Review and Monitoring of Therapeutic Interventional Clinical Research
Purpose of the review
- To conduct a scientific review of all newly proposed and ongoing institutional clinical cancer research protocols.
- To monitor all clinical cancer research protocols for sufficient progress on an annual basis.
- To terminate cancer protocols if found deficient in accrual or scientific progress.
Protocols that will be reviewed by the Cancer Protocol Review Committee/Therapeutic Interventional (CPRC/TI). The CPRC/TI will review hypothesis driven studies of therapeutic interventions administered to cancer patients or individuals at increased risk of cancer. The following types of protocols will be reviewed:
I. Primary Therapy of Cancer
- Surgical therapy
- Gene therapy
- Combined modality therapy
II. Prevention of Cancer
• Surgical prevention
III. Supportive Therapy
- Pain prevention or control
- Infection prevention and control
- Transfusion support
- Nutrition support
IV. Complementary and Alternative Therapy
Protocols not reviewed by the CPRC/TI
- Non-Therapeutic Interventional Trials (These are reviewed by the CPRC/NTI)
- Single case compassionate use protocols
- Treatment/management guidelines not asking a research question
- The review process is based on standard NIH/NCI review directives.
- Meeting time: The CPRC/TI meets on the first and third Tuesday of each month.
- Protocols will be reviewed within two meetings of the date they are submitted.
- The CPRC Manager reviews all submissions for completeness of the CPRC application, assigns a protocol number, and routes CPRC communications to CPRC members.
- CPRC Standard Submission Form (PDF)
- A CPRC submission form must be attached to all protocols submitted to the committee for review.
- All research proposals requiring scientific review by the CPRC are to be submitted to the CPRC Manager.
Required for CPRC/TI Review
- The protocol must be approved by the relevant interdisciplinary site specific cancer care team(s) (ISC)* *Phase I studies should be reviewed by all relevant ISC's.
- If the newly submitted protocol competes with other protocols open at this institution, all competing protocols are to be named on the submission form.
- If there are competing protocols the method of prioritization is to be noted on the submission form.
- The study accrual goals are to be provided on the submission form: national accrual*, total local accrual, and annual local accrual. *Does not apply to study open only at this institution.
- The page reference to inclusion of women and minorities* is to be listed on the submission form. *NIH Phase III Clinical trials require a statement reflecting inclusion of women & minorities
- A Data and Safety Monitoring Plan is required for all protocols submitted to the CPRC/TI. Investigator-initiated studies can refer to the Data and Safety Monitoring Plan summary (PDF) for additional information.
- Essential Protocol Components. All protocols must contain the following components:
- Title: Adequately describes the study.
- Background: Sufficient material to justify the proposed protocol.
- Research objectives: Primary and secondary objectives that are clearly stated and reasonably achievable by the study.
- Eligibility and study requirements: An appropriate study population must be clearly defined.
- Treatment or study plan: Protocol treatment is clearly specified, as are modifications to be made based on toxicity, modifications which may be made at the discretion of the investigator, and criteria for removing a patient from protocol treatment.
- Adverse event reporting: The protocol shall adhere to FDA and CTEP guidelines for toxicity reporting.
- Drug information: The drug description for all drugs including known toxicities and formulae when available; means of supply; methods of storage; methods of procurement are to be included. Package inserts are unacceptable.
- Definition of outcomes: All outcomes described adequately.
- Statistical section: Should fully describe endpoints, method of analysis, justification of proposed study accrual, and time frame.
- Schema: Diagram, algorithm, or visual representation describing the proposed research plan.
- List of data items: Identifies required forms to be completed, intervals at which forms must be submitted, location to which forms are submitted.
- Data and Safety Monitoring Plan: indicates compliance with Cancer Center Data and Safety Monitoring guidelines.
