Abstract
This systematic review evaluates the representation of women in randomized clinical trials (RCTs) of US Food and Drug Administration (FDA)–supervised medical devices.
Women have been historically underrepresented in clinical research.1 When underrepresented in device trials, data on performance of devices in women may be lacking as it is influenced by sex-related covariates, such as body size, hormonal variations, comorbidities, and parity.1
Methods
This systematic review evaluated women’s representation in high-risk medical implant trials published from January 2016 to May 2022. Additional methods are described in the eMethods in Supplement 1. The PRISMA reporting guideline was followed.
Representation rate was calculated by women randomized/total number randomized; if not available, women evaluated/total evaluated. The participation-to-prevalence ratio (PPR) for devices was calculated as the percentage of women participating/women with the intervention in the general population (eMethods in Supplement 1). Categorical data were compared using the χ2 test and continuous data using the Mann-Whitney U or Kruskal-Wallis test. Two-sided P < .01 was significant. Analyses were conducted using SPSS, version 29.
Results
Of 195 trials included (Figure), most were conducted from 2013 to 2022. Cardiovascular (131 [67%]) and orthopedic (39 [20%]) devices were common device categories. Common devices were stents (75 trials [38%]), valves (31 [16%]), and pacemakers (13 [7%]). In 152 trials (78%), the comparator was another device.
Figure. PRISMA Flow Diagram.
PubMed, CENTRAL, and Web of Science were searched for randomized clinical trials (RCTs) of high-risk medical implants from January 2016 to May 2022. Included data and references are given at https://data.mendeley.com/datasets/y5fst3jk4v/1.
Number of women randomized was reported in 135 trials and number of women evaluated in 141. Percentage of women randomized ranged between 7% and 100% (median, 33%; IQR, 24%-48%). Age of included women was reported in 1 trial. Mean overall age was older than 50 years in 175 trials (90%).
Median percentage of women included is presented in the Table. Cardiovascular trials included a significantly lower percentage of women compared with other fields, with stents being the device with the lowest percentage. No association was demonstrated between the number of randomized patients and the number of women included.
Table. Characteristics of Trials and Their Association With Women’s Representation.
| Characteristic | Trials, No. | Women represented, median (IQR), % | P value |
|---|---|---|---|
| Categorya | |||
| Cardiovascular | 128 | 29 (23-40) | .01 |
| Orthopedic | 37 | 46 (33-71) | |
| Otherb | 24 | 47 (33-54) | |
| Device | |||
| Valve | 30 | 44 (32-51) | .01c |
| Stent | 73 | 27 (23-33) | |
| Pacemaker | 13 | 30 (23-44) | |
| Pump | 14 | 24 (21-51) | |
| Prosthesis | 34 | 43 (32-74) | |
| Other | 25 | 40 (32-52) | |
| Primary outcomed | |||
| Hard | 130 | 32 (25-45) | .02e |
| Soft | 33 | 46 (29-60) | |
| Surrogate | 26 | 28 (21-47) | |
| Allocation generationf | |||
| Low risk | 137 | 32 (25-47) | .86 |
| Unclear risk | 45 | 37 (24-48) | |
| High risk | 7 | 41 (21-67) | |
| Allocation concealmentf | |||
| Low risk | 71 | 32 (23-42) | .09 |
| Unclear risk | 56 | 34 (24-48) | |
| High risk | 62 | 37 (25-55) | |
| Publication year | |||
| 2016 | 24 | 36 (26-51) | .34 |
| 2017 | 29 | 28 (22-42) | |
| 2018 | 31 | 32 (23-50) | |
| 2019 | 41 | 33 (24-46) | |
| 2020 | 29 | 33 (25-54) | |
| 2021 | 18 | 40 (33-52) | |
| 2022 | 16 | 30 (20-46) | |
| Start year | |||
| Before 2010 | 33 | 37 (22-46) | .94 |
| 2010-2015 | 114 | 32 (25-46) | |
| 2016-2020 | 42 | 34 (24-50) | |
| Center number | |||
| Single center | 69 | 35 (24-54) | .56 |
| Multicenter | 120 | 32 (24-47) |
Percentage of women represented was significantly lower for cardiovascular trials than for orthopedic and other device trials.
Ear, nose, and throat; endocrinology; neurology; gastroenterology; and pulmonary.
Percentage of women represented was significantly lower for stents than for all other devices.
Outcome categories are described in the eMethods in Supplement 1.
Percentage of women represented was significantly higher for soft outcomes than for hard and surrogate outcomes.
The definitions of allocation generation and concealment are based on the Cochrane handbook (risk-of-bias tool for randomized clinical trials) (https://training.cochrane.org/handbook/current).
The PPR for most common devices was lower than 0.8: 0.77 (95% CI, 0.66-0.94) for stent, 0.76 (95% CI, 0.67-0.88) for valve, 0.69 (95% CI, 0.52-1.19) for orthopedic prosthesis, and 0.56 (95% CI, 0.49-1.19) for pump trials. For pacemaker trials, it was 1.00 (95% CI, 0.77-1.47). We found no significant trend over time in percentage of women included by year of publication and year of trial start.
Discussion
Women’s inclusion in drug trials has improved in past decades.2 However, trials assessing devices have been addressed less.3
We found that device trials randomized a median of 33% of women. The PPR for most common devices was less than 0.8, implying underrepresentation of women, as has been demonstrated in older device trials showing lower representation than drug or lifestyle interventions.4
These results were found despite the US Food and Drug Administration’s (FDA’s) 2014 guidance addressing this issue.5 Recently, the Centers for Devices and Radiological Health issued a strategic plan for improving women’s representation in device trials.1
Obstacles to women’s inclusion include concerns about fetal consequences, underdiagnosis or underreferral of women, perceived recruitment challenges, and inclusion and exclusion criteria favoring men.6 Median age older than 50 years in included trials refutes the fetal concerns explanation. Manufacturing devices to fit both genders may be limiting.2
Solutions proposed include equal enrollment of women to their share in the population with disease or planning a sample size that could detect gender differences. A study of trials of FDA-approved devices found minimal differences in efficacy or safety by gender.2 The most limiting step for women’s recruitment is the screening stage; higher awareness of physicians may improve enrollment. Women-led studies are more likely to include women.6 Stakeholders should consider implementing gender equity criteria for researchers involved.
A study limitation is that reasons for underrepresentation of women could not be obtained. Proportion of women screened was reported in only 2 trials. Data on women’s retention in trials were not collected.
Our review highlights underrepresentation of women in device trials across medical fields. Improved awareness and initiatives are essential to ensure adequate enrollment, considering potential gender-specific differences in medical device performance.
eMethods.
Data Sharing Statement
References
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Associated Data
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Supplementary Materials
eMethods.
Data Sharing Statement
