Dataset Information

Ethical issues in the design and conduct of stepped-wedge cluster randomized trials in low-resource settings.

ABSTRACT: BACKGROUND:Stepped-wedge cluster randomized trials (SW-CRTs) are increasingly popular in health-related research in both high- and low-resource settings. There may be specific ethical issues that researchers face when designing and conducting SW-CRTs in low-resource settings. Knowledge of these issues can help to improve the ethical conduct of SW-CRTs in a global health context. METHODS:We performed an ethical analysis of two studies using SW-CRT designs in low-resource settings: the Que Vivan Las Madres study conducted from 2014 to 2017 in Guatemala and the Atmiyata study conducted from 2017 to 2018 in rural parts of India. For both case studies, we identified and evaluated the classification of the study as research or nonresearch and the ethical issues regarding the justification of the design, including the delayed rollout of an intervention that had a promising effect. RESULTS:In our case studies, some minor ethical issues surfaced about the registration and stakeholder pressure on the order of randomization, but both included good justification for the design and delayed rollout. Our analysis did, however, demonstrate that careful consideration of the role of randomization and registration of the trials is important. DISCUSSION:SW-CRTs can provide an opportunity for rigorous evaluation of interventions destined to be rolled out on the basis of limited evidence. Furthermore, in SW-CRTs, the underlying objective is often to provide a robust evaluation of the effectiveness for generalized dissemination, and this makes the SW-CRT no less a research study than any other form of cluster randomized trial. CONCLUSION:The design and conduct of stepped-wedge cluster randomized trials raises at least two ethical issues that need special consideration in both high- and low-resource settings: the justification for using the design, specifically the delayed rollout of the intervention to the control group, and the classification of the study as research or nonresearch. In our case studies, these issues did not seem to raise special ethical scrutiny in low-resource settings. Further ethical evaluation will hopefully result in specific ethical guidelines for the use of SW-CRTs in both high- and low-resource settings to contribute to responsible functioning of these trials and adequate protection of participants.

SUBMITTER: Joag K

PROVIDER: S-EPMC6921381 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ethical issues in the design and conduct of stepped-wedge cluster randomized trials in low-resource settings.

Joag Kaustubh K Ambrosio Guillermo G Kestler Edgar E Weijer Charles C Hemming Karla K Van der Graaf Rieke R

Trials 20191219 Suppl 2

<h4>Background</h4>Stepped-wedge cluster randomized trials (SW-CRTs) are increasingly popular in health-related research in both high- and low-resource settings. There may be specific ethical issues that researchers face when designing and conducting SW-CRTs in low-resource settings. Knowledge of these issues can help to improve the ethical conduct of SW-CRTs in a global health context.<h4>Methods</h4>We performed an ethical analysis of two studies using SW-CRT designs in low-resource settings: ...[more]

PMID: 31852547

Similar Datasets

Project description:BackgroundRandomized controlled trial (RCT) trial designs exist on an explanatory-pragmatic spectrum, depending on the degree to which a study aims to address a question of efficacy or effectiveness. As conceptualized by Schwartz and Lellouch in 1967, an explanatory approach to trial design emphasizes hypothesis testing about the mechanisms of action of treatments under ideal conditions (efficacy), whereas a pragmatic approach emphasizes testing effectiveness of two or more available treatments in real-world conditions. Interest in, and the number of, pragmatic trials has grown substantially in recent years, with increased recognition by funders and stakeholders worldwide of the need for credible evidence to inform clinical decision-making. This increase has been accompanied by the onset of learning healthcare systems, as well as an increasing focus on patient-oriented research. However, pragmatic trials have ethical challenges that have not yet been identified or adequately characterized. The present study aims to explore the views of key stakeholders with respect to ethical issues raised by the design and conduct of pragmatic trials. It is embedded within a large, four-year project that seeks to develop guidance for the ethical design and conduct of pragmatic trials. As a first step, this study will address important gaps in the current empirical literature with respect to identifying a comprehensive range of ethical issues arising from the design and conduct of pragmatic trials. By opening up a broad range of topics for consideration within our parallel ethical analysis, we will extend the current debate, which has largely emphasized issues of consent, to the range of ethical considerations that may flow from specific design choices.MethodsSemi-structured interviews with key stakeholders (e.g. trialists, methodologists, lay members of study teams, bioethicists, and research ethics committee members), across multiple jurisdictions, identified based on their known experience and/or expertise with pragmatic trials.DiscussionWe expect that the study outputs will be of interest to a wide range of knowledge users including trialists, ethicists, research ethics committees, journal editors, regulators, healthcare policymakers, research funders and patient groups. All publications will adhere to the Tri-Agency Open Access Policy on Publications.

