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Data and Safety Monitoring Plan Writing Guidance - National Institute of Mental Health (NIMH)

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field--type-text-with-summary field--label-hidden field__item"><h2>Guidance for Developing a Data and Safety Monitoring Plan for Clinical Trials Sponsored by NIMH</h2> <p>(Version date: April 16, 2015)</p> <h2>Purpose</h2> <p>The National Institute of Mental Health (NIMH) has developed the following guidance for investigators developing a data and safety monitoring plan (DSMP) to ensure the safety of research participants and protecting the validity and integrity of study data in clinical trials supported by NIMH.</p> <h2>Scope</h2> <p>This guidance applies to data and safety monitoring for all NIMH-supported clinical trials (including grants, cooperative agreements, and contracts).</p> <h2>Introduction</h2> <p>It is the policy of the National Institutes of Health (NIH) that each Institute and Center (I/C) have a system in place for the appropriate oversight and monitoring of NIH-funded&nbsp;<a href="http://grants.nih.gov/grants/glossary.htm#ClinicalTrial" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/glossary.htm#ClinicalTrial', 'eventVal': 0});" rel="external">clinical trials&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>. Accordingly, the NIMH has developed a&nbsp;<a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="17e69009-1f1f-4eb1-9a56-c448d8afb785" href="/funding/clinical-research/nimh-policy-governing-the-monitoring-of-clinical-trials" title="NIMH Policy Governing the Monitoring of Clinical Trials">Policy Governing the Monitoring of Clinical Trials</a>. All grant applications and contract proposals for clinical trials submitted for&nbsp;<a href="http://grants.nih.gov/grants/policy/nihgps_2013/nihgps_ch4.htm#human_subjects_data_safety_monitoring" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/policy/nihgps_2013/nihgps_ch4.htm#human_subjects_data_safety_monitoring', 'eventVal': 0});" rel="external">NIMH Extramural funding&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>&nbsp;must include a proposed&nbsp;<a href="http://grants.nih.gov/grants/glossary.htm#DataandSafetyMonitoringPlan" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/glossary.htm#DataandSafetyMonitoringPlan', 'eventVal': 0});" rel="external">DSMP&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>&nbsp;as part of the research application&rsquo;s &ldquo;Human Subjects&rdquo; section. In an effort to facilitate the development of a DSMP, the following guidelines have been provided to assist in protecting the health, rights, and safety of research participants.</p> <h2>Determining the Appropriate Level of Monitoring</h2> <p>The type of monitoring entity or monitoring plan may differ greatly between studies. All clinical trials will be monitored, at minimum, by the&nbsp;<a href="http://grants.nih.gov/grants/glossary.htm#ProgramDirector/PrincipalInvestigator(PD/PI)" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/glossary.htm#ProgramDirector/PrincipalInvestigator(PD/PI)', 'eventVal': 0});" rel="external">Principal Investigator (PI)&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>&nbsp;and&nbsp;<a href="http://grants.nih.gov/grants/glossary.htm#InstitutionalReviewBoard(IRB)" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/glossary.htm#InstitutionalReviewBoard(IRB)', 'eventVal': 0});" rel="external">Institutional Review Board (IRB)&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>&nbsp;and may require additional monitoring by an Independent Safety Monitor (ISM) or&nbsp;<a href="http://grants.nih.gov/grants/guide/notice-files/not98-084.html" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/guide/notice-files/not98-084.html', 'eventVal': 0});" rel="external">Data Safety Monitoring Board&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>&nbsp;(DSMB) (See&nbsp;<a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="17e69009-1f1f-4eb1-9a56-c448d8afb785" href="/funding/clinical-research/nimh-policy-governing-the-monitoring-of-clinical-trials">Policy Governing Monitoring of Clinical Trials</a>). The method or level of monitoring should correspond to the risk involved; the population being studied; and the size, scope, and complexity of the trial. For example, close monitoring by the PI may be an appropriate format for monitoring studies with low-risk interventions, however, in some instances, the&nbsp;<a href="http://grants.nih.gov/grants/glossary.htm#ProgramOfficial(PO)/ProgramOfficer/ProjectOfficer" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/glossary.htm#ProgramOfficial(PO)/ProgramOfficer/ProjectOfficer', 'eventVal': 0});" rel="external">Program Official (PO)&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>, PI or the IRB may determine that an ISM may be required. The NIH requires data and safety monitoring for all clinical trials. Multi-site clinical trials and most phase III clinical trials will require monitoring in the form of DSMBs. In June 2000, the NIH issued&nbsp;<a href="http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html" onclick=" dataLayer.push({'event': 'eventTracker', 'eventCat': 'Outbound Links', 'eventAct': 'Click', 'eventLbl': 'grants.nih.gov/grants/guide/notice-files/NOT-OD-00-038.html', 'eventVal': 0});" rel="external">further guidance on data and safety monitoring for phase I and phase II trials&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>. The NIMH has developed <a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="4dcead14-8d1e-4c15-b985-da3e9d17b899" href="/funding/clinical-research/nimh-guidance-on-risk-based-monitoring">guidance on risk-based monitoring</a> to assist investigators with determining the appropriate level of monitoring for a given study.