|
Data and Safety Monitoring Boards and Other Review Mechanisms
Clinical trials must be conducted at a high standard of quality that assures the research question is answered in a reliable, valid, and unbiased manner, while protecting the rights and welfare of the participating human subjects. Accordingly, the safety of subjects in a clinical trial must be monitored and potential harms minimized, while ensuring that a trial continues for an adequate period of time to answer its scientific questions, but is discontinued if the design of the study is no longer appropriate.
In 1998, NIH issued a policy statement – further clarified in 2000 - that each Institute and Center (IC) 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. The NIH requirement for data and safety monitoring and IC oversight for all clinical trials - commensurate with the risks, size and complexity of the trial - is separate and distinct from the requirement for study review and approval by an Institutional Review Board (IRB).
The 1998 and 2000 statements also described when monitoring should be in the form of a Data and Safety Monitoring Board (DSMB - see “Pertinent Resources, Policies, and Regulations” below). A DSMB is an independent advisory body of pertinent experts appointed to assess, at regular intervals, the progress of a clinical trial (or several trials), accumulating outcome data, reports of adverse events, and as appropriate, critical efficacy endpoints, in a manner that contributes to the safety of subjects and the continuing validity and scientific merit of the trial. The DSMB provides recommendations regarding study modification, suspension, or early stopping, as appropriate. While all interventional studies are required to have a data and safety monitoring plan, the establishment of a DSMB to perform the monitoring function may be required by NIH or individual IC policy, based on the characteristics of the clinical trial.
Other federal agencies are developing policies and guidance related to data and safety monitoring as well. The Food and Drug Administration (FDA) proposed guidance for data monitoring committees in November 2001, and the final FDA guidance, “Establishment and Operation of Clinical Trial Data Monitoring Committees (DMCs),” was issued on March 28, 2006, OHRP issued guidance in July 2002 on continuing review that addresses the role of DSMBs and IRBs, but despite these clarifications, local IRBs have different perceptions of their roles and some have required that unblinded interim data from other multicenter trial sites be provided to them. In October 2005, OHRP issued draft guidance for public comment related to the review and reporting of adverse events and unanticipated problems that addressed what interactions should occur between IRBs and DSMBs; the comments on this guidance are being considered by OHRP and coordinated with the FDA. The Centers for Disease Control and Prevention (CDC) and the Agency for Healthcare Research and Quality (AHRQ) are each considering the development of a data and safety monitoring policy. Internationally, the issue of data and safety monitoring in clinical trials is also being addressed, and the World Health Organization (WHO) and the European Medicines Agency (EMEA) have each issued guidelines on the use of independent monitoring committees as part of clinical trial management.
Federal guidance on data and safety monitoring activities continues to evolve, while at the same time, IRBs are being urged to be more responsible for subject safety, including monitoring of clinical studies. This situation raises questions about:
-
the types of studies that should require DSMBs;
how DSMBs should fit into overall data monitoring plans;
the comparability of NIH and FDA standards for DSMBs; and
the relative roles of DSMBs and IRBs.
The CRpac program is working to coordinate the development of these various policies to promote consistency and harmony to the extent possible.
Pertinent Resources, Policies, and Regulations
European Medicines Agency:
Food and Drug Administration:
National Institutes of Health:
Office for Human Research Protections:
World Health Organization:
|
