Protocol Review Committee Amendment Review Process

Please submit the following electronically through OnCore’s Electronic Protocol Review and Monitoring System (ePRMS) Console. If you have questions or concerns regarding access to this console, please contact prc.ycc.committees@yale.edu

As of April 1, 2021 the PRC revised the amendment workflow. Refer to the amendment matrix. The revision is as follows:

• Amendments to Investigator-Initiated studies (unless externally sponsored with proof of approval from the peer institution’s PRMS) must be approved by the PRC before the amendment is submitted to the IRB of record.
• All other amendments may be submitted to the PRC and IRB of record concurrently.
• IRB of record processes the amendment and issues the approval letter without need for PRC confirmation.
• An amendment that receives IRB approval prior to receiving PRC approval, must be implemented at Yale (i.e. enrolling on amended protocols that have an IRB approved ICF)
• Should any significant scientific or prioritization-related issues arise during PRC review resulting in disapproval of the amendment, the IRB of record must be notified of the determination and the impact on ongoing conduct of the study at Yale.

Please reference the ePRMS submitter overview for instructions on submitting protocols in OnCore’s ePRMS.

PRC review is required for the following amendment changes:

• Drug (compound, dosage, or schedule)
• Eligibility (significant changes such as additional disease areas or updates reflecting a change in standard of care (SOC), etc.)
• Methods of response evaluation
• Study Objectives (primary and secondary)
• Statistical/analysis plan (study endpoints; statistical approach and methods; power analysis, including sample size)

PRC does not review the following amendment types:

• National Clinical Trials Network studies,
• Experimental Therapeutics Clinical Trials Network studies
• Externally peer reviewed studies, or
• Investigator initiated studies received from a non-Yale site with an acceptable or provisionally acceptable Protocol Review and Monitoring System (PRMS)
• Amendments to non-therapeutic or observational studies

All amendment submissions must include:

• Protocol (tracked version, if available)
• Protocol (clean version)
• Summary of Changes document for protocol – if embedded within the protocol, extract the pages and attach as a separate document. If not provided by sponsor, one must be prepared by study team for submission to PRC.
• Investigator’s Brochure (only if accompanying an amendment to the protocol) - if embedded within the protocol, extract the pages and attach as a separate document.
• Summary of Changes document for the Investigator’s Brochure (if available)
• Sponsor correspondence releasing the amendment and other relevant communication (if amendment is initiated by an external sponsor)
• Amendment Cover Sheet and DART Form

Amendments are submitted electronically through OnCore’s Electronic Protocol Review and Monitoring System (ePRMS) Console.

If the submitter does not have access to ePRMS, contact the PRC Regulatory Analyst at prc.ycc.committees@yale.edu for instruction on gaining access to ePRMS.

The following significant amendments changes should be submitted for Full Committee review:

• Study Design Changes
• Eligibility
• Study Drug (adding and/or removing an intervention)

All other amendment changes may be submitted for expedited review, if required. See Criteria for Amendment Review section above.

Changes involving only the statistical/analysis plan (study endpoints; statistical approach and methods; power analysis, including sample size) will be sent for expedited statistical review, while all other changes will be sent for expedited Chair or designee review.

Reference the amendment cover sheet. Submit a completed cover sheet with amendment documents.

Amendments reviewed by the full committee will be assigned to the next meeting agenda’s available slot.

Amendments requiring expedited review are reviewed by the PRC Chair, Vice Chair, or appropriate designee. If the assigned reviewer determines that further examination of the protocol is warranted, an additional scientific or biostatistical review may be requested prior to approval. Alternatively, the protocol may be placed on the PRC agenda for further discussion by the full committee per the reviewer’s request.

The PRC actions on full committee reviews are: approval, approval with recommendations, approval pending a required response, tabled, or disapproval. The actions on expedited reviews are: approval, approval with recommendations, approval pending a required response, schedule for full committee review or disapproval. A letter is provided to the PI which states the decision.

Submissions approved pending a required response receive an additional letter once the required response is affirmed, and the study is then either approved or disapproved. PRC review decisions are entered into ePRMS by PRC administrative staff, generating an automatic notification to the PI and study team.