Fraser Health Research Ethics Board Annual Report

Transcription

1 Fraser Health Research Ethics Board Annual Report April 1, 2009 to March 31, 2010

2 FRASER HEALTH RESEARCH ETHICS BOARD ANNUAL REPORT APRIL 1 ST 2008 TO MARCH 31 ST 2009 Table of Contents 1. Introduction Background 1 3. The Fraser Health Research Ethics Board Composition of the Board Recruitment to the FHREB Responsibilities of the FHREB Conflict of Interest FHREB Education Ethical Standards and Services to FH Researchers FHREB Standard Requirements Standard Operating Procedures Quality Assurance Ethical Issues Database Research Ethics Education Review of the 2 nd Draft Edition of the Tri-Council Policy Research Ethics Web Site Researcher Study Database Administrative Operations Staff Customer Service Pre-review Research Ethics Board Workload Distribution of Requests for Ethical Review Safety Reporting Disposition of the Review Compliance with Annual Renewal Service Standards for Review Compliance with FHREB Requirements Studies Suspended by the FHREB Key Performance Indicators Challenges Ahead. 18 i

3 10. Conclusion 19 Figures Figure 1 Requests for Ethical Review. 8 Figure 2 Comparison of Volume from Figure 3 Requests for Ethical Review Full Board vs. Delegated Review.. 9 Figure 4 Comparison for Ethical Review Full Board vs. Delegated Figure 5 Total Number of Unexpected Serious Adverse Events.. 10 Figure 6 Disposition of Delegated Reviews of New Projects. 12 Figure 7 Disposition of Full Board Reviews of New Projects. 13 Figure 8 Disposition of Modifications Required for Full Board Reviews of New Projects.. 14 Figure 9 Timeline for Full Board Reviews New Studies. 15 Figure 10 Timeline for Expedited Reviews New Studies. 16 Figure 11 Timeline for Amendments Reviewed Expedited vs. Full Board. 16 Figure 12 Timeline for Yearly Renewals Reviewed Expedited vs. Full Board.. 17 Tables Table 1 FHREB Membership List. 3 Table 2 Disposition of Amendments Reviewed.. 14 Table 3 Disposition of Renewals Reviewed 14 Appendices Appendix 1 Terms of Reference for FH Research Ethics Board Members. 20 Appendix 2 Terms of Reference fro FHREB Research Ethics Board Chair. 22 Appendix 3 Potential Conflict of Interest Declaration for FH REB Members. 24 Appendix 4 Revisions to Application Forms, Guidance Notes & Consent Form Templates 27 Appendix 5 Summary of Fraser Health Research Ethics Board Good Clinical Practice Review Project 28 Appendix 6 Panel on Research Ethics BRIEFING NOTE.. 30 Appendix 7 Research Study Database Web Page.. 32 ii

4 FRASER HEALTH RESEARCH ETHICS BOARD ANNUAL REPORT APRIL 1 ST, 2009 TO MARCH 31 ST, INTRODUCTION The protection of the rights and safety of human research subjects who voluntarily agree to participate in research is the keystone of any research program that is grounded in the principles of scientific validity and reliability. The integrity of the research process itself is dependent on the collection of data that is free from bias and thus must rely on the free and willing participation of research subjects. Protecting the rights and safety of human research subjects in order to ensure the integrity of the research process is the purpose of the Fraser Health Authority s Research Ethics Board [FHREB]. The FHREB strives to render thoughtful, fair and reasonable decisions that are based on the ethical principles of beneficence, distributive justice, respect and non-maleficence, and in so doing has worked hard to develop relationships with Fraser Health researchers that are based on trust and mutual respect. The outcome of the FHREB s exercise of due diligence in its review of new and ongoing research studies is an ongoing improvement in the overall quality of the research conducted in Fraser Health, in addition to the researcher s knowledge about the requirements for conducting ethical research. Over the past year, the FHREB has continued to refine its policies and procedures in order to clarify its standard requirements for research submissions, has kept abreast of national and provincial changes in guidelines and legislation that impact research ethics, provided ongoing education and has continued to be responsive to the inquiries of our research community. This report is one aspect of the FHREB s effort to maintain the transparency and accountability of the ethical review process in FH. The FHREB is very pleased to present its 5 th annual report for the fiscal year. 2. BACKGROUND The FHREB 1 was formed in December 2004 to be responsible for review and ongoing oversight of all research studies involving humans conducted by FH researchers at all FH sites in the region. These researchers include FH employees and privileged physicians and a relatively new group of affiliated academic researchers whose primary appointments are with the University of British Columbia, Simon Fraser University, the University of the Fraser Valley, Royal Roads University, Trinity Western University, the University of Northern British Columbia, McGill University, and the University of Victoria. The FHREB operates according to the principles and standards detailed in the Government of Canada s national standard for research ethics, the Tri-council Policy Statement on the Ethical Conduct of Research in Human Subjects (TCPS) 2. In addition, the FHREB complies with Health Canada regulations and 1 Prior to December 2004, the Clinical Investigation Committee (RCH-based) and the South Fraser Regional Review Committee (SMHbased) conducted ethical reviews for FH researchers. 2 Canada: Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Social Sciences and Humanities Research Council of Canada. August 1998 (with 2000, 2002, 2005 amendments). 1