Project description:Background:Pragmatic cluster randomized trials (CRTs) offer an opportunity to improve health care by answering important questions about the comparative effectiveness of treatments using a trial design that can be embedded in routine care. There is a lack of empirical research that addresses ethical issues generated by pragmatic CRTs in hemodialysis. Objective:To identify stakeholder perceptions of ethical issues in pragmatic CRTs conducted in hemodialysis. Design:Qualitative study using semi-structured interviews. Setting:In-person or telephone interviews with an international group of stakeholders. Participants:Stakeholders (clinical investigators, methodologists, ethicists and research ethics committee members, and other knowledge users) who had been involved in the design or conduct of a pragmatic individual patient or cluster randomized trial in hemodialysis, or their role would require them to review and evaluate pragmatic CRTs in hemodialysis. Methods:Interviews were conducted in-person or over the telephone and were audio-recorded with consent. Recorded interviews were transcribed verbatim prior to analysis. Transcripts and field notes were analyzed using a thematic analysis approach. Results:Sixteen interviews were conducted with 19 individuals. Interviewees were largely drawn from North America (84%) and were predominantly clinical investigators (42%). Six themes were identified in which pragmatic CRTs in hemodialysis raise ethical issues: (1) patients treated with hemodialysis as a vulnerable population, (2) appropriate approaches to informed consent, (3) research burdens, (4) roles and responsibilities of gatekeepers, (5) inequities in access to research, and (6) advocacy for patient-centered research and outcomes. Limitations:Participants were largely from North America and did not include research staff, who may have differing perspectives. Conclusions:The six themes reflect concerns relating to individual rights, but also the need to consider population-level issues. To date, concerns regarding inequity of access to research and the need for patient-centered research have received less coverage than other, well-known, issues such as consent. Pragmatic CRTs offer a potential approach to address equity concerns and we suggest future ethical analyses and guidance for pragmatic CRTs in hemodialysis embed equity considerations within them. We further note the potential for the co-creation of health data infrastructure with patients which would aid care but also facilitate patient-centered research. These present results will inform planned future guidance in relation to the ethical design and conduct of pragmatic CRTs in hemodialysis. Trial Registration:Registration is not applicable as this is a qualitative study.

Project description:BACKGROUND:Cluster randomised trials with unequal sized clusters often have lower precision than with clusters of equal size. To allow for this, sample sizes are inflated by a modified version of the design effect for clustering. These inflation factors are valid under the assumption that randomisation is stratified by cluster size. We investigate the impact of unequal cluster size when that constraint is relaxed, with particular focus on the stepped-wedge cluster randomised trial, where this is more difficult to achieve. METHODS:Assuming a multi-level mixed effect model with exchangeable correlation structure for a cross-sectional design, we use simulation methods to compare the precision for a trial with clusters of unequal size to a trial with clusters of equal size (relative efficiency). For a range of scenarios we illustrate the impact of various design features (the cluster-mean correlation - a function of the intracluster correlation and the cluster size, the number of clusters, number of randomisation sequences) on the average and distribution of the relative efficiency. RESULTS:Simulations confirm that the average reduction in precision, due to varying cluster sizes, is smaller in a stepped-wedge trial compared to the parallel trial. However, the variance of the distribution of the relative efficiency is large; and is larger under the stepped-wedge design compared to the parallel design. This can result in large variations in actual power, depending on the allocation of clusters to sequences. Designs with larger variations in cluster sizes, smaller number of clusters and studies with smaller cluster-mean correlations (smaller cluster sizes or smaller intra-cluster correlation) are particularly at risk. CONCLUSION:The actual realised power in a stepped-wedge trial might be substantially higher or lower than that estimated. This is particularly important when there are a small number of clusters or the variability in cluster sizes is large. Constraining the randomisation on cluster size, where feasible, might mitigate this effect.

Dataset Information

Ethical issues in the design and conduct of stepped-wedge cluster randomized trials in low-resource settings.

Publications

Ethical issues in the design and conduct of stepped-wedge cluster randomized trials in low-resource settings.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets