Clinical Research Operations

Surgery Branch (SB) Scientific Review Committee (SRC)

Purpose: To identify within the Surgery Branch (SB), NCI the process and standards for scientific review and approval of new clinical research and proposed protocol amendments to ensure that:

• CCR clinical trials are scientifically rigorous, including sound design, rationale, biostatistical foundation, and

• Are nationally relevant, likely to accrue targeted population(s) and make important contributions to the field.

• The final responsibility for scientific review lies with the Chief of the Surgery Branch. The scientific knowledge of the members of the SB Scientific Review Committee justifies its expertise in reviewing clinical trials in the research realm of surgery, immunotherapy, melanoma, renal cancer, endocrine cancers, lung cancers, gastrointestinal cancers, and breast cancers.

• This Standard Operating Procedure (SOP) establishes the standards for scientific review in conjunction with the minimum standards established by the Center for Cancer Research (CCR).

Step 1: Submit clinical trial to Protocol Coordinator/Scientific Review Committee

The Principal Investigator (PI) will send the protocol for review to the Branch Protocol Support Office (PSO).  The Branch Chief and the PSO will complete a preliminary review, and distribute the protocol to the SB SRC, Research Nurse for the protocol, and other experts as needed.  A CCR statistician will be consulted for the statistical section prior to protocol distribution.

Documents related to branch review of protocols will be uploaded into iRIS per CCR policy. 

Step 2: Protocols must undergo comprehensive scientific review by a Scientific Review Committee with requisite scientific knowledge prior to NCI IRB submission

Standing Scientific Review Committee (SRC) Meetings

• Surgery Branch Protocol Review will be held as needed.
• The composition (and future changes) of the SRC will be submitted to the CCR leadership for approval.
• The Branch Chief will determine whether expertise outside the Surgery Branch should be elicited.  The PI may recommend outside experts for review of the protocol if necessary. 

Receipt of Protocol Documents

• The reviewers and PSO staff will have approximately 5 days to review the protocol  and PI portion of the Strategic Alignment and Resource Planning Checklist prior to the protocol review meeting.   
• Approximately five days prior to each protocol review meeting, the PSO will distribute the protocol documents to SB SRC, Research Nurse for the protocol, the statistician(s) and other experts as needed.

Review Process

• The Branch Chief will assign a primary and secondary reviewer who will present the protocol at the meeting, and provide written comments to the PSO for distribution at the meeting.
  • Primary reviewers may not have conflict of interest (COI) or be an associate investigator (AI) on the clinical trial under review.
  • If the secondary reviewer is an AI, a general expert not associated with the trial should be involved in the review and vote. 
• A Surgery Branch Executive Secretary Ex-Officio will attend the meeting to participate in the discussion and take minutes.   
• If the Branch Chief is the PI on the protocol, an SB SRC member will be appointed as ad hoc chair; and the Scientific Director will be responsible for final scientific review approval.
• Protocol Review Meeting Agenda
  • Objectives
  • Background and rational
  • Eligibility Criteria
    • Eligibility assessment
  • Study Implementation
    • Study Design
    • Drug Administration
    • On Study evaluation
    • Off treatment and off study criteria
  • Supportive Care
    • Data Collection and Evaluation
    • Response and Toxicity evaluation criteria
    • Laboratory correlates
    • Statistical Analysis
  • Informed Consent Document
• PI will give a summary of the protocol. 
• The primary and secondary reviewers will present the protocol to the group followed by a group discussion of the protocol and protocol related issues below, and the criteria outlined in the CCR SOP Assessment Checklist (see attached).
  • Patient population: 
    • Competing trials
    • Is the current referral volume enough to meet accrual goals
    • Measures to ensure enrollment
  • Intellectual property:
    • Does the PI or any AIs have IP associated with this protocol?
  • For industry-sponsored trials:
    • Assurance that the sponsor is willing to provide the agent has been received
    • CRADA negotiations have/have not begun
    • Anticipated start date of trial
  • For Surgery Branch sponsored IND trials:
    • Status of Manufacturing information:
      • Anticipated date for completion of manufacturing, testing, and documentation for IND submission.
      • If Industry collaborator is supplying the investigational agent, see # c above, and has company agreed to provide X-ref.
    • Status of Pharm/Tox studies:
      • Status of non-clinical proof of concept studies
      • Status of IND-directed toxicology (if applicable)
    • Status of IND:
      • Date of Pre-IND meeting if required
      • Anticipated timeline for IND submission
    • Adequate resources are available
      • TIL Lab
      • SB support staff
      • Monitoring staff
    • If the protocol requires CCR resources/funds, approval of the Scientific Director must be obtained prior to submission to the NCI IRB.
  • A quorum of five SB SRC members is required for review. 
  • A majority vote of SRC members present at the meeting is required for protocol approval. 
  • Decision categories will be:  ”Disapproved”, ”Approved with Stipulations-SRC Review, “Approved with Stipulations-Review by the SRC Chair”, and “Approved” 

Step 3: The Scientific Protocol Review process will be documented

PI Responses and Re-review:

• Written feedback will be submitted to the PI, within 7 calendar days after the review, through the Scientific Review Chair with a copy to the statistician(s).
• The PI, in conjunction with the PSO staff, will revise the protocol and consent based on the reviewer’s comments.  The PI (with PSO staff) will send a response within 14 calendar days with a revised protocol (with changes highlighted in track change mode) and rationale for any stipulations not addressed. 
• The final documents will be submitted to the Branch Chief., the primary and secondary reviewers, and statistician(s) for final review and approval.  This review will be conducted within 7 calendar days of receipt of the response.
• If additional comments, recommendations or stipulations are indicated, the Committee Chair will submit these in writing to the PI within 7 calendar days
• Documentation of the SRC meeting, PI response, SRC approval and approved protocol and consent will be submitted to iRIS for the IRB review within 7 calendar days or by the IRB deadline.
• If the protocol requires sponsor approval, the documentation in #5 above will be submitted in IRIS in the indicated timeframe once sponsor approval is obtained.
• In the case of protocol disapproval by the Scientific Review Committee, the PI may appeal the decision through: additional discussion with the Branch Chief initially, followed by discussion with the Scientific Director if resolution is not achieved.

Step 4: Amendments with substantive scientific changes will be reviewed by the statistician and Scientific Review Committee

Review of Amendments:

Amendments should be discussed with the Committee Chairperson(s) to determine requirements for Scientific Review, using the following guidelines:

• Statistician(s) and Scientific Review Committee required:
  • A change in protocol primary objectives.
  • Treatment or agent(s) change(s) that materially affect trial evaluation.
• Statistician(s) review required and Scientific Review at the discretion of the Chair:
  • Change in trial design of more than trivial consequence.  For example, adding arms or removing arms to a randomized or phase II trial, or changing stratification factors. 
  • Adding additional patients to a phase II trial other than replacement of inevaluable patients.
• The following amendment changes do NOT require review by the statistician(s) or Scientific Review Committee:
  • Adding cohorts to a phase I trial after failure to reach MTD.
  • Adding limited patients for more than anticipated inevaluable patients or to keep positive study open until implementation of a subsequent trial.
  • Minor changes considered administrative, regulatory or of limited scientific concern. 

Step 5: Activities/actions of the clinical trials review process will be documented

Actions defined in this SOP will be uploaded in iRIS to allow for metrics evaluation of the clinical trial review process.

Interdepartmental Communication Reports will inform affected individuals/groups of new clinical trials efforts to allow for pre-planning.

Resource:

View/Print the NCI Assessment Checklist: Scientific Review of Clinical Trials.