5 guidelines concerning the ethical review of clinical drug 3, device 4 and natural health product 5 trials, and with U.S. legislation governing the ethical review of studies funded by U.S. government agencies and/or regulated by the U.S. Food and Drug Administration 6. The FHREB ensures that any other Canadian and provincial legislation that is applicable to the conduct of research by a public body is adhered to by FH researchers. Any questions about this report can be directed to Drs. Allan Belzberg and Marc Foulkes, Co-Chairs of the FH Research Ethics Board. 3. THE FRASER HEALTH RESEARCH ETHICS BOARD 3.1 Composition of the Board As of March 31, 2010, the membership of the FHREB was comprised of thirteen full time members, two of which are rotating members who share the role of legal representative. Arun Chocklingham, PhD resigned from the board in December The credentials, roles, affiliation with FH and terms of office for each member are described in Table 1 on the following page. 3 September 1, Regulations Amending the Food and Drug Act Regulations ( Clinical trials) at 4 Part 3 of the Medical Devices Regulations at 5 Part 4 of the Natural Health Product Regulations at CFR and 21CFR at And 2

6 Table 1 FHA Research Ethics Board Membership List & Assurance VOTING MEMBER NAME FIRST LAST 1 * Dr. Marc R. Foulkes Male / Canadian Citizen 2 * Dr. Allan Belzberg Male / Canadian Citizen 3 Dr. Michael Vince Male / Canadian Citizen 4 Prof. Lindsay Meredith Male / Canadian Citizen 5 Nancy Magnee Female / Canadian Citizen HIGHEST DEGREES PRIMARY SCIENTIFIC OR TERM EARNED NONSCIENTIFIC SPECIALTY MD, FRCPC Anaesthesia Dec 1, 07 to Dec 1, 10 MD, FRCPC Nuclear Medicine Dec 1, 07 to Dec 1, 10 PhD Lab Chemistry Dec 1, 07 to Dec 1, 10 PhD Ethics Dec 1, 07 to Dec 1, 10 Community Member Dec 1, 07 to Dec 1, 10 AFFILIATION WITH INSTITUTION Yes Yes No as of Jul 31, 05 No No 6 ** Camille Ciarniello LLB Law Dec 1, 09 to No Female / Canadian Citizen Dec 1, 10 7 ** Mara Stickland LLB Law Dec 1, 09 to No Female / Canadian Citizen Dec 1, 10 8 Michael Wasdell BSc, MA Statistician June to Yes Male / Canadian Citizen (Psychology) June MaryEllen Gillan MA Community Jan to No Female / Canadian Citizen Member Jan Dr. Aaron Tejani Pharm. D. Pharmacy Jan to Yes Male / Canadian Citizen Jan Dr. Amin Aminbakhsh MD, FRCPC Cardiologist/ Oct to Yes Male / Canadian Citizen Echocardiography Oct Dr. Sonia Singh MD, MHSc Family Physician Feb to Yes Female / Canadian Citizen Feb Dr. Anton Grunfeld MD, FRCPC Emergency Feb to Yes Male / Canadian Citizen Physician Feb *** Dr. Bob Gillies Pharm. D. Pharmacy No Term Yes Male / Canadian Citizen *** Warren Bourgeois PhD Ethics No Term No Male / Canadian Citizen *** Robert E. Krider PhD Community No Term No Male / Canadian Citizen Member * Co-chair ** Alternate *** Substitute Member (only if a Voting Member is unable to attend a meeting) Date of Appointment Letter Ex officio: Susan Chunick, Director, Department of Evaluation and Research Services 3

7 3.1 Responsibilities of the FHREB FHREB members are responsible for reviewing the scientific and ethical integrity of each individual research study under the terms of the FH policy The Ethical Conduct of Research and Other Studies Involving Human Subjects. 7 These responsibilities include ensuring that: 1) the study is of value and that the research methodology is sufficient to answer the research question; 2) all ethical norms related to recruitment of study subjects, consent and study procedures, safety management and conflict of interest are complied with by the researcher, and that; 3) consent forms and data collection instruments comply with FHREB standards. In addition, to their role as co-chairs of the FHREB, both Drs. Belzberg and Foulkes are delegated by the board members to conduct delegated review of new studies that meet the criteria for minimal risk as defined by the TCPS and FHREB policy. The delegated review process is also used to review: 1) applications for amendment and renewal of previously approved studies that do not require full board review, 2) local and international serious adverse events and protocol violations, 3) principal investigator responses to requests for modifications arising from full board or delegated review and, 4) any other study-related correspondence. Refer to Appendices 1 and 2 for terms of reference for the FHREB and FHREB co-chairs. 3.3 Conflict of Interest All FHREB members are required to complete a conflict of interest disclosure form [see Appendix 3] on an annual basis to ensure that any associations with industry sponsors of research are made known. Any members found to have a conflict of interest are excused from the review of the applicable research study. 3.4 FHREB Education Two continuing education workshops were held for the FHREB during this year. A half day education workshop was held on April 25 th, 2009 with participants from the University of British Columbia research ethics boards. The invited speaker was David Lee, Director, Office of Legislative and Regulatory Modernization, Policy, Planning and International Affairs Directorate (PPIAD) for the Health Products and Food Branch, Health Canada. He spoke on Modernizing the Food and Drugs Act to Accommodate a Product Lifecycle Approach and on Tissue Banking. The FHREB advised Mr. Lee that the number of pharmacogenetic studies conducted as a component of industry-sponsored clinical trials seemed to be increasing and of the tendency for industry to want to retain genetic material for an indefinite time period. A briefing note was prepared for Mr. Lee, upon his request, so that he could follow up on this issue as the Act is revised. The business part of the agenda was concerned with discussing the Draft 2 nd Edition of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS) and confirming the Protocol Review Checklist for use by the board. 7 Fraser Health Authority. Approved April The Ethical Conduct of Research and Other Studies Involving Human Subjects. 4

