Ensuring the safety of study participants is of utmost importance in all Microbicide Trials Network (MTN) studies.
The MTN follows strict national and international procedures, with a multi-tiered safety review system that ensures participants are monitored closely and study teams can respond to concerns in a timely manner.
Participant safety is the collective responsibility of many individuals, including, but not limited to, study investigators and site staff who have direct contact with participants. Others who are key to the process include staff at the MTN Statistical and Data Management Center (SDMC) who assess incoming adverse event reports on a daily basis; MTN Protocol Safety Physicians within the Leadership and Operations Center (LOC) who review summary safety reports and address concerns raised by site clinicians or the SDMC on an as-needed basis; and a Protocol Safety Review Team that conducts monthly reviews of safety data via conference call. The Protocol Safety Review Team consists of at least one Protocol Safety Physician, the Medical Officers from the U.S. National Institute of Allergy and Infectious Diseases (NIAID)Division of AIDS (DAIDS) and/or other institutes of the National Institutes of Health; the study’s Protocol Chair, SDMC Clinical Safety Associates and others, depending on the protocol design and the particular safety considerations for the study.
Some studies may also involve regular reviews of participant safety data by a Study Monitoring Committee (SMC), while Phase IIb and Phase III studies are subject to both SMC reviews and reviews conducted by an independent Data Safety and Monitoring Board (DSMB) chartered by DAIDS/NIAID. The members of the DSMB are independent experts in a variety of fields — for example, biostatistics, medicine, clinical trial design and medical ethics – and they have no conflicts of interest in the outcomes of the studies they review.
A DSMB reviews data that are not available to the investigators or anyone else, while a clinical trial is in progress. Based on its review of interim data, a DSMB may, at any time, recommend that a trial, or part of a trial, be stopped if there are concerns about safety, compelling evidence for a product’s effectiveness or if it is clear that a product is not effective in the study’s participants, a concept called futility. NIAID leadership in turn decides whether to accept the DSMB’s recommendations. Before a Phase IIb or Phase III trial begins, study teams define the specific “stopping rules” that would cause the study to close for efficacy, harm or futility.
More information about safety monitoring and reporting in MTN trials can be found in the MTN Manual of Operational Procedures, specifically in Section 14, Study Implementation; Section 16, Safety Considerations; and Section 17, Study Oversight.