Procedures for Scientific Review and Monitoring
The Protocol Review and Monitoring Committee (PRMC) is the new title for the Protocol Review Committee (PRC) as of June 2015. The PRC, where direct protocol review is conducted as part of the University of Vermont Cancer Center’s Protocol Review and Monitoring System, was established in April of 1993 in response to NCI’s policy statement dated December 7, 1992.
The PRMC reviews clinical research focused on cancer as well as research using specimens from human subjects, either prospectively or retrospectively. The clinical research may be interventional or observational in design. The research may also be designed to evaluate the delivery, process, management, organization, or financing of health care regarding cancer patients. The PRMC also reviews cancer registry studies and bio-repositories. The PRMC does not review non-human laboratory studies (such as mouse or cell-line studies). The PRMC also does not review retrospective chart review studies.
The PRMC is charged with the review of all clinical cancer protocols proposed at the University of Vermont and at the University of Vermont Medical Center prior to initiation and on an ongoing basis with the following goals:
- To evaluate the scientific rationale for the protocol.
- To determine that high quality and appropriate clinical trials and statistical design have been incorporated in the protocol.
- To determine that the Informed Consent Form accurately reflects the scientific content of the protocol.
- To determine that appropriate physician and facility resources for performance of the protocol are available.
- To prioritize the protocol based on scientific merit and consideration of other protocols available within the institution.
- To advise the Cancer Center Director on the merits of the protocol for allocation of shared resources.
- To monitor the progress of cancer-related protocols.
Clinical research that must be reviewed by the PRMC includes but is not limited to the following:
- Physical interventions for the treatment, staging or diagnosis of cancer or cancer-related problems.
- Interventions to obtain specimens from cancer patients for the sole purpose of performing basic laboratory studies related to cancer.
- Interventions to obtain specimens from normal subjects for the sole purpose of performing basic laboratory research studies related to cancer.
- Use of stored specimens from cancer patients or normal subjects for basic laboratory research related to cancer.
- Physical interventions for the prevention of cancer.
- Physical and non-physical interventions for the determination, management, and study of cancer risk in normal subjects.
- Physical interventions for the detection of cancer in normal subjects.
- Diagnostic tests that affect medical decision-making for the cancer patient.
- Behavioral and nutritional studies that are cancer-related, such as those studies that increase behaviors (e.g., cancer screening, food intake), eliminate or reduce behaviors (e.g., smoking, sun exposure), and/or improve coping and quality of life/reduce the negative effects of treatment.
IRB approval to activate requires compliance with this adopted definition of the scope of the PRMC review process, and requires PRMC approval.
Protocol Submission Criteria and Process
The protocol review process is initiated by the PI and coordinator submitting required protocol documents to the UVM Compliance Specialist on behalf of the PRMC. The protocol and supporting documents may be submitted simultaneously to the UVM Institutional Review Board (IRB) for review, but the study cannot be activated until both the IRB and PRMC approve it.
The UVMCC Compliance Specialist assigns new protocols to specific PRMC members one week prior to the PRMC meeting. Each protocol is assigned to two members (a primary and secondary reviewer with relevant expertise) as well as PRMC representatives from appropriate complementary specialties, such as biostatistics, clinical research, and/or pharmacy. Prior to the monthly PRMC meeting, each assigned reviewer completes a form, the PRMC Review Form, to document their review of the protocol. This form includes items such as clarity of goals, appropriateness of study design, adequacy of patient population, and relevance to the University of Vermont Cancer Center's goals and importance of study. The reviewers then discuss the protocol at the PRMC meeting with the rest of the committee.
