What s New in GCP? FDA, OHRP Issue Harmonized Guidance on Transferring IRB Oversight of Clinical Studies

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1 Vol. 8, No. 8, August 2012 Happy Trials to You What s New in GCP? FDA, OHRP Issue Harmonized Guidance on Transferring IRB Oversight of Clinical Studies Reprinted from the Guide to Good Clinical Practice with permission of Thompson Publishing Group, th St., Washington, D.C ; To learn more about the Guide to Good Clinical Practice, visit: The FDA and the Department of Health and Human Services Office for Human Research Protections (OHRP) issued harmonized guidance June 12 on transferring clinical investigation oversight to another institutional review board. Both guidances noted that, although the two guidances may appear somewhat different due to minor variations in formatting and some necessary variations due to differences in the regulated entities under FDA s and OHRP s jurisdiction, the intent was to provide harmonized guidance to IRBs, sponsors, institutions, investigators and other entities involved in the study oversight transfer process. When Coast IRB went out of business, the FDA and OHRP started looking at the mechanisms for the transfer of clinical trial oversight from one IRB to another. OHRP said the guidance addresses: What is the regulatory background for research project transfer? What actions may apply when the research project remains at the same institution, but responsibility for IRB review is transferred either from an internal to an external IRB, or from an external IRB to another external IRB? What actions may apply when the research project remains at the same institution, but responsibility for IRB review is transferred from one internal IRB to another internal IRB? What actions may apply when the research project is transferred to a new engaged institution? (See Table 1.) The draft guidances discuss eight steps to be considered when transferring oversight of a previously approved clinical investigation between two IRBs: Identify the studies to be transferred. Ensure the availability and retention of pertinent records. Establish an effective date for the transfer. Conduct a review of the research by the receiving IRB, where appropriate. Confirm or establish the date for the next continuing review of each study. Determine whether the informed consent form needs to be revised. Notify key parties. Update the IRB registration information. The agencies noted that the list is not meant to be exhaustive, as the circumstances involved in the transfer may vary. Continuous IRB Oversight Needed The agencies said that a transfer of IRB oversight should be accomplished in a way that assures continuous IRB oversight with no lapse in either IRB approval or the protection of

2 human subjects, and with minimal disruption of research. They recommended the original IRB work closely with clinical investigators, sponsors and the receiving IRB throughout the transfer process to ensure an orderly transition and continued protection of human subjects. The guidance added that effective communications between these groups, along with regulators, data safety monitoring boards, and clinical research organizations, is critical to ensuring a smooth transition. The agencies recommended that the transfer process be documented in a written agreement between the original and receiving IRBs, noting the transfer between IRBs in the same institution may be covered by the institution s established procedures. The guidance said the number of research projects, the risk posed by them, and the circumstances leading to the transfer will influence subsequent actions in the transfer process, e.g., whether records are obtained from the original IRB or the investigator, how the transfer date is established, and whether the receiving IRB decides to conduct a review before accepting responsibility for the research. Before an IRB accepts transferred oversight, it should obtain copies of pertinent records, such as the research protocol, approved consent form, investigator s brochure, minutes of the IRB meeting at which the research was reviewed, and correspondence with the investigator and/or sponsor. The agencies noted that, in some cases, an institution or sponsor may not agree to transfer the records to the proposed IRB. If that is the case, the transfer of study oversight to that IRB should not take place, the guidance said. The agencies said that both the original and the receiving IRBs should maintain adequate records regarding the transferred research projects, including any written agreement between the IRBs, the titles of the protocols being transferred, the research sites affected, the names of the associated investigators, the identities of the IRBs, the date(s) on which the receiving IRB accepts responsibility for oversight of the research projects, and communications with affected investigators, sponsors and regulatory agencies. The guidance said the original and receiving IRBs have the flexibility to work out any suitable arrangement for handling the transfer and maintenance of the records, so long as the records remain accessible for inspection and copying by authorized regulatory representatives. The agencies recommended setting a transfer date for each study. Although there is no regulatory requirement to establish a transfer date, the guidance said, such an action promotes continuity, helps prevent a lapse in IRB coverage, and minimizes confusion regarding which IRB is responsible for review and action if, for example, an unanticipated problem should arise or research needs to be quickly suspended or terminated. If the transfer is due to the closure of an IRB, the agencies said that, if oversight by a new IRB cannot be obtained by the closure date, approval for the research would be considered suspended or terminated, the research would stop, and there would be no further subject enrollment. The guidance noted that, when a large number of studies are transferred, it may be preferable to phase in the transfer over a period of weeks or months to aid a smooth transition. To Review or Not To Review Neither FDA nor HHS regulations require a receiving IRB to review studies prior to the next continuing review date established by the original IRB; however, both agencies said that such a review is often conducted in practice, adding the review can be either an initial or continuing review. OHRP said the receiving IRB may decide not to conduct a review prior to 2

