1. Purpose

The functions of the NICHD Data and Safety Monitoring Committee (DSMC) include:

  • to review new NICHD intramural intervention protocols prior to implementation and suggest protocol changes related to the design, reporting and statistical analysis of safety and efficacy endpoints, as appropriate
  • to review and provide guidance to the NICHD and NICHD IRB on major proposed changes to protocols
  • to examine endpoint and toxicity data from NICHD intramural intervention protocols on a schedule to be determined based on the protocol
  • to make recommendations to the NICHD concerning continuation, termination, or other modification of studies based on the observed beneficial or adverse effects of any of the treatments under study
  • to review the general progress of the study and to assist in resolving any problems which may arise

2. Membership

The DSMC members and chairperson will be appointed by the NICHD Clinical Director with the approval of the Scientific Director and will reflect the disciplines and medical specialties necessary to interpret the data from studies performed in the NICHD intramural clinical research program. The core DSMC will consist of an interdisciplinary group of four to six permanent members who will include at least one statistician and one ethicist. The other permanent members will scientists acquainted with the research issues related to the various trials. On occasion trials will require expertise in other areas and the core committee will be supplemented by appropriate ad hoc members. To assure the independence and impartiality of the DSMC, members will have no professional or financial interests dependent on the outcome of the trials. Members will be appointed to serve terms of one to three years which will be renewable.

3. DSMC Functions

The DSMC has the general charge of ensuring, through advice to the investigators and the NICHD, that the trial is conducted safely and ethically and that the trial meets its primary objectives. This includes the interests of currently enrolled patients, but also includes the interests of patients to be enrolled in the future and patients outside the study. To these ends, the committee has the following functions:

Review of Safety Data: A Protocol Data Coordinating Component (PDCC) of the nascent NICHD clinical trials database (or equivalent database for ongoing trials) will be used to provide reports of adverse events among trial participants to the DSMC on a regular schedule. Deaths or other serious events will be reported to the DSMC Chair and appointed medical monitors as soon as they occur. To assure patient safety in each trial, the committee will develop individualized methods for monitoring adverse events as needed.

Review of Efficacy Data: On a schedule determined before data are collected, the DSMC may examine prospectively-selected outcome data provided via the PDCC for early evidence of efficacy or lack of it. Throughout the trial, the committee will monitor study assumptions about incidence rates and sample size. The DSMC will evaluate, as appropriate, outcome data according to guidelines for data monitoring outlined in published procedures. Based on data reviewed at these interim evaluations, the committee may recommend to the NICHD and its IRB early termination of the trial either because of established efficacy of treatment or because of the unlikelihood that a meaningful assessment of treatment effect could be established by the planned end of the trial. Stopping rules will be specified in advance of the analysis, and agreed upon by the DSMC, the investigator(s), and the NICHD IRB. The DSMC may also recommend to the PI and IRB extensions in trial length or increases in sample size, as well as other relevant modifications to the protocol.

Review of Data Quality and Trial Operations: to ensure the highest possible quality of the data, the committee will regularly monitor aspects of the functioning of the PDCC, which include the following:

  • the flow of study forms
  • the timeliness of safety and efficacy data
  • compliance to the study protocol, by patients and investigators
  • the number of study withdrawals
  • the number of study anomalies including codebreaking and non-compliance to randomized study assignment
  • the recruitment and eligibility rates
  • any other measures reflecting quality of data

On the basis of such a review the DSMC will recommend any necessary modifications in trial operations.

4. Type of Studies Requiring a DSMC

A DSMC will be convened whenever disinterested and unbiased evaluations of emerging data from NICHD intramural intervention protocols are needed.

5. Meetings

The Committee will meet approximately four times a year. Additional meetings and conference calls may be scheduled when necessary for adequate monitoring. Any member of the Committee may request a meeting if they feel data provided within interim reports warrant an additional meeting. The agenda for each meeting will be developed by the NICHD Office of the Clinical Director in conjunction with the DSMC chair. Material presented at all sessions will be confidential.

At the initial DSMC review for a proposed clinical trial, the committee will discuss the objectives of the protocol and potentially suggest revisions to the PI and to the IRB. The DSMC may also forward a recommendation to the NICHD Clinical Director, Scientific Director, and IRB that a proposal be rejected.

When data are to be reviewed, the meeting will be divided into an open session, a closed session and a closed administrative session. The open session may be attended by parties with interest in the trial. In the open session, aggregate statistics (i.e., total, with no treatment group breakdown) on trial progress such as patient accrual, baseline characteristics, and forms statistics are presented and discussed. In the closed session, data including outcome results by randomized treatment group are presented and discussed. For this reason only DSMC members and PDCC representatives attend the closed session. Study investigators may be invited in the discussions at times during the closed sessions, to provide information, but they may not view the documents under discussion or otherwise compromise the study masking. In the administrative session, attended only by voting DSMC members and an NICHD representative, the committee discusses, votes, and makes its recommendations and decisions. If there is a tie, the Chair will be the deciding vote. If there is not unanimous support for a decision, the recommendations will include a minority report. These recommendations are then sent to the NICHD Clinical Director and Scientific Director.

6. Reports

After the DSMC's written report has been reviewed by the NICHD Clinical and Scientific Directors, the report will be sent to the study investigators and to the IRB of each participating institution.

7. Interaction with IRBs

The IRB must review and grant final approval prior to initiation of the study. The investigator shall submit the final IRB-approved protocol to the DSMC. In the event the NICHD or other IRB involved in a study requires revision or other action on a protocol, a copy of the IRB report will be forwarded to the DSMC for its consideration and advice to the investigators.

For all ongoing trials under its purview, the DSMC will have regular meetings to review study safety and efficacy data as described above. The committee may also require ad hoc meetings to address unexpected or exigent safety events. Each of these meetings will result in the formal recommendation to the Clinical Director and IRB concerning the continuation of the study. Relevant information from these ad hoc meetings will be sent promptly to the Clinical Director and the IRB. To assist the IRB in their annual review of ongoing study protocols, the DSMC will routinely provide the summary recommendations from each DSMC meeting to all appropriate IRBs. A DSMC member will be available to attend IRB meetings, if necessary, for discussion of any safety issues or any recommendation for a change in study protocol.

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