Loopholes in the Research Ethics System? Informed Consent Waivers in Cluster Randomized Trials with Individual‐Level Intervention

2020 ◽  
Vol 42 (6) ◽  
pp. 21-28
Author(s):  
Alex John London ◽  
Monica Taljaard ◽  
Charles Weijer
Keyword(s):  
Informed Consent ◽  
Research Ethics ◽  
Randomized Trials ◽  
Cluster Randomized Trials ◽  
Individual Level ◽  
Cluster Randomized

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

2020 ◽  
Vol 17 (3) ◽  
pp. 253-263 ◽  
Author(s):  
Monica Taljaard ◽  
Cory E Goldstein ◽  
Bruno Giraudeau ◽  
Stuart G Nicholls ◽  
Kelly Carroll ◽  
...  
Keyword(s):  
Health Care ◽  
Informed Consent ◽  
Random Sample ◽  
Randomized Trials ◽  
Cluster Randomized Trials ◽  
Cluster Randomization ◽  
Pragmatic Trials ◽  
Individual Level ◽  
Health Care Interventions ◽  
Cluster Randomized

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.

Inadequacy of ethical conduct and reporting of stepped wedge cluster randomized trials: Results from a systematic review

2017 ◽  
Vol 14 (4) ◽  
pp. 333-341 ◽  
Author(s):  
Monica Taljaard ◽  
Karla Hemming ◽  
Lena Shah ◽  
Bruno Giraudeau ◽  
Jeremy M Grimshaw ◽  
...  
Keyword(s):  
Informed Consent ◽  
Research Ethics ◽  
Randomized Trials ◽  
Cluster Randomized Trials ◽  
Stepped Wedge ◽  
Research Participants ◽  
Ethics Review ◽  
Research Ethics Review ◽  
Stepped Wedge Trials ◽  
Cluster Randomized

Background/aims The use of the stepped wedge cluster randomized design is rapidly increasing. This design is commonly used to evaluate health policy and service delivery interventions. Stepped wedge cluster randomized trials have unique characteristics that complicate their ethical interpretation. The 2012 Ottawa Statement provides comprehensive guidance on the ethical design and conduct of cluster randomized trials, and the 2010 CONSORT extension for cluster randomized trials provides guidelines for reporting. Our aims were to assess the adequacy of the ethical conduct and reporting of stepped wedge trials to date, focusing on research ethics review and informed consent. Methods We conducted a systematic review of stepped wedge cluster randomized trials in health research published up to 2014 in English language journals. We extracted details of study intervention and data collection procedures, as well as reporting of research ethics review and informed consent. Two reviewers independently extracted data from each trial; discrepancies were resolved through discussion. We identified the presence of any research participants at the cluster level and the individual level. We assessed ethical conduct by tabulating reporting of research ethics review and informed consent against the presence of research participants. Results Of 32 identified stepped wedge trials, only 24 (75%) reported review by a research ethics committee, and only 16 (50%) reported informed consent from any research participants—yet, all trials included research participants at some level. In the subgroup of 20 trials with research participants at cluster level, only 4 (20%) reported informed consent from such participants; in 26 trials with individual-level research participants, only 15 (58%) reported their informed consent. Interventions (regardless of whether targeting cluster- or individual-level participants) were delivered at the group level in more than two-thirds of trials; nine trials (28%) had no identifiable data collected from any research participants. Overall, only three trials (9%) indicated that a waiver of consent had been granted by a research ethics committee. When considering the combined requirement of research ethics review and informed consent (or a waiver), only one in three studies were compliant. Conclusion The ethical conduct and reporting of key ethical protections in stepped wedge trials, namely, research ethics review and informed consent, are inadequate. We recommend that stepped wedge trials be classified as research and reviewed and approved by a research ethics committee. We also recommend that researchers appropriately identify research participants (which may include health professionals), seek informed consent or appeal to an ethics committee for a waiver of consent, and include explicit details of research ethics approval and informed consent in the trial report.

xtgeebcv: A command for bias-corrected sandwich variance estimation for GEE analyses of cluster randomized trials

2020 ◽  
Vol 20 (2) ◽  
pp. 363-381 ◽  
Author(s):  
John A. Gallis ◽  
Fan Li ◽  
Elizabeth L. Turner
Keyword(s):  
Randomized Trials ◽  
Variance Estimation ◽  
Public Health Education ◽  
Standard Errors ◽  
Future Research ◽  
Type I ◽  
Cluster Randomized Trials ◽  
Finite Sample ◽  
Individual Level ◽  
Cluster Randomized

