A qualitative study on stakeholders\u2019 views on the participation of pregnant women in the APOSTEL VI study: a low-risk obstetrical RCT

BackgroundThere is ambiguity with regard to what counts as an acceptable level of risk in clinical research in pregnant women and there is no input from stakeholders relative to such research risks. The aim of our paper was to explore what stakeholders who are actively involved in the conduct of clinical research in pregnant women deem an acceptable level of risk for pregnant women in clinical research. Accordingly, we used the APOSTEL VI study, a low-risk obstetrical randomised controlled trial, as a case-study.MethodsWe conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed healthcare professionals, Research Ethics Committee members (RECs) and regulators who are actively involved in the conduct of clinical research in pregnant women, in addition to pregnant women recruited for the APOSTEL VI case-study in the Netherlands.ResultsThree themes characterise the way stakeholders view risks in clinical research in pregnant women in general. Additionally, one theme characterises the way healthcare professionals and pregnant women view risks with respect to the case-study specifically. First, ideas on what constitutes an acceptable level of risk in general ranged from a preference for zero risk for the foetus up to minimal risk. Second, the desirability of clinical research in pregnant women in general was questioned altogether. Third, stakeholders proposed to establish an upper limit of risk in potentially beneficial clinical research in pregnant women in order to protect the foetus and the pregnant woman from harm. Fourth and finally, the case-study illustrates that healthcare professionals’ individual perception of risk may influence recruitment.ConclusionsHealthcare professionals, RECs, regulators and pregnant women are all risk adverse in practice, possibly explaining the continuing underrepresentation of pregnant women in clinical research. Determining the acceptable levels of risk on a universal level alone is insufficient, because the individual perception of risk also influences behaviour towards pregnant women in clinical research. Therefore, bioethicists and researchers might be interested in changing the perception of risk, which could be achieved by education and awareness about the actual benefits and harms of inclusion and exclusion of pregnant women.

Canadian physician perspectives on the inclusion of pregnant women in trials of intervention for COVID-19

INTRODUCTION: In contrast to many areas of health research, the field of HIV/AIDS has pursued research with pregnant women as a key component of its research agenda. Several large trials have made vivid a number of critical ethical questions for research with pregnant women broadly--including how risks and benefits can and should be traded off between the woman, the fetus, and the future child--offering an important opportunity for building an adequate ethical framework for research in pregnancy, more generally. METHODS: As a part of a multidisciplinary research project addressing barriers and opportunities to conducting research with pregnant women (the PHASES project--Pregnancy and HIV/AIDS: Seeking Equitable Study), we examined several large HIV network studies conducted in the last five years that required risk/benefit tradeoffs between woman, fetus and future child in conjunction with U.S. research regulations and the research ethics literature. Selected studies were analyzed in conjunction with U.S. research regulations and the research ethics literature. RESULTS: We describe three challenging tradeoff scenarios encountered in HIV network studies and develop an approach that is consistent with US regulations governing research with pregnant women. CONCLUSION: The inclusion of pregnant women in clinical research can be justified based on 1) the prospect of direct and indirect benefit to fetus; 2) the imposition of no more than minimal risk for studies involving no prospect of benefit to fetus; or 3) a reasonable ratio of maternal benefit to fetal risk. Tradeoffs between the fetus and the future child risk should be responsive to potential participants’ values.

View of Volume 66, Special Issue, September 2021 Although the inclusion of pregnant women in clinical research has been widely promoted over the last decade, there is still a lack of evidence-based knowledge concerning risk and efficacy of medications used for obstetric and non-obstetric illnesses. It has been argued that solidarity is of key importance in changing the status quo for the group of rare disease patients, for whom, just like pregnant women, a poor evidence-base exists regarding treatments. Therefore, we explore the potential role of solidarity in changing the status quo in the field of pregnant women. By way of an in-depth analysis of the concept of solidarity developed by Barbara Prainsack and Alena Buyx, we assess the role of solidarity in the group of rare disease patients and apply the conditions for solidarity to the group of pregnant women. From this analysis, we derive three lessons for the group of pregnant women: 1) being able to self-organize can have a significant effect on the ability to demand change, 2) organizing and action can be triggered by commonalities, such as shared experiences 3) enabling change involves enacted commitments to accept a cost to assist others with whom one recognizes a similarity in a relevant respect. In this presentation, we argue that an active involvement of pregnant women described as an act of solidarity should be stimulated. With that, engagement and solidarity from other stakeholders involved are necessary to raise awareness about the shared experiences of pregnant women and to realize the infrastructure for active involvement.

