Developing a framework for the ethical design and conduct of pragmatic trials in healthcare: a mixed methods research protocol

Monica Taljaard (Corresponding Author), Charles Weijer, Jeremy M Grimshaw, Adnan Ali, Jamie C Brehaut, Marion K Campbell, Kelly Carroll, Sarah Edwards, Sandra Eldridge, Christopher B Forrest, Bruno Giraudeau, Cory E Goldstein, Ian D Graham, Karla Hemming, Spencer Phillips Hey, Austin R Horn, Vipul Jairath, Terry P Klassen, Alex John London, Susan MarlinJohn C Marshall, Lauralyn McIntyre, Joanne E McKenzie, Stuart G Nicholls, P Alison Paprica, Merrick Zwarenstein, Dean A Fergusson

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
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BACKGROUND: There is a widely recognized need for more pragmatic trials that evaluate interventions in real-world settings to inform decision-making by patients, providers, and health system leaders. Increasing availability of electronic health records, centralized research ethics review, and novel trial designs, combined with support and resources from governments worldwide for patient-centered research, have created an unprecedented opportunity to advance the conduct of pragmatic trials, which can ultimately improve patient health and health system outcomes. Such trials raise ethical issues that have not yet been fully addressed, with existing literature concentrating on regulations in specific jurisdictions rather than arguments grounded in ethical principles. Proposed solutions (e.g. using different regulations in "learning healthcare systems") are speculative with no guarantee of improvement over existing oversight procedures. Most importantly, the literature does not reflect a broad vision of protecting the core liberty and welfare interests of research participants. Novel ethical guidance is required. We have assembled a team of ethicists, trialists, methodologists, social scientists, knowledge users, and community members with the goal of developing guidance for the ethical design and conduct of pragmatic trials.

METHODS: Our project will combine empirical and conceptual work and a consensus development process. Empirical work will: (1) identify a comprehensive list of ethical issues through interviews with a small group of key informants (e.g. trialists, ethicists, chairs of research ethics committees); (2) document current practices by reviewing a random sample of pragmatic trials and surveying authors; (3) elicit views of chairs of research ethics committees through surveys in Canada, UK, USA, France, and Australia; and (4) elicit views and experiences of community members and health system leaders through focus groups and surveys. Conceptual work will consist of an ethical analysis of identified issues and the development of new ethical solutions, outlining principles, policy options, and rationales. The consensus development process will involve an independent expert panel to develop a final guidance document.

DISCUSSION: Planned output includes manuscripts, educational materials, and tailored guidance documents to inform and support researchers, research ethics committees, journal editors, regulators, and funders in the ethical design and conduct of pragmatic trials.

Original languageEnglish
Article number525
Publication statusPublished - 27 Sept 2018

Bibliographical note

This work is supported by the Canadian Institutes of Health Research through the Project Grant competition (competitive, peer-reviewed), award number PJT-153045. Jeremy Grimshaw holds a Canada Research Chair in Health Knowledge Transfer and Uptake. Charles Weijer holds a Canada Research Chair in Bioethics. Sarah Edwards is funded by the UCL/UCLH Biomedical Research Centre (BRC). Vipul Jairath hold a personal Endowed Chair at Western University (John and Susan McDonald Endowed Chair). Joanne McKenzie is supported by an NHMRC Career Development Fellowship (1143429). The University of Aberdeen’s Health Services Research Unit is core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Ian D Graham is a CIHR Foundation Grant recipient (FDN# 143237).


  • pragmatic randomized controlled trials
  • clinical trials
  • research ethics
  • informed consent
  • usual care interventions
  • patient-centered research
  • mixed methods
  • ethics guidelines
  • comparative effectiveness research
  • large simple trials


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