Cluster randomized trials, where clusters (for example, schools or clinics) are randomized to comparison arms but measurements are taken on individuals, are commonly used to evaluate interventions in public health, education, and the social sciences. Analysis is often conducted on individual-level outcomes, and such analysis methods must consider that outcomes for members of the same cluster tend to be more similar than outcomes for members of other clusters. A popular individual-level analysis technique is generalized estimating equations (GEE). However, it is common to randomize a small number of clusters (for example, 30 or fewer), and in this case, the GEE standard errors obtained from the sandwich variance estimator will be biased, leading to inflated type I errors. Some bias-corrected standard errors have been proposed and studied to account for this finite-sample bias, but none has yet been implemented in Stata. In this article, we describe several popular bias corrections to the robust sandwich variance. We then introduce our newly created command, xtgeebcv, which will allow Stata users to easily apply finite-sample corrections to standard errors obtained from GEE models. We then provide examples to demonstrate the use of xtgeebcv. Finally, we discuss suggestions about which finite-sample corrections to use in which situations and consider areas of future research that may improve xtgeebcv.

scholarly journals Power analyses for moderator effects with (non)randomly varying slopes in cluster randomized trials

Methodology ◽  
2021 ◽  
Vol 17 (2) ◽  
pp. 92-110
Author(s):  
Nianbo Dong ◽  
Jessaca Spybrook ◽  
Benjamin Kelcey ◽  
Metin Bulus
Keyword(s):  
Statistical Power ◽  
Randomized Trials ◽  
Future Research ◽  
Size Difference ◽  
Detectable Effect ◽  
Cluster Randomized Trials ◽  
Individual Level ◽  
Moderator Effects ◽  
Cluster Randomized ◽  
Power Analyses

Researchers often apply moderation analyses to examine whether the effects of an intervention differ conditional on individual or cluster moderator variables such as gender, pretest, or school size. This study develops formulas for power analyses to detect moderator effects in two-level cluster randomized trials (CRTs) using hierarchical linear models. We derive the formulas for estimating statistical power, minimum detectable effect size difference and 95% confidence intervals for cluster- and individual-level moderators. Our framework accommodates binary or continuous moderators, designs with or without covariates, and effects of individual-level moderators that vary randomly or nonrandomly across clusters. A small Monte Carlo simulation confirms the accuracy of our formulas. We also compare power between main effect analysis and moderation analysis, discuss the effects of mis-specification of the moderator slope (randomly vs. non-randomly varying), and conclude with directions for future research. We provide software for conducting a power analysis of moderator effects in CRTs.

scholarly journals Learning From Cluster Randomized Trials in Education: An Assessment of the Capacity of Studies to Determine What Works, For Whom, and Under What Conditions

2020 ◽  
Vol 42 (3) ◽  
pp. 354-374
Author(s):  
Jessaca Spybrook ◽  
Qi Zhang ◽  
Ben Kelcey ◽  
Nianbo Dong
Keyword(s):  
Randomized Trials ◽  
Educational Interventions ◽  
School Type ◽  
Cluster Randomized Trials ◽  
Individual Level ◽  
The Past ◽  
Moderator Effects ◽  
What Works ◽  
Cluster Randomized ◽  
Cluster Level

Over the past 15 years, we have seen an increase in the use of cluster randomized trials (CRTs) to test the efficacy of educational interventions. These studies are often designed with the goal of determining whether a program works, or answering the what works question. Recently, the goals of these studies expanded to include for whom and under what conditions an intervention is effective. In this study, we examine the capacity of a set of CRTs to provide rigorous evidence about for whom and under what conditions an intervention is effective. The findings suggest that studies are more likely to be designed with the capacity to detect potentially meaningful individual-level moderator effects, for example, gender, than cluster-level moderator effects, for example, school type.

scholarly journals Participant Informed Consent in Cluster Randomized Trials: Review

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e40436 ◽  
Author(s):  
Bruno Giraudeau ◽  
Agnès Caille ◽  
Amélie Le Gouge ◽  
Philippe Ravaud
Keyword(s):  
Informed Consent ◽  
Randomized Trials ◽  
Cluster Randomized Trials ◽  
Cluster Randomized

Challenges in the research ethics review of cluster randomized trials: International survey of investigators

2013 ◽  
Vol 10 (2) ◽  
pp. 257-268 ◽  
Author(s):  
Shazia H Chaudhry ◽  
Jamie C Brehaut ◽  
Jeremy M Grimshaw ◽  
Charles Weijer ◽  
Robert Boruch ◽  
...  
Keyword(s):  
Research Ethics ◽  
Randomized Trials ◽  
International Survey ◽  
Cluster Randomized Trials ◽  
Ethics Review ◽  
Research Ethics Review ◽  
Cluster Randomized

scholarly journals Variability in research ethics review of cluster randomized trials: a scenario-based survey in three countries

Trials ◽  
2014 ◽  
Vol 15 (1) ◽  
Author(s):  
Monica Taljaard ◽  
Jamie C Brehaut ◽  
Charles Weijer ◽  
Robert Boruch ◽  
Allan Donner ◽  
...  
Keyword(s):  
Research Ethics ◽  
Randomized Trials ◽  
Cluster Randomized Trials ◽  
Ethics Review ◽  
Research Ethics Review ◽  
Cluster Randomized
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