3 Actions for Consideration Transfer of Review 1. Identifying those studies for which IRB oversight is being transferred. 2. Ensuring the availability and retention of pertinent records. 3. Establishing an effective date for transfer of oversight, including records, for the research projects. 4. Conducting a review of the study(ies) by the receiving IRB, where appropriate, before it accepts responsibility for the study(ies). 5. Confirming or establishing the date for the next continuing review. 6. Determining whether the consent form needs to be revised. Table 1. Transfer of IRB Responsibilities when a Research Project Moves from One Engaged Institution to Another Responsibility to Another IRB The institutions and IRBs need to clarify responsibilities and logistics. OHRP recommends the transferring IRB or institution make the pertinent records available to the receiving IRB. The engaged institution needs to have access to IRB records for at least three years after project closure at that institution. Record retention requirements can be met through a variety of arrangements. Usually the transferring and receiving institutions establish the effective date for project transfer and advise their respective IRBs. The receiving IRB needs to conduct an initial or continuing review of the project. The receiving IRB establishes a new continuing review date, or confirms the continuing review date set by the original IRB. The IRB may require changes to the consent form. 7. Notifying the key parties. The key parties are notified by the investigator, transferring institution, receiving institution, or the transferring IRB. 8. Addressing IRB regulatory issues. Source: OHRP If the new IRB is internal to the newly engaged, FWA-holding institution, no IRB Authorization Agreement is necessary. If the new IRB is external to the newly engaged institution, an IRB Authorization agreement is necessary. Continuation of Review Responsibility by the Original IRB The institutions need to clarify responsibilities and logistics, even though the IRB remains unchanged. Since the IRB remains the same, there is no need to make the records available to a receiving IRB. The receiving institution, however, may request copies of certain records held by the IRB or transferring institution. The engaged institution needs to have access to IRB records for at least three years after project closure at that institution. Record retention requirements can be met through a variety of arrangements. Usually the transferring and receiving institutions establish the effective date for project transfer and advise the IRB. The IRB needs to review and approve an amendment to the research project. Usually the continuing review date remains the same. The IRB may require changes to the consent form. The key parties are notified by the investigator, transferring institution, receiving institution, or the IRB. The newly engaged, FWA-holding institution needs to establish an IRB Authorization Agreement with the original IRB. 3

