Process of UPCI Protocol Review
All clinical cancer research protocols conducted at the University of Pittsburgh Medical Center (UPMC) must be submitted to the UPCI PRC for review prior to approval. Investigators are provided with a template to assist in construction of protocols and to help ensure that the necessary elements required in a clinical cancer protocol are included. The UPCI also has a public web site that provides instructions on the process of protocol and form submission. In addition, a detailed PRC checklist must be completed at the time of protocol submission. This checklist documents approvals of the protocol that have been given by clinical research programs at previous meetings. Included in the checklist is an outline of UPCI resources being requested by the investigator in order to conduct the study. In addition, the checklist includes a detailed priority list defining the relationship between the study and other studies conducted by the research program, in relation to disease stage or prior treatments. Also included in the checklist is information regarding prior peer review and funding sources, as well as the possible need for General Clinical Research Center (GCRC) resources.
Protocols submitted to the PRC with complete requested information are scheduled for PRC review within two weeks. Each protocol is assigned for review by two scientific reviewers and by a UPCI biostatistician. The exceptions to this procedure are cooperative group studies and the multi-center phase III studies, which are assigned only a single scientific reviewer. Reviews of Phase III trials focus on the priority within the disease-site program or group, as well as on the likelihood of the study achieving accrual goals based on the record of comparable studies. The decision to expedite the review of these studies is based on the extensive review of the study that has already occurred by either the NCI or other external review bodies. Moreover, since such studies are multi-institutional, our experience has been that it has been unproductive to consider revisions to the actual protocols. Rather, the PRC review focuses on the following points: 1) whether the protocol is considered to be scientifically sound and of interest to the program and the UPCI, 2) whether accrual targets are likely to be reached, and 3) the priority of the study relative to any competing protocols. Since the UPMC Cancer Centers includes an academic center as well as community-based patient care centers, there is recognition of the need to have protocols available that are suitable for both types of centers and their respective patient populations.
Prior to the PRC meeting, each reviewer completes a written review summarizing the protocol and critiquing its design, including the background, objectives, methodology, treatment plan, biostatistical design issues, data collection and analysis, and data and safety monitoring plan. A sample consent form is also reviewed. At least one week prior to the meeting of PRC Committee A or B, the packet of protocols for review is distributed to all members. Review and input from all members is sought not only for scientific issues but also for questions regarding prioritization, implementation, ancillary testing, third party coverage for care under each protocol, utilization of outpatient, inpatient, ancillary lab support, and pharmacy issues. Ms. Hofacker oversees the assembly and distribution of initial protocol packets to each reviewerand the collation of reviews, writes the PRC minutes for each study, coordinates the assembly of the investigators' comments and reviewers' final opinions, and forwards the protocols to the IRB and GCRC.
At the time of the PRC meeting, the scientific reviewers and the biostatistical reviewer discuss in detail all of the protocol's important scientific elements as well as resource utilization and the feasibility of meeting accrual goals. Following discussion by the full committee, a voice vote is taken, which in most cases reflects a consensus reached during the discussion. The committee may make one of four recommendations: 1) full approval; 2) approval with clarifications to be reviewed and found acceptable by the chair only; 3) approval with clarifications to be reviewed and found acceptable by the chair and the reviewers; or 4) reconsideration, requiring re-review by the entire sub-committee. Within 48 hours of the PRC meeting, an itemized list of questions generated from the review is sent via email to the principal investigator. Protocols that require the principal investigator to clarify or revise a portion of the study must have those responses reviewed and accepted by either the committee chair or the committee chair and the reviewers prior to PRC approval.
Following PRC review, documentation is recorded in the UPCI Clinical Trials Management Application (CTMA). A PRC approval memo is generated from within the database and emailed to the investigator, and documentation of the approval is entered into CTMA for later reporting, as are all other regulatory reviews (e.g. GCRC, IRB, FDA, NCI, etc.) and approvals. After PRC approval, protocols are prepared by CRS for review by the University IRB. At present, the preparatory phase includes developing a University IRB-formatted protocol summary and consent form, according to the University IRB's guidelines. A protocol budget and fiscal review are completed to clarify which costs associated with the conduct of the study are standard of care and which are research costs, as well as to resolve any contractual issues. The preparatory phase is under the purview of the Clinical Trials Unit. In addition, PRMS coordinates IND application submissions for new protocols requiring FDA review, and ensures the timely submission of Adverse Drug Reaction Reports to sponsors, IRB, and other appropriate regulatory committees. PRMS is also responsible for preparation of IRB protocol summaries and consent forms that meet the Office of Human Research Protection (OHRP), FDA, IRB, and HIPAA guidelines.