1. Towards ethical guidance for pragmatic randomized controlled trials
Charles Weijer
Department Here

2. Objectives
Why do pragmatic RCTs raise ethical issues and where should we look for guidance?
An example of an ethical issue: Can health providers be research participants in pragmatic RCTs?
Towards ethical guidance: An overview of the project.
Ethical issues in pragmatic RCTs

3. Why do pragmatic RCTs raise ethical issues?
Does an intervention work in real-world conditions?
Broadly generalizable results that can support decisions by patients, providers and policy makers
Pragmatic RCTs commonly involve usual care interventions administered by health providers in clinical settings
Pragmatic RCTs blur the practice-research distinction.
Ethical issues in pragmatic RCTs

4. Why do pragmatic RCTs raise ethical issues?
Pragmatic RCTs may employ emerging designs
Cross-over CRT
Stepped wedge CRT
Cohort multiple randomized design
Randomized registry trial
Emerging designs raise novel ethical issues not considered by current research regulations.
Ethical issues in pragmatic RCTs

5. Towards ethics guidance…which way?
Existing regulations
Familiar rules used by research ethics committees
Regulations were not written with novel pragmatic designs in mind
When there is a lack of fit, to what does one appeal?
Ethical issues in pragmatic RCTs

6. Towards ethics guidance…which way?
New ethical principles
Perhaps a whole new ethical framework is needed
But new ethical principles themselves are likely to be contested
As these principles were not the foundation of contemporary regulation, there is potential for conflict.
Ethical issues in pragmatic RCTs

7. Towards ethics guidance…which way?
Internationally-accepted ethical principles
Ethical principles are not contested
Provide a foundation to critically evaluate the suitability of current regulations
Sufficiently abstract to allow for flexibility in solutions
As these principles were the foundation for regulations, the potential for conflict is minimized.
Ethical issues in pragmatic RCTs

8. Ethical issues in pragmatic RCTs

9. In pragmatic RCTs, can health providers be research participants?
Ethical issues in pragmatic RCTs

10. The C-spine Study (PI: C. Vaillancourt)
Stepped wedge CRT
Can a strategy allowing paramedics to assess selective low-risk trauma patients with the CCR and transport them without immobilization be safe and benefit patients and the health system?
Unit of randomization: Emergency medical services
Unit of intervention: Patients and paramedics
Unit of observation: Patients and paramedics.
Ethical issues in pragmatic RCTs

11. The C-spine Study Study intervention:
Paramedic training: videos; classroom; written quiz
Paramedics authorized by medical directive
Evaluate patients in the field
Data collection:
Assessment form: paramedic “comfort” in following the rule; patient factors
ICES: ED visit; hospital data; repeat admission.
Ethical issues in pragmatic RCTs

12. Who are the research participants?
An individual whose interests may be affected as a result of study interventions or data collection procedures
A research participant is an individual…
who is the intended recipient of an experimental (or control) intervention; or
who is the direct target of an experimental (or control) manipulation of his/her environment; or
with whom an investigator interacts for the purpose of collecting data about that individual; or
about whom an investigator obtains identifiable private information for the purpose of collecting data about that individual.
Ethical issues in pragmatic RCTs

13. Who are the research participants?
In the C-spine study, the research participants are:
Patients:
(1) Intended recipient of the study intervention
(3) Interacted with to collect study data
(4) Identifiable private health data
Paramedics:
(1) Intended recipients of the study intervention
(3) Interacted with to collect study data.
Ethical issues in pragmatic RCTs

14. Implications
Researchers and RECs commonly fail to recognize health providers as research participants
Health providers are entitled to the protections set out in research regulations
It falls within the purview of the REC to protect their liberty and welfare interests
Study participation ought to pose an acceptable balance of benefits to harms
Informed consent is required unless conditions for a waiver of consent obtain.
Ethical issues in pragmatic RCTs

15. Project EMPIRICAL STUDIES ETHICAL ANALYSES CONSENSUS PROCESS
Ethical issues in pragmatic RCTs

16. Empirical studies Key informant interviews with 12-20 experts
Identification and review of a random sample of 300 published pragmatic RCTs
Survey of trialists (authors of the 300 published pragmatic RCTs)
Survey of research ethics chairs in Canada, US, UK, France, Australia
Embedded focus group discussions and a community survey with trial participants (patients) and gatekeepers.
Ethical issues in pragmatic RCTs

17. Ethical analyses
Are interventions in pragmatic RCTs research or practice?
What research ethics oversight is required?
Which study designs are appropriate?
Who are the research participants?
Do patients and health providers have an ethical obligation to participate?
From whom, how and when is informed consent required?
Who are the gatekeepers and what are their responsibilities?
How should benefit-harm analyses be conducted?
How ought vulnerable groups be protected?
Ethical issues in pragmatic RCTs

18. Consensus process International expert panel
Trialists/ methodologists (4-6); ethicists (4-6); quality improvement experts (1-2); REC chairs (2-4); patient representatives (2-4); funders (2); and regulators (2)
No more than 1/3 from research team
Empirical studies and ethical analyses
Three day consensus conference
Draft guidance
E-consultation
Final guidance.
Ethical issues in pragmatic RCTs

19. Research team Ethical issues in pragmatic RCTs Principal Investigators
Dean Fergusson
Ottawa Hospital Research Institute, Canada
Monica Taljaard
Charles Weijer
Rotman Institute of Philosophy, Canada
Co-Investigators
Jamie Brehaut
Marion Campbell
University of Aberdeen, United Kingdom
Allan Donner
Western University, Canada
Sarah Edwards
University College London, United Kingdom
Sandra Eldridge
Barts and the London School of Medicine, United Kingdom
Christopher Forrest
University of Pennsylvania, United States
Bruno Giraudeau
Université François-Rabelais de Tours, France
Ian Graham
Jeremy Grimshaw
Karla Hemming
University of Birmingham, United Kingdom
Spencer Hey
Harvard Medical School, United States
Vipul Jairath
Western University, Canada
Terry Klassen
University of Manitoba, Canada
Alex London
Carnegie Mellon University, United States
Susan Marlin
Clinical Trials Ontario, Canada
John Marshall
University of Toronto, Canada
Lauralyn McIntyre
Ottawa Hospital Research Institute, Canada
Joanne McKenzie
Monash University, Australia
Alison Paprica
Merrick Zwarenstein
Students, Trainees & Fellows
Cory Goldstein
Rotman Institute of Philosophy, Canada
Austin Horn
Ethical issues in pragmatic RCTs