Oversight and Monitoring of Clinical Research funded by the NIMH

Notice Number: NOT-MH-19-027

Key Dates
Release Date: April 08, 2019

Related Announcements

This notice supercedes the following notices:

NOT-MH-16-013

NOT-MH-15-025

NOT-MH-05-013

Issued by
National Institute of Mental Health (NIMH)

Purpose

The NIH has launched a series of initiatives to enhance the accountability and transparency of clinical research, and in particular, clinical trial research (https://grants.nih.gov/policy/clinical-trials.htm). In addition to the NIH policies and efforts, the NIMH has additional clinical oversight and monitoring policies to support the achievement of grant objectives and to ensure that the NIMH remains a responsible steward of public funds.

For the extramural research community, this Guide Notice consolidates and summarizes the NIMH's policies and efforts related to the oversight and monitoring of clinical research and, in particular, clinical trials, throughout grant lifecycle, from pre-award discussion with program staff (e.g., trial design, data safety monitoring) through post-award activities and support (e.g., reportable events, recruitment monitoring, on-site monitoring by NIMH staff). More information on NIMH policies related to clinical research can be found on the NIMH Clinical Research webpage: https://www.nimh.nih.gov/funding/clinical-research/index.shtml.

  1. NIMH Policy Governing the Monitoring of Clinical Trials (http://www.nimh.nih.gov/funding/clinical-research/nimh-policy-governing-the-monitoring-of-clinical-trials.shtml).

This policy explains the need for a clear and well-developed data and safety monitoring plan (DSMP), highlights the critical elements of a DSMP, and outlines the appropriate levels of monitoring for a clinical trial. This policy ensures that the appropriate monitoring systems are in place and that the NIMH is notified by recipients, in a timely manner, about all recommendations, guidance, and directives made in the course of monitoring the grant. The recommendations, guidance, and directives from monitoring activities are in addition to Institutional Review Board (IRB) guidance, Food and Drug Administration (FDA) requirements, or specific NIH guidelines (e.g., NIH Guidelines for Research Involving Recombinant DNA Molecules). None of these monitoring and compliance efforts should delay urgent decisions necessary for participant safety.

In addition, the NIMH has developed two guidance documents to help researchers ensure the safety of research participants and protect the validity and integrity of study data:

  • The Guidance on Risk-Based Monitoring defines three levels of risk (i.e., minimal risk, greater-than-minimal risk, and significantly-greater-than-minimal risk); and identifies the NIMH’s monitoring recommendations and expectations to mitigate the risks at each level.
  • The Data and Safety Monitoring Plan Writing Guidance assists researchers in developing a data and safety monitoring plan (DSMP) by highlighting key considerations for determining the appropriate level of monitoring and defining the critical elements of an acceptable DSMP.
  1. Policy Governing Independent Safety Monitors (ISM) and Independent Data and Safety Monitoring Boards (DSMB) (http://www.nimh.nih.gov/funding/clinical-research/policy-governing-independent-safety-monitors-and-independent-data-and-safety-monitoring-boards.shtml)

    This policy establishes expectations for the conduct of NIMH-supported clinical trials that utilize an ISM or independent DSMB to ensure the safety of research participants, regulatory compliance, and data integrity. Specifically, the policy addresses roles and membership, independence, responsibilities and review, review schedule, and monitoring reports. This is in addition to IRB guidance, FDA requirements, or specific NIH guidelines.

  2. NIMH Reportable Events Policy (http://www.nimh.nih.gov/funding/clinical-research/nimh-reportable-events-policy.shtml)

This policy establishes the NIMH’s expectations of NIMH-funded researchers relating to the submission of reportable events, i.e., Adverse Events (AEs), Serious Adverse Events (SAEs), Unanticipated Problems Involving Risks to Subjects or Others, protocol violations (significant divergences from the IRB-approved protocol), non-compliance (serious or continuing), suspensions or terminations by monitoring entities (e.g., Institutional Review Board (IRB), Independent Safety Monitor (ISM), (DSMB), and suspensions or terminations by regulatory agencies (e.g., Office for Human Research Protections (OHRP) or the Food and Drug Administration (FDA). This policy specifies reporting to the NIMH and does not replace regulations or policies requiring reporting of these events to other monitoring entities or regulatory agencies.

  1. NIMH Recruitment of Participants in Clinical Research Policy (https://www.nimh.nih.gov/funding/grant-writing-and-application-process/nimh-recruitment-of-participants-in-clinical-research-policy.shtml)

This policy applies to all clinical trials and clinical research studies proposing to enroll 150 or more subjects per study. This policy ensures that investigators establish recruitment milestones from the outset of a clinical research project and that progress is monitored three times a year throughout the course of the grant (i.e., investigators are expected to submit reports on actual recruitment progress on April 1, August 1, and December 1). Principal Investigators (PIs) can use their eRA commons username and password to enter recruitment milestone data through the NIMH Recruitment Milestone Reporting (RMR) System (wwwapps.nimh.nih.gov/rmr/displayHome.action). PIs are encouraged to visit the FAQs and points to consider guidance for RMR activities.

  1. (Clinical Research Education Support and Training (CREST) (https://www.nimh.nih.gov/funding/clinical-research/nimh-clinical-research-education-support-and-training-crest-program.shtml) :

The NIMH Clinical Research Education, Support, and Training (CREST) Program provides ongoing educational and technical support from NIMH staff for clinical research project grants which are selected for phone or email consultation and/or site visit(s). The Crest Program aims to ensure that the reported clinical research study data are accurate, complete, and verifiable, the conduct of the study is in compliance with the study protocol, Good Clinical Practice (GCP) and the regulations of applicable agencies, and the rights and well-being of human subjects are protected, in accordance with 45 CFR 46 (Protection of Human Subjects) and, as applicable, 21 CFR part 50 (Protection of Human Subjects). Research project grants selected for inclusion in the CREST Program might include: clinical research studies with “significantly-greater-than-minimal risk” to subjects (e.g., an intervention or invasive procedure with high potential for SAEs; see NIMH Risk-Based Monitoring Guidance); a study intervention under an FDA Investigational New Drug or Investigational Device Exemption; or other studies identified by NIMH staff that may benefit from inclusion in CREST. CREST is separate and distinct from “for cause” audits of clinical research. Research grants may be included in CREST at any time during the grant lifecycle, although, generally, grants are identified and selected for the program at the initiation of the grant.

Inquiries

Please direct all inquiries to:

Eugene Kane
National Institute of Mental Health (NIMH)
Telephone: 301-443-3241
Email: NIMHOCR@mail.nih.gov
Website: http://www.nimh.nih.gov/about/organization/od/office-of-clinical-research-ocr.shtml