How to review a Biomedical Protocol

Transcription

1 How to review a Biomedical Protocol IDENTIFYING AND ADDRESSING UNDERLYING RISK, ETHICS AND SAFETY ISSUES CAREB-ACCER Preconference Workshop April 27, 2017 Trillium Health Partners, Research Operations Delilah Ofosu-Barko, Research Operations Manager Augustina Ampofo, Research Ethics Board Coordinator

2 Disclaimer The views and opinions expressed in this presentation are those of the presenter(s) and do not necessarily represent official policy or position of Trillium Health Partners. The views and opinions expressed in this presentation are those of the presenter(s) and do not represent official policy or position of CAREB-ACCER. All names and examples used in case studies are fictional, any likeness to actual circumstances or persons, either living or dead, is strictly coincidental. 2

3 Introductions Who Are We? Budget Financials Feasibility 3

4 Introductions Who Are We? Human Research Protections Budget Financials Feasibility 4

5 Introductions Who Are We? Human Research Protections Responsible Conduct of Research Budget Financials Feasibility 5

6 Workshop Goals & Objectives Objective: Highlight, review and discuss approaches to identify underlying risk, ethics and safety issues in the review and oversight of biomedical research protocols Goal: 1. Identify and use strategies to recognize and address therapeutic misconception among researchers/research teams 2. Effectively evaluate study specific circumstances and embed appropriate research ethics oversight in the initial and ongoing review of multi-jurisdictional research 3. Assess and effectively distinguish unique local risks presented through engagement in interventional investigations 4. Interpret and determine how and when to review and identify effective solutions for the research ethics review of multicomponent projects 6

7 Biomedical Research research with the goal of understanding normal and abnormal human functioning, at the molecular, cellular, organ system and whole body levels, including development of tools and techniques to be applied for this purpose; developing new therapies or devices that improve health or the quality of life of individuals, up to the point where they are tested in human subjects. Biomedical research may also include studies on human subjects that do not have a diagnostic or therapeutic orientation Source: Canadian Institutes of Health Research/Instituts de recherché en santé du Canada, Ethics in Research: A Science Lifecycle Approach 7

8 Approach & Participation Options Interactive Dialogue Real time polling Sli.do Web-based tool - anonymous means of gathering attendee opinions in real time to facilitate interactive dialogue Access: Internet connection Accessible through: Mobile phone, laptop, tablets Poll participation: voluntary Go to: Slido.com Enter event code 8

9 Audience Poll - #1 Which of the following areas are you confident in your ability to identify and address risk, safety and ethics issues through your current research ethics review and oversight processes? 1. Therapeutic Misconception among Researchers/Researcher Teams 2. Multi-Jurisdictional Research 3. Distinguishing risk in relation to local clinical practice vs. interventional investigations 4. multicomponent projects with human subject research as an embedded component To participate in the live poll Go to: slido.com Enter: #6687 9

10 Audience Poll - #1 - RESULTS 10

11 Analysis Framework Gaps & Opportunities REB review and oversight for proposed and ongoing conduct NOT just study documents Vacuum vs iterative approach to study review Approaches/Strategies Submission details as a proxy for study conduct Leverage past experience to build on working knowledge Timing of REB submissions Analyze study logistical plan(s) 11

12 Complementary Analysis Framework Analyze Logistical Plan

13 Complementary Analysis Framework Submission as Proxy Analyze Logistical Plan

14 Complementary Analysis Framework Submission as Proxy Analyze Logistical Plan Leverage Past Experience

15 Complementary Analysis Framework Submission as Proxy True picture of risk, safety and ethics issues Analyze Logistical Plan Leverage Past Experience

16 Complementary Analysis Framework Submission as Proxy True picture of risk, safety and ethics issues Analyze Logistical Plan Analyze to Identify Leverage Past Experience

17 Audience Poll - #2 What tools and techniques do you typically use in your analysis framework? 1. Use of submission details as a proxy for conduct 2. Leveraging past experiences to build on working knowledge 3. Analysis of study logistical plan(s) 4. Other To participate in the live poll Go to: slido.com Enter: #

18 Audience Poll - #2 - RESULTS 18

19 Putting the Framework into Practice Application of the Analysis Framework in Different Contexts 1. Identifying and Managing therapeutic misconception among researchers/research teams 2. Managing research ethics oversight for multi-jurisdictional research 3. Assessing risk in relation to local clinical practice vs interventional investigations 4. Identifying and managing research ethics oversight in multicomponent projects with human subjects research as an embedded component 19

20 THERAPEUTIC MISCONCEPTION AMONG RESEARCHERS/RESESARCH TEAMS 20

21 Therapeutic Misconception among Researchers/Research Teams Therapeutic Misconception Definition Therapeutic misconception exists when individuals do not understand that the defining purpose of clinical research is to produce generalizable knowledge, regardless of whether the subjects enrolled in the trial may potentially benefit from the intervention under study or from other aspects of the clinical trial. Henderson GE, Churchill LR, Davis AM, et al. Clinical Trials and Medical Care: Defining the Therapeutic Misconception. PLoS Medicine. 2007;4(11):e324. doi: /journal.pmed

