70 - Measuring Compliance with Policy for Processing Planned Protocol Deviations

Background:  Our medical centers policy is to review planned deviations prior to implementation as single-subject protocol exception requests (SSERs). This policy is informed by FDA’s bioresearch monitoring requirement: “In the case of deviations which are planned exceptions to the protocol… should be reviewed and approved by the IRB…prior to implementation...”(FDA Compliance Program 7348.811)

Program

Description:  Our Reporting Possible Unanticipated Problems Involving Risks to Subjects or Others (UPIRSOs) policy requires “SSERs… must be submitted for the IRB’s review and approval prior to implementation.” Researchers are instructed to submit SSERs as reportable new information (RNI) to the IRB as soon as a deviation is planned. Externally sponsored studies must include a sponsor’s waiver with the RNI. SSER RNIs can be prioritized for expedited review when they are time-sensitive and eligible for expedited IRB review. Occasionally they may apply to multiple subjects.

The Office of Research Compliance & Quality Improvement Post-Approval Monitoring (PAM) team recently conducted a re-examination of our SSER review process to ensure it remains relevant. We reviewed all SSER submissions processed in a one-year period. We evaluated the rate at which SSERs were submitted, which departments submitted, the nature of the exceptions, and compliance with waiver requirements. We included SSERs from studies that rely on external IRBs.

Program

Assessment:  Our analysis found that the majority of SSER submissions are for planned deviations from protocol-defined eligibility criteria. In accordance with the UPIRSO Reporting policy, all SSER submissions included a sponsor’s (or equivalent) waiver. Our average turnaround time for these submissions is more than twice as fast as other RNIs. After review by a qualified IRB member (when our institution is the IRB of record and the submission is eligible for expedited IRB review), approval is issued for these one-time protocol modifications.

We found a similar rate of submission between reliance studies and studies where we are the IRB of record. Our review process differs for studies with an external IRB as we do not approve planned deviations for studies reviewed by an external IRB. Rather the study team submits these planned deviations with approval from the IRB of record and our PAM team provides acknowledgement.

Limitations: There is significant variation between IRBs in the policies and procedures for how planned deviations are reviewed. This can create a challenge in processing time-sensitive exception requests when the study is relying on an external IRB.

Discussion:  Review of SSERs processed during this period led to renewed support for our current policy, which ensures:
-Provision of sponsor waivers for planned deviations;
-Local IRB consideration of subject safety in cases where an industry or investigator-sponsor has granted a waiver;
-Documentation for the investigational drug service (IDS) that a planned dosing deviation has been assessed by the sponsor and IRB;
-Consistently rapid turnaround times reinforcing researchers’ compliance with the policy; and
-Compliance with FDA inspection manual instructions, yielding no related findings in any FDA inspections since the policy was implemented.