Ethical and policy issues in cluster randomized trials

 
 

Overview

Our understanding of the ethics of research is largely based on the paradigm of individually randomized controlled trials in which patients are randomly allocated to differing treatments and then followed for outcomes. Cluster randomized trials (CRTs) differ from individually randomized trials in that intact social units—rather than individuals—are randomly allocated to study interventions.


CRTs challenge our understanding of research ethics for two reasons. First, in a CRT, the units of randomization, experimentation, and observation may differ within a single study. Thus, determining who ought to be considered a research participant and from whom informed consent is required is not straightforward. Second, CRTs involve groups of people—whole communities, neighborhoods, hospitals, prisons, primary care practices, or school classrooms—and the moral status of groups is not well understood.

This study was funded by CIHR and brought together an international team of investigators under co-PIs Dr. Jeremy Grimshaw and Dr. Monica Taljaard at the Ottawa Hospital Research Institute and Dr. Charles Weijer. The research strategy consisted of a “mixed methods” approach which included empirical research to document current practices and conceptual research to analyze ethical issues. The empirical component of the study documented ethical issues encountered by researchers in semi-structured interviews, explored challenges faced by REBs in a three-country survey of REBs, and explored the reporting of ethical and methodological issues in CRTs in a random sample of 300 CRTs.

A series of papers in Trials systematically analyzed ethical issues in CRTs. In the introductory paper, we set out a standard ethical framework and explained how CRTs only partially fit within it. We identified six questions that must be addressed if the CRT is to be set upon a firm moral foundation. Subsequent articles addressed each of these questions: Who are research participants in CRTs? When must informed consent be obtained? Does clinical equipoise apply? How ought benefits and harms be analyzed? How should vulnerable participants be protected? What is the role and authority of gatekeepers?

The study team assembled a 19-person expert panel, consisting of leading CRT researchers, ethicists, REB members, consumer advocates, regulators, and health lawyers, that met in Ottawa on November 28-30, 2011 to draft new ethical guidelines for CRTs. Draft guidelines were written, made available for public comment, and approved by all members of the expert panel. The Ottawa Statement on the Ethics Design and Conduct of Cluster Randomized Trials was published in PLoS Medicine in November 2012.

 

Members

Principal investigators

Monica Taljaard (Ottawa Hospital Research Institute)

Jeremy Grimshaw (Ottawa Health Research Institute)

Charles Weijer (Western University)

Co-investigators

Judith Belle Brown (Western University)

Robert Boruch (University of Pennsylvania)
Jamie Brehaut (Ottawa Health Research Institute)
Allan Donner (Western University)
Martin Eccles (Newcastle University)

Raphael Saginur (Ottawa Hospital Research Institute)

Merrick Zwarenstein (Western University)

Trainees

Ariella Binik (McMaster University)

Antonio Gallo (Mount Sinai Hospital)

Andrew McRae (University of Calgary)

Angela White (Western University)

 

Media

Leading innovation in the ethics of cluster randomized trials. YouTube


Ethics in Cluster Randomized Trials Consensus Conference. Ottawa. November 28, 2012. YouTube

 

Publications

Study protocol

Taljaard M, Weijer C, Grimshaw J, Belle Brown J, Binik A, Boruch R, Brehaut JC, Chaudhry S, Eccles MP, McRae A, Saginur R, Zwarenstein M, Donner A. Study protocol: Ethical and policy issues in cluster randomized trials: rationale and design of a mixed methods research study. Trials 2009; 10: 61.


Empirical studies

Taljaard M, McGowan J, Grimshaw JM, Brehaut JC, McRae A, Eccles
MP, Donner A. Electronic search strategies to identify reports of cluster randomized trials in MEDLINE: low precision will improve with adherence to reporting standards. BMC Medical Research Methodology 2010; 10: 15.


Taljaard M, McRae A, Weijer C, Bennett C, Dixon S, Taleban J, Skea Z, Brehaut J, Eccles MP, Donner A, Saginur R, Boruch RF, Grimshaw JM. Inadequate reporting of research ethics review and informed consent in cluster randomized trials: review of a representative sample of published trials. British Medical Journal 2011; 342: d2496.


Ivers N, Taljaard M, Dixon S, Bennett C, McRae A, Taleban J, Skea Z, Brehaut J, Boruch RF, Eccles M, Grimshaw JM, Weijer C, Zwarenstein M, Donner A. Impact of the CONSORT extension for cluster randomised trials on quality of reporting and study methodology: review of a random sample of 300 trials from 2000 to 2008. British Medical Journal 2011; 343: d5886.


