Collaboration and Efficiency in IRB review of Multi-Site Research

Transcription

1 Collaboration and Efficiency in IRB review of Multi-Site Research Human Subject Research Community Conference University of Miami Student Activities Center (SAC) September 11, 2014 Cynthia Hahn VP, Clinical Research and Regulatory Affairs North Shore-LIJ Health System

2 Background Central IRBs may improve efficiency, increase quality, and reduce variability of multicenter trials Supported by FDA OHRP DHHS Research institutions differ in their willingness to use central IRBs

3 Clinical Trials Transformation Initiative The Clinical Trials Transformation Initiative (CTTI) is a public-private partnership to identify and promote practices that will increase the quality and efficiency of clinical trials. Members include representatives of government agencies industry representatives (pharmaceutical, biotech, device, and clinical research organizations), patient advocacy groups, professional societies, investigator groups, academic institutions, and other interested parties.

4 Use of Central IRBs for Multicenter Clinical Trials Goal Identify solutions to address barriers to the adoption of central IRBs for multicenter clinical trials Objectives were to: Solicit current perceptions of barriers Develop a strategy to address the identified barriers Assess reactions to proposed solutions to remove these barriers

5 Current Central IRB Models & Practices Shared Models Federated: Time and coordination challenges, continuing review can be an issue Facilitated (Old NCI CIRB): Did not reduce administrative burden enough Non-Shared Model Complete Reliance Consortium

6 Current Central IRB Models & Practices Independent Federal Academic

7 Use of Central IRBs for Multicenter Clinical Trials Methods Literature Search (70 studies): More commentary than empirical and focused on efficiency but not quality Convened an Expert Advisory Panel: had trouble defining the terms, delivered a list of potential barriers Conducted Stakeholder Interviews: General query first and then asked for feedback on proposed solutions for each barrier

8 Findings

9 Flynn KE, Hahn CL, Kramer JM, Check DK, Dombeck CB, et al. (2013) Using Central IRBs for Multicenter Clinical Trials in the United States. PLoS ONE 8(1): e doi: /journal.pone

10 Need to clarify terms Central IRB = Single IRB-of-record for a given protocol To which sites cede all regulatory responsibility for scientific oversight and integrity of the protocol from initial review to termination of the research including informed consent A range of entities may serve as a central IRB e.g., independent IRBs, federal IRBs, another institution s IRB Implies that an institution not choosing to use the single IRB-ofrecord would not participate in that protocol

11 Categories of Barriers Legal & regulatory Local context Quality Administrative & logistic Financial Conflicts of interest

12 Common themes Concerns seemed to be associated with conflation of the responsibilities of the institution with the ethical review responsibilities of the IRB Remaining discomfort due to lack of experience using centralized review

13 Recommendation #1 CTTI recommends using a central IRB (defined as a single IRB of record for all sites) to improve the quality and efficiency of multicenter clinical trials.

14 Recommendation #2 To address blurred distinctions between responsibilities for ethics review and other institutional obligations, CTTI recommends that sites and IRBs use a CTTI-developed guide ( Considerations Document ) to support communication and contractual relationships between institutions and a central IRB.

15 Considerations Document Considerations in Assigning Responsibilities to a Central IRB and a Local Institution for a Multicenter Clinical Trial Roles defined: Central IRB Institution Either Central IRB or Institution Both Central IRB and Institution

16 Recommendation #3 CTTI recommends that sponsors in a position to require the use of central IRB review for multisite trial networks should do so in order for relevant stakeholders to gain experience with central IRB review. The resulting experiences may foster greater comfort and trust with the central IRB model.

