Feature

How to improve representation of women in device trials

Underrepresentation of women in clinical trials evaluating CV devices has been a persistent problem, but a multipronged approach coupled with understanding of why women may be more reluctant to enroll in such studies can help overcome this hurdle, according to a new position statement published in JACC: Cardiovascular Interventions.

Although the prevalence of CVD is similar for men and women, men comprise 70% to 80% of enrollees in CV device trials, according to the statement. Moreover, not only do fewer women participate in clinical trials, significantly fewer women receive CV devices or undergo CV procedures, including diagnostic cardiac catheterization, stent implantation and implantable cardioverter defibrillators. This difference in treatment patterns may potentially arise from bias, particularly when considering the fact that outcomes from studies primarily involving men form the basis for treatment guidelines, according to the statement.

Currently, the NIH and FDA have guidance and policies in place to increase female participation in CV trials, yet enrollment of women still remains low.

“This call to action aims to halt the perpetuating cycle of female underrepresentation in CV studies, through a comprehensive multistakeholder engagement and awareness campaign, and streamlining clinical trial design to ensure more robust sex specific data,” the statement authors wrote.

Unique concerns

In an effort to include more women in clinical trials, the statement authors sought to identify barriers to female participation and subsequently highlighted several factors that may affect women’s decisions.

Notably, women generally have “more risk-averse behavior than men in making decisions, a difference that is amplified by stress,” according to the statement. Trial randomization and the fear of adverse health effects of participation therefore may prevent women from enrolling in CV device studies. To combat this, the statement authors recommended that physicians and researchers emphasize the safety and reliance on standards of care in these trials to mitigate concerns that women may have.

Women also appear more likely to seek input from family members, friends and researchers when it comes to making decisions.

“Although patient autonomy is paramount, informed decision making for women will often include a greater network of trusted individuals, including family and friends. Therefore, educational and awareness campaigns must include a broader sphere of influential individuals, aiming to demystify clinical research methods and to emphasize the broader societal benefits,” the statement authors wrote.

Further, women, especially as primary caregivers, seem to be particularly susceptible to study burden. Previous research has demonstrated that women opted not to participate in a CV trial due to transportation issues, for example. This concern is partially attributable to the requirements attached to follow-up visits, according to the statement.

Lack of investigator engagement, awareness and leadership, however, may be the primary cause for low enrollment of women in CV trials. Only 4.5% of interventional cardiologists are women and fewer than 20% of these women achieve leadership positions, according to the statement.

“Whether by choice or omission, a minority of cardiology subspecialists are women. In the case of interventional cardiology, which likely is the single most important source of patient enrollment in device trials, the fraction is minute,” they wrote.

“The current female cardiology constituency faces a steep climb to close the known gap in sex disparities in CV outcomes, in referrals to CV device–related procedures, and in enrollment in clinical trials.”

Importance of multiple stakeholders

The position statement writing group comprises members of the Women in Innovation subcommittee of the Society for Cardiovascular Angiography and Interventions — who serve as experts in interventional and structural cardiology, clinical trials and academic research — and AdvaMed, which represents the device industry.

In the statement, the authors offer a multistakeholder approach to tackling the problem of underrepresentation of women in clinical trials.

“The proposed approach to reduce existing gaps in female participation is to engage clinicians, academics and industry partners through AdvaMed to commit to the national dissemination and implementation of established regulatory guidelines for clinical trials,” the authors wrote.

To ease the burden of clinical trials, for instance, the position statement recommends alternative strategies for follow-up, including the use of technology, the inclusion of more flexible hours and home visits and allowing primary care providers to conduct follow-up.

Additionally, a broad-based public education campaign regarding the safety of clinical research targeting patients and their support networks is necessary to mitigate women’s distrust of the medical system and trials. Use of easy-to-understand language and phone calls, text messages, email and social media is also beneficial, according to the statement.

Increased education of clinicians and researchers that highlights the importance of clinical trials and their effect on future guidelines and standards of care is also essential to eliminating enrollment bias, the experts noted. Currently, there are no specific recommendations, as no one strategy will work for all circumstances and best practices will need to change was understanding of CVD in women changes, according to the statement.

Finally, stakeholder engagement, including cooperation and coordination between clinicians, investigators and industry, is imperative to the success of this campaign, the experts stated. Their willingness to adhere to guidance and recommendations set forth by agencies such as the FDA and the NIH is the best way to close the gap between men and women in research and clinical care.

