Gatekeeping is motivated by the general assumption of vulnerability of patients, coupled with an emphasis on the duty to protect patients. Research is easily perceived as a threat to patient well-being, and the benefits appear to be overlooked. The patients' perspective concerning study participation is needed to gain a full understanding and to address gatekeeping in palliative care research.

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.

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The only reason why pregnant women are potentially vulnerable is to the extent that they are increasingly exposed to higher risks due to a lack of scientific knowledge. Accordingly, the discussion can advance to the development of practical strategies to promote fair inclusion of pregnant women in clinical research.

The "cohort multiple randomized controlled trial," a new design for pragmatic trials, embeds multiple trials within a cohort. The cohort multiple RCT is an attractive alternative to conventional RCTs in fields where recruitment is slow, multiple new (competing) interventions for the same condition have to be tested, new interventions are highly preferred by patients and doctors, and the risk of disappointment bias, cross-over, and contamination is considerable. To prevent these unwanted effects, the cohort multiple RCT provides information on randomization to the intervention group/arm only, and only after randomization (i.e., prerandomization). To some, especially in a clinical setting, this is not ethically acceptable. In this article, we argue that prerandomization in the cohort multiple randomized controlled trial (cmRCT) can be avoided by adopting a staged-informed consent procedure. In the first stage, at entry into the cohort, all potential participants are asked for their informed consent to participate in a cohort study and broad consent to be either randomly selected to be approached for experimental interventions or to serve as control without further notice during participation in the cohort. In a second stage, at the initiation of an RCT within the cohort, informed consent to receive the intervention is then only sought in those randomly selected for the intervention arm. At the third stage, after completion of each RCT, all cohort participants receive aggregate disclosure of trial results. This staged-informed consent procedure avoids prerandomization in cmRCT and aims to keep participants actively engaged in the research process.

ObjectivesTo systematically review reasons for the willingness to participate in biomedical human subjects research in low‐ and middle‐income countries (LMICs).MethodsFive databases were systematically searched for articles published between 2000 and 2017 containing the domain of ‘human subjects research’ in ‘LMICs’ and determinant ‘reasons for (non)participation’. Reasons mentioned were extracted, ranked and results narratively described.ResultsNinety‐four articles were included, 44 qualitative and 50 mixed‐methods studies. Altruism, personal health benefits, access to health care, monetary benefit, knowledge, social support and trust were the most important reasons for participation. Primary reasons for non‐participation were safety concerns, inconvenience, stigmatisation, lack of social support, confidentiality concerns, physical pain, efficacy concerns and distrust. Stigmatisation was a major concern in relation to HIV research. Reasons were similar across different regions, gender, non‐patient or patient participants and real or hypothetical study designs.ConclusionsAddressing factors that affect (non‐)participation in the planning process and during the conduct of research may enhance voluntary consent to participation and reduce barriers for potential participants.

BackgroundVarious papers have addressed pros and cons of the stepped wedge cluster randomized trial design (SWD). However, some issues have not or only limitedly been addressed. Our aim was to provide a comprehensive overview of all merits and limitations of the SWD to assist researchers, reviewers and medical ethics committees when deciding on the appropriateness of the SWD for a particular study.MethodsWe performed an initial search to identify articles with a methodological focus on the SWD, and categorized and discussed all reported advantages and disadvantages of the SWD. Additional aspects were identified during multidisciplinary meetings in which ethicists, biostatisticians, clinical epidemiologists and health economists participated. All aspects of the SWD were compared to the parallel group cluster randomized design. We categorized the merits and limitations of the SWD to distinct phases in the design and conduct of such studies, highlighting that their impact may vary depending on the context of the study or that benefits may be offset by drawbacks across study phases. Furthermore, a real-life illustration is provided.ResultsNew aspects are identified within all disciplines. Examples of newly identified aspects of an SWD are: the possibility to measure a treatment effect in each cluster to examine the (in)consistency in effects across clusters, the detrimental effect of lower than expected inclusion rates, deviation from the ordinary informed consent process and the question whether studies using the SWD are likely to have sufficient social value. Discussions are provided on e.g. clinical equipoise, social value, health economical decision making, number of study arms, and interim analyses.ConclusionsDeciding on the use of the SWD involves aspects and considerations from different disciplines not all of which have been discussed before. Pros and cons of this design should be balanced in comparison to other feasible design options as to choose the optimal design for a particular intervention study.