Andrew McRae MD, FRCPC University of Calgary
Financial Disclosures None Disclaimer i Resemblance of example trials to real studies IS deliberate
Objectives 1. Review recent changes to Canadian research guidelines 2. Review guidelines for waivers of consent for observational studies and resuscitation research 3. Discuss challenges relating eat gto privacy vacyguidelines es and provincial legislation 4. Discuss ethical issues in EM education/knowledge translation research
Canadian Research Ethics Guidelines Tri Council Policy: Ethical Conduct for Research Involving Humans Originally published 1998 2 nd Edition: Published 2010 Drafts and public comment period 2008 20092009
TCPS 2 nd edition Reorganization of elements of first edition Few changes specific to EM research New sections/requirements: Qualitative research Clinical i l Trial Registration i Research in publicly declared emergencies
TCPS 2 nd edition www.pre.ethics.gc.ca
Example study 1 3 arm RCT: NS vs. 7.5% HTS vs. 7.5% HTS/Dextran Blunt/penetrating trauma Signs of shock Outcomes: Survival at 24h, 30 days, hemodynamics
Consent Terminology : TCPS Article 3.8: Consent for Research in Individual Medical Emergencies Exception from Requirement for Informed Consent US Regulations for Emergency Research Waiver of Consent Used for minimal risk, observational studies Deferred Consent Outdated term shouldn t be used
Emergency Research Without Consent Research should address the emergency health problem of the subject Vulnerable subjects not a population lti of convenience Subject population appropriate for research question
TCPS 2, Article Atil 3.8 38 Consent in Individual Medical Emergencies 1. a serious threat t to the prospective participant i t requires immediate intervention; 2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care; 3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant; 4. the prospective participant i t is unconscious or lacks capacity to understand the risks, methods and purposes of the research project; 5. third party authorization cannot be secured in sufficient time, despite diligent and documented d efforts to do so; and 6. no relevant prior directive by the participant is known to exist.
TCPS 2, Article Atil 3.8 38 Consent in Individual Medical Emergencies 1. a serious threat t to the prospective participant i t requires immediate intervention; 2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care; 3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant; 4. the prospective participant i t is unconscious or lacks capacity to understand the risks, methods and purposes of the research project; 5. third party authorization cannot be secured in sufficient time, despite diligent and documented d efforts to do so; and 6. no relevant prior directive by the participant is known to exist.
TCPS 2, Article Atil 3.8 38 Consent in Individual Medical Emergencies 1. a serious threat t to the prospective participant i t requires immediate intervention; 2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care; 3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant; 4. the prospective participant i t is unconscious or lacks capacity to understand the risks, methods and purposes of the research project; 5. third party authorization cannot be secured in sufficient time, despite diligent and documented d efforts to do so; and 6. no relevant prior directive by the participant is known to exist.
TCPS 2, Article Atil 3.8 38 Consent in Individual Medical Emergencies 1. a serious threat t to the prospective participant i t requires immediate intervention; 2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care; 3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant; 4. the prospective participant i t is unconscious or lacks capacity to understand the risks, methods and purposes of the research project; 5. third party authorization cannot be secured in sufficient time, despite diligent and documented d efforts to do so; and 6. no relevant prior directive by the participant is known to exist.
TCPS 2, Article Atil 3.8 38 Consent in Individual Medical Emergencies 1. a serious threat t to the prospective participant i t requires immediate intervention; 2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care; 3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant; 4. the prospective participant i t is unconscious or lacks capacity to understand the risks, methods and purposes of the research project; 5. third party authorization cannot be secured in sufficient time, despite diligent and documented d efforts to do so; and 6. no relevant prior directive by the participant is known to exist.
TCPS 2, Article Atil 3.8 38 Consent in Individual Medical Emergencies 1. a serious threat t to the prospective participant i t requires immediate intervention; 2. either no standard efficacious care exists or the research offers a realistic possibility of direct benefit to the participant in comparison with standard care; 3. either the risk is not greater than that involved in standard efficacious care, or it is clearly justified by the prospect for direct benefits to the participant; 4. the prospective participant i t is unconscious or lacks capacity to understand the risks, methods and purposes of the research project; 5. third party authorization cannot be secured in sufficient time, despite diligent and documented d efforts to do so; and 6. no relevant prior directive by the participant is known to exist.
Major Differences from US Regulations US: Life Threatening Conditions Liberally interpreted Defined Therapeutic Window Community Disclosure and Consultation
Emergency Research Without Consent: Practical Aspects Experimental interventions done without consent What about data collection interventions? Consent from subject or SDM obtained ASAP Inform/debrief f about interventions i already done Consent for ongoing trial participation/data collection What about data already collected?
Example study 2 Observational study: U/S findings in cardiac arrest Can U/S findings predict mortality? Cardiac U/S in pauses in CPR per standard care, recording of images Comparison of recorded U/S findings with patient outcomes as ascertained from records
TCPS 2, Article 37 3.7 Waiver of Informed Consent for Minimal Risk Research (a) the research involves no more than minimal risk to the participants; (b) the lack of the participant s consent is unlikely to adversely affect the welfare of the participant; (c) it is impossible or impracticable to carry out the research and to answer the research question properly, given the research design, if the prior consent of the participant is required; (d) whenever possible and appropriate, after participation, i or at a later time during the study, participants will be debriefed and provided with additional pertinent information in accordance with Articles 3.2 and 3.4, at which point they will have the opportunity to refuse consent in accordance with itharticle 3.1; and (e) the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions.
