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

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

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

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

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

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

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

Ethical issues in pragmatic RCTs

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

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

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

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

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

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

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

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

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

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

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