17 Experience is needed Enthusiastic stakeholder support for the project and proposed solutions Remaining discomfort from lack of experience

18 Project #2: Advancing the Use of Central IRBs To assess and propose solutions for remaining areas of concern for using a single central IRBs for multicenter clinical trials Collected Tools and Templates Developing Best Practice IRB Authorization Agreement Expert Meeting: June 2014

19 IRB Authorization Agreements (IAA) Whether your institution agrees to rely on an external IRB or agrees to serve as the central IRB. An IRB Authorization or Reliance Agreement must be executed The IRB Authorization or Reliance Agreement should outline the responsibilities of each party How you get from agreement to implementation well that s another story

20 Quality Human Research Protections Research Protection Program Distinctions of a Quality Program as per AAHRP Strong integrated plan for human research protection Strong program for scientific review Strong and highly motivated organizational leader Program for review of resources for the HRPP Research specific IRBs Strong network of communication among units Policy and procedure to identify and manage organizational conflict of interest Strong quality improvement programs Strong education programs for researchers and staff Highly competent IRB chairs, members, or staff Impressive educational materials for the community

21 More InformationResearch Protection Program First IRB Project: Second IRB Project: Cyndi Hahn: (516)

22 Collaboration and Efficiency in IRB review of Multi-Site Research Human Subject Research Community Conference University of Miami Student Activities Center (SAC) September 11, 2014 David Forster Chief Compliance Officer WIRB-Copernicus Group

23 Topics Benefits of Institutional Use of a Central IRB Considerations in utilizing a central IRB: Issues for both the Institution and the IRB to address Issues for the Institution to address Issues for the Central IRB to address Issues that could be addressed by either entity.

24 Benefits to Central IRB Use More efficient for sponsors who wish to include an institution as a site. Faster timelines for protocol-wide approval, Consistency in review across sites. Reduces administrative burden of the institution through fewer IRB reviews, maintenance of IRB records, scheduling and conducting IRB meetings, etc. (However, it does not eliminate institutional administrative requirements.)

25 Meshing the Bureaucracies The most important aspect of use of a central IRB is assigning duties and arranging communication. This is true for a one-time use of a central IRB, or a systematic relationship.

26 Responsibilities Shared by the Institution and Central IRB Enter into an IRB authorization agreement (IAA). Can be short or quite extensive, depending on the relationship. For a single use, it may be appropriate to use the template IAA available at OHRP s website at uthagree.html. For a more extensive relationship, the IAA will often take the form of a lengthy contract.

27 Responsibilities Shared by the Institution and Central IRB Establish a plan for sharing of information between the institution and the IRB, such as: Questions about research administration and establishing policy, Submission of new research, Submission of changes in research, The role of the institution in communication versus the PI s and research staff.

28 Responsibilities of the Institution, Non-protocol Specific Coordinate the timing of IRB review with other necessary reviews, such as: Radiation safety, Pharmacy and therapeutic committee, Institutional Biosafety Committee, and Conflict of Interest. Institution must determine whether these reviews will be concurrent or sequential.

29 Responsibilities of the Institution, Non-protocol Specific Maintain program for education of investigators and research staff and training inhuman subjects research. Maintain policies and procedures for the conduct of human subjects research as appropriate for the particular institution. Maintain appropriate institution-specific required credentialing of staff.

30 Responsibilities of the Institution, Non-protocol Specific If institution conducts federally-funded research, maintain an approved FWA.

31 Responsibilities of the Institution, Non-protocol Specific Conduct a privacy and security review as required by HIPAA with respect to the mechanisms for permitting the use and disclosure of Protected Health Information (PHI) for clinical trials, including certain tasks that can only be done by the covered entity, such as allowing decedent research and the use of Limited Data Sets. (Note that either the IRB or institution can approve authorizations and waivers of authorization for research).

32 Responsibilities of the Institution, Protocol Specific Ensure that the investigator/researcher is conducting research and recruiting potential research participants in accordance with IRBapproved protocol, procedures, and documents.

