When and how should we cluster and cross over: methodological and ethical issues (letter 1)
To the Editor,
The editorial by Goldstein et al.1 expresses concern regarding the methods and ethics of our Benzodiazepine-Free Cardiac Anesthesia for Reduction in Postoperative Delirium (B-Free) trial, suggesting that waived consent cannot be justified when interventions are administered directly to individuals. In our view, however, international guidelines and current practice support the concept that trials evaluating treatments administered directly to individual patients can fulfill the requirements for a waiver of individual consent, provided that they have minimal risk.
There are many completed and ongoing cluster trials that test policies related to the use of pharmacologic and other interventions where waiver of consent has been accepted. Such trials include: conventional vs incremental antibiotic prophylaxis strategies on the incidence of pacemaker infection;1 saline compared with buffered crystalloid intravenous fluid on the incidence of acute kidney injury;2...
Financial disclosure and conflicts of interest
This submission was handled by Dr. Gregory L. Bryson, Deputy Editor-in-Chief, Canadian Journal of Anesthesia.
- 2.Canadian Institutes of Health Research; Natural Sciences and Engineering Research Council of Canada; Social Sciences and Humanities Research Council of Canada. Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans - December 2014. Available from URL: http://www.pre.ethics.gc.ca/eng/policy-politique/initiatives/tcps2-eptc2/Default/ (accessed July 2018).
- 3.U.S. Department of Health and Human Services; Food and Drug Administration. IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects - July 2017 Available from URL: https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM566948.pdf (accessed July 2018).
- 5.U.S. National Library of Medicine. Benzodiazepine-free Anesthetic for Reduction of Delirium (B-Free). ClinicalTrials.gov identifier: NCT03053869. Registered February 15, 2017. Available from URL: https://ClinicalTrials.gov/ct2/show/NCT03053869 (accessed July 2018)