Inclusion of pregnant and breastfeeding women in nonobstetrical randomized controlled trials

Cultural differences between researchers and potential participants in clinical trials could result in communication barriers, which are likely to hinder awareness and pose challenges to the informed consent process. An intercultural communication approach to the informed consent process could facilitate potential participants’ understanding; strategies such as the involvement of family members, cultural insiders, cultural mediators during the consent process should be adopted to overcome language and cultural barriers. The article highlights as well barriers related to the interaction between gender and multicultural issues in cross-cultural communication and stresses some culturally-sensitive strategies for the inclusion of pregnant women in clinical research. Consent procedures tailored to local cultural patterns with a focus on the use of new technologies are discussed.

BackgroundNotwithstanding the need to produce evidence-based knowledge on medications for pregnant women, they remain underrepresented in clinical research. Sometimes they are excluded because of their supposed vulnerability, but there are...

The article deals with the need of compulsory participation of pregnant women in clinical research of drugs. By the beginning of the 90‑s of the last century, the majority of drugs prescribed to women was characterized by unsubstantial evidence of effectiveness and safety for women. Moreover, pregnant women almost did not participate in clinical research. Though pregnancy is a dynamic condition that can be compared with itself only. Then supervisory bodies created some documents regulating compulsory participation of the population in the research of drugs. However, until now, women are not sufficiently involved in the research of new original drugs, and pregnant women do the same very rarely. Possible scenarios of participation of pregnant women in clinical research have been reviewed. In particular, research of drugs used in therapy of abnormal conditions associated with pregnancy; drugs to treat chronic and acute pathological processes not related to pregnancy, and when a woman gets pregnant during the research have been distinguished. The importance of inclusion of pregnant women into the trials of effectiveness and safety of drugs in the presence of socially significant diseases, including the ones found during COVID‑19 pandemics, is postulated.

Pregnant women had a large demand for diagnosis and treatment, but the clinical research was not sufficient, and there were many barriers for pregnant women to participate in clinical research. This study aimed to systematically identify these barriers and facilitators, map them with Theoretical Domains Framework (TDF) and Behavior Change Techniques (BCTs) to inform the development of interventions promoting pregnant women's involvement in clinical research. This was a mixed-methods systematic review. PubMed, Embase, Cochrane Library, APA PsycInfo, CINAHL, China National Knowledge Infrastructure, WanFang, VIP Database for Chinese Technical Periodicals, Chinese Biomedical Literature Database, and related references were searched. Qualitative, quantitative, and mixed-methods studies exploring barriers and facilitators to pregnant women's participation in clinical trials were included. The barriers and facilitators were extracted, after transforming the quantitative data into qualitative data, all qualitative data were used to thematic synthesis. The identified barriers and facilitators were mapped into TDF and BCTs. A total of 103 studies (66 qualitative, 24 quantitative, and 13 mixed-methods) were included. Three main themes were formed: personal factors, environmental factors and research characteristics, with identified barriers and facilitators within each theme. "Knowledge," "Environmental Context and Resources," and "Beliefs about Consequences" were the main domains where barriers and facilitators identified by pregnant women and researchers were mapped in TDF. Additionally, the barriers and facilitators identified by pregnant women also mapped on "Social Influences" and "Goals." "Instruction on how to perform a behavior," "restructuring the physical environment," "salience of consequences," "social support (unspecified)," "goal setting (outcome)" were the main BCTs identified based on barriers and facilitators. The barriers and facilitators to clinical research participation identified in this study involved three main themes of personal, environmental, and research characteristics, which mainly mapped to five TDF domains. Based on these barriers and facilitators, 23 BCTs were identified. Future research should focus on developing behavior change interventions, assessing their efficacy and implementability.