33 Responsibilities of the Institution, Protocol Specific Determine and designate the IRB of record for the protocol. Obtain IRB approval of research protocols involving human subjects. For Public Health Service (PHS)-funded research, conduct a conflict of interest (COI) review pursuant to the regulations on Promoting Objectivity in Research, 42 CFR Part 50, Subpart F. Notify the IRB promptly in writing of serious or continuing non-compliance or unanticipated problems involving risks to subjects or others.

34 Responsibilities of the Central IRB, Non-protocol Specific Maintain a program for education and training in human subjects research for IRB members and staff. Register with FDA and OHRP, as applicable. Notify institution if accreditation status changes.

35 Responsibilities of the Central IRB, Non-protocol Specific If review is for an institution that conducts federally-funded research, the central IRB must commit to adhere to the requirements of the institution s Federal-Wide Assurance (FWA).

36 Responsibilities of the Central IRB, Protocol Specific Ensure the research complies with applicable regulations, for example, the Common Rule (45 CFR 46), FDA Regulations 21 CFR Parts 50, 56, 312, and 812, other applicable federal regulations, state law, and applicable international standards.

37 Responsibilities of the Central IRB, Protocol Specific Collect, review, and take into account sitespecific information provided by the individual sites, such as: special considerations regarding local populations, any restrictions placed on the clinical trial by the institution, or institutional policy.

38 Responsibilities of the Central IRB, Protocol Specific Review and approve the informed consent form and any other research-related documents or media. The institution may wish to have certain language in the consent form, such as: Conflict of interest, Compensation for injury, Payment.

39 Responsibilities of the Central IRB, Protocol Specific Provide the investigator with copies of all IRB decisions. Provide the institution with copies of IRB approval documents, IRB rosters, and meeting minutes upon request, or in accord with the IRB authorization agreement. Notify the institution promptly in writing of findings of serious or continuing non-compliance, unanticipated problems, and IRB suspension or termination.

40 Responsibilities that Could be Addressed by Either Entity Reporting to sponsors and federal agencies IRB decisions of: serious or continuing non-compliance, unanticipated problems involving risks to subjects or others, or suspension or termination of central IRB approval. Investigating and determining potential corrective/remedial actions in the event of non-compliance.

41 Responsibilities that Could be Addressed by Either Entity Receiving and addressing subject complaints. Evaluation of investigator qualifications. Reviewing and approving authorizations and waivers of authorization for research.

42 Responsibilities that Could be Addressed by Either Entity Evaluate the local context in which the research will be conducted, including consideration of any specific requirements of state or local laws, regulations, policies, or standards. If this responsibility is assumed by the institution, they should inform the central IRB of any relevant requirements or findings from the analysis that would affect conduct of the clinical trial at that institution.

43 Collaboration and Efficiency in IRB review of Multi-Site Research Human Subject Research Community Conference University of Miami Student Activities Center (SAC) September 11, 2014 Colleen Gorman Senior Director, Business Process Owner, Investigator Site Pfizer, Inc.

44 Topics Use of Central IRB s in Industry Sponsored Studies Considerations Operational Ease AAHRPP

45 Use of Central IRB Pfizer has approximately 6,000 active investigator sites at any one time 60% utilize a central IRB Use of central IRBs is higher in US than ex-us

46 Considerations Operational Ease Timeline Predictability Transparency Consistency in review

47 Human Research Protection Association for the Accreditation of Human Research Protection Programs (AAHRPP) AAHRPP accreditation is a public affirmation of your commitment to protecting research participants Pfizer supports sites in achieving AAHRPP accreditation Requires that central IRB s used for a study be AAHRPP accredited

48 Human Research Protection In 2012, Pfizer explored accreditation as a sponsor Required all trials were reviewed by an AAHRPP accredited IRB Pfizer Ethics Review Committee (PERC) Executed by WIRB Conducts review of all protocols without an AAHRPP accredited IRB Evaluates protocol and ICD from a Human Research Protection perspective In March 2013, Pfizer became the first sponsor to receive AAHRPP accreditation