NCI National Clinical Trials Network (NCTN) Program Guidelines

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Part 4: Appendices – VII. NCTN Program Data & Safety Monitoring Policy for Phase 3 & Randomized Phase 2 Trials written confirmation by the Chief, CIB prior to their official appointment and participation in DSMB/DMC activities. The committee will include physicians and statisticians from within and outside the Network Group selected based on their experience, reputation for objectivity, absence of conflicts of interest (or the appearance of same), and knowledge of good clinical trial methodology. The committee must include a consumer representative and a voting statistician from outside the group. A NCI/DCTD physician and a NCI/DCTD Biometric Research Branch (BRB) statistician, as designated by the Chief, CIB will be non-voting members and must be free to attend all sessions of the DSMB/DMC including closed and executive sessions. The designated Network Group Statistician, or his or her designee, will also be a non-voting member of the DSMB/DMC. For those Network Groups which are funded as CCOP Research Bases, a designee named by the Division of Cancer Prevention (DCP) Community Oncology and Preventive Trials Research Group (COPTRG) program director will be a non-voting member and must be free to attend all sessions. The DSMB/DMC may be constituted fully by individuals who are not members of the Network Groups. Alternatively, the DSMB/DMC may have voting members who are also members of the Network Group; however, the majority of the voting DSMB/DMC members cannot be affiliated with the Network Group and voting quorums for a DSMB/DMC meeting require that the majority of voting members not belong to the Network Group. Network Group members who are members of the DSMB/DMC must see themselves as primarily representing patient interests and not the interests of the Network Group or designated Network Group Chair. Members of the study team or the leadership of the disease committee or scientific research committees of the Network Group (e.g., chair or vice-chair of the disease committee) conducting a study will recuse themselves from all DSMB/DMC discussions concerning that study and will not receive DSMB/DMC reports concerning that study. Additionally, the study statistician will not be a voting member of the DSMB/DMC for his/her trial. The designated Network Group Chair, Principal Investigator(s)/Program Director(s) on the Network Group Operations Center grant using the multiple Principal Investigator option, or any member of the executive leadership of the Network Group (including vice-chairs and executive officers, but not disease-committee chairs or members of Network Group executive committees, as long as they are not also vice-chairs or executive officers) cannot attend closed or executive sessions of the DSMB/DMC. In addition, the designated Network Group Chair, Principal Investigator(s)/Program Director(s) on the Network Group Operations Center grant using the multiple Principal Investigator option, or any member of the executive leadership of a Network Group, cannot be a member of the DSMB/DMC of a different Network Group. The size of the DSMB/DMC should be limited, and it is unlikely that more than 10 people would be required to constitute a DSMB/DMC. Meetings DSMB/DMC meetings will be held at least once every six months. Each randomized clinical trial should have specified interim analysis times, although the DSMB/DMC should be apprised at each meeting of the status of all trials for which it is responsible, e.g., accrual, toxicity concerns, and the next formal monitoring date as specified in the protocol. DSMB/DMC meetings should be in person (rather than by telephone) generally, and especially when new members of the DSMB/DMC have been appointed. At a minimum, DSMB/DMC meetings must be held in person every 18 months, and any possible exceptions to this must be approved by NCI/DCTD. It is recommended that a written report outlining the current status of each trial to be monitored be sent to the DSMB/DMC members by the study statistician at least three weeks prior to the DSMB/DMC meeting. The Study Chair may prepare a report addressing specific toxicity concerns or other concerns about the conduct of the study. The statistician's report may contain recommendations on whether to close the study, whether to report the results, whether to continue accrual or follow-up and whether DSMB/DMC Page 228 of 241
