National Institute of Neurological Disorders and Stroke Extramural Guidelines for Monitoring Patient Safety in Clinical Trials

In order to ensure and maintain the scientific integrity of human subject research projects and to protect the safety of human subjects, the National Institute of Neurological Disorders and Stroke (NINDS) appoints Performance and Safety Monitoring Boards (PSMBs). PSMBs have the responsibility to assure the NINDS that participants in a research project are not being exposed to unnecessary or unreasonable risks as a result of the pursuit of scientific objectives. PSMBs also have the responsibility to assure the NINDS that research projects involving human subjects maintain high standards of quality throughout the duration of these projects. The NINDS policy provides that a PSMB shall be established for all research projects receiving any funding from the National Institute of Neurological Disorders and Stroke (NINDS) and exposing human subjects to significant risk from participation in the research. This policy generally refers to phase III clinical trials; for earlier phases (phase I and II Clinical Trials) see section below.

An NINDS PSMB may monitor more than one trial. Once established, a PSMB will continue until completion of the research project or until human subjects in a research project are no longer exposed to significant risk from participation in the research.

The PSMB will be established prior to the initiation of the project. The number and expertise of the PSMB members will depend on the nature and complexity of the research project. The members of the PSMB will be selected so that as a group they have appropriate clinical expertise and knowledge about the design, monitoring, and analysis of clinical research projects necessary to conduct an ethical and scientifically rigorous study. The PSMB will deliberate, reach decisions, and make recommendations independently from the research project investigators. Each member of the PSMB is responsible for notifying the PSMB chair if any potential conflicts of interest develop after the initiation of the study.

If a non-NINDS PSMB is also involved in oversight of the trial, an NINDS-appointed PSMB will continue to provide general oversight for the research and will receive reports of the activities and recommendations of the non-NINDS PSMB.

The PSMB advises the NINDS. Advice from the PSMB does not substitute for approval and evaluation by other organizations within the Department of Health and Human Services including the Office for Protection from Research Risks, the NIH, and the NINDS. The advice of the PSMB to the NINDS is also independent of any local rules or regulatory bodies such as Institutional Review Boards at participating institutions.

Policy for Phase I-II Clinical Trials:

For phase I and II clinical trials, the investigators must submit a description of the data and safety monitoring plan as part of the research application. A detailed monitoring plan is a necessary part of the protocol and must be approved by the NINDS before the study begins. The overall elements of the monitoring plan may vary depending on the potential risk, complexity, and nature of the study. They may range from independent PSMB's to continuous, close monitoring by the study investigator or an independent individual. The NINDS is responsible for overseeing the monitoring of these trials to ensure the safety of participants and the validity and integrity of the data. An NINDS PSMB may be appropriate for phase I or II clinical trials, for example if studies are blinded (masked), or involve particularly high risk interventions or vulnerable populations.

For additional information on Performance and Safety Monitoring please go to the following sites:

• http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html
  
• http://grants.nih.gov/grants/guide/notice-files/not98-084.html
  
• http://grants.nih.gov/grants/guide/notice-files/not99-107.html