By- Susan Lubejko PhD- Mittal Consulting

In March 2025, FDA released two new guidance documents with potentially big implications for the clinical studies conducted by medical device sponsors.  

Sex-Specific Data in Medical Device Clinical Studies 

On March 31, 2025, FDA’s Center for Devices and Radiological Health (CDRH) released its final guidance document Evaluation of Sex-Specific Data in Medical Device Clinical Studies. Within this document, FDA encourages consideration of the sex of subjects when designing clinical studies and provides recommendations for ways to encourage the enrollment of both men and women in clinical trials. Additionally, FDA provides recommendations for the statistical analysis of study data and expectations for reporting of sex-specific data gleaned from device studies. 

According to the guidance document, consideration of sex-specific data in drug and device clinical studies is rooted in concerns dating back to the 1970s, where it was concluded that women were severely underrepresented in clinical studies for drugs in the United States due to concerns for their child-bearing potential. In the decades since, FDA has participated in several public conversations on this topic, culminating in a 2014 guidance document providing recommendations for sex-specific data, and ultimately, last month’s guidance update.  

Consideration of sex differences during clinical studies is important – intrinsic factors, such as hormones and body size, and extrinsic factors, including diet and sociocultural issues, may impact the effect a medical device has on male and female bodies. Within their updated guidance, FDA provides a number of examples of devices where this was shown to be true. However, there are several noted barriers to enrollment of women in clinical studies, such as fear of fetal consequences if a participant becomes pregnant, inclusion and exclusion criteria that unintentionally exclude women, and family responsibilities that limit women from completing studies in their entirety.  

The release of this guidance has potentially big implications for all medical device sponsors that must complete a clinical study for the premarket application for their device – 510(k)s, premarket approvals (PMAs), De Novo reclassification requests, and humanitarian device exemptions (HDEs) are all within the scope of these recommendations. FDA does, however, note exemptions to this effort, such as for devices that are inherently sex-specific, such as pregnancy tests, or for IVDs that rely on test samples with no sex information. Importantly, FDA notes the intent to use these guidelines when assessing all clinical device studies, from new and ongoing IDEs, completed studies that will be used to supporting a marketing application, and ongoing postmarket studies. It is possible that these guidelines may be most burdensome for sponsors in the time between the clinical study and their marketing application, if FDA requires more information to appropriately assess remaining sex-specific questions of safety and effectiveness.  

FDA’s Recommendations for Sex-Specific Data 

1. “Achieving Appropriate Enrollment” 

FDA first recommends that sponsors use background information and their own clinical data to determine whether sex differences may be relevant to the evaluation of their device, and provide this information on applications for new IDEs, on the marketing application for completed studies, and in interim and final reports for postmarket studies.  

For new or ongoing studies, sponsors should consider ways to increase the enrollment of women. These include enrolling investigational sites that would be expected to have a high proportion of women as patients, revising enrollment criteria if the original criteria unintentionally exclude women, and responsibly enrolling women that are of child-bearing age with proper precautions in place to avoid pregnancy during the trial. Interestingly, sponsors of studies that heavily recruit women should consider using complementary strategies to bolster enrollment of men.  

2. “Study Design and Data Interpretation” 

In addition to devising strategies to support the enrollment of both sexes, FDA also recommends that sponsors consider potential sex differences in their study design from the beginning.  Clinical trials should aim to include men and women consistent with disease prevalence, and pre-specified analyses by sex should be considered in the statistical analysis plan for new studies. Sex-specific analyses should be performed to look for meaningful sex differences in the primary effectiveness and safety endpoints, as well as key secondary endpoints. 

3. “Recommendations for Reporting” 

Finally, FDA provides recommendations for reporting the results of a clinical study, both to FDA and to the public. FDA notes that it is becoming increasingly important for healthcare providers to understand potential effects of patient sex when evaluating the use of a medical device. FDA recommends that both the demographic information of the population studied and any effects on key endpoints are conveyed.  

FDA’s Study Data Technical Conformance Guide 

Last month, FDA additionally released its updated Study Data Technical Conformance Guide. The scope of this document covers Investigational New Drug (IND), New Drug Application (NDA), Abbreviated New Drug Application (ANDA), and Biologics License Application (BLA) documents submitted to FDA’s Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER). While this document does not cover applications sent to CDRH (510(k), De Novo, PMA, etc.), sponsors working on combination products that have a primary home in CDER or CBER may find this document informative. The Technical Conformance Guide provides technical recommendations for submitting human and animal study data on the above application types. Major topics within include the specifications for file formatting required by FDA, controlled terminology, recommendations for submitting study data using electronic Common Technical Document (eCTD) format, and expectations for data traceability.