Cluster over individual randomization: are study design choices appropriately justified? Review of a random sample of trials

• Published in: Clinical trials (London, England) England), 2020-06, Vol.17 (3), p.253-263
• Main Authors: Taljaard, Monica, Goldstein, Cory E, Giraudeau, Bruno, Nicholls, Stuart G, Carroll, Kelly, Hey, Spencer Phillips, Brehaut, Jamie C, Jairath, Vipul, London, Alex John, Eldridge, Sandra M, Grimshaw, Jeremy M, Fergusson, Dean A, Weijer, Charles
• Format: Article
• Language: English
• Subjects: Australia; Canada; Clinical trials; Cluster Analysis; Clusters; Confidence intervals; Contamination; Ethical standards; Ethics, Research; Europe; Health care; Humans; Identification methods; Informed consent; Informed Consent - ethics; Informed Consent - statistics & numerical data; Medical ethics; Medical research; Patients; Pragmatic Clinical Trials as Topic - ethics; Prevalence; Randomized Controlled Trials as Topic - ethics; Randomized Controlled Trials as Topic - statistics & numerical data; Research Design; Research ethics; United States
• ISSN: 1740-7745; 1740-7753
• DOI: 10.1177/1740774519896799

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 individual