8 The second workshop, held on January 9 th, 2010, focused on the development of adaptive research designs as a novel approach to increasing the efficiency with which the required statistical sample size of patients is obtained in clinical trials. This workshop was presented by Dr. Robert Peterson, Director, Child Health, B.C. In addition, Drs. Belzberg and Foulkes and Susan Chunick, Director, Research Administration and Development 8 and Rosa Haywood, Research Ethics Coordinator attended the Canadian Association of Research Ethics Boards annual conference held in Vancouver and reported back to the FHREB. 4. ETHICAL STANDARDS AND SERVICES TO FH RESEARCHERS 4.1 FHREB Standard Requirements Over the course of the year, several changes were made to the Guidance Notes for Initial Ethical Review, Amendment, Renewal and Study Closure and consent form templates to clarify the expectations of the FHREB regarding particular ethical issues and requirements regarding notification and disclosure to research subjects. [See Appendix 4]. 4.2 Standard Operating Procedures The standard operating procedures (SOPs) for the administration of the FHREB including the administration of its appeal process have been updated to reflect new decisions made during the previous year. In addition, a review of the SOPS was undertaken to ensure that they are aligned with the United States Office of Health Research Protections requirements for the conduct of research sponsored, funded or regulated by the United States government. This review and revision process will be finalized in Quality Assurance In the spirit of ongoing quality assurance, the FHREB approved the implementation of the second education and monitoring program for regulated clinical drug trials. Like the first program carried out during , an independent consultant was hired to conduct a mock Health Canada inspection of the FHREB records for six regulated clinical trials and to review the research records for these trials at their respective sites. It is expected that the FHREB and onsite reviews will be conducted between April and November 2010, with the final report delivered by December Ethical Issues Database An administrative log, listing FHREB decisions regarding ethical issues, which are not specific to a particular study but which affect FHREB Policies, Guidance Notes and Consent Templates, has been created. This repository integrates and summarizes all of the FHREB decisions made with respect to a particular issue, for example, consent for screening prospective subjects, so that it can be used as a resource for any other issues that may arise on a related topic, as well as provide a historical record about how that decision was made. The analysis of the historical issues is now complete and will be maintained on an ongoing basis. 4.4 Research Ethics Education Two ethics-related workshops targeted to researchers, research coordinators and FH pharmacy residents were conducted with a total of twenty participants. 8 At the time of writing, Research Administration and Development had become the Department of Evaluation and Research Services. 5

9 4.5 Review of the 2 nd Draft Edition of the Tri-council Policy A revised version of the 2 nd Draft of the Tri-council Policy Statement was released to the public for further comment in December This second draft was compared to the first draft of the second edition. The FHREB was satisfied that the majority of its concerns that had been identified in a letter sent to the Panel on Research Ethics had been addressed. It is expected that the final revision will be submitted in April 2010 to the Tri-Council the Canadian Institutes of Health Research [CIHR], the Natural Sciences and Engineering Research Council of Canada [NSERC], and the Social Sciences and Humanities Research Council of Canada [SSHRC]. 4.6 Research Ethics Web Site All ethics review procedures, including meeting schedules, and applicable guidances, forms and templates are posted and updated on an ongoing basis to the FH Research web site at A feature of this web site is the Research Study Database at which provides comprehensive information on an individual study basis including its approval status. 4.7 Going Paperless The FHREB initiated paperless review for a number of the REB members by ing, rather than mailing, the meeting documentation, to those that opted for this alternative. This reduced the number of paper copies per initial application, submitted by the principal investigator, from eleven to six. 4.8 Streamlining Ethical Review for University of British Columbia Affiliated Researchers The FHREB agreed to allow UBC principal investigators, who are affiliated with FH, to submit a UBC ethics application form for ethical review as an alternative to submitting a FH application for initial review form because the forms are very similar and in order to reduce the work of completing two forms. UBC researchers would also be required to include a document describing additional FH-specific information in the application package. Researchers will be given this information as part of a set of instructions when they apply to become an affiliated researcher. 5. ADMINISTRATIVE OPERATIONS 5.1 Support Ms. Susan Chunick is the Director for the Department of Evaluation and Research Services with responsibility for developing, implementing and monitoring ethical review process standards for FH, providing policy guidance to the FHREB, ensuring that the FHA is compliant with all applicable international, Canadian and provincial legislation, guidelines and standards, and for overseeing the administration of the FHREB. In addition, Ms. Chunick conducts workshops on ethical review and the overall conduct of research for FHA employees and privileged physicians. Ms. Rosa Haywood resigned as the Research Ethics Coordinator for the FHREB in September 2009 and was replaced by Dina Shafey, PhD in November The responsibilities or the Research Ethics Coordinator is to co-ordinate and administer the day to day operations of the FHREB. These include providing support to individual researchers, conducting the pre-review process, processing all decisions of the FHREB, providing assistance to the FHREB co-chairs and participating in developing and presenting workshops on ethical 6

