Electronic Thesis and Dissertation Repository


Doctor of Philosophy


Epidemiology and Biostatistics


Allan Donner

2nd Supervisor

Charles Weijer

Joint Supervisor


Research Questions: This dissertation examines how ethical challenges in CRTs are addressed in practice. This dissertation also provides guidance as to who must be considered a research subject in a CRT, and when consent must be sought from research subjects.

Methods: The association between consent practices in healthcare CRTs and particular trial features were examined using multivariable logistic regression modelling. Information on ethical challenges encountered by CRT researchers in practice was obtained by analyzing semi-structured interviews with experienced CRT investigators. Two normative questions, “Who is the research subject in CRTs?” and “When is consent required in CRTs?” were also addressed.

Results: Consent in CRTs is associated with smaller cluster sizes, and the use of individual-level experimental and data collection interventions. CRT researchers are most concerned with issues around informed consent, and less concerned with issues related to the analysis of harms and benefits in CRTs.

Research subjects are individuals who are intervened upon by investigators; who interact with investigators; or who contribute identifiable private information. Consent must be sought for CRT participation from research subjects. Consent is not required from cluster members who are not research subjects. Consent after randomization of clusters is permissible if necessary. Some CRTs may meet criteria for a waiver of informed consent.

Conclusions: This dissertation describes the state of the art of ethics practices in CRTs, and presents guidance around consent issues in CRTs that will inform the development of international ethics guidelines for CRTs.