CHARLES WEIJER

Charles’ current research explores ethical issues in pragmatic randomized controlled trials (RCTs), which evaluate health interventions in real-world settings. Pragmatic RCTs thereby aim to provide patients, health providers and health system managers with reliable information on the safety, effectiveness and cost of treatments. Although ethical guidelines exist to protect participants in research, they were not written with pragmatic RCTs in mind. The lack of fit between current guidance and pragmatic RCTs leads to inadequate protections and unnecessary obstacles. In some instances, research participants are left unprotected in research; in other cases, socially important research is hindered.

Charles co-leads a research team, comprising 25 philosophers, trialists and biostatisticians from five countries, that will develop guidance for the ethical design and conduct of pragmatic RCTs. Questions addressed include: When stepped wedge RCTs seek to study the roll-out of government policies, ought they be considered research or program evaluation? When pragmatic RCTs compare routinely available medical treatments, should the study interventions be classified as research or practice? Does clinical equipoise apply to pragmatic RCTs evaluating policy, knowledge translation or public health interventions? Must patients in pragmatic RCTs always be informed about trial participation and provide informed consent? When may a waiver of consent be used in pragmatic RCTs and what justifies such use? What is the role of gatekeepers in pragmatic RCTs? The team will address these (and other) questions through a combination of ethical analysis and empirical study. This work will feed into a consensus process that will generate ethical guidance for researchers and research ethics committees globally.

Goldstein CE, Giraudeau B, Weijer C, Taljaard M. When and how should we cluster and cross over: methodological and ethical issues. Canadian Journal of Anaesthesia 2018; 65(7): 760-765.

Horn AR, Weijer C, Grimshaw JG, Brehaut J, Fergusson D, Goldstein CE, Taljaard M. An ethical analysis of the SUPPORT trial: addressing challenges posed by pragmatic comparative effectiveness randomized controlled trials with usual care interventions. Kennedy Institute of Ethics Journal 2018; 28(1): 85–117.

Hemming K, Taljaard M, Forbes G, Eldridge S, Weijer C. Ethical implications of excessive cluster sizes in cluster randomized trials. BMJ Quality & Safety 2018 Feb 20. pii: bmjqs-2017-007164.

Hey SP, Weijer C, Taljaard M, Kesselheim AS. Research ethics for emerging trial designs: does equipoise need to adapt? British Medical Journal; 2018; 360: k226.

Weijer C, Goldstein CE, Taljaard M. TwiC or treat? Are Trials within Cohorts ethically defensible? Clinical Trials 2018; 15(1): 21-24.

Hey SP, London AJ, Weijer C, Rid A, Miller F. Is the concept of clinical equipoise still relevant to research? British Medical Journal 2017; 359: j5787.

Campbell MK, Weijer C, Goldstein CE, Edwards SJL. Do doctors have a duty to take part in pragmatic randomised trials? British Medical Journal 2017; 357: j2817.

Hemming K, Eldridge S, Forbes G, Weijer C, Taljaard M. How to design efficient cluster randomised trials. British Medical Journal 2017; 358: j3064.

Bambery B, Selgelid M, Weijer C, Savulsecu J, Pollard A. Ethical criteria for human challenge studies in infectious diseases. Public Health Ethics 2016; 9(1): 92–103.

Weijer C, Bruni T, Gofton T, Young GB, Norton L, Peterson A, Owen AM. Ethical considerations in functional magnetic resonance imaging research in acutely comatose patients. Brain 2016; 139(1) 292–299.

Weijer C, Miller PB, Graham M. The duty of care and equipoise in randomized controlled trials. In: Arras JD, Kukla R, Fenton E (eds.). Routledge Companion to Bioethics. Routledge: New York, 2015: 200–214.

Weijer C, Peterson A, Webster F, Graham M, Cruse D, Fernández-Espejo D, et al.. Ethics of neuroimaging after serious brain injury. BMC Medical Ethics 2014: 15: 41.

Taljaard M, Weijer C, Grimshaw JM, Eccles MP and the Ottawa Ethics of Cluster Randomized Trials Consensus Group. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomised Trials: A précis for researchers and research ethics committees. British Medical Journal 2013; 346: f2838.

Weijer C, Grimshaw JM, Eccles MP, McRae AD, White A, Brehaut JC, Taljaard M and the Ottawa Ethics of Cluster Randomized Trials Consensus Group. The Ottawa Statement on the Ethical Design and Conduct of Cluster Randomized Trials. PLoS Medicine 2012; 9(11): e1001346.

Taljaard M, McRae A, Weijer C, Bennett C, Dixon S, Taleban J, et al.. Inadequate reporting of research ethics review and informed consent in cluster randomized trials: review of a representative sample of published trials. British Medical Journal 2011; 342: d2496.

Weijer C, Grimshaw JM, Taljaard M, Binik A, Boruch R, Brehaut JC, et al.. Ethical issues posed by cluster randomized trials in health research. Trials 2011; 12: 100.