10 review. In addition to this and as a strategy to improve and sustain the consistency of ethical review, a pre-review of all new applications, consent forms and other documentation submitted for full board and delegated review is conducted. 5.2 Customer Service The FHREB office provides timely advice in response to inquiries from FH researchers and assistance in preparing applications for ethical review and related documentation upon request. The standard timeline for response to inquiries is within one business day. 5.3 Pre-review A pre-review of consent forms and study-related documentation is conducted by the Research Ethics Coordinator for all new applications for full board review as well as for minimal risk studies that are submitted for delegated review and all applications for renewal. This provides assurance to researchers that the same standards regarding content and language are being applied consistently by the FHREB while allowing the FHREB members to focus more specifically on examining the scientific aspects of the research protocol and analyzing difficult ethical issues. 6. RESEARCH ETHICS BOARD WORKLOAD The FHREB participated in the Research Ethics Board Operational Practices Survey, a national survey of 31 Canadian research ethics boards conducted by the University Health Network, Toronto, Ontario, and compared favourably with the other research ethics boards across Canada in its category, in particular with respect to timelines for delegated review. The following section describes the workload of the FHREB and its responsiveness with respect to timelines. 6.1 Distribution of Requests for Ethical Review All FH researchers with new studies submit an initial application for ethical review which must be reviewed and receive approval by the FHREB before any research-related procedures can be conducted in the health authority. The types of studies reviewed include clinical drug and device trials which are carried out by FHA privileged physicians and a variety of health services research which is carried out across many healthcare disciplines. Applications for amendments to previously approved studies are also received throughout the year for studies that require a change to the research protocol, consent form, or the addition of other documentation. All amendments must be approved by the FHREB prior to implementation with the exception of those that require immediate implementation in order to ensure subject safety. Both Health Canada and the U.S. Food and Drug Administration require that the review of amendments that meet prescribed criteria be conducted by the full board for regulated clinical trials. In addition, annual renewal of previously approved studies is mandatory for all studies that are continuing to collect data from human subjects, secondary data sources and/or tissue banks. U.S. funded studies and/or those regulated by the U.S. Food and Drug Administration also receive full board review of their renewal application. Other types of correspondence to the FHREB, including notification of study closures or terminations, data safety monitoring board reports, and protocol deviations, are acknowledged by the FHREB. 7

11 Throughout this fiscal year, 597 requests for ethical review were received and completed by the FHREB. Although this volume was virtually identical to that of (594), Figure 2 shows that the amount of work required to review these requests increased with the growth in the number of initial applications and renewals. In contrast, the number of close-out reports decreased. On average, 217 active studies were conducted per month. Figure 1 shows the type, number and proportion of requests for ethical review; Figure 2 compares this distribution with the two previous years. Figure 1 Request for Ethical Review April 1/09 to March 31/10 N= % % % % % new applications amendments renewals acknowledgements study close-outs 8

12 Figure 2-3 Year Comparison of Volume from 2007 to new applications amendments renewals acknowledgements study close-outs Figure 3 compares the number of studies that received full board review with the number delegated to the FHREB co-chairs for review, and Figure 4 compares this distribution for the previous two years. Delegated review for new applications can occur when the study is considered to be of minimal risk only to the prospective subject or is retrospective in design, for amendments and renewals that do not require full board review, and for review of serious adverse events and for close-out reports (81 reviewed). Figure Requests for Ethical Review Full Board vs. Delegated April 1/09 to March 31/ New Applications Amendments Renewals Acknowledgements Delegated Reviews Full Board Reviews 9

13 Figure 4 - Comparison for Ethical Review Full Board vs. Delegated New Applications Amendments Renewals Acknowledgements 6.2 Safety Reporting Full Board Delegated Full Board Delegated Full Board Delegated Under delegated review, the review of safety-related information as one aspect of providing ongoing monitoring of active clinical drug and device trials. The aim of this review is to ensure that any unexpected adverse event experienced by a local FH research subject has been handled appropriately and that any significant pattern of adverse events from other non-local sites is recognized. Adverse events related to research studies are defined as noxious and unintended responses to a medicinal product related to any dose. 9 Non-local serious adverse event reports are those that are sent by the sponsor to the principal investigator from other sites conducting the same study world-wide. These reports are reviewed but are not followed up as those sites are not within the FHREB s jurisdiction. Figure 5 compares the number and type of Serious Adverse Event reports for this fiscal year with the previous two years. While the number of local serious adverse events has increased by 10 to 11% from year to year, this trend is to be expected as the number of initial applications and applications for renewal of ongoing studies continues to grow. 9 Health Canada, Health Products and Food Branch: Clinical Safety Data Management Definitions and Standards for Expedited Reporting, ICH Topic E2A 10

14 Figure 5 - Comparison of Total # of Serious Adverse Event Reports Processed for Active and Completed Studies from 2007 to Number of Individual SAEs Local SAEs Non-Local SAEs In addition to Serious Adverse Event reports, the FHREB co-chairs also review and follow-up the outcome, if required, of protocol violations related to clinical drug and device trials that are reported. A violation is defined as an unanticipated or unintentional divergence or departure from the expected conduct of an approved study that is not consistent with the current research protocol, consent document or study addenda. 10 Eleven Protocol Violations were reviewed by the FHREB co-chairs. Of these, one study had two violations and a second study had three violations. There was one violation for each of the other six studies. All violations were managed appropriately by the principal investigators for these studies and did not require further follow up. 6.3 Disposition of the Review Figures 6 to 7 illustrate the result (i.e. the decision) of the delegated and full board reviews. Studies that are not approved after first review receive either a request for modifications, or in the case of studies receiving full board review, may be deferred to a subsequent REB meeting upon receipt of the researcher s response. All principal investigators are expected to reply to the request for either modification or deferral within 6 months of the decision, otherwise the study is considered closed. The review and approval of the researcher s response to a request for modification memo is delegated by the full board to one of the FHREB co-chairs under the delegated review process or reviewed by the FHREB if deferred from an earlier meeting. 10 Fraser Health: Guidance Note for Submitting Protocol Violations to the FHREB,

