NCI National Clinical Trials Network (NCTN) Program Guidelines

PART 1: Overview of NCTN Program Section IV – Terms/Conditions of Award – NCI/DCTD Responsibilities
3.3 Study/Trial Closure
CTEP may request that a phase 1 or phase 2 study be closed to accrual for reasons including the
following: (1) insufficient accrual rate; (2) poor protocol performance; (3) protection of patient safety;
(4) study results are already conclusive; (5) emergence of new information that diminishes the scientific
importance of the study question; and (6) unavailability of study agent. NCI will not provide
investigational agents or permit expenditures of NCI funds for a phase 1 or phase 2 study after
requesting closure (except for patients on treatment and follow-up).
All NCTN phase 3 trials (and phase 2/3 trials) are subject to CTEP’s Slowly Accruing Guidelines for Phase
3 Trials as described in Part 4 – Appendices - Section I.G. of these Guidelines. In addition, the Lead
NCTN Program Director may at any time request that a Network Group’s DSMB consider closing a
phase 3, phase 2/3, or other phase 2 protocols to accrual for the same reasons as those listed above for
phase 1 and phase 2 studies. NCI will also not provide investigational agents or permit expenditures of
NCI funds for a phase 3 trials that has been closed (except for patients on treatment and follow-up if
appropriate). In future, slowly accruing guidelines for phase 1 and phase 2 trials may also be instituted
by NCI/DCTD for the NCTN Program.
3.4 Data and Safety Monitoring Boards (Data Monitoring Committees)
The Lead NCTN Program Director, assisted by the Co-Program Directors and the Biometric Research
Branch (BRB) staff, will assess Network Group compliance with NCI established policies on Data and
Safety Monitoring Boards (DSMBs), also known as Data Monitoring Committees (DMCs), for Network
Group phase 3 trials as well as phase 2/3 and any other phase 2 trials monitored by the DSMB. These
policies must address both the membership of the DSMB/DMC and its operational policies. One or
more CTEP staff or other NCI/DCTD staff (designated by the Chief of the Clinical Investigations
Branch/Lead NCTN Program Director at CTEP) and one BRB staff (designated by the Chief of BRB) will
serve as non-voting members at each Network Group DSMB/DMC meeting.
The membership of the Group’s DSMB/DMC and its policy must be approved by Lead NCTN Program
Director. In addition, Lead NCTN Program Director, assisted by the Co-Program Directors and the BRB
staff, must review and approve each Network Group Operations Center’s policy (developed in
conjunction with the associated Network Group Statistics and Data Management Center) regarding its
data and safety monitoring plans for phase 1 and phase 2 trials as well as pilot studies and feasibility
studies. Information on NIH DSMB policies is provided by the following URLs:
http://grants.nih.gov/grants/guide/notice-files/not98-084.html
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html
http://www.cancer.gov/clinicaltrials/conducting/dsm-guidelines
Information on CTEP’s policy on monitoring of phase 3 trials and randomized phase 2 trials by Network
Group DSMBs/DMCs is provided in Part 4 – Appendices – Section VIII of these Guidelines.
Because NCI/DCTD staff serve as non-voting members of the Network Group Operation Center
DSMBs/DMCs to ensure compliance with NIH/NCI policies and protocol requirements, NCI/DCTD staff
members recuse themselves from NCI/DCTD review of substantive protocol amendments (e.g.,
amendments for increases in sample size or significant changes in trial design) for any study that is also
under review by a DSMB/DMC of which they are members, if confidential outcome data on that study
have been previously presented to the DSMB/DMC. When this situation arises, the amendment is
reviewed by NCI/DCTD staff members who are not members of that DSMB/DMC.
4. Quality Assurance and Onsite Auditing
The Clinical Trials Monitoring Branch (CTMB) is responsible for establishing guidance for the conduct of
quality assurance audits. CTMB provides oversight and monitors compliance of the Network Groups, CCOP
Research Bases, and CTSU with the NCI’s monitoring guidelines. Compliance with applicable federal
regulations is also monitored by CTMB.
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