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.

[1]  J. Grimshaw,et al.  Accommodating quality and service improvement research within existing ethical principles , 2018, Trials.

[2]  A. Zgierska,et al.  Enhancing system-wide implementation of opioid prescribing guidelines in primary care: protocol for a stepped-wedge quality improvement project , 2018, BMC Health Services Research.

[3]  Lihui Zhao,et al.  Effect of a Quality Improvement Intervention on Clinical Outcomes in Patients in India With Acute Myocardial Infarction: The ACS QUIK Randomized Clinical Trial , 2018, JAMA.

[4]  J. Grimshaw,et al.  Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review , 2017, Clinical trials.

[5]  Mark D. Huffman,et al.  Acute coronary syndrome quality improvement in Kerala (ACS QUIK): Rationale and design for a cluster‐randomized stepped‐wedge trial , 2017, American heart journal.

[6]  J. Wason,et al.  Stepped wedge cluster randomized controlled trial designs: a review of reporting quality and design features , 2017, Trials.

[7]  J. Menikoff,et al.  The Common Rule, Updated. , 2017, The New England journal of medicine.

[8]  Rieke van der Graaf,et al.  International Ethical Guidelines for Health-related Research involving Humans , 2017 .

[9]  C. Grady,et al.  Deciphering assumptions about stepped wedge designs: the case of Ebola vaccine research , 2016, Journal of Medical Ethics.

[10]  Susan Michie,et al.  Explanation and elaboration of the SQUIRE (Standards for Quality Improvement Reporting Excellence) Guidelines, V.2.0: examples of SQUIRE elements in the healthcare improvement literature , 2016, BMJ Quality & Safety.

[11]  B. Thombs,et al.  Transparency of Outcome Reporting and Trial Registration of Randomized Controlled Trials Published in the Journal of Consulting and Clinical Psychology , 2015, PloS one.

[12]  J. Carroll,et al.  Ethical oversight in quality improvement and quality improvement research: new approaches to promote a learning health care system , 2015, BMC medical ethics.

[13]  D. Osrin,et al.  Logistic, ethical, and political dimensions of stepped wedge trials: critical review and case studies , 2015, Trials.

[14]  R J Lilford,et al.  The stepped wedge cluster randomised trial: rationale, design, analysis, and reporting , 2015, BMJ : British Medical Journal.

[15]  M. Bottrell.  The Ethics of Quality Improvement : Practitioners ’ Perspectives Ms , 2014 .

[16]  Steven N Goodman,et al.  The research-treatment distinction: a problematic approach for determining which activities should have ethical oversight. , 2013, The Hastings Center report.

[17]  Steven N Goodman,et al.  An ethics framework for a learning health care system: a departure from traditional research ethics and clinical ethics. , 2013, The Hastings Center report.

[18]  J. Grimshaw,et al.  The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials , 2012, PLoS medicine.

[19]  Celia A Taylor nee Brown,et al.  Systematic review of stepped wedge cluster randomized trials shows that design is particularly used to evaluate interventions during routine implementation. , 2011, Journal of clinical epidemiology.

[20]  R. Savel,et al.  Critical care checklists, the Keystone Project, and the Office for Human Research Protections: A case for streamlining the approval process in quality-improvement research* , 2009, Critical care medicine.

[21]  M. A. Baily,et al.  Harming through protection? , 2008, The New England journal of medicine.

[22]  M. Bottrell.  The Ethics of Quality Improvement : Practitioners ’ Perspectives , 2003 .

[23]  J. Karlawish,et al.  Determining when quality improvement initiatives should be considered research: proposed criteria and potential implications. , 2000, JAMA.