15 Studies that are delegated for initial review are considered minimal risk as they do not use invasive interventions and therefore have fewer safety concerns and are also less complex, and therefore some may be approved upon initial review as indicated by Figure 6. Figure 6- Disposition of DELEGATED Reviews of New Projects April 1/09 to March 31/10 N= Approved on 1st Review Deferred Approved after 2nd Modifications Required Modifications Required Approved after 1st Modifications Required 4 out of the 51 studies that received a modifications required memo were closed by the Principal Investigator before receiving ethical approval. Figure 7 illustrates that all studies receiving full board review require some degree of protocol or consent form revision or clarification upon first review to respond to ethical concerns raised by the FHREB. Deferred studies must come back to the full board for review upon receipt of the principal investigator s response to the deferral notice because of substantive concerns regarding the scientific merit, design or ethical issues relating to subject recruitment, consent or safety. Sometimes the complexity of the ethical issues creates the need for a review process that is lengthy and involves more than one deferral and/or modification. The FHREB offers the principal investigator every opportunity to satisfy the FHREB of its concerns. 12

16 Figure 7 - Disposition of FULL BOARD Reviews of New Projects April 1/09 to March 31/10 N= Deferred Modifications Required Out of the 8 deferred studies listed on Figure 7, 5 received ethical approval, 3 studies were withdrawn by the Principal Investigator before receiving ethical approval. Figure 8 illustrates that all studies initially reviewed by the full board and that responded to the request for modifications were approved upon Delegated Review by the FHREB co-chairs. 13

17 Figure 8 - Disposition of Modifications Required for FULL BOARD Reviews of New Projects April 1/09 to March 31/10 N=42 (5 Terminated, i.e. study withdrawn by the principal investigator) 6 31 Approved after 1st Modification Approved after 2nd Modification Tables 2 and 3 illustrate the disposition of the approvals for amendments and renewals of previously approved studies. Table 2: Disposition of Amendments Reviewed Between April 1/09 and March 31/10 Approved 1 st Review Modifications Required Approved after 1 st Modification Notice Full Board Review (n=2) Delegated Review (n=156) Total n=158 Table 3: Disposition of Renewals Reviewed Between April 1/09 and March 31/10 Approved 1 st Review Modifications Required Approved after 1 st Modification Notice Full Board Review (n=18) Delegated Review (n=117) Total n= Compliance with Annual Renewal Annual renewal of previously approved studies is a mandatory requirement for all ongoing studies. In order to ensure compliance, a follow up memo is sent to all principal investigators within two weeks of the expiry of the initial approval or subsequent renewal. A total of 135 studies were renewed within the one year approval period. There were thirty-two studies that received a Final Notice for Renewal Letter indicating that the study required either an application for renewal or a close-out notification as the ethics 14

18 approval had already expired. Out of these thirty-two, fourteen studies were renewed slightly over the expiry date and eighteen were subsequently closed. 6.5 Service Standards for Review The FHREB office strives to issue decisions of the full board or delegated review within five business days of the decision. The principal investigator may decide to respond at any time within a six month period following the date of the decision. For full board review, Figure 9 illustrates that the median number of business days is two for the modification or deferral decision to be ed to the researcher; the balance of the time (i.e. 47 days) reflects the time to receive the response from the principal investigator before final review and approval. The median number of business days from review to approval for Delegated studies is 11 days. The median of three business days for delegated reviews to receive the review decision is a day longer because the FHREB is informed of all approvals and notifies the FHREB Co-ordinator if there are any concerns within three business days, at which time the Letter of Authorization is ed to the principal investigator. It is important to note that the longer time for approval of full board decisions is a function of the time it may take for a sponsor to accept the required FHREB changes and to communicate their approval to the local FHA principal investigator. All timelines in the following figures are reported in median number of business days. Studies that were reviewed but did not receive final approval in this fiscal year are not included; the timeline data for these studies will be reported in the next fiscal year. Figure 9 - Timeline for Full Board Reviews New Studies April 01/09 to March 31/ Median Business 25 Days Business Days from Meeting to Approval Business Days from Meeting to 1st Modifications/Deferral Business Days from 1st Modifications/Deferral Notice to Approval The proportion of studies meeting the median statistic of 2 business days from the meeting date to 1 st modification/deferral sent is 81%. 86% of research studies were sent the 1 st modification/deferral within 5 business days. Figure 10 provides similar information for new applications reviewed under Delegated Review. 15

19 Figure 10 - Timeline for Delegated Reviews New Studies April 01/09 to March 31/10 25 Median Business Days Business Days from Received Date to Approval Date w/o Modifications Business Days from Received Date to 1st Modifications Notice Sent Business Days from 1st Modifications Notice to Approval Figures 11 and 12 illustrate the timelines for review of amendment and renewal applications. Figure 11 - Timeline for Amendments Reviewed Delegated vs. Full Board April 01/08 to March 31/09 7 Median Business Days Days from Received Date to Approval Date w/o Modifications Days from Received Date to Modifications Notice Sent Amendments - Delegated Amendments - Full board Amendments - Full board Amendments - Delegated 16