“The time has come to take conscious ownership in breaking the endless status quo and take decisive action to improve outcomes and provide equal care for our female patients,” the experts wrote.

Further considerations

The new position statement is important because it goes beyond the scope of highlighting the issue of underrepresentation of women in clinical trials and instead proposes strategies for tackling the problem, Fatima Rodriguez, MD, MPH, and Robert A. Harrington, MD, both from Stanford University, wrote in an accompanying editorial.

Rodriguez and Harrington noted, however, that the statement is a first step and that other points need to be addressed. Mandates as opposed to guidelines for government- and industry-funded CV trials, for example, may be more effective in improving women’s participation in clinical trials. Monitoring and assessment of strategies are also necessary to determine their success across trial designs and devices and reevaluation of such plans will be important, Rodriguez and Harrington added.

The lack of women cardiologists, which is briefly touched on in the position statement, likely also plays a role in the low enrollment of women in CV trials, according to Rodriguez and Harrington.

“Clinical cardiovascular care of women and their engagement in the clinical research process might be greatly facilitated by greater numbers of women cardiologists and investigators to mirror the percentage of women training in internal medicine residency programs. This is a particular area of concern for interventional cardiology, which has < 10% women in the field and undoubtedly contributes to the clinical trials’ enrollment disparities discussed by the authors. Efforts by the American College of Cardiology to increase the numbers of women cardiologists, including in interventional cardiology, should have a positive effect on women’s participation in clinical trials,” they wrote. – by Melissa Foster

For more information:

Ghare MI, et al. JACC Cardiovasc Interv. 2019;doi:10.1016/j.jcin.2018.10.048.

Rodriguez F, et al. JACC Cardiovasc Interv. 2019;doi:10.1016/j.jcin.2018.11.012.

Disclosures: Please see the position statement for a full list of the authors’ relevant financial disclosures. Rodriguez reports she has received research support from Verily Life Sciences and has been a consultant to Health-Pals and Novo Nordisk. Harrington reports he has received institutional research grants from Apple, Sanofi, AstraZeneca, Portola, Janssen, Bristol-Myers Squibb, Novartis, CSL and The Medicines Company; he has been a consultant and served on advisory boards for Element Science, MyoKardia and WebMD; and he has served on the board of directors of Signal Path, American Heart Association and Stanford HealthCare.

Underrepresentation of women in clinical trials evaluating CV devices has been a persistent problem, but a multipronged approach coupled with understanding of why women may be more reluctant to enroll in such studies can help overcome this hurdle, according to a new position statement published in JACC: Cardiovascular Interventions.

Although the prevalence of CVD is similar for men and women, men comprise 70% to 80% of enrollees in CV device trials, according to the statement. Moreover, not only do fewer women participate in clinical trials, significantly fewer women receive CV devices or undergo CV procedures, including diagnostic cardiac catheterization, stent implantation and implantable cardioverter defibrillators. This difference in treatment patterns may potentially arise from bias, particularly when considering the fact that outcomes from studies primarily involving men form the basis for treatment guidelines, according to the statement.

Currently, the NIH and FDA have guidance and policies in place to increase female participation in CV trials, yet enrollment of women still remains low.

“This call to action aims to halt the perpetuating cycle of female underrepresentation in CV studies, through a comprehensive multistakeholder engagement and awareness campaign, and streamlining clinical trial design to ensure more robust sex specific data,” the statement authors wrote.

Unique concerns

In an effort to include more women in clinical trials, the statement authors sought to identify barriers to female participation and subsequently highlighted several factors that may affect women’s decisions.

Notably, women generally have “more risk-averse behavior than men in making decisions, a difference that is amplified by stress,” according to the statement. Trial randomization and the fear of adverse health effects of participation therefore may prevent women from enrolling in CV device studies. To combat this, the statement authors recommended that physicians and researchers emphasize the safety and reliance on standards of care in these trials to mitigate concerns that women may have.

Women also appear more likely to seek input from family members, friends and researchers when it comes to making decisions.

“Although patient autonomy is paramount, informed decision making for women will often include a greater network of trusted individuals, including family and friends. Therefore, educational and awareness campaigns must include a broader sphere of influential individuals, aiming to demystify clinical research methods and to emphasize the broader societal benefits,” the statement authors wrote.

Further, women, especially as primary caregivers, seem to be particularly susceptible to study burden. Previous research has demonstrated that women opted not to participate in a CV trial due to transportation issues, for example. This concern is partially attributable to the requirements attached to follow-up visits, according to the statement.

