Reporting Adverse Events to Institutional Review Boards in Multi-Center Clinical Trials

National Heart, Lung, and Blood Institute
National Institutes of Health

June 27, 2005

Purpose of This Document

This document outlines National Heart, Lung, and Blood Institute (NHLBI) procedures for complying with the NIH policy regarding adverse event reporting in existing and new multi-center trials that have an NHLBI-appointed Data and Safety Monitoring Board (DSMB). NHLBI-supported studies that have an investigator-appointed DSMB are not covered by this document, but are expected to comply with standard adverse event reporting procedures.

These procedures do not replace standard adverse event reporting requirements for NHLBI-funded studies, or any standard DSMB policies or procedures. Adverse events are defined in each trial protocol, Manual of Operation, Statement of Work, or other regulatory materials consistent with good clinical practice.

The NIH Policy

On June 11, 1999, Guidance on Reporting Adverse Events to Institutional Review Boards for NIH-Supported Multi-Center Clinical Trials was published in the NIH Guide for Grants and Contracts. The Guidance requires that a DSMB provide the following information to all Institutional Review Boards (IRB) associated with the trial:

• a description of the DSMB procedures;
• identification of the DSMB members' areas of expertise, excluding names; and
• feedback after each DSMB meeting.

In addition, the Office of Human Research Protection (OHRP), DHHS issued a memorandum dated July 11, 2002, Continuing Review of DSMB-Monitored Clinical Trials , which authorizes IRBs to rely on current statements from DSMBs that the DSMBs have reviewed study-wide adverse events, interim findings, and any recent literature that may be relevant to the research.

Preparation of Summary Report

Communication of DSMB recommendations to IRBs is accomplished by a Summary Report that is prepared by the DSMB Executive Secretary and distributed to investigators as described below. The report is prepared after the Director, NIHLBI concurs with any DSMB recommendations. Unless conditions warrant immediate implementation of DSMB recommendations, Summary Reports are distributed as soon as possible and no later than 30 days after the DSMB meeting. The Coordinating Center or NHLBI staff will distribute the Summary Report to each Principal Investigator, with instructions to each Principal Investigator to forward the Summary Report to the local IRB.

Gene Transfer Trials:

• Gene transfer trials have reporting requirements above and beyond those for trials of other interventions. They must follow the NIH Guidelines for Research Involving Recombinant DNA Molecules .
  
  
• The NHLBI has a DSMB that oversees participant safety aspects of all gene transfer studies that it supports. Therefore, regardless of whether the individual study has its own data monitoring group, all data will be reviewed by the NHLBI DSMB.
  
  
• For information about reporting adverse events to the NIH Office of Biotechnology Activities, please follow instructions found at the NIH Office of Biotechnology Activities Recombinant DNA and Gene Transer Page.
  
  

Requests from an IRB for Additional Information

If an IRB, whether for a data coordinating center or a clinic, requests information beyond what was agreed to at the beginning of the trial and beyond the above guidelines, the NHLBI Program or Project Officer must be informed immediately. The response to each request will depend on the nature of the request, whether or not the DSMB had identified safety concerns, the kind of trial, the stage of the trial, and perhaps whether the IRB is for a coordinating center or a clinic.

New Multi-Center Clinical Trials

The process of reporting adverse events in NHLBI multi-center trials will be addressed in the Statement of Work, Protocol, Manual of Procedures, solicitations, and awards as appropriate and will include such items as:

• A notice that a DSMB will be established for this trial;
• The purpose of the DSMB;
• Identification of the DSMB members' areas of expertise, excluding names;
• The DSMB meeting schedule;
• A description of the DSMB procedures;
• A notice that a Summary Report will be prepared within 30 days after each DSMB meeting and will be distributed by the Coordinating Center to each Principal Investigator with instructions that each Principal Investigator forward the Summary Report to the local IRBs;
• Description of the Summary Report; and
• A statement that if safety concerns are identified, the Project or Program Officer will communicate these promptly to the investigators.

Resource Documents

• Establishing Data and Safety Monitoring Boards and Observational Study Monitoring Boards
• Responsibilities of DSMBs Appointed by NHLBI
• Responsibilities of DSMBs Appointed by Participating Institutions
• Responsibilities of OSMBs Appointed by the NHLBI
• Serious Adverse Event Reporting to the NHLBI—Policy
• Policy on Human Subjects Research Data and Safety Monitoring Plans—Guidance
• Data Quality Assurance in Clinical Trials and Observational Studies—Guidelines