20 Figure 12 - Timeline for Yearly Renewals Reviewed Delegated vs. Full Board April 01/09 to March 31/10 5 Median Business Days Renewals - Delegated 0 Days from Received Date to Approval Date w/o Modifications Days from Received Date to Modifications Notice Sent Renewals - Full board Renewals - Full board Renewals - Delegated 7. COMPLIANCE WITH FHREB REQUIREMENTS 7.1 Protocol Violation In October 2009, Dr. Marc Foulkes, co-chair, FHREB reviewed a protocol violation submitted by a FH research site for delegated review; this violation stated that two subjects had had their blood submitted for Ribonucleic Acid (RNA) and genetic study sampling even though the subjects had previously refused to give consent for genetic testing and RNA sampling. The investigators also stated that the following actions had been taken to rectify the situation: (1) the study sponsor was notified of the protocol deviation; (2) notification for RNA sample destruction was sent to the study sponsor; and (3) a procedure to flag all case report forms by identifying the subject s genetic consent status was implemented at the site. After reviewing the protocol deviation, Dr. Foulkes requested the following information from the study s Principal Investigator: (1) corporate (i.e. from the company sponsor) documentation and written confirmation that the RNA samples had been destroyed; (2) documentation and confirmation that the subjects had been informed of this deviation as well as the subjects response to this violation; and (3) the date that the error was discovered and the date when the sponsor was notified of the error. In January 2010, the study investigators responded to this request for information and included most of the information requested by Dr. Foulkes; however the corporate documentation and confirmation of the destruction of the RNA samples from the sponsor was not included as it had not yet been received by the site from the sponsor. In March 2010, the FHREB received the corporate documentation as previously requested. 17

21 This deviation was presented to the full board in November 2009 by Dr. Foulkes who agreed with the action taken by Dr. Foulkes. The FHREB requested that Dr. Foulkes report back once all requirements had been met and agreed that this study would be a candidate for a mock Health Canada inspection and agreed that no further action was required upon receipt of the required documentation. This case was not referred to the FH Research Inquiry and Investigation Committee as it was felt that appropriate actions were taken by the principal investigators to redress the non-conformities. 8. KEY PERFORMANCE INDICATORS The FHREB has developed the following key performance indicators [KPI] as measures of compliance with ethical standards and overall safety of research conducted in FH. a. Compliance with the requirement for annual renewal of research studies set by Health Canada, the Canadian Institutes of Health Research, the U.S. Food and Drug Administration and the U.S. Department of Health and Human Services in order to maintain eligibility to either conduct clinical trials or receive funding for research. This KPI in addition applies to all research conducted in FH as it reflects adherence to ethical standards and FH research policies. % of all regulated and non-regulated studies continuing to recruit subjects, access secondary data or tissue that are renewed within one year from date of initial ethical review or subsequent annual renewal: 85 % b. Local Serious Adverse Event Rate: This KPI illustrates that FH research subjects experience an extremely low rate of adverse events that are unexpected and related or possibly related to the study drug used in clinical trial research. % of local unexpected serious adverse events per total of all local and non-local serious adverse events for active and completed studies: 2 % c. Subject Complaints and Appeals: There were no subject complaints made to the FHREB. In addition, there were no requests for appeals of FHREB decisions brought forward by FH principal investigators to the VIHA Research Ethics Board; the VIHA Research Ethics Board functions as the appeal board for the FHREB. 9. CHALLENGES AHEAD The FHREB continues to evolve and keep current with best practices in the ethical review of research. As research ethics is always in evolution, the FHREB is sensitive to the desire of researchers for the application of consistent standards while at the same time striving to ensure that absolute requirements regarding ethical review continue to be implemented. At the same time, the FHREB must be attuned to upcoming revisions to the Tri-Council Policy Statement and its obligations to revise FH research policies accordingly. Any changes will be communicated to the FH research community. In addition, the FHREB will continue to participate in a provincial exercise, carried out under the auspices of the Michael Smith Foundation for Health Research, to investigate the need for harmonization of ethical review processes in British Columbia for multi-site research. As FH continues to receive more requests by non-fh researchers to conduct studies in FH, the FHREB will continue to evaluate how the review process can be streamlined to eliminate any unnecessary redundancy. 18

22 10. CONCLUSION The undersigned are pleased to confirm that the FH Research Ethics Board has been in compliance with the Tri-Council Policy Statement: Ethical Conduct for Conducting Research Involving Humans and other regulatory requirements, as applicable, for the 2009 to 2010 fiscal year. Respectfully submitted, 2010 September September 14 Dr. Allan Belzberg Date Dr. Marc Foulkes Date FHREB co-chair FHREB co-chair 19

23 APPENDIX 1 TERMS OF REFERENCE FH RESEARCH ETHICS BOARD MEMBERS APPROVED: 2007 August 09 1 st revision: 2007 October 17 The members of the FH Research Ethics Board [FHREB] are responsible for carrying out the following activities and functions and operates under the authority of FH Policy The Ethical Conduct of Research and Other Studies Involving Human Subjects. 1. Complete the Introductory Tutorial for the Tri-council Policy Statement: Ethical Conduct of Research Involving Human Subjects at 2. Review all submissions that meet the criteria for full board review that are assigned for a full board meeting prior to the meeting date. These include applications for initial ethical review, applications for amendment and renewal of previously approved studies that meet specific criteria for full board review, and responses to studies that have been deferred from a previous board review. 3. Submit written comments to the FHREB office at the conclusion of the REB meeting for compilation into the modifications or deferral memoranda. 4. Ensure that the study complies with the applicable Canadian federal and provincial and U.S. regulations when applicable and that all research complies with the Tri-Council Policy for Ethical Conduct for Research Involving Humans and other non-regulatory requirements. 5. Make a decision about the outcome of the review for each study as follows: a) approve if all FHREB requirements have been met satisfactorily, or b) request that the investigator modify the study and/or respond to questions concerning the study prior to approval, or c) refer to an external source for review, or d) not approve. 6. Develop guidance notes, policies and procedures for ethical review in collaboration with the Director, Research Administration and Development. 7. Participate in educational activities, evaluations, audits or investigations related to the oversight of research ethics at FH. 8. Declare any conflict of interest pertaining to studies on the full board agenda before discussion begins. 9. Declare conflict of interest on an annual basis. 20

