographics such as age, race, and ethnicity. In addition, FDA released an Action Plan in August 2014 that describes the approach to enhance the collection and availability of demographic subgroup data in clinical trials. The priorities of this plan are to:
- Improve the completeness and quality of demographic subgroup data collection, reporting, and analysis (Quality),
- Identify barriers to subgroup enrollment in clinical trials and employ strategies to encourage greater participation (Participation), and
- Make demographic subgroup data more available and transparent (Transparency).
With FDA focused on sex-specific and other demographics data, the clinical research industry will have to address these issues through different methods of study design, enrollment, and statistical analysis. How will this final guidance document influence study design in medical device trials moving forward? How will data collection and enrollment in medical device studies be affected?