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 submission of required protocol information to the PRMC by the Principal Investigator (P.I.). The protocol may be submitted simultaneously to the UVM Institutional Review Board (IRB) for review, but cannot be activated until both the IRB and PRMC approve it.
Externally peer-reviewed protocols (NCI or cooperative group) are assigned a single primary reviewer; protocols without external peer review (investigator-initiated protocols or industry protocols) are assigned two primary reviewers. A full copy of the protocol is distributed to each reviewer. Reviewers are usually members of the PRMC; ad hoc reviewers may be recruited to provide special expertise at the discretion of the Chair. All externally peer-reviewed protocols receive directed reviews for resource utilization by the Nursing Service, Pharmacy Service and Data Management Office. All investigator-initiated and industry protocols also receive directed reviews for resource utilization by the Nursing Service, Pharmacy Service and Data Management Office as well as a separate review by the Biostatistics Office. Each primary reviewer completes a "Protocol Checklist" which 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 PRMC meets once a month (the second Tuesday of the month) with meetings timed to occur approximately one week before the meeting of the IRB (third Wednesday of the month) so that progress of a protocol through the review system is not unnecessarily delayed. Principal Investigators (PI)may attend the PRMC meeting but are not required to attend for the review to move forward. Each protocol is presented by the reviewer(s) and discussed by the full Committee, followed by a Committee vote. Based upon reviewer(s) comments and those of other members, one of the following recommendations is made: 1) approve, 2) approve with revisions, 3) table, or 4) disapprove. This information is transmitted to the investigator and to the IRB. If a protocol is Approved or Approved with Revisions and it competes with another protocol, a priority (high, moderate or low) is assigned by Committee consensus. The PI is informed in writing of the Committee’s action and, if appropriate, member comments. If a protocol is Approved or Disapproved, no response is required. If a protocol is Approved with Revisions or Tabled, a written response is expected. If no response is received within 90 days, the protocol is considered to have been withdrawn. The status of each protocol for which a response is pending is reviewed at each meeting as Old Business. If a protocol has been Approved with Revisions, the PRMC Chair may grant "Interim Approval" immediately upon receipt of a satisfactory response, with Approval being certified at the next PRMC meeting. If a protocol has been Tabled, the response must be reviewed and discussed at the next PRMC meeting before the protocol status is changed.
Once a protocol is approved the investigator 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 Data Safety and Monitoring Committee (DSMC). All PRMC meetings are minuted and a master copy is kept in the PRMC file. Minutes are reviewed and approved at the next 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 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, reviewers are asked to evaluate 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 Protocol Checklist allows a simple check-off, reviewers are encouraged to provide comments describing any areas of concern. Other members of the PRMC receive a copy of the Lay Summary of the protocol although they may request a full copy for review.
To assist investigators and reviewers alike, the IRB has developed a Human Research Protocol Form (PDF). Failure to follow the Model 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).
As noted above, externally reviewed protocols are assigned one primary reviewer, while investigator-initiated protocols (and industry studies) are assigned two primary 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.
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.