24 10. Honoraria: All REB members, excluding the co-chairs, are paid $ per meeting attended. i. Honoraria Paid to Non-FH Employees: Cheques for the honoraria are sent directly to the REB members, who are physicians or non-fh employees by FH Finance, at the address of their choice. There are no restrictions on the use of the honoraria by REB members who are non-fh employees or who are physicians. ii. Honoraria Paid to FH Employees: Honoraria for REB members who are FH employees may be claimed by that member with the submission of the following documentation to the Research Ethics Co-ordinator: a. expense receipts, b. as per FH Travel and Business Expense policy, the expense claim must be filled out on an Employee Expense Report, and, c. a written justification for that expense made to the Director of Research Administration and Development who will approve the request. A cheque requisition form is sent to FH Finance for reimbursement of the approved funds to that REB member. Honoraria to REB members who are FH employees may be used for the type of expenses that FH employees would normally be able to claim and that are related to the work of the Research Ethics Board. This would normally include expenses related to education, conferences, and other out-ofpocket expenses. Other expenses may be considered upon presentation of an adequate written justification. Any purchase of equipment and supplies that is approved by the Director of Research Administration and Development must be made through FH Material Services as per the FH Research Policy Section 4.3c. 21

25 APPROVED: 2007 August 09 1 st revision: 2007 October 17 APPENDIX 2 TERMS OF REFERENCE FHREB RESEARCH ETHICS BOARD CHAIR The Chair(s) of the FHREB is responsible for carrying out the following activities and functions, and operates under the authority of the FH Policy The Ethical Conduct of Research and Other Studies Involving Human Subjects. The terms of reference for the FHREB co-chairs, in addition, to those of the FHREB Members, are listed below. 1. Chair the full board meetings of the FHREB and ensure that the board meets Tri-Council Policy and Health Canada requirements for quorum at each meeting. 2. Review and edit as required the comments submitted by board members following a meeting and prior to distribution to the investigators as requests for modification or deferral memoranda. 3. Review all applications for initial review, amendments and renewals of previously approved research, that qualify for expedited review under the minimal risk criteria and: a) approve if all FHREB requirements have been met satisfactorily, or; b) request that the investigator modify the study and/or respond to questions concerning the study prior to approval, or; c) refer to the FHREB for review and approval. 4. Review investigators responses to requests for modifications that arise either from a full board meeting or from an initial expedited review of minimal risk studies, amendments and renewals and approve if all FHREB requirements have been met satisfactorily. 5. Develop guidance notes, policies and procedures for ethical review in collaboration with the board members and the Research Administration and Development Director. 6. Inform investigators of subject safety related issues that may arise during the course of a study and that require a response from the investigator. These may include, among others, following up serious adverse event reports, protocol violations and data safety monitoring board reports upon reviewing studies using interventions for which regulatory authorities (e.g. Health Canada, FDA) have issued safety alerts. 7. Review and respond to investigator s reports of serious adverse events and protocol deviations. 8. Acknowledge close-out notices from investigators. 9. Participate in Health Canada inspections or NCEHR site visits as required. 10. Participate in investigations related to breach of compliance with Tri-Council policy FH policy on The Ethical Conduct of Research and other Studies Involving Human Subjects and the FH Research Policy. 22

26 11. Prepare the FHREB annual report in collaboration with the Director, Research Administration and Development. 12. Respond to investigator s inquiries as appropriate. 13. Honoraria: REB co-chairs are paid $ per meeting. This also includes the expedited review of minimal risk applications which is conducted on a weekly basis. iii. iv. Honoraria Paid to Non-FH Employees: Cheques for the honoraria are sent directly to the REB members, who are physicians or non-fh employees by FH Finance, at the address of their choice. There are no restrictions on the use of the honoraria by REB members who are non-fh employees or who are physicians. Honoraria Paid to FH Employees: Honoraria for REB members who are FH employees may be claimed by that member with the submission of the following documentation to the Research Ethics Coordinator: a. expense receipts, b. as per FH Travel and Business Expense policy, the expense claim must be filled out on an Employee Expense Report, and, c. a written justification for that expense made to the Director of Research Administration and Development who will approve the request. A cheque requisition form is sent to FH Finance for reimbursement of the approved funds to that REB member. Honoraria to REB members who are FH employees may be used for the type of expenses that FH employees would normally be able to claim and that are related to the work of the Research Ethics Board. This would normally include expenses related to education, conferences, and other out-ofpocket expenses. Other expenses may be considered upon presentation of an adequate written justification. Any purchase of equipment and supplies that is approved by the Director of Research Administration and Development must be made through FH Material Services as per the FH Research Policy Section 4.3c. 23

