NCI National Clinical Trials Network (NCTN) Program Guidelines

PART 1: Overview of NCTN Program Section IV – Terms/Conditions of Award – NCI/DCTD Responsibilities
review/approval by a CTEP collaborator (e.g., collaborator providing investigational agent for the
trial) and if/when the CTEP collaborator gives official approval, CTEP issues a final full approval for
the study with or without recommendations. On occasion, an approval may come with a required
modification specified in the approval letter and/or attached Consensus Evaluation/Consensus
Review that will need to be incorporated into the study proposal at the time of protocol review.
This is done for minor modifications so that the trial proposal does not need to go back as a
pending when the modification is straightforward.
Pending – The CTEP PRC or NCI SSC has significant questions about the proposed study. The
proposed study can be approved if the investigators satisfactorily address the concerns included in
the written consensus review/evaluation adequately (i.e., comments requiring a response).
Disapproved – In the judgment of CTEP’s PRC or the NCI SSC, the study cannot be approved.
In addition, all Concepts and non-intervention study proposals that are prioritized for further
development by NCI SSCs or an NCI/DCTD-approved NCTN Correlative Science Committee must
undergo expedited review by CTEP before final approval is given in order to ensure significant safety,
feasibility, and regulatory issues are adequately addressed, including ensuring that there are adequate
resources available for the study proposal or trial given the resource allocation constraints for the
disease area, and to prevent duplication. However, it is expected that this final review/approval by
CTEP can be accomplished in an expedited manner in most cases as designated NCI/DCTD staff
participate as full members on the various NCI SSCs or NCI/DCTD-approved NCTN Correlative Science
Committees and significant issues in these areas are incorporated into the evaluation/prioritization
discussion.
Also, any approved NCTN Concept for a phase 3 or phase 2/3 trial is submitted to FDA for comment and
any approved NCTN LOI/Concept with an investigational device/biomarker for the particular clinical
setting may also be submitted to FDA for comment even if the study is not identified as being
specifically designed for a licensing indication for an agent or device.
3.2 Protocol Development Review/Approval and Amendment Review/Approval
The protocol document must be reviewed and approved by NCI/DCTD prior to distribution by a
Network Group to its sites for local IRB review (or NCI Central IRB review) and trial activation (i.e.,
opening the study to patient enrollment after approval of the study by at least one IRB). All approved
adult phase 3 study protocols also require approval by the NCI Adult Central Institutional Review Board
(CIRB) after approval of the protocol document by CTEP; however, distribution of the trial may proceed
to sites using other IRBs prior to final CIRB approval. Any changes/modifications requested by the NCI
CIRB at the time of its initial review may require an amendment to the study after distribution if CTEP
believes any of the requested changes/modifications should be in master protocol document (either in
the informed consent or in other sections of the protocol document). Minor changes in the informed
consent document may be limited to the approved CIRB version of the informed consent document
(IRB) for its sites only. After the trial is activated, all protocol amendments submitted on the trial
require NCI CIRB approval prior to final approval of the amendment by CTEP. In select cases, phase 2
trials may also be required by NCI/DCTD to be reviewed by the NCI CIRB, especially those phase 2
studies that may be opened widely across the entire NCTN.
All pediatric study protocols (except phase 1 study protocols - although these may be included in the
future) require approval by the NCI Pediatric CIRB prior to final approval of the study protocol
document by NCI/DCTD.
Any change to the protocol document subsequent to its approval by CTEP must be submitted to CTEP’s
Protocol and Information Office (PIO) in writing for review and approval by CTEP prior to
implementation of the change, with the exception of administrative updates. Additional information
on the procedures for protocol amendment can be found in the Investigator’s Handbook.
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