Miller PB, Weijer C. The trust-based obligations of the state and physician-research to patient-subjects. Journal of Medical Ethics 2006; 32(9): 542–547.

Miller PB, Weijer C. Fiduciary obligations in clinical research. Journal of Law, Medicine & Ethics 2006; 34(2): 424–440.

Weijer C, Miller PB. When are research risks reasonable in relation to anticipated benefits? Nature Medicine 2004; 10(6): 570–573.

Miller PB, Weijer C. Rehabilitating equipoise. Kennedy Institute of Ethics Journal 2003; 13(2): 93–118.

Weijer C. The ethical analysis of risk. Journal of Law, Medicine & Ethics 2000; 28(4): 344–361.

Weijer C, Emanuel EJ. Protecting communities in biomedical research. Science 2000; 289(5482): 1142–1144.

Weijer C, Goldsand G, Emanuel EJ. Protecting communities in research: current guidelines and limits of extrapolation. Nature Genetics 1999; 23(3): 275–280.

Weijer C. Placebo–controlled trials in schizophrenia: Are they ethical? Are they necessary? Schizophrenia Research 1999; 35(3): 211–218.

Project Title: Developing a framework for the ethical design and conduct of pragmatic randomized controlled trials
Role: Co-Principal Investigator
Funding: 2017–2021

Project Members: Monica Taljaard (Ottawa Health Research Institute (OHRI)), Dean Fergusson (OHRI); Jamie Brehaut (OHRI); Marion Campbell (University of Aberdeen); Allan Donner (Western University); Sarah Edwards (University College London); Sandra Eldridge (Barts and the London School of Medicine); Christopher Forrest (University of Pennsylvania); Bruno Giraudeau (Université François-Rabelais de Tours); Ian Graham (OHRI); Jeremy Grimshaw (OHRI); Karla Hemming (University of Birmingham); Spencer Hey (Harvard Medical School); Vipul Jairath (Western University); Terry Klassen (University of Manitoba); Alex London (Carnegie Mellon University); Susan Marlin (Clinical Trials Ontario); John Marshall (University of Toronto); Lauralyn McIntyre (OHRI); Joanne McKenzie (Monash University); Alison Paprica (University of Toronto); Merrick Zwarenstein (Western University).

Brief Description: To make informed decisions, patients, health providers and health system managers need reliable evidence of treatment safety, effectiveness and cost. Pragmatic randomized controlled trials (RCTs) are designed to provide such evidence by evaluating treatments in real-world conditions. But pragmatic RCTs raise difficult ethical issues that challenge researchers and research ethics committees. Our research team, comprising 25 philosophers, trialists and biostatisticians from five countries, will develop guidance for the ethical design and conduct of pragmatic RCTs.

Project Title: Ethics of Neuroimaging After Serious Brain Injury
Role: Nominated Principal Investigator
Funding: 2014–2018

Project Members: Adrian Owen (Co-Principal Investigator, Western), Tenielle Gofton (Western), Andrea Lazosky (Western), Kathy Speechley (Western), Fiona Webster (Toronto), Bryan Young (Western)
Brief Description: With 50,000 new cases occurring each year in Canada, severe brain injuries place an enormous burden on patients, families, and the healthcare system. Patient outcome after severe brain injury is highly variable. Following a period of coma lasting days or weeks, some patients make a good recovery, while others progress into a vegetative or minimally conscious state. As it is difficult to predict who will make a good recovery after severe brain injury, families and physicians are forced to make treatment decisions in the face of uncertainty. Further the diagnosis of vegetative and minimally conscious states is itself difficult, with error rates as high as 43%. Recent advances in neuroimaging allow for the detection of intact brain functions that cannot be found by routine bedside examination. Neuroimaging offers the prospect of improved prediction of patient outcome and increased diagnostic accuracy. Remarkably, in 3 cases, neuroimaging has been used to communicate with patients thought to be vegetative or minimally conscious. Neuroimaging after severe brain injury raises difficult ethical issues that must be addressed before it can be responsibly adopted in practice. Our research team brings together philosophers, neurologists, and neuroscientists to provide answers to these difficult problems.

Project Title: Ethical and Policy Issues in Cluster Randomized Trials
Role: Co-Principal Investigator
Funding: 2008–2013

Project Members: Monica Taljaard (Ottawa Health Research Institute (OHRI)), Jeremy Grimshaw (OHRI), Judith Belle Brown (Western), Robert Boruch (University of Pennsylvania), Jamie Brehaut (OHRI), Allan Donner (Western), Martin Eccles (Newcastle University), Raphael Saginur (OHRI), Merrick Zwarenstein (University of Toronto).
Brief Description: The project addresses ethical and policy challenges posed by cluster randomized trials, a key technology in knowledge translation research. Since cluster trials randomize socially intact groups such as hospitals or physicians’ practices, it is unclear whether current ethical concepts in research ethics apply to such studies. The project will explore a set of six questions on the ethics of cluster randomized trials and will seek to develop international guidelines for cluster trials.