TCPS 2, Article 37 3.7 Waiver of Informed Consent for Minimal Risk Research (a) the research involves no more than minimal risk to the participants; (b) the lack of the participant s consent is unlikely to adversely affect the welfare of the participant; (c) it is impossible or impracticable to carry out the research and to answer the research question properly, given the research design, if the prior consent of the participant is required; (d) whenever possible and appropriate, after participation, i or at a later time during the study, participants will be debriefed and provided with additional pertinent information in accordance with Articles 3.2 and 3.4, at which point they will have the opportunity to refuse consent in accordance with itharticle 3.1; and (e) the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions.
TCPS 2, Article 37 3.7 Waiver of Informed Consent for Minimal Risk Research (a) the research involves no more than minimal risk to the participants; (b) the lack of the participant s consent is unlikely to adversely affect the welfare of the participant; (c) it is impossible or impracticable to carry out the research and to answer the research question properly, given the research design, if the prior consent of the participant is required; (d) whenever possible and appropriate, after participation, or at a later time during the study, participants will be debriefed and provided with additional pertinent information in accordance with Ati Articles 32 3.2 and d34 3.4, at which hpoint tthey will illhave the opportunity to refuse consent in accordance with Article 3.1; and (e) the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions.
What does impracticable mean? Argument to REB that consent would make study impossible/invalid. Consider: Size of population Difficulty of contacting subjects (moved, died) Risk of bias Undue logistical/financial challenge of seeking consent
TCPS 2, Article 37 3.7 Waiver of Informed Consent for Minimal Risk Research (a) the research involves no more than minimal risk to the participants; (b) the lack of the participant s consent is unlikely to adversely affect the welfare of the participant; (c) it is impossible or impracticable to carry out the research and to answer the research question properly, given the research design, if the prior consent of the participant is required; (d) whenever possible and appropriate, after participation, i or at a later time during the study, participants will be debriefed and provided with additional pertinent information at which point they will have the opportunity to refuse consent ; and (e) the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions.
TCPS 2, Article 37 3.7 Waiver of Informed Consent for Minimal Risk Research (a) the research involves no more than minimal risk to the participants; (b) the lack of the participant s consent is unlikely to adversely affect the welfare of the participant; (c) it is impossible or impracticable to carry out the research and to answer the research question properly, given the research design, if the prior consent of the participant is required; (d) whenever possible and appropriate, after participation, i or at a later time during the study, participants will be debriefed and provided with additional pertinent information in accordance with Articles 3.2 and 3.4, at which point they will have the opportunity to refuse consent in accordance with itharticle 3.1; and (e) the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions.
Changes in guideline wording 3.7(e): the research does not involve a therapeutic intervention, or other clinical or diagnostic interventions. Evaluation of therapies covered by 3.8 What about evaluation of diagnostic tests in emergency situations? Eg. Accuracy of U/S for PTX in trauma Blood samples for novel biomarkers/other hypothesisgenerating research
REB application for this study Observational study Emphasize no alteration in routine care Study interventions: recording of U/S images, records review Use waiver of consent for minimal i risk ik research
Example study 3 Cohort study Patients discharged from ED with Dx: Biliary Colic Identified using EDIS by research assistants Data collection: demographics, treatment, imaging Phone f/u at 1 week post presentation Analgesic use, medical care, adverse outcomes
Information and Privacy Research Subject Custodian Researcher
Use of identifiable information for secondary purposes Waiver of consent (TCPS 2, 3.7) often applicable Minimal risk Seeking consent not practicable Exception: Private information cannot be used to contact research subjects Custodians must seek consent for contact Provincial Privacy Legislation
Follow up in observational studies Interpretation # 1: Private information collected may not be used to contact research subjects at all Consent for contact must be obtained by data custodians before contact by investigators Bad for research Interpretation #2: Private info can t be used SOLELY to contact research subjects Example study: Collection of data including demographic info Can use information to contact for f/u Information letter sent prior to contact may be helpful Prospective data collection (including consent) obviates the issue
Database/registry issues Use of data in existing registries Waiver of consent Linkage New databases/registries i Waiver of consent Minimal Risk Feasability: is risk of bias sufficent?
Example study 4 Off service residents rotating through ED RCT: online lecture series vs. no intervention Pre test before intervention Post test at week 2 of rotation Outcome: difference in pre post test score Δ
Example study 5 Cluster RCT: Educational interventions for implementation of C spine rule 6 EDs: intervention; 6 EDs: control Interventions: t Education session, Xray ordering policy, literature/pocket cards, Reminders on xray reqs Outcome measures: % of patients with C spine xray, Missed C spine injuries, adverse outcomes, LOS, patient satisfaction
Education Research in Emergency Medicine Issues: Who is the research subject? The target of the intervention (healthcare providers)? Patients? When, and from whom, is consent required? Healthcare providers if feasible Patients If subjects, and only if not covered by waiver of consent
Example study 4 Who are the research subjects? Off service residents? Patients? Consent required? Residents Yes Patients Not research subjects No consent required
Example 5 Who is the research subject? Physicians: recipients of experimental interventions Patients? Only if they interact with research team or if identifiable information collected Is consent required? Healthcare professionals if feasible Patients If subjects: consent or waiver If not subjects: not required
QUESTIONS? COMMENTS? HORROR STORIES? WORDS OF WISDOM/EXPERIENCE?
Summary New version of TCPS Few wholesale changes Some changes important for EM research Consent regulations for EM research Trials of therapeutic interventions Observational Research Education/KT research Privacy Protections
Resources TCPS 2 www.pre.ethics.gc.ca Privacy guidance www.cihr irsc.gc.ca i Your local l REB andrew.mcrae@albertahealthservices.ca ca