4 the next continuing review date, especially if such a review is not deemed to substantively add to human subject protections. In such a circumstance, some receiving IRBs nonetheless may request the IRB chairperson, another IRB member, an IRB administrator, or another qualified administrative staff member to perform an informal assessment of the research project. However, FDA said that review by the receiving IRB is strongly recommended where the quality of the review by the original IRB may be questionable, for example, where the transfer occurs because of noncompliance by the original IRB, as reflected in an FDA warning letter to that IRB. The agency added that receiving IRBs also should consider an initial review for higher risk studies, such as those involving an exception from the informed consent requirements under 21 CFR 50.24, unapproved therapies with a high risk of morbidity and/or mortality, novel therapies including new cellular or gene therapies, and those flagged by the original IRB for more frequent review. The receiving IRB also may decide to conduct an initial review if it believes there may be local issues that would warrant a review, or if the receiving IRB has no familiarity with the original IRB, such that it may not be comfortable wholly relying on the original IRB s review and approval. Both agencies noted that IRBs have the authority to suspend or terminate approval of research when the research is not conducted in accordance with the receiving IRB s requirements or has been associated with unexpected serious harm to subjects (21 CFR and 45 CFR (b)(5)). If the receiving IRB does not conduct an initial or continuing review at the time of the transfer, the date of the original IRB approval is presumed to remain in effect for the full approval period established at the time of the most recent review by the original IRB, the guidance said. If the receiving IRB decides that a new anniversary date will be set, the new date must be within one year of the receiving IRB s approval. The guidance noted that, if a change in IRB oversight results in changes in the contact information regarding subject rights and/or whom to contact in the event of researchrelated injury, the new contact information must be provided to subjects. For new subjects, the informed consent, assent and/or parental permission forms must be revised to reflect the new contact information, but already consented subjects can be notified of the change via postcard or other communications. What to Do When an Investigator Moves? The FDA guidance also noted that a sponsor may decide to transfer a clinical investigation to a different research site, such as when a clinical investigator relocates. Because the transfer involves changes to the research (e.g., conducting the research in a new location, consent form revisions, possible changes of key staff), a protocol amendment must be submitted to the IRB for review and approval. In many cases, this amendment represents a minor change to the research that the IRB may review under an expedited review procedure. The FDA added that even if the IRB remains the same when a study is transferred to a new research site, IRB review/approval for the new research site is required, because such a move is considered a change in previously approved research. Additionally, the sponsor must notify FDA of any change in research site, clinical investigator, and/or IRB. For drug or biologics studies, this notification can generally be accomplished through an investigational new drug (IND) protocol or information amendment, whereas for device studies, it can generally be accomplished in an investigational device exemption (IDE) annual report. OHRP said, When the research project moves to a new institution and responsibility for review is transferred to another IRB, the receiving IRB must conduct an initial or continuing 4

5 review of the research project before the new institution becomes engaged in the human subjects research project (45 CFR (b)). However, if appropriate officials at the original and new institutions have executed an Authorization Agreement for the new institution to rely on the original IRB at the original institution, a new initial or continuing review is not necessary. However, as the transfer involves changes to the research, a protocol amendment must be submitted to the original IRB (45 CFR (b)(4)) and, as noted in the FDA guidance, in many cases this represents a minor change to the research that the original IRB may review under an expedited review procedure (45 CFR (b)(2)). The FDA said that 21 CFR (e) requires that any IRB that decides to review FDAregulated research involving new types of FDA-regulated products, or decides to discontinue reviewing FDA-regulated research, must revise its IRB registration within 30 days of the change in product type review or permanent cessation of the IRB s review of research. A receiving IRB may therefore need to revise its registration if it previously did not review clinical investigations of FDA-regulated products or if it will assume the review for a new type of FDA-regulated product upon the acceptance of clinical investigations from an original IRB Similarly, the original IRB may need to update its registration information if it will no longer be reviewing a certain type of FDA-regulated product, will no longer be reviewing FDA-regulated research, or plans to disband. The agencies noted that sometimes a transfer may be temporary, such as during a natural disaster. In those cases, not all eight steps may need to be taken. The transfer procedure back to the original IRB may only involve identifying studies for which IRB oversight is being transferred, ensuring availability and retention of pertinent records, establishing an effective date for the transfer, and notifying the key parties, OHRP s guidance said. To Find Out More The FDA guidance is available at The OHRP guidance is available at Other Recent Developments in the Guide to Good Clinical Practice Billing Clinical Trial Procedures Becoming More Complex Social Media May Be New But Old Regs Still Rule FDA Starts Working Through Medical Countermeasure Workshop Items 5