22 Audience Poll - #3 What has been your level of awareness of, and experience in managing, therapeutic misconception among researchers/research teams? 1. Not aware & not able to manage it 2. Aware & able to manage it 3. Aware & not able to manage it 4. Unsure of what it is/looks like & how to manage it To participate in the live poll Go to: slido.com Enter: #

23 Audience Poll - #3 - RESULTS 23

24 Therapeutic Misconception among Researchers/Research Teams What it can look like/contributing Factors Belief that participation of patient will save/prolong life; prevent disease progression Portraying research participation as clinical treatment Empathic relationships with patients and families driving a desire to help Associated Risks Creates and/or perpetuates therapeutic misconception amongst potential and existing participants Can impact the consent process Ability to assess patient/sdm/lar* capacity to consent for research Liability exposure of clinician *SDM substitute decision-maker; LAR legally authorized representative 24

25 Therapeutic Misconception among Researchers/Research Teams Application of the Analysis Framework 1. Analyze Study Logistical Plan Considerations for internal assessment of therapeutic misconception Capacity assessments as part of consent process 2. Submission as Proxy Language use throughout submission material o Consent documents o submission forms and amendment materials 3. Leverage Past Experience Participant and/or family complaints/queries 25

26 Therapeutic Misconception among Researchers/Research Teams Case Scenario Dr. Goode has submitted a new protocol for an investigational drug in stage 4 prostate cancer patients Dr. Goode is requesting a delegated review indicating 2 of his patients urgently require enrollment The consent form uses language such as this treatment when referring to the investigational product You have past experience of a family complaint of false promises of preventing disease progression by Dr. Goode s team in a previous trial Using the analysis framework; how might you/your REB approach this scenario? 26

27 Therapeutic Misconception among Researchers/Research Teams Summary Goal Workshop Milestone Recognition of therapeutic misconception among researchers/research teams as an underlying risk, ethics and safety issue Analysis framework - approach to identify associated risk, ethics and safety issues Analysis outcome - means to address underlying risk, ethics and safety issues 27

28 MANAGING RESEARCH ETHICS OVERSIGHT FOR MULTIJURISDICTIONAL RESEARCH 28

29 MANAGING RESEARCH ETHICS OVERSIGHT FOR MULTIJURISDICTIONAL RESEARCH Multijurisdictional Research Definition Research involving multiple institutions and/or multiple REBs Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, and Social Sciences and Humanities Research Council of Canada, Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, December

30 Audience Poll - #4 How frequently have you/your REB encountered challenges in the review and ongoing oversight of multijurisdictional biomedical research studies? 1. Not at all 2. Seldom 3. Frequently 4. Very Frequently To participate in the live poll Go to: slido.com Enter: #

31 Audience Poll - #4 - RESULTS 31

32 MANAGING RESEARCH ETHICS OVERSIGHT FOR MULTIJURISDICTIONAL RESEARCH Implications for REB Review & Oversight Current State Biomedical research design modeling existing care models Research activity following patientparticipant on their patient care journey Clinical transfer of medical oversight Requirement to distinguish research activities from clinical care activities Requirement to oversee research activity across the participants research journey Requirement to ensure investigator and REB oversight, roles and responsibilities remain clear and compliant 32

33 Managing Research Ethics Oversight for Multijurisdictional Research Application of the Analysis Framework 1. Analyze Study Logistical Plan Have considerations been made for the transfer/delegation of research-related responsibility to other sites in participants research journey Have all participating sites contributed to and committed to the study logistical plan 2. Submission as Proxy Has research oversight responsibilities for participants been clearly articulated 3. Leverage Past Experience Participant and/or family complaints Historic non-compliance History of protocol violations for similar study designs 33

34 Managing Research Ethics Oversight for Multijurisdictional Research Case Scenario Dr. Luck has submitted a new protocol for an investigational drug in patients with glomerular disease participants will receive investigational agent infusions at your institution, have specialized diagnostic testing at another site, and have an invasive biopsy procedure done at a third site The specialized diagnostic test and biopsy are routine procedures, however they are being done solely for research purposes Dr. Luck s submission to your REB only speaks to the investigational agent infusions and related follow-up procedures, indicating that this is the only activity at the site and that all other procedures are standard of care Using the analysis framework; how might you/your REB approach this scenario? 34

35 Managing Research Ethics Oversight for Multijurisdictional Research Summary Goal Workshop Milestone Recognition of the risk, ethics and safety issues presented by multijurisdictional research Analysis framework - approach to identify associated risk, ethics and safety issues Analysis outcome - means to address underlying risk, ethics and safety issues 35

36 LOCAL CLINICAL PRACTICE VS INTERVENTIONAL INVESTIGATIONS 36

37 LOCAL CLINICAL PRACTICE VS INTERVENTIONAL INVESTIGATIONS Local Practice Considerations No standard practice within organization No established best practice in field approach used varies across organizations locally, nationally, internationally 37