McRae AD, Bennett C, Brown JB, Weijer C, Boruch R, Brehaut J, Chaudhry S, Donner A, Eccles M, Grimshaw J, Zwarenstein M, Taljaard M. Researchers’ perceptions of ethical challenges in cluster randomized trials: A qualitative analysis. Trials 2013; 14: 1.


McRae AD, Taljaard M, Weijer C, Bennett C, Skea Z, Boruch R, Brehaut J, Eccles MP, Grimshaw JM, Donner A. Reporting of patient consent in healthcare cluster randomized trials is associated with the type of study interventions and publication characteristics. Journal of Medical Ethics 2013; 39(2): 119–24.


Chaudhry SH, Brehaut JC, Grimshaw JM, Weijer C, Boruch R, Donner A, Eccles MP, McRae AD, Saginur R, Skea ZC, Zwarenstein M, Taljaard M. Challenges in the research ethics review of cluster randomized trials: International survey of investigators. Clinical Trials 2013; 10(2): 257–68.


Taljaard M, Chaudhry SH, Brehaut JC, Weijer C, Boruch R, Donner A, Eccles MP, McRae AD, Saginur R, Zwarenstein M, Grimshaw JG. Survey of consent practices in cluster randomized trials: improvements are needed in ethical conduct and reporting. Clinical Trials 2014; 11(1): 60–69.


Taljaard M, Brehaut JC, Weijer C, Boruch R, Donner A, Eccles MP, McRae AD, Saginur R, Zwarenstein M, Grimshaw JM. Variability in research ethics review of cluster randomized trials: Scenario-based survey in three countries. Trials 2014; 15: 48.



Ethical analyses

Weijer C, Grimshaw JM, Taljaard M, Binik A, Boruch R, Brehaut JC, Donner A, Eccles MP, Gallo A, McRae AD, Saginur R, Zwarenstein M. Ethical issues posed by cluster randomized trials in health research. Trials 2011; 12: 100.


McRae AD, Weijer C, Binik A, White A, Grimshaw JM, Baruch R, Brehaut JC, Donner A, Eccles M, Saginur R, Zwarenstein, M Taljaard M. Who is the research subject in cluster randomized trials? Trials 2011; 12: 183.


McRae AD, Weijer C, Binik A, Grimshaw JM, Baruch R, Brehaut JC, Donner A, Eccles MP, Saginur R, White A, Taljaard M. When is informed consent required in cluster randomized trials in health research? Trials 2011; 12: 202.


Binik A, Weijer C, McRae AD, Grimshaw JM, Baruch R, Brehaut JC, Donner A, Eccles MP, Saginur R, Taljaard M, Zwarenstein M. Does clinical equipoise apply to cluster randomized trials in health research? Trials 2011: 12: 118.


Gallo A, Weijer C, White A, Grimshaw JM, Baruch R, Brehaut JC, Donner A, Eccles MP, McRae AD, Saginur R, Zwarenstein M, Taljaard M. What is the role and authority of gatekeepers in cluster randomized trials in health research? Trials 2012; 13: 116.



Guidelines

Weijer C, Grimshaw JM, Eccles MP, McRae AD, White A, Brehaut JC, Taljaard M and the Ottawa Ethics of Cluster Randomized Trials Consensus Group. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials. PLoS Medicine 2012; 9(11): e1001346. [9 pages]



Using the guidelines

Taljaard M, Weijer C, Grimshaw JM, Eccles MP and the Ottawa Ethics of Cluster Randomized Trials Consensus Group. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomised Trials: A précis for researchers and research ethics committees. British Medical Journal 2013; 346: f2838.


Taljaard M, Weijer C, Grimshaw J. Ethical issues in cluster randomized trials in knowledge translation. In: Strauss SE, Tetroe J, Graham ID (eds.). Knowledge Translation in Health Care. Second edition. Oxford: BMJ Books, Wiley Blackwell, 2013: pp. 378–391.


Weijer C, Taljaard M, Grimshaw JM, Edwards SJL, Eccles MP and the Ottawa Ethics of Cluster Randomized Trials Consensus Group. The Ottawa statement on the ethical design and conduct of cluster randomized trials: a short report. Research Ethics 2014; 10(2): 77–85.


Taljaard M, Weijer C, Grimshaw JM. Ethical implications of cluster randomized trials. International Encyclopedia of the Social and Behavioral Sciences (2nd ed.) 2015: 897–905.

 

©2020 Charles Weijer