Women's views about contraception requirements for biomedical research participation.

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.

Research with pregnant women: a call to action.

Despite a global need for the use of medication during pregnancy, the medical research community lacks robust evidence for safety and efficacy of treatments and preventives often taken by pregnant women. Given the biological differences between pregnant women and the rest of the population, the need to gather data on the ways in which medications behave in the pregnant body is critical to the health of pregnant women and their offspring. Three ethical reasons are central to this need: 1. Pregnant women deserve access to effective treatment, 2. Pregnant women deserve access to safe treatment, and 3. Pregnant women deserve equitable access to trials carrying the prospect of direct benefit. In this paper, we introduce and frame this Supplement Issue, which presents important conference proceedings of the 2016 Global Forum on Bioethics in Research meeting held in Buenos Aires, Argentina, on the 3rd and 4th of November.

Toward an ethically responsible approach to vaginal birth after cesarean.

Determining approach to delivery after a previous cesarean is among the most contentious areas of obstetrics. We present a framework for ethically responsible guidelines and practice regarding vaginal birth after cesarean. We describe ethical complexities of 3 key issues that mark the debate: the cesarean delivery rate, safety, and patient autonomy. We then describe a taxonomy of considerations that should inform a responsible framework for guideline development and highlight critical distinctions between types of guidelines that have been blurred in the past. We then forward 2 central claims. First, in otherwise uncomplicated birth after a single previous cesarean, both vaginal birth after cesarean and repeat cesarean should be regarded as reasonable options; women, rather than policymakers, providers, insurance carriers, or hospitals, should determine delivery approach. Second, in complicated cases, providers and policymakers should carefully calibrate the strength of evidence to ensure differential risk and cost are adequate to justify directive guidelines given important variations in values women bring to childbirth.

The National Children's Study: a golden opportunity to advance the health of pregnant women.

With a $3 billion investment by the federal government, the National Children's Study (NCS) recently began recruitment. The NCS is a golden-and potentially missed-opportunity to study one of the most underrepresented populations in clinical research: pregnant women. As the nation's largest-ever study of children's health, the NCS will examine the effects of the environment on children from before birth to 21 years of age, with participants sampled primarily through women during pregnancy. Thus the NCS presents a rare opportunity to study the health of women during and after pregnancy, in addition to the health of their children. On both moral and policy grounds, we make the case for inclusion of women's health outcomes in the NCS.

Risk and the pregnant body.

Reasoning well about risk is most challenging when a woman is pregnant, for patient and doctor alike. During pregnancy, we tend to note the risks of medical interventions without adequately noting those of failing to intervene, yet when it's time to give birth, interventions are seldom questioned, even when they don't work. Meanwhile, outside the clinic, advice given to pregnant women on how to stay healthy in everyday life can seem capricious and overly cautious. This kind of reasoning reflects fear, not evidence.

Mode of delivery: toward responsible inclusion of patient preferences.

Deciding when and how to incorporate patient preferences regarding mode of delivery is challenging for both obstetric providers and policymakers. An analysis of current guidelines in four clinical scenarios (prior cesarean, twin delivery, breech presentation, and maternal request for cesarean) indicates that some guidelines are highly prescriptive whereas others are more flexible, based on physicians' discretion or (less frequently) patient preferences, without consistency or explicit rationale for when such flexibility is permissible, advisable, or obligatory. Although patient-choice advocates have called for more patient-responsive guidelines, concerns also have been raised, especially in the context of discussions of cesarean delivery on maternal request, about the dangers of unfettered patient-preference-driven clinical decisions. In this article, we outline a framework for the responsible inclusion of patient preferences into decision making regarding approach to delivery. We conclude, using this framework, that more explicit incorporation of patient preferences is called for in the first three scenarios and indicate why expanding access to cesarean delivery on maternal request is more complicated and would require more data and further consideration.

The second wave: Toward responsible inclusion of pregnant women in research.

Though much progress has been made on inclusion of non-pregnant women in research, thoughtful discussion about including pregnant women has lagged behind. We outline resulting knowledge gaps and their costs and then highlight four reasons why ethically we are obliged to confront the challenges of including pregnant women in clinical research. These are: the need for effective treatment for women during pregnancy, fetal safety, harm from the reticence to prescribe potentially beneficial medication, and the broader issues of justice and access to benefits of research participation. Going forward requires shifting the burden of justification from inclusion to exclusion and developing an adequate ethical framework that specifies suitable justifications for excluding pregnant women from research.

Risks, values, and decision making surrounding pregnancy.

Assessing, communicating, and managing risk are among the most challenging tasks in the practice of medicine and are particularly difficult in the context of pregnancy. We analyze common scenarios in medical decision making around pregnancy, from reproductive health policy and clinical care to research protections. We describe three tendencies in these scenarios: 1) to consider the probabilities of undesirable outcomes alone, in isolation from women's values and social contexts, as determinative of individual clinical decisions and health policy; 2) to regard any risk to the fetus, including incremental risks that would in other contexts be regarded as acceptable, as trumping considerations that may be substantially more important to the wellbeing of the pregnant woman; and 3) to focus on the risks associated with undertaking medical interventions during pregnancy to the exclusion of demonstrable risks to both woman and fetus of failing to intervene. These tendencies in the perception, communication, and management of risk can lead to care that is neither evidence-based nor patient-centered, often to the detriment of both women and infants.

Procreative liberty, biological connections, and motherhood.

Given the complex and dramatic array of issues currently facing us in reproductive ethics, bioethicists working on the topic might be forgiven feelings of trepidation when they cast their minds toward the next century. Currently, technologies such as artificial insemination by donor (AID), once the source of intense controversy, are used on a routine basis; mainstream newspapers carry advertisements offering "excellent compensation" to ova "donors;" courts are arguing whether women who serve as gestational or "surrogate" mothers have any parental rights; and proposals resurface to jail pregnant women who take street drugs. Sorting out which developments are to be welcomed and which are to be resisted -- and why -- will require us not only to clarify some of our most basic value commitments, but also to reflect on our understanding of concepts, such as motherhood, that we previously had the luxury of thinking obvious. Let me highlight two issues I think we will be forced to confront as we try to navigate the ethics of reproduction into the twenty-first century -- namely, the value of biological connection and the meaning of motherhood.