“Women are not small men” Tackling underrepresentation of women in HIV clinical studies

Industry Insights

10/03/2021

Dr Vanessa Cooper

 

For National Women and Girls HIV/AIDS Awareness Day in the USA, Sprout Health Solutions wants to take this opportunity to bring attention to one of the health inequalities affecting women around the world – underrepresentation in clinical studies.  In this blog, we look at the barriers to recruitment, enrolment, and retention of women in HIV treatment and prevention trials and explore ways that these barriers are being addressed.

 

Women and girls with HIV

Women and girls account for 51% of people living with HIV globally.1 Yet women have been underrepresented in clinical studies including trials of antiretroviral treatment (19% women), vaccine (38% women) and cure (11% women).2

 
The serious consequences of underrepresentation of women

Clinical trials are fundamental for evaluating the efficacy and safety of new drugs and interventions. There can be sex differences in how HIV drugs are absorbed in the body (pharmacokinetics), and in the response to the drug (pharmacodynamics).3 It is important to understand what these differences are and whether they result in variances in the safety or effectiveness of treatment.

 
Using behavioral science to understand and tackle underrepresentation

There are many reasons for the underrepresentation of women in HIV clinical studies. We looked to the literature to identify barriers to the enrolment and retention of women in clinical studies. We used the Capability, Opportunity, Motivation and Behavior (COM-B)5 theoretical model to categorize these and identify strategies to address them.

 

COM-B component
Barriers
Strategies to address barriers

Capability

 

  • Busy lives including work and/or caregiving roles6
  • HIV-related stigma6
  • Socio-economic inequalities and domestic violence6
  • Home visits
  • Digitalized trials7
  • Reminders for appointments and completion of study tasks
Opportunity
  • Exclusion criteria (pregnancy, female sex)
  • Perceptions of physicians/study co-ordinators that women are less interested in clinical trials8
  • Partnering with community organizations and healthcare professionals in the design and conduct of trials9
  • Identification of and recruitment of study sites where women receive HIV care9
  • Targeted recruitment of women9
Motivation
  • Distrust of research and researchers stemming from historical events such as the Tuskegee syphilis experiment and experiences of discrimination in health care11
  • Beliefs about the value or benefits of participation12,13
  • Concerns e.g. about randomization, safety, side effects, confidentiality
  • Provide clear and accessible information13
  • Address concerns about participation13
  • Activities such as clinic-based support groups, lunch and learns and educational programs to create connection and address concerns about trial participation9
  • Establishing a good rapport between study staff and patients14
  • Emphasize available support and show appreciation for involvement13

 

Attitudes to female participants are changing

Attitudes and behaviors concerning the involvement of women in clinical studies are changing. In the past, women were often excluded because of concerns about fluctuating hormones and pregnancy, and it was widely believed that women would have the same response to drugs as men.3 In the 1990s, the FDA implemented a series of guidance documents, lifting a ban on women of child-rearing potential from taking part in early phase research.3 The FDA also recommended that clinical studies should be representative of the population who would eventually be prescribed the drug; and stated that new drug applications should present safety and efficacy data for relevant subgroups including sex, race and age.

 
Efforts to improve representation of women in HIV clinical trials

Efforts to increase representation of women living with HIV in clinical studies have included many of the strategies outlined above, including targeted recruitment from HIV clinics where more women receive care, partnering with community organizations in the design and conduct of trials, addressing women’s concerns about clinical research and making it easier for them to participate.9 Using digital technology to enhance recruitment, engagement and retention along with data collection and analytics may also help some women to complete study visits and tasks.

 
Conclusion

Representation of women in HIV clinical studies is improving, but efforts to keep the dialogue in the public eye and maintain the momentum will be key to achieve equitable access to clinical studies. Ensuring that clinical studies are designed to recruit and retain a specific number of women will provide data of the effects of treatment in women and facilitate comparisons by sex. The meaningful involvement of women living with HIV in the design and implementation of research and the use of behavior science to identify and address barriers to participation will also help enhance recruitment and retention.

 

 References

 

  1. World Health Organization https://www.who.int/gho/hiv/epidemic_status/cases_adults_women_children_text/en/. Accessed 10. March, 2021.
  2. Curno MJ, Rossi S, Hodges-Mameletzis I, Johnston R, Price MA, Heidari S. A Systematic Review of the Inclusion (or Exclusion) of Women in HIV Research: From Clinical Studies of Antiretrovirals and Vaccines to Cure Strategies. J Acquir Immune Defic Syndr. 2016;71(2):181-188.
  3. Liu KA, Mager NA. Women’s involvement in clinical trials: historical perspective and future implications. Pharm Pract (Granada). 2016;14(1):708.
  4. Sengupta S, Strauss RP, Miles MS, Roman-Isler M, Banks B, Corbie-Smith G. A conceptual model exploring the relationship between HIV stigma and implementing HIV clinical trials in rural communities of North Carolina. N C Med J. 2010;71(2):113-122.
  5. Michie S, Atkins, L., West, R. . The behaviour change wheel: A guide to designing interventions. London: Silverback; 2014.
  6. Cargill VA, Stone VE. HIV/AIDS: a minority health issue. Med Clin North Am. 2005;89(4):895-912.
  7. Inan OT, Tenaerts, P., Prindiville, S.A. et al. Digitizing clinical trials. npj Digit Med. 2020;3.
  8. Stone VE, Mauch MY, Steger KA. Provider attitudes regarding participation of women and persons of color in AIDS clinical trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1998;19(3):245-253.
  9. Falcon R, Bridge DA, Currier J, et al. Recruitment and retention of diverse populations in antiretroviral clinical trials: practical applications from the gender, race and clinical experience study. J Womens Health (Larchmt). 2011;20(7):1043-1050.
  10. Pahus L, Suehs CM, Halimi L, et al. Patient distrust in pharmaceutical companies: an explanation for women under-representation in respiratory clinical trials? BMC Med Ethics. 2020;21(1):72.
  11. Scharff DP, , Matthews, K. J., Jackson, P. et al. More than Tuskegee: Understanding mistrust about research participation. J Health Care Poor Underserved. 2010;21:879-897.
  12. Sullivan PS, Khosropour CM, Luisi N, et al. Bias in online recruitment and retention of racial and ethnic minority men who have sex with men. J Med Internet Res. 2011;13(2):e38.
  13. Clark LT, Watkins L, Pina IL, et al. Increasing Diversity in Clinical Trials: Overcoming Critical Barriers. Curr Probl Cardiol. 2019;44(5):148-172.
  14. Barnett J, Aguilar S, Brittner M, Bonuck K. Recruiting and retaining low-income, multi-ethnic women into randomized controlled trials: successful strategies and staffing. Contemp Clin Trials. 2012;33(5):925-932.