Guidelines for Establishing and Operating a Data and Safety Monitoring Board

Introduction

This document has been created to assist grantees in establishing and operating a Data and Safety Monitoring Board (DSMB) for clinical trials sponsored by the National Institute on Drug Abuse (NIDA). Monitoring by a DSMB is required by NIH for some trials or may be implemented by a grantee whenever he/she feels it is appropriate. Investigators may however use alternative approaches to operate their DSMBs, as long as they are in compliance with the current NIH requirements on this topic. DSMBs are playing an increasingly important role in the process of ensuring the highest standards for research participants medical safety and data quality of clinical trials. Clinical investigator grantees, IRBs, NIH, as well as regulators, industry, and sponsors are all affected by the emerging role of DSMBs.

The purpose of the DSMB is to assure that the safety of study subjects is protected while the scientific goals of the study are being met. Specifically, the DSMB is charged with monitoring the safety of participants and the quality of the data, as well as the appropriate termination of studies either when significant benefits or risks have been uncovered or when it appears that the clinical trial cannot be concluded successfully.

NIH requires data and safety monitoring, generally, in the form of DSMBs for phase III clinical trials. For earlier trials (phase I and II), a DSMB may be appropriate if the studies have multiple clinical sites, are blinded (masked), are First-in-Man, or employ particularly high-risk interventions or vulnerable populations. A DSMB might be considered for practical reasons such as for trials with high chance of early termination for safety or efficacy reasons, or to have an independent review group that may help to add validity to the trial.

NIH policy provides each IC with the flexibility to implement the requirement for data and safety monitoring as appropriate for its clinical research activities. More information about those policies can be found at:

• http://grants.nih.gov/grants/guide/notice-files/not98-084.html
• http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html

Grant applications involving clinical trials that are required to have a DSMB must submit a general description of the DSMB plan as part of the Data and Safety Monitoring Plan (DSMP). The Scientific Review Group reviews the DSMP and includes any comments or concerns in the summary statement for that application. A detailed DSMP including the operations of the DSMB must be submitted to and approved by NIDA before the trial begins. The DSMB should have clear standard operating procedures. The responsibility for compliance with the DSMP rests with the grant recipient. NIDA's guidelines for DSMP can be found at: www.drugabuse.gov/Funding/DSMBSOP.html

These guidelines are in compliance with, and do not take the place of Institutional Review Board (IRB) guidelines, Food and Drug Administration (FDA) regulations, or special NIH policies or guidelines; e.g., NIH Guidelines for Research Involving Recombinant DNA Molecules. Specifically, Phase I and II gene transfer trials must comply with additional requirements imposed by NIH Guidelines, e.g., reporting of adverse events to the Office of Science Policy.

Background

In June of 1998, NIH issued a policy stating that "each Institute or Center (IC) in NIH should have a system for the appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for all NIH-supported or conducted clinical trials." According to this policy, data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III); etc. It includes all types of intervention studies, whether medication or non-medication (e.g., behavioral, prevention, diagnostic) trials and monitoring should be commensurate with the study risks. The role of DSMBs has increased due to the increased number of trials with mortality or severe morbidity as endpoints, the greater need to monitor the quality of the data of clinical trials, and the demand for approaches to the issue of early termination of trials for safety or efficacy reasons. The decision to establish a DSMB rests with the sponsoring Institute or Center and is commensurate with the level of risks, type of clinical trial, and/or the number of treatment sites participating in the study.

The International Conference on Harmonization (ICH) mentions Data Monitoring Committees (DMC) in the guidelines, ICH E3 (Structure and Content of Clinical Study Reports), ICH E6 (Good Clinical Practice), and ICH E9 (Statistical Principles for clinical trials.) They describe appropriate administrative and statistical analysis procedures for trial safety monitoring and analysis of study data required for the DSMB to fulfill its responsibilities. ICH E6 (Good Clinical Practice) guidelines state that the sponsor may consider establishing an independent data-monitoring committee to assess the progress of a clinical trial, including the safety data and the critical efficacy endpoints at intervals, and to recommend to the sponsor whether to continue, modify or stop a trial. The committee should have written operating procedures and maintain written records of all its meetings. More information about ICH guidelines can be obtained at: http://www.ich.org/(link is external)