38 Audience Poll - #5 To what extent is an analysis of local (within your institution) standard practice factored into your REBs review and assessment of risk in a biomedical research study? 1. Not at all 2. Inconsistently 3. Frequently 4. To a great degree To participate in the live poll Go to: slido.com Enter: #

39 Audience Poll - #5 - RESULTS 39

40 LOCAL CLINICAL PRACTICE VS INTERVENTIONAL INVESTIGATIONS Things to Consider Local clinical practice is coordinated with interdependent factors that support the resulting care pathway Modifications to local clinical practice in the adoption of external practice standards within established guidelines for research purposes introduces new risks Implications for REB Review & Oversight Requirement to identify changes to local clinical practice as necessitated by study protocol Requirement to determine risk profile of study as a result of changes to local practice Requirement to ensure appropriate procedures are in place to minimize and prevent unanticipated risks resulting from changes in local clinical practice 40

41 Local Clinical Practice vs Investigational Interventions Application of the Analysis Framework 1. Analyze Study Logistical Plan Have considerations been made for the resulting impacts to institution based on practice change necessitated by study protocol Have education sessions been planned for impacted services/departments 2. Submission as Proxy Have risks associated with local practice change been articulated in submission material (submission form, site consent documents) 3. Leverage Past Experience Historic non-compliance History of protocol violations for similar study designs 41

42 Local Clinical Practice vs Investigational Interventions Case Scenario Dr. Almost has submitted a new protocol for an investigational drug which uses a marketed drug, not in use at your institution, as an active comparator The study protocol implies that the active comparator is established best practice/standard of care Dr. Almost s REB submission does not mention there would be a change to local clinical practice in conducting this study, and as such does not highlight any risks associated with the active comparator, only the investigational agent Using the analysis framework; how might you/your REB approach this scenario? 42

43 Local Clinical Practice vs Investigational Interventions Summary Goal Workshop Milestone Recognition of the importance of understanding the local risk, ethics and safety issues presented by certain investigational intervention trials Analysis framework - approach to identify associated risk, ethics and safety issues Analysis outcome - means to address underlying risk, ethics and safety issues 43

44 RESEARCH ETHICS REVIEW OF MULTICOMPONENT PROJECTS 44

45 RESEARCH ETHICS REVIEW OF MULTICOMPONENT PROJECTS Multicomponent Projects Non-human subjects research projects Quality improvement initiatives Quality assurance initiatives Clinical initiatives 45

46 Audience Poll - #6 Does your REB have an established approach for reviewing multicomponent projects which have human subjects research as a limited embedded component of overall project activity? 1. Yes 2. No 3. Not Sure To participate in the live poll Go to: slido.com Enter: #

47 Audience Poll - #6 - RESULTS 47

48 RESEARCH ETHICS REVIEW OF MULTICOMPONENT PROJECTS Implications for REB Review & Oversight Things to Consider Methodological rigor can be applied in various circumstances; methodology alone does not distinguish human subjects research from non-human subjects research activity Leaders of clinical initiatives (changes in service delivery models, changes in care pathways, quality improvement projects etc.) are increasingly seeking to incorporate evaluative components to their initiatives Research questions can be asked of data generated through non-human subjects research activities 48 Requirement to distinguish research activities from other non-human subjects clinical initiatives Requirement to understand the scope and jurisdiction of REB review and oversight Requirement to disentangle non-human subjects research activities from human subjects research activities in the review and oversight of such activity

49 Research Ethics Review of Multicomponent Projects Application of the Analysis Framework 1. Analyze Study Logistical Plan Have considerations been made for the transition in activity from non-human subjects research to human-subjects research Have adequate protections been put in place to facilitate complaint research ethics conduct 2. Submission as Proxy Have the interdependencies of the research project and non-human subjects research project been highlighted 3. Leverage Past Experience Historic non-compliance History of protocol violations for similar study designs History of research ethics breaches for similar study designs 49

50 Research Ethics Review of Multicomponent Projects Case Scenario Nurse Dunn is leading a corporate clinical initiative to decrease hospital readmission rates for the elderly; this initiative is mandated by the LHIN* and is being done in collaboration with the local CCAC** Nurse Dunns project charter indicates that the initiative is a quality improvement initiative, however Nurse Dunn has also embedded a research component to answer the following question: Does the community first initiative have an impact on quality of life for the elderly? This question will be answered by administering a survey to all elderly patients in addition to the standard of care quality of life questionnaires they receive and complete *LHIN local health integration network; ** - CCAC community care access centre Using the analysis framework; how might you/your REB approach this scenario? 50

51 Research Ethics Review of Multicomponent Projects Summary Goal Workshop Milestone Identifying effective solutions for the research ethics oversight of multicomponent projects Analysis framework - approach to identify associated risk, ethics and safety issues Analysis outcome - means to address underlying risk, ethics and safety issues 51

52 Thank you! Delilah Ofosu-Barko, Research Operations Manager Trillium Health Partners, Institute for Better Health ext