Women’s views about contraception requirements for biomedical research participation

Abstract

The scientific and ethical importance of including women of reproductive age in biomedical research is widely acknowledged. Concerns about preventing fetal exposure to research interventions have motivated requirements for contraception among reproductive aged women in biomedical studies–often irrespective of risks and benefits or a woman’s actual potential for pregnancy, raising important questions about when such requirements are appropriate. The perspectives of women themselves on these issues are largely unexplored. We conducted 140 interviews, 70 in the U.S. and 70 in Malawi, with women either living with or at-risk for HIV, exploring their views about the practice of requiring contraception in clinical trials. A majority of women interviewed from both countries indicated overall support for the practice, with seven themes characterizing advantages and disadvantages raised: reproductive control, health effects, prevention of fetal harm, burden on women, deferral to authority, autonomy regarding enrollment and birth control method, and relationship concerns. While women in the US frequently raised prevention of fetal harm as a key advantage, many other positives noted by women in both countries were related to contraception use in general, not specific to a trial context. With regard to disadvantages, U.S. women tended to focus on biomedical risks such as side effects and impact on fertility, whereas Malawian women focused on the social risks of contraception requirements, including violations of trust in marital relations and suspicions of potential infidelity. Given the potential benefits and burdens highlighted, contraception in research should be sensitive to actual fetal risk assessments; directed where justified at optimizing effective pregnancy prevention; responsive to women’s reproductive preferences; and made available as an ancillary benefit even where risk thresholds do not justify requirement–in order to facilitate trials that are both ethical and robustly oriented around the interests and lives of women who will participate in them.

The HIV drug optimization agenda: promoting standards for earlier investigation and approvals of antiretroviral drugs for use in adolescents living with HIV

“…Especially in resourcelimited settings key issues pertaining to the use of contraceptives in adolescent girls such as cultural norms, religious beliefs, community perspectives and stigma (for HIV and contraceptive use), might pose major enrolment concerns and could be addressed during the trial planning phase [31]. Raising community awareness and education is also crucial [32].…”

Unintended drug exposure during pregnancy in clinical trials – a survey in early drug development

“…Despite the advice provided in the ICH M3(R2) guidance [ 2 ] and the Clinical Trial Facilitation Group (CTFG) recommendations [ 3 ], unintended pregnancies in biomedical research are still a matter of concern as evidenced in recent publications [ 4 , 5 , 6 , 7 ]. A 2018 paper [ 6 ] reports wide variation in pregnancy testing plans in clinical trials, leading to the potential for inadequate protection against embryonic or fetal exposure in some cases and unnecessary burdens on research participants in others.…”

“…An industry survey on birth control in clinical trials revealed that few companies collected data in a manner that would allow retrospective understanding of the reasons for the failure of birth control in clinical trials [ 7 ]. Among other causes, one reason for unintended pregnancies in the setting of clinical trials could be that the perspectives of women themselves on contraception in research are largely unexplored [ 4 ].…”

A retrospective analysis of incident pregnancy in Phase 1 and 2a HIV-1 vaccine study participants does not support concern for adverse pregnancy or birth outcomes

“…The studies included in our analysis that took place during the same time period as the HVTN 503 trial recorded an average incident pregnancy rate of 4.6/100 w-yr, which was higher than the 2.3/100 w-yr recorded in subsequent trials and may in part be due to increasing availability of contraception options and, at least at some sites, a more structured approach to providing on-site effective contraception during this time. Indeed, HIV prevention researchers have actively sought correlates of incident pregnancy to identify potential participants with higher pregnancy risk prior to study entry and exclude them for reasons of trial efficiency and due to the lack of pre-clinical safety data in pregnancy 10,[20][21][22] . Increasing attention is being given to addressing vaccine safety during pregnancy and the ethics of conducting vaccine research among pregnant women 8,15,16,23 , including the rights and needs of high-risk populations who generally form the study population for efficacy trials of novel HIV prevention products 24 .…”