PAGE BREAK

Lack of investigator engagement, awareness and leadership, however, may be the primary cause for low enrollment of women in CV trials. Only 4.5% of interventional cardiologists are women and fewer than 20% of these women achieve leadership positions, according to the statement.

“Whether by choice or omission, a minority of cardiology subspecialists are women. In the case of interventional cardiology, which likely is the single most important source of patient enrollment in device trials, the fraction is minute,” they wrote.

“The current female cardiology constituency faces a steep climb to close the known gap in sex disparities in CV outcomes, in referrals to CV device–related procedures, and in enrollment in clinical trials.”

Importance of multiple stakeholders

The position statement writing group comprises members of the Women in Innovation subcommittee of the Society for Cardiovascular Angiography and Interventions — who serve as experts in interventional and structural cardiology, clinical trials and academic research — and AdvaMed, which represents the device industry.

In the statement, the authors offer a multistakeholder approach to tackling the problem of underrepresentation of women in clinical trials.

“The proposed approach to reduce existing gaps in female participation is to engage clinicians, academics and industry partners through AdvaMed to commit to the national dissemination and implementation of established regulatory guidelines for clinical trials,” the authors wrote.

To ease the burden of clinical trials, for instance, the position statement recommends alternative strategies for follow-up, including the use of technology, the inclusion of more flexible hours and home visits and allowing primary care providers to conduct follow-up.

Additionally, a broad-based public education campaign regarding the safety of clinical research targeting patients and their support networks is necessary to mitigate women’s distrust of the medical system and trials. Use of easy-to-understand language and phone calls, text messages, email and social media is also beneficial, according to the statement.

Increased education of clinicians and researchers that highlights the importance of clinical trials and their effect on future guidelines and standards of care is also essential to eliminating enrollment bias, the experts noted. Currently, there are no specific recommendations, as no one strategy will work for all circumstances and best practices will need to change was understanding of CVD in women changes, according to the statement.

Finally, stakeholder engagement, including cooperation and coordination between clinicians, investigators and industry, is imperative to the success of this campaign, the experts stated. Their willingness to adhere to guidance and recommendations set forth by agencies such as the FDA and the NIH is the best way to close the gap between men and women in research and clinical care.

PAGE BREAK

“The time has come to take conscious ownership in breaking the endless status quo and take decisive action to improve outcomes and provide equal care for our female patients,” the experts wrote.

Further considerations

The new position statement is important because it goes beyond the scope of highlighting the issue of underrepresentation of women in clinical trials and instead proposes strategies for tackling the problem, Fatima Rodriguez, MD, MPH, and Robert A. Harrington, MD, both from Stanford University, wrote in an accompanying editorial.

Rodriguez and Harrington noted, however, that the statement is a first step and that other points need to be addressed. Mandates as opposed to guidelines for government- and industry-funded CV trials, for example, may be more effective in improving women’s participation in clinical trials. Monitoring and assessment of strategies are also necessary to determine their success across trial designs and devices and reevaluation of such plans will be important, Rodriguez and Harrington added.

The lack of women cardiologists, which is briefly touched on in the position statement, likely also plays a role in the low enrollment of women in CV trials, according to Rodriguez and Harrington.

“Clinical cardiovascular care of women and their engagement in the clinical research process might be greatly facilitated by greater numbers of women cardiologists and investigators to mirror the percentage of women training in internal medicine residency programs. This is a particular area of concern for interventional cardiology, which has < 10% women in the field and undoubtedly contributes to the clinical trials’ enrollment disparities discussed by the authors. Efforts by the American College of Cardiology to increase the numbers of women cardiologists, including in interventional cardiology, should have a positive effect on women’s participation in clinical trials,” they wrote. – by Melissa Foster

For more information:

Ghare MI, et al. JACC Cardiovasc Interv. 2019;doi:10.1016/j.jcin.2018.10.048.

Rodriguez F, et al. JACC Cardiovasc Interv. 2019;doi:10.1016/j.jcin.2018.11.012.

Disclosures: Please see the position statement for a full list of the authors’ relevant financial disclosures. Rodriguez reports she has received research support from Verily Life Sciences and has been a consultant to Health-Pals and Novo Nordisk. Harrington reports he has received institutional research grants from Apple, Sanofi, AstraZeneca, Portola, Janssen, Bristol-Myers Squibb, Novartis, CSL and The Medicines Company; he has been a consultant and served on advisory boards for Element Science, MyoKardia and WebMD; and he has served on the board of directors of Signal Path, American Heart Association and Stanford HealthCare.