Procedures for Scientific Review and Monitoring

The Protocol Review and Monitoring Committee (PRMC) reviews research with a focus on cancer as well as research using specimens from human subjects, either prospectively or retrospectively. The clinical trial 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 biorepositories. 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 research studies 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:

1. To evaluate the scientific rationale for the protocol.
2. To determine that high quality and appropriate clinical trials and statistical design have been incorporated in the protocol.
3. To determine that appropriate physician and facility resources for performance of the protocol are available.
4. To prioritize the research study based on scientific merit and consideration of other studies available within the institution.
5. To advise the Cancer Center Director on the merits of the study for allocation of shared resources.
6. To monitor the progress of cancer-related clinical trials
   

Clinical research that must be reviewed by the PRMC includes but is not limited to the following:

1. Physical interventions for the treatment, staging or diagnosis of cancer or cancer-related problems.
2. Interventions to obtain specimens from cancer patients for the sole purpose of performing basic laboratory studies related to cancer.
3. Interventions to obtain specimens from normal subjects for the sole purpose of performing basic laboratory research studies related to cancer.
4. Use of stored specimens from cancer patients or normal subjects for basic laboratory research related to cancer.
5. Physical interventions for the prevention of cancer.
6. Physical and non-physical interventions for the determination, management, and study of cancer risk in normal subjects.
7. Physical interventions for the detection of cancer in normal subjects.
8. Diagnostic tests that affect medical decision-making for the cancer patient.
9. 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

The UVM IRB requires compliance with this adopted definition of the scope of the PRMC review process and requires PRMC approval prior to providing IRB approval.

Protocol Submission Criteria and Process

The research protocol and supporting documents may be submitted simultaneously to the UVM Institutional Review Board (IRB) for review, however, a study cannot be activated and participants may not be enrolled until both the IRB and PRMC approve it.  Please note, the PRMC requires a full protocol that has been written according to ICH GCP Guidelines and will not accept an IRB Protocol Summary Template Document.  However, the UVM IRB will accept this full protocol document in lieu of their IRB Protocol Summary Template Document to reduce duplication efforts.

New research studies must be submitted to the PRMC via e-mail to PRMC@med.uvm.edu.  All submissions must be accompanied by a Protocol Submission Form (PSF) signed by the study PI and the Transdisciplinary Team (TDT) form completed and signed by the study specific disease team leader.  The PRMC Coordinator will assign new studies to specific PRMC members to review at least two weeks prior to the PRMC meeting. Each study 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 the PRMC Reviewer Assessment Form to document their review of the protocol. This form includes items such as scientific rationale and literature review, clarity of goals, appropriateness of study design, and adequacy of patient population, based on the recommendation from the TDT.  For treatment trials only, the reviewers will also assess the study’s innovation and potential clinical impact.  Should a reviewer have questions during the review of the study, they may contact the PI for clarification.  The reviewers then discuss the proposed research study during the scheduled PRMC meeting with at least a quorum of the committee present.

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). Each research study 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: approved, approved, pending clarification (no revisions required), approved, pending minor revisions to the protocol, tabled until further clarifications/revisions to the protocol are provided or disapproved.  

After the meeting minutes have been transcribed and finalized, the PI will be notified in writing of the committee’s action and, if applicable, member comments. If a study is either approved or disapproved by committee vote, no response or further action from the PI is necessary. If a study is approved, pending clarification (no revisions required) by committee vote, the study responses will receive an administrative review and approval.  If a study is approved, pending minor revisions to the protocol, by committee vote, the study responses will most likely receive an administrative review and approval.  If substantial changes are made that affect the science of the study, the response and study revisions will be placed on the next full board agenda for review.  If a study is tabled until further clarifications/revisions to the protocol are provided, a written response from the PI is expected and the response and study revisions will be placed on the next PRMC agenda. If no response is received within 90 days of receipt of the PRMC memo, the PI will receive a reminder from the PRMC that their response is still outstanding.  Should an investigator fail to respond within 120 days, the PRMC may withdraw the study from consideration. 

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.

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.  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.

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.

Study Progress

Once a study is approved by the PRMC, the PI is required to update the PRMC with protocol amendments including any changes that may impact the science of the study, participant accrual, study closure, future plans/publications and permanent study closure. 

Any substantive amendments 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, but will be administratively reviewed in accordance with local IRB requirements.

The UVMCC PRMC is charged with monitoring the progress of cancer studies. All cancer studies approved by the PRMC require at a minimum of a yearly review of the protocols it has approved to ensure accrual and continued scientific relevance.   During each monthly full committee meeting, the PRMC reviews the accrual of patients onto active cancer studies that were activated during that same month in subsequent years. 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 contributing to low rates of accrual.