Part 4: Appendices – VII. NCTN Program Data & Safety Monitoring Policy for Phase 3 & Randomized Phase 2 Trials discussion is needed. In the event a study will be considered for closure due to slow accrual, the CTEP members of the DSMB/DMC may discuss with other CTEP staff the possibility of early closure due to slow accrual. Although no confidential information would be disclosed, this would allow the CTEP members of the DSMB/DMC to bring to the DSMB/DMC meeting any information from CTEP concerning early closure that might be useful in the DSMB/DMC deliberations. Major modifications to the study design not motivated by confidential outcome data or patient safety/toxicity data (e.g., increasing the sample size because of more rapid than expected accrual) must be discussed with NCI/DCTD/CTEP before being presented to the DSMB/DMC for consideration. If NCI/DCTD/CTEP is willing to approve the modifications, the Network Group may then seek DSMB/DMC approval before submitting an official amendment to CTEP’s Protocol and Information Office. With respect to implementation of phase 2 decision rules in phase 2/3 designs of clinical trials, any protocolspecified phase 2 decision-rule analysis must be performed within 6 weeks from the date the required number of events are observed. If the trial follows the decision rule (i.e., continues or stops depending on whether the continuation threshold is met), then the Network Group notifies the DSMB/DMC and Chief, CIB of the status of the trial (i.e. continuing or stopping) based on the protocol-specified phase 2 decision rule. In the unlikely event that the study statistician wishes to request permission not to follow the protocol prespecified decision rule, such a request must first be discussed with NCI/DCTD/CTEP by conference call within 2 weeks. This request (change in the design of the trial) needs to be approved by the CTEP Associate Director or his/her designee in consultation with the Chief, CIB who will notify the Network Group Operations Center in writing of NCI decision regarding the request. If NCI/DCTD/CTEP is willing to approve the request, the Network Group must then seek DSMB/DMC approval within 3 weeks before submitting an official amendment to CTEP’s Protocol and Information Office to change the design of the trial regarding the phase 2 decision rule. The review of each trial may include three parts. The first part will be an open session in which members of the study team and disease committee and NCI/DCTD staff not on the DSMB/DMC may be present at the request of the DSMB/DMC to answer questions. In this part, the focus is on accrual, compliance and toxicity issues, and no outcome results may be presented. Following the open session, there will be a closed session limited to DSMB/DMC members and possibly the study statistician in which outcome results will be presented either by a member of the DSMB/DMC, the designated Network Group Statistician, or the study statistician. It is generally recommended that outcome data be presented to the DSMB/DMC in an unblinded manner. However, if the Network Group desires to keep outcome data blinded (perhaps on some specific trials), then this is acceptable provided that any DSMB/DMC member request for unblinding for a trial will be honored. Following this closed session, there will be a fully closed, executive session in which the DSMB/DMC discusses outcome results, and then votes. At the executive session, those present are limited to DSMB/DMC members. Recommendations DSMB/DMC recommendations should be based upon results for the current study being monitored as well as upon data available to the DSMB/DMC from other related studies. The study committees, NCI/DCTD staff, and individual DSMB/DMC members will assure that the DSMB/DMC is advised about relevant nonconfidential results from other related studies that become available. It will be the responsibility of the DSMB/DMC, with advice from the study committee, to determine the extent to which this information is relevant to decisions to continue or modify the current study. The DSMB/DMC will provide recommendations to the designated Network Group Chair to change a study or to continue a study unchanged. In the event a change is recommended by the DSMB/DMC, the study statistician may send his/her written report that was prepared prior to the DSMB/DMC meeting to the Page 229 of 241
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NCTN Program Guidelines Table of Co
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PART 1: Overview of NCTN Program Se
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PART 1: Overview of the NCTN Progra
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PART 2: Submission of Competing New
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PART 2: Submission of New/Competing
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Page 189 and 190: TYPE OF STUDY PART 3: Submission No
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Page 195 and 196: PART 4: Appendices Section II - Req
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Page 233 and 234: Part 4: Appendices - IX. Common Bud
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Page 237 and 238: Part 4: Appendices - VII. Accrual I
Page 239 and 240: Part 4: Summary of Updates to Guide
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NCI National Clinical Trials Network (NCTN) Program Guidelines

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