Monica Taljaard1,2, Cory E Goldstein3, Bruno Giraudeau4,5, Stuart G Nicholls1, Kelly Carroll1, Spencer Phillips Hey6,7, Jamie C Brehaut1,2, Vipul Jairath8,9, Alex John London10, Sandra M Eldridge11, Jeremy M Grimshaw1,2,12, Dean A Fergusson1,2,12, Charles Weijer3. 1. Clinical Epidemiology Program, Ottawa Hospital Research Institute (OHRI), The Ottawa Hospital, Ottawa, ON, Canada. 2. School of Epidemiology and Public Health, University of Ottawa, Ottawa, ON, Canada. 3. Rotman Institute of Philosophy, Western University, London, ON, Canada. 4. Université de Tours, Université de Nantes, INSERM, SPHERE U1246, Tours, France. 5. INSERM CIC1415, CHRU de Tours, Tours, France. 6. Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. 7. Center for Bioethics, Harvard Medical School, Boston, MA, USA. 8. Division of Gastroenterology, Department of Medicine, Western University, London, ON, Canada. 9. Division of Epidemiology and Biostatistics, University Hospital, Western University, London, ON, Canada. 10. Department of Philosophy and Center for Ethics and Policy, Carnegie Mellon University, Pittsburgh, PA, USA. 11. Centre for Primary Care and Public Health, Queen Mary University of London, London, UK. 12. Department of Medicine, University of Ottawa, Ottawa, ON, Canada.
Abstract
BACKGROUND: Novel rationales for randomizing clusters rather than individuals appear to be emerging from the push for more pragmatic trials, for example, to facilitate trial recruitment, reduce the costs of research, and improve external validity. Such rationales may be driven by a mistaken perception that choosing cluster randomization lessens the need for informed consent. We reviewed a random sample of published cluster randomized trials involving only individual-level health care interventions to determine (a) the prevalence of reporting a rationale for the choice of cluster randomization; (b) the types of explicit, or if absent, apparent rationales for the use of cluster randomization; (c) the prevalence of reporting patient informed consent for study interventions; and (d) the types of justifications provided for waivers of consent. We considered cluster randomized trials for evaluating exclusively the individual-level health care interventions to focus on clinical trials where individual randomization is only theoretically possible and where there is a general expectation of informed consent. METHODS: A random sample of 40 cluster randomized trials were identified by implementing a validated electronic search filter in two electronic databases (Ovid MEDLINE and Embase), with two reviewers independently extracting information from each trial. Inclusion criteria were the following: primary report of a cluster randomized trial, evaluating exclusively an individual-level health care intervention, published between 2007 and 2016, and conducted in Canada, the United States, European Union, Australia, or low- and middle-income country settings. RESULTS: Twenty-five trials (62.5%, 95% confidence interval = 47.5%-77.5%) reported an explicit rationale for the use of cluster randomization. The most commonly reported rationales were those with logistical or administrative convenience (15 trials, 60%) and those that need to avoid contamination (13 trials, 52%); five trials (20%) were cited rationales related to the push for more pragmatic trials. Twenty-one trials (52.5%, 95% confidence interval = 37%-68%) reported written informed consent for the intervention, two (5%) reported verbal consent, and eight (20%) reported waivers of consent, while in nine trials (22.5%) consent was unclear or not mentioned. Reported justifications for waivers of consent included that study interventions were already used in clinical practice, patients were not randomized individually, and the need to facilitate the pragmatic nature of the trial. Only one trial reported an explicit and appropriate justification for waiver of consent based on minimum criteria in international research ethics guidelines, namely, infeasibility and minimal risk. CONCLUSION: Rationales for adopting cluster over individual randomization and for adopting consent waivers are emerging, related to the need to facilitate pragmatic trials. Greater attention to clear reporting of study design rationales, informed consent procedures, as well as justification for waivers is needed to ensure that such trials meet appropriate ethical standards.
BACKGROUND: Novel rationales for randomizing clusters rather than individuals appear to be emerging from the push for more pragmatic trials, for example, to facilitate trial recruitment, reduce the costs of research, and improve external validity. Such rationales may be driven by a mistaken perception that choosing cluster randomization lessens the need for informed consent. We reviewed a random sample of published cluster randomized trials involving only individual-level health care interventions to determine (a) the prevalence of reporting a rationale for the choice of cluster randomization; (b) the types of explicit, or if absent, apparent rationales for the use of cluster randomization; (c) the prevalence of reporting patient informed consent for study interventions; and (d) the types of justifications provided for waivers of consent. We considered cluster randomized trials for evaluating exclusively the individual-level health care interventions to focus on clinical trials where individual randomization is only theoretically possible and where there is a general expectation of informed consent. METHODS: A random sample of 40 cluster randomized trials were identified by implementing a validated electronic search filter in two electronic databases (Ovid MEDLINE and Embase), with two reviewers independently extracting information from each trial. Inclusion criteria were the following: primary report of a cluster randomized trial, evaluating exclusively an individual-level health care intervention, published between 2007 and 2016, and conducted in Canada, the United States, European Union, Australia, or low- and middle-income country settings. RESULTS: Twenty-five trials (62.5%, 95% confidence interval = 47.5%-77.5%) reported an explicit rationale for the use of cluster randomization. The most commonly reported rationales were those with logistical or administrative convenience (15 trials, 60%) and those that need to avoid contamination (13 trials, 52%); five trials (20%) were cited rationales related to the push for more pragmatic trials. Twenty-one trials (52.5%, 95% confidence interval = 37%-68%) reported written informed consent for the intervention, two (5%) reported verbal consent, and eight (20%) reported waivers of consent, while in nine trials (22.5%) consent was unclear or not mentioned. Reported justifications for waivers of consent included that study interventions were already used in clinical practice, patients were not randomized individually, and the need to facilitate the pragmatic nature of the trial. Only one trial reported an explicit and appropriate justification for waiver of consent based on minimum criteria in international research ethics guidelines, namely, infeasibility and minimal risk. CONCLUSION: Rationales for adopting cluster over individual randomization and for adopting consent waivers are emerging, related to the need to facilitate pragmatic trials. Greater attention to clear reporting of study design rationales, informed consent procedures, as well as justification for waivers is needed to ensure that such trials meet appropriate ethical standards.
Entities:
Keywords:
Cluster randomized trials; informed consent; pragmatic trials; research ethics review; waivers of consent
Authors: Jennifer Zhe Zhang; Stuart G Nicholls; Kelly Carroll; Hayden Peter Nix; Cory E Goldstein; Spencer Phillips Hey; Jamie C Brehaut; Paul C McLean; Charles Weijer; Dean A Fergusson; Monica Taljaard Journal: J Med Ethics Date: 2021-11-15 Impact factor: 5.926
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Authors: Ahmed A Al-Jaishi; Kelly Carroll; Cory E Goldstein; Stephanie N Dixon; Amit X Garg; Stuart G Nicholls; Jeremy M Grimshaw; Charles Weijer; Jamie Brehaut; Lehana Thabane; P J Devereaux; Monica Taljaard Journal: Trials Date: 2020-08-28 Impact factor: 2.279
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