The PRMC meets once a month (the second Tuesday of the month) with meetings timed to occur the week prior to the UVM IRB meeting (third Wednesday of the month). Though not required, Principal Investigators (PIs) and coordinators may attend the PRMC meeting to present their protocol. Each protocol is presented by the assigned reviewers and discussed by the full committee, followed by a committee vote. Based upon reviewer comments and those of other members, one of the following recommendations is made: 1) approve, 2) approve with revisions, 3) table, or 4) disapprove. The UVMCC Compliance Specialist informs the PI and coordinator in writing of the committee’s action and, if appropriate, member comments. If a protocol is Approved or Disapproved, no response from the PI is required. If a protocol is Approved with Revisions or Tabled, a written response from the PI is expected. If no response is received within 90 days, the protocol is considered to have been withdrawn from consideration. The status of each protocol for which a response is pending is reviewed at each PRMC meeting as Old Business. If a protocol has been Approved with Revisions, the PRMC reviewers will review and vote upon the PIs response via email. If a protocol has been Tabled, the PI’s response must be reviewed and discussed at the next PRMC meeting by the full committee before the protocol status is changed.
Once a protocol is approved the PI is required to update the PRMC with patient accrual, serious adverse events, study closure, and future plans and publications. All of this information is communicated to the Cancer Center’s Compliance Specialist and the Data Safety and Monitoring Committee (DSMC). Minutes of each PRMC meeting are reviewed and approved at the next committee meeting and are distributed to PRMC members, the IRB, and to the Cancer Center Director.
Any substantive amendment to an ongoing investigator-initiated or industry protocol must be submitted to the PRMC for review and approval. Cooperative group amendments are not reviewed by the PRMC.
Protocol Review Criteria
The criteria for non-peer reviewed protocols are more rigorous than those for externally peer-reviewed protocols. In the case of the latter, the PRMC’s focus is whether the protocol competes with an investigator-initiated study and the use of Cancer Center resources. In the case of non-peer reviewed protocols, the PRMC evaluates the protocol goals, study design, background information, eligibility criteria (including inclusion of women and minorities), evaluation criteria, provisions for toxicity and side effects, feasibility of completion, use of nursing data management and pharmacy resources, and Informed Consent Form. Although the PRMC Review Form allows a simple check-off, reviewers are encouraged to provide comments describing any areas of concern. Other members of the PRMC (not assigned as reviewers to the protocol) are provided access to a copy of the protocol document and they may request additional supporting documents.
To assist investigators and reviewers alike, the IRB has developed a Human Research Protocol Form (PDF). Failure of the PI to follow the protocol format will result in a delay in review (i.e., a study that does not include the required elements will not be reviewed until all elements have been addressed).
Externally-reviewed protocols are assigned one primary PRMC reviewer, while investigator-initiated protocols (and industry studies) are assigned two primary PRMC reviewers. All investigator-initiated and industry protocols are reviewed by a biostatistician and every protocol must include a statistical considerations section. All investigator-initiated and industry studies also receive directed reviews for resource utilization i.e. Nursing, Pharmacy and Data Management by representatives of those support services that are on the committee.
The local accrual goals of a new protocol are also assessed by the PRMC for feasibility.
Monitoring by PRMC
Level of Risk
Interventional investigator-initiated trials will be assigned a level of risk, meant to categorize each study based on risks to patients that are inherent in the study. This assignment is done by the PRMC at the time of initial review. The PI and coordinator will be notified of this risk level assignment on the PRMC Approval memo. The assigned risk level will determine the level of oversight required by the Data Safety and Monitoring Committee (DSMC).
The UVM Cancer Center’s scientific review committee is charged with monitoring the progress of cancer studies. All cancer studies approved by the PRMC require submitting Quarterly Reports to the PRMC Coordinator. Lab-based specimen collection studies will submit a semi-annual Study Progress Form instead of a Quarterly Report. The Quarterly Reports are based on quarters of the calendar year and are due 15 days after a quarter is over. The accrual data from Quarterly Reports are compiled and presented to the PRMC regularly. Each month at their Full Committee meeting, the PRMC reviews the accrual of patients onto cancer studies. The PRMC may decide to contact PIs and coordinators if the committee determines that the rate of accrual is low for a study. The PRMC will ask the PI to comment on any barriers they might be experiencing in enrolling patients that may be contrinuting to low rates of accrual.