- Cooperative Group Review Criteria: The Committee takes into account the existing review process. The following areas are considered:
- Scientific relevance, hypothesis
- Method, study design
- Administrative issues, use of resources locally
- ISC approval
- Biostatistics Review: The protocol is reviewed for the following biostatistical information:
- The endpoints of the study
- Patient characteristics that may affect response
- The design of the study
- Accrual goal and statistical power to test the hypothesis
- A plan for data management
- Method(s) for data analysis
- Criteria for stopping the trial If the biostatistician does NOT approve the statistical component, the CPRC Manager will contact the PI and arrange a meeting between the biostatistician and the PI to clarify the concerns raised by the biostatistician. Investigators are encouraged to use biostatistics consulting in advance of the review.
- All proposed changes in a protocol (including adjustment of accrual goal) are to be submitted to the Cancer Protocol Review Committee.
- The PI should provide appropriate justification for the proposed changes and a brief summary of the changes with the location of each change referenced.
- Decisions follow the same criteria as given under Committee Decisions.
Annual review and monitoring of the protocols will be performed. The following will be considered during annual review:
- Adherence to stopping rules
- Continued scientific merit
- Decisions follow the same criteria as given below under Committee Decisions.
Audits will be undertaken by the subcommittee on each protocol at least every two years. Three patients will be reviewed for:
- Informed consent
- Adhere to toxicity criteria
- Response criteria
- Off study criteria
- Adverse drug or treatment reactions
- Decisions: Decisions follow the same criteria as given below under Committee Decisions.
A. Following discussion, the Committee votes to Approve, Approve with Stipulations, Defer or Disapprove the protocol.
- Approved for opening to accrual contingent upon obtaining IRB approval and completion of all other protocol activation steps.
Approved with Stipulations
- Approval from the CPRC, but the PI needs to address minor issues. The CPRC Chair will provide final approval for implementation.
- Approval of the scientific merit, but deferment of the protocol until the PI addresses prioritization with competing protocols. The PI will be asked to provide a rationale for approving the protocol and a means for integrating the study into the site-specific program. The Chair will provide final approval.
- Sufficient problems exist with the protocol such that substantial revisions and formal reconsideration by the CPRC are required.
- The protocol is not approved for opening to accrual at the UMN.
B. In the case of cooperative group review items and annual monitor items the committee accepts the recommendation of a single reviewer, after committee discussion. Decisions for cooperative group and annual monitor items use the same terms and definitions listed above under Committee Decisions, letter A.
The Cancer Protocol Review Committee will recommend termination of local protocols if any of the following circumstances apply:
- Accrual goal is met. The PI will continue to submit progress reports to the IRB as long as patient follow-up is required.
- There is no requirement for follow-up.
- The endpoint of the protocol is reached.
- New scientific findings have obviated the need for the protocol.
- Conduct of the research is of such poor quality as to make the findings of the protocol questionable. A decision of closure will be relayed to the IRB.
A. The appeal process for disapproval or closure of protocols will consist of the following:
- The PI will request in writing, to the CPRC Chair, a re-review of the protocol.
- The PI will be invited to meet with the CPRC Chair and the CTO Coordinator. The PI may invite any other persons they deem relevant to the discussion. The goal of the meeting will be to work toward resolution of any issues preventing approval of the study.
- Following the re-review, the CPRC can reverse the original decision, ask for further revisions, call for an external review, or ratify the original decision.
A. Approved: Notification of the CPRC's decision to "Approve" is sent to investigators using the Decision Summary Form. This is done within two working days of the CPRC meeting, if possible.
B. Not Approved: For decisions other than "Approved" a letter is prepared and sent along with the decision summary form within five working days of the meeting. This letter explains the decision and provides the investigator with specific items to respond to.
- PI No Response: If the PI is not planning to respond to a CPRC decision of "approved with stipulations" or "deferred," the investigator is requested to notify the CPRC office.
- Disapprove: When a protocol is disapproved, the procedures given above in the Appeal section are to be followed.
C. When the protocol is to be resubmitted, it must be returned with the original assigned number. A new identifier will be assigned.
D. Any hard copy communication from the CPRC/TI Chair, CTO Coordinator or CPRC Manager regarding a protocol decision or otherwise concerning the status of a CPRC/TI protocol is copied and filed with its respective protocol.
E. Any hard copy communication from investigators or relevant parties regarding the status of a CPRC/TI protocol is filed with its respective protocol.