Pregnant women deserve more from clinical research. Justice requires a research agenda that adequately addresses the health needs of pregnant women, and fair inclusion criteria that support the safe and responsible participation of pregnant women in relevant research. In recent years, there have been successful global efforts to expand paediatric clinical research and to achieve appropriate gender balance in clinical trials. Significant challenges remain, however, with respect to the fair inclusion of pregnant women in clinical research. Indeed, pregnant women continue to be routinely excluded from such research without justification beyond the generic beliefs that vulnerable foetuses must be protected from research-related harm and that one effective way to meet this obligation is to exclude pregnant women from clinical research.

U.S. researchers and scholars often point to two legal factors as significant obstacles to the inclusion of pregnant women in clinical research: the Department of Health and Human Services' regulatory limitations specific to pregnant women's research participation and the fear of liability for potential harm to children born following a pregnant woman's research participation. This article offers a more nuanced view of the potential legal complexities that can impede research with pregnant women than has previously been reflected in the literature. It reveals new insights into the role of legal professionals throughout the research pathway, from product conception to market, and it highlights a variety of legal factors influencing decision-making that may slow or halt research involving pregnant women. Our conclusion is that closing the evidence gap created by the underrepresentation and exclusion of pregnant women in research will require targeted attention to the role of legal professionals and the legal factors that influence their decisions.

BackgroundSince pregnant women are severely underrepresented in clinical research, many take the position that the exclusion of pregnant women from research must be justified unless there are compelling “scientific reasons” for their exclusion. However, it is questionable whether this approach renders research with pregnant women fair. This paper analyzes and evaluates when research with pregnant women can be considered as fair and what constitutes scientific reasons for exclusion.MethodsConceptual ethical and methodological analysis and evaluation of fair inclusion.ResultsFair inclusion of pregnant women means (1) that pregnant women who are eligible are not excluded solely for being pregnant and (2) that the research interests of pregnant women are prioritized, meaning that they ought to receive substantially more attention. Fairness does not imply that pregnant women should be included in virtually every research project, as including only a few pregnant women in a population consisting only of women will not help to determine the effectiveness and safety of a treatment in pregnant women. Separate trials in pregnant women may be preferable once we assume, or know, that effects of interventions in pregnant women differ from the effects in other subpopulations, or when we assume, or know, that there are no differences. In the latter case, it may be preferable to conduct post-marketing studies or establish registries. If there is no conclusive evidence indicating either differences or equivalence of effects between pregnant and non-pregnant women, yet it seems unlikely that major differences or exact equivalence exist, the inclusion of pregnant women should be sufficient. Depending on the research question, this boils down to representativeness in terms of the proportion of pregnant and non-pregnant women, or to oversampling pregnant women.ConclusionsFair inclusion of pregnant women in research implies that separate trials in pregnant women should be promoted. Inclusion of pregnant women has to be realized at the earliest phases of the research process. In addition to researchers and research ethics committees, scientific advisory councils, funders, drug regulatory agencies, pharmaceutical companies, journal editors and others have a joint responsibility to further develop the evidence base for drug use in pregnant women.

Enrolling Pregnant Women: Issues in Clinical 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.

Historically, women have been underrepresented in clinical research, requiring physicians to extrapolate medical recommendations for women from clinical research done in cohorts consisting predominantly of male participants. While government-funded clinical research has achieved gender parity in phase-3 clinical trials across many biomedical disciplines, improvements are still needed in several facets of women's health research, such as the inclusion of women in early-phase clinical trials, the inclusion of pregnant women and women with physical and intellectual disabilities, the consideration of sex as a biological variable in preclinical research, and the analysis and reporting of sex and gender differences across the full biomedical research continuum. The National Institutes of Health (NIH) Office of Research on Women's Health and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the 25th Annual Women's Health Congress, held in Arlington, VA in April, 2017, to highlight gains made and remaining needs regarding the representation of women in clinical research, to introduce innovative procedures and technologies, and to outline revised policy for future studies. Six speakers presented information on a range of subjects related to the representation of women in clinical research and federal initiatives to advance precision medicine. Topics included the following: the return on investment from the NIH-funded Women's Health Initiative; progress in including women in clinical trials for FDA-approved drugs and products; the importance of clinical trials in pregnant women; FDA initiatives to report drug safety during pregnancy; the NIH-funded All of Us Research Program; and efforts to enhance FDA transparency and communications, including the introduction of Drug Trials Snapshots. This article summarizes the major points of the presentations and the discussions that followed.