Stepped-wedge trials should be classified as research for the purpose of ethical review

Background: All studies classified as research involving human participants require research ethics review. Most regulation and guidance on ethical oversight of research involving human participants was written for pharmacotherapy interventions. Interpretation of such guidance for cluster-randomized trials and stepped-wedge trials, which commonly evaluate complex non-therapeutic interventions such as knowledge translation, public health, or health service delivery interventions, can pose challenges to researchers and regulators. Current guidance: The Ottawa Statement on the Ethical Design and Conduct of Cluster-Randomized Trials provides guidance on the ethical oversight and consent procedures for cluster-randomized trials, and while not explicit, this includes stepped-wedge trials. Yet, stepped-wedge trials have unique characteristics that differentiate them from standard cluster-randomized trials. In particular, they can be used to evaluate knowledge translation interventions within the context of a routine health system rollout; they may have a non-randomized design; and the decision to implement the intervention is not always made by the researcher. Many stepped-wedge trials do not undergo ethical review and do not report trial registration. This suggests that those undertaking these studies and research ethics committees perceive them as non-research activities. Recommendations: Through an ethical analysis of two case studies, we argue that stepped-wedge trials, like parallel arm cluster trials, are systematic investigations designed to produce generalizable knowledge. We contend that stepped-wedge trials usually include human research participants, which may be patients, health care providers, or both. Stepped-wedge trials are therefore research involving human participants for the purpose of ethical review. Nevertheless, the use of a waiver or alteration of consent may be appropriate in many stepped-wedge trials due to the infeasibility of obtaining informed consent and the low-risk nature of the interventions. To ensure that traditional ethical principles such as respect for persons are upheld, these studies must undergo research ethics review.

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Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review

Clinical Trials ◽

10.1177/1740774517703057 ◽

2017 ◽

Vol 14 (4) ◽

pp. 333-341 ◽

Cited By ~ 14

Author(s):

Monica Taljaard ◽

Karla Hemming ◽

Lena Shah ◽

Bruno Giraudeau ◽

Jeremy M Grimshaw ◽

...

Keyword(s):

Informed Consent ◽

Research Ethics ◽

Randomized Trials ◽

Cluster Randomized Trials ◽

Stepped Wedge ◽

Research Participants ◽

Ethics Review ◽

Research Ethics Review ◽

Stepped Wedge Trials ◽

Cluster Randomized

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants—yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28%) had no identifiable data collected from any research participants. Overall, only three trials (9%) indicated that a waiver of consent had been granted by a research ethics committee. When considering the combined requirement of research ethics review and informed consent (or a waiver), only one in three studies were compliant. Conclusion The ethical conduct and reporting of key ethical protections in stepped wedge trials, namely, research ethics review and informed consent, are inadequate. We recommend that stepped wedge trials be classified as research and reviewed and approved by a research ethics committee. We also recommend that researchers appropriately identify research participants (which may include health professionals), seek informed consent or appeal to an ethics committee for a waiver of consent, and include explicit details of research ethics approval and informed consent in the trial report.

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Challenges in the research ethics review of cluster randomized trials: International survey of investigators

Clinical Trials ◽

10.1177/1740774513475530 ◽

2013 ◽

Vol 10 (2) ◽

pp. 257-268 ◽

Cited By ~ 13

Author(s):

Shazia H Chaudhry ◽

Jamie C Brehaut ◽

Jeremy M Grimshaw ◽

Charles Weijer ◽

Robert Boruch ◽

...

Keyword(s):

Research Ethics ◽

Randomized Trials ◽

International Survey ◽

Cluster Randomized Trials ◽

Ethics Review ◽

Research Ethics Review ◽

Cluster Randomized

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Statistical Properties of Stepped Wedge Cluster-Randomized Trials in Infectious Disease Outbreaks

10.1101/2020.05.01.20087429 ◽

2020 ◽

Cited By ~ 1

Author(s):

Lee Kennedy-Shaffer ◽

Marc Lipsitch

Keyword(s):

Infectious Disease ◽

Randomized Trials ◽

Disease Outbreaks ◽

Statistical Properties ◽

Cluster Randomized Trials ◽

Stepped Wedge ◽

Infectious Disease Outbreaks ◽

New Methods ◽

Stepped Wedge Trials ◽

Cluster Randomized

ABSTRACTRandomized controlled trials are crucial for the evaluation of interventions such as vaccinations, but the design and analysis of these studies during infectious disease outbreaks is complicated by statistical, ethical, and logistical factors. Attempts to resolve these complexities have led to the proposal of a variety of trial designs, including individual randomization and several types of cluster randomization designs: parallel-arm, ring vaccination, and stepped wedge designs. Because of the strong time trends present in infectious disease incidence, however, methods generally used to analyze stepped wedge trials may not perform well in these settings. Using simulated outbreaks, we evaluate various designs and analysis methods, including recently proposed methods for analyzing stepped wedge trials, to determine the statistical properties of these methods. While new methods for analyzing stepped wedge trials can provide some improvement over previous methods, we find that they still lag behind parallel-arm cluster-randomized trials and individually-randomized trials in achieving adequate power to detect intervention effects. We also find that these methods are highly sensitive to the weighting of effect estimates across time periods. Despite the value of new methods, stepped wedge trials still have statistical disadvantages compared to other trial designs in epidemic settings.

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Variability in research ethics review of cluster randomized trials: a scenario-based survey in three countries

Trials ◽

10.1186/1745-6215-15-48 ◽

2014 ◽

Vol 15 (1) ◽

Cited By ~ 11

Author(s):

Monica Taljaard ◽

Jamie C Brehaut ◽

Charles Weijer ◽

Robert Boruch ◽

Allan Donner ◽

...

Keyword(s):

Research Ethics ◽

Randomized Trials ◽

Cluster Randomized Trials ◽

Ethics Review ◽

Research Ethics Review ◽

Cluster Randomized

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Statistical Properties of Stepped Wedge Cluster-Randomized Trials in Infectious Disease Outbreaks

American Journal of Epidemiology ◽

10.1093/aje/kwaa141 ◽

2020 ◽

Vol 189 (11) ◽

pp. 1324-1332 ◽

Cited By ~ 1

Author(s):

Lee Kennedy-Shaffer ◽

Marc Lipsitch

Keyword(s):

Infectious Disease ◽

Randomized Trials ◽

Disease Outbreaks ◽

Statistical Properties ◽

Cluster Randomized Trials ◽

Stepped Wedge ◽

Infectious Disease Outbreaks ◽

New Methods ◽

Stepped Wedge Trials ◽

Cluster Randomized

Abstract Randomized controlled trials are crucial for the evaluation of interventions such as vaccinations, but the design and analysis of these studies during infectious disease outbreaks is complicated by statistical, ethical, and logistical factors. Attempts to resolve these complexities have led to the proposal of a variety of trial designs, including individual randomization and several types of cluster randomization designs: parallel-arm, ring vaccination, and stepped wedge designs. Because of the strong time trends present in infectious disease incidence, however, methods generally used to analyze stepped wedge trials might not perform well in these settings. Using simulated outbreaks, we evaluated various designs and analysis methods, including recently proposed methods for analyzing stepped wedge trials, to determine the statistical properties of these methods. While new methods for analyzing stepped wedge trials can provide some improvement over previous methods, we find that they still lag behind parallel-arm cluster-randomized trials and individually randomized trials in achieving adequate power to detect intervention effects. We also find that these methods are highly sensitive to the weighting of effect estimates across time periods. Despite the value of new methods, stepped wedge trials still have statistical disadvantages compared with other trial designs in epidemic settings.

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