Common PRC Contingencies/FAQ
Common Items that Result in PRC Contingent Approval:
- Clear Data and Safety Monitoring for Pharma/Other Institution studies
- If a protocol indicates that DSM activities will be described in a separate DSM Charter this Charter must be submitted with the PRC submission. Failure to do so will result in an immediate Contingent Approval (and likely further delay the study’s ability to be reviewed at the IRB).
- Safety information must include:
- Outline of safety information to be reviewed
- For Phase I trials: define dose escalation rules clearly.
- Mechanism of safety information review ((e.g., via Committee? Via regular teleconferences with Investigators?)
- Frequency of reviews (i.e. after x number of patients enrolled, monthly, quarterly, etc.)
- Mechanism of dissemination of findings to participating sites
- For multicenter Phase I trials, detailed plan for notifying centers is required for PRC approval
- Description of persons (i.e. PI, participating investigators, separate group of physicians) ultimately making decisions related to the safety information (i.e., the constitution of the DSMC should be clearly outlined, and/or who will be responsible for assuring review of safety information, if this will not be done via DSMC)
- Outline of safety information to be reviewed
- Clear indication regarding plans for future use of specimens should be outlined in the protocol
- This should include specifics on what tests will be performed on specimens, including those to be held for future use.
- Duration of storage should be stated in the protocol and consent form.
- If there are plans for indefinite storage of specimens, then the consent form MUST include an option for patients to opt out of indefinite storage.
- If limited, please ensure this is indicated as no longer than 15 years on the consent.
- If there is no specific plan for storage of specimens for future use, it is expected that there be a statement from the Sponsor denoting specimens will only be used for research related to the study drug or disease in question.
- If there is a lab manual referenced in the protocol that will provide details on how samples will be managed, this must be submitted to the PRC with the submission. Failure to do so will result in a Contingent Approval decision (and will likely delay review at the IRB).
Although any statistician can provide input for a trial, it is recommended that the UNC Linebeger Biostatistical Core be used to provide oversight and guidance regarding the development of a study design and statistical underpinnings. The LCCC Biostats Core is experienced in advising on a variety of studies, and can provide invaluable input on how best to address the requirements of PRC statistical review. The LCCC Biostatistics Core provides free “clinics” on a regular basis as well as a general contact email. At this time, it is recommended that new investigators seeking guidance email the general contact email to obtain advisement on how best to move forward. For further information, please see details on their website here.
- Duration of time the study has been open to active accrual (i.e. some studies are approved and opened but may be put on hold for other reasons – staffing, sponsor delays, amendments, etc.)
- If a trial is actively screening but patients are ineligible, please include the number of patients screened and reason for ineligibility
- Plan for increasing accrual
- If you elect to lower accrual goals to reflect current trends, and this is a UNC Investigator Initiated study, please ensure that the study statistics have been appropriately updated to reflect these changes, and submit a revised protocol and statistician signoff to reflect these changes.
- If the duration of accrual will be extended as a result of lowering annual accrual goals (e.g., if lowering annual accrual from 10 to 1 means that the study will take 10 times as long to complete), you MUST provide a clear, scientific justification for why the study will remain scientifically meaningful. I.e., if the study will take longer than initially expected, is the topic to be studied still relevant? Consider that other methods, treatments, or devices may have been introduced which may make the study focus no longer pertinent, particularly if it is expected to complete at a later date. The PRC will consider these factors when determining whether or not to close a study due to poor performance.
Studies which are low accruing and provide sufficient rationale may be approved for continuance without issue, or receive a six month re-review. The object of a six month re-review decision is to allow for an additional period of accrual to determine if the changes/updates/rationale provided at time of renewal review has been successful in achieving the stated goals. If these goals are not met within that window, the PRC may elect to close a study to accrual at time of re-review.