27 APPENDIX 3 POTENTIAL CONFLICT OF INTEREST DECLARATION FOR FRASER HEALTH RESEARCH ETHICS BOARD MEMBERS Please complete the sections below to provide information to the FHREB Co-Chairs and Director of Research Services about circumstances concerning you and/or your partner(s) and/or immediate family members (including children, whether living in the household or not) that could lead to a conflict of interest with the business of Fraser Health Research Ethics Board (FHREB). Include any relevant details from the past two years of your life, including your current situation. Exact details of remuneration are not required. 1. Personal Details: Surname: Postal Address: Given Names: Hospital Department (if applicable): Hospital Division (if applicable): Citizenship: Canadian Landed Immigrant Other: Phone Number: Fax Number: Address: 2. Research Support: Yes No Provide brief details, including names of sponsors and types of support (e.g. salary, grants, equipment, fees). Self: Partner and/or Immediate Family members: 3. Consultancy Activities: Yes No Provide brief details, including name(s) of companies who have utilized your services and amount of time spent on consulting. Self: Partner and/or Immediate Family members: 4. Fees or honoraria for writing research proposals or publications: Yes No 24

28 Provide details about the organization from which you received the fees. Self: Partner and/or Immediate Family members: 5. Speaker fees and/or educational awards/honoraria: Yes No Provide details about the organization from which you received the fees. Self: Partner and/or Immediate Family members: 6. Travel assistance to attend conferences or meetings: Yes No Provide details about the organization from which you received the assistance. Self: Partner and/or Immediate Family members: 7. Membership(s) on Research Professional Boards or Institutional Boards (for profit and not-for-profit): Yes No List memberships. Provide details about the organization from which you received the fees. Self: Partner and/or Immediate Family members: 8. Ownership of stock, stock options, or other equity holdings: Yes No No declaration is expected for managed or mutual funds. Self: Partner and/or Immediate Family members: 25

29 9. Any additional financial or other relationship which could be a potential conflict of interest (such as patent rights, intellectual property rights): Yes No Self: Partner and/or Immediate Family members: 10. I understand that it is my responsibility to indicate to the FHREB Co-Chairs when I have a conflict of interest with an application coming before the committee. Signature: Date: Printed Name: 26

30 Appendix 4 REVISIONS TO APPLICATION FORMS, GUIDANCE NOTES AND CONSENT FORM TEMPLATES Document Version # and Date Application for Initial Ethical Review Form Version 2009 July 24 Researcher Response Form Version July 24 Application for Amendment of Previously Version July 24 Approved Studies Request for Annual Renewal Form Version February 09 Study Closure Form Non Clinical Version July 24 Study Closure Form Clinical Version July 24 Guidance Notes for New Applications for Ethical Version March 23 Review Guidance Notes for Amendment Version July 24 Guidance Notes for Renewal Version July 24 8 Subject Information and Consent Form Version November 10 Requirement Template Temporary Optional Consent Form Version March 04 Consent Form Checklist Version 2010 February 18 27

31 Appendix 5 Appendix 6 Panel on Research Ethics BRIEFING NOTE Date: May 26 th, 2009 Item Draft 2 nd Edition of the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans Submitted By Fraser Health Authority Research Ethics Board see attached membership list 1. Definition of Research: Please clarify the reason for removing generalizable from the definition of research. The revised definition of research while being broader to reflect the types of methodologies that may be used by the social science and humanities research community, does not reflect the traditional goal of research to contribute to generalizable knowledge such that the application of this new knowledge can lead to the development of new principles, laws, theories. The goal of generalizing the research results to a wider population is the key feature that distinguishes research from other activities, such as program evaluation and quality improvement and performance measurement, that may use research methods but for a narrowly defined purpose. Focusing on the goal of research still accommodates the type of research that may utilize small samples because of the inherent nature of that type of inquiry. Recommendation: Define research according to its intended purpose, i.e. to contribute to generalizable knowledge, and refrain from a general definition that is based primarily on the research process, i.e. disciplined inquiry/systematic investigation. 2. Re Chapter 2: Scope and Approach: N of 1 studies are classified as research in Chapter 11. However, they are not identified as research that requires REB review and approval. Clarify if it is the intention that REB s should review and approve case studies prior to publication. This is particularly important in a clinical environment where many physicians report on single cases in peer reviewed journals. If case studies 28

32 must receive ethical review and approval, the workload of the REB s will increase, perhaps substantially. Clarify if compassionate use of an unapproved drug will require REB approval. The role of REB s in reviewing and acting on serious and unexpected adverse events requires clarification. It is obvious that REB s have a part to play in receiving and acting upon adverse events of this nature from their local clinical trial site; however the role of REB s in reviewing international adverse events from other clinical trial sites is controversial. It would be extremely helpful to have clarification of the REB s obligation in reviewing and acting upon international adverse events. 3. Article 3.2 Section F: Is it expected that REB s will have to police the implementation of this article once the study is completed? Would it be sufficient to include a statement in the consent form that participants can contact the researcher if the participant wishes to know the results of the study with a note explaining that these results may not be available for sometime after the study is completed? 4. Article 3.4 It would be helpful to provide an example of a plan that an REB could accept for studies where questionnaires are used for participants with fragile mental status. Could this be provided in an appendix? 5. Article 6.20 The FHREB requests clarification regarding the jurisdiction of the Appeal Committee regarding the ethical acceptability of the research study. An example of the appeal process that a REB might follow would be helpful. 6. Use of Subject vs. Participant Feedback on the difference between a subject and a participant: This perspective was obtained from patient advocacy group member who attended a CIHR Café Scientifique on Ethics that was held in Vancouver, BC. This member thought that subjects are the object of a study; while participants are more involved and provide their opinion on how the study is shaped. Might it be important to consider which label is the most appropriate to use for the type of research being conducted? Has there been any other public input on the use of subject vs. participant? 29

33 Appendix 7 Research Study Database Web Page 30