There 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. We conducted a prospective qualitative study using 35 in-depth semi-structured interviews and one focus group. We interviewed healthcare professionals, Research Ethics Committee members 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. Three 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. Healthcare 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. (shrink)

Recruitment challenges in clinical research are widespread, particularly for traditionally under-represented groups. Referral relationships—in which research partners and clinical partners agree to collaborate on selected research studies or programmes, with the expectation that the clinical partners refer appropriate patients as potential participants—may help alleviate these challenges. Referral relationships allow research partners access to expanded and more diverse pools of participants by increasing the engagement of medical providers, leveraging providers’ connections with patients and providing structural support for study participation. Clinical partners (...) can also benefit from the resources offered by research involvement, and patients may benefit from improved access to studies. Yet despite their potential, referral relationships can raise ethical concerns. Here, we discuss ethical considerations for referral relationships in clinical research to address these concerns. When establishing relationships, fair participant selection should guide the sites and studies involved. When defining the terms of a relationship, partners should build trust and respect, collaborating so that health centres or hospitals and communities benefit from their research involvement with the mitigation of associated burdens. When implemented, referral relationships should continue to honour fair participant selection, reduce misunderstanding or miscommunication about research and protect patients’ privacy and confidentiality. Overall, when conducted ethically, referral relationships can help address study recruitment challenges and promote fair access to research opportunities. (shrink)