</p> <h2>Required Elements of a Data and Safety Monitoring Plan</h2> <p>A DSMP should include a general description of a plan establishing the overall framework for the oversight and monitoring of a study. When formulating the DSMP, the PI, and the study team should consider the protocol, phase, intervention(s), target population, subject safety and privacy, risks and benefits involved in the study, data integrity and confidentiality, study coordination, and how the team will address each of these elements. When modifications to the DSMP are made before the trial begins (e.g., in response to the peer review or IRB review), a final IRB-approved monitoring plan must be submitted to the NIMH PO prior to the commencement of human subjects activities. The minimum required DSMP content should include the following elements.</p> <p><strong>If these elements are noted elsewhere in the application or proposal, they need not be repeated but should be referenced in the DSMP section</strong>:</p> <ol> <li>Summary of the Protocol: <ul> <li>A brief description of the study design (e.g., <a href="http://grants.nih.gov/grants/glossary.htm#Intervention" rel="external">interventions&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a>, procedures, tests and scans, biospecimen collection, interviews and focus groups, study visits)</li> <li>Primary and secondary outcome measures/endpoints</li> <li>Sample size and target population</li> <li>Inclusion/exclusion criteria and how the criteria will be evaluated</li> <li>For multi-site trials, a list of proposed participating clinical sites and data coordinating centers and a description of each site&rsquo;s role</li> </ul> </li> <li>Roles and Responsibilities (Note this must be listed in DSMP section): <ul> <li>Identification and description of individuals responsible for monitoring the trial (e.g., PI, ISM, DSMB), their roles, qualifications, and the frequency of the monitoring activities. If the monitoring entity is an ISM or a DSMB, provide the NIMH PO and Office of Clinical Research (OCR) review with a list of the proposed membership and assurances to ensure that there are no conflicts of interest with the study team or proposed institutions.</li> </ul> </li> <li>Trial Safety: <ul> <li>Description of any specific events that would preclude a participant from continuing the intervention</li> <li>Description of any procedures in place for managing any medication related issues (e.g., medication washout, allergic reactions, drug interactions, discontinuation/stoppage of medication, use of rescue mediations)</li> <li>Description of the potential risks and the measures in place to protect participants against foreseeable risks</li> <li>Description of the consent/assent procedures (e.g., by whom, how and under what conditions will a subject be consented)</li> <li>Description of the mechanisms in place to protect subject privacy (e.g., interviews will take place in a private room, whether results of testing data will be shared with participant&rsquo;s legally authorized representative, privacy for minors, secure means of communication between investigators and participant, e.g., telephone, web portal)</li> <li>Description of the trial stopping rules for the study, if any (e.g., increased suicidal ideation, greater than expected morbidity or mortality rate)</li> <li>Description of the plan for management of <a href="https://grants.nih.gov/faqs#/hs-informed-consent.htm" rel="external">incidental findings&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a> (e.g., a brain tumor or potential structural abnormality discovered during a scan)</li> <li>Description of the process for the disclosure of any conflicts of interest that may potentially challenge participant safety or bias the data and how the conflict will be managed</li> <li>For multi-center studies, a description of the procedures for ensuring compliance with the monitoring plan including requirements for data reporting across study sites</li> <li>Description of the data security in place to protect the confidentiality of the data (e.g., password protected encrypted electronic records) and any limits to confidentiality (e.g., suicidal ideation, child abuse)</li> </ul> </li> <li>Reportable Events: <ul> <li>Description of the process and timelines (e.g., hours, days) for collecting and reporting Adverse Events (AEs), Serious Adverse Events (SAEs), and Unanticipated Problems Involving Risks to Subjects or Others to appropriate monitoring and regulatory entities (See <a data-entity-substitution="canonical" data-entity-type="node" data-entity-uuid="514f7ab4-f157-49af-a21b-57bbaa29143e" href="/funding/clinical-research/nimh-reportable-events-policy">NIMH Reportable Events Policy for definitions and timeframes</a>)</li> <li>Specific plan and timeframe for reporting IRB and/or ISM/DSMB actions to the NIMH (e.g., protocol violations, non-compliance, suspensions, terminations)</li> </ul> </li> <li>Data Management, Analysis, and Quality Assurance: <ul> <li>Identification of data sources (e.g., questionnaires, medical records, biospecimen collections, audio/video recordings)</li> <li>Description of the security measures in place to protect data sources including how the data will be labeled and stored</li> <li>Quality assurance measures for subject recruitment, enrollment, enrollment targets, and for the validity and integrity of the data. <a href="https://www.fda.gov/regulatory-information/search-fda-guidance-documents/e6r2-good-clinical-practice-integrated-addendum-ich-e6r1" rel="external">E6 Good Clinical Practice (R2): 1.46&nbsp;<i class="fa-solid fa-arrow-up-right-from-square ext-link-icon"></i></a> defines quality assurance as &ldquo;All those planned and systematic actions that are established to ensure that the trial is performed and the data are generated, documented (recorded), and reported in compliance with Good Clinical Practice (GCP) and the applicable regulatory requirement(s)&rdquo;</li> </ul> </li> </ol> </div> </div> </div> </body></html> </div> </div> </article> </main> </div> <aside id="sidebar" class="layout-sidebar-second" role="complementary"> <!DOCTYPE html PUBLIC "-//W3C//DTD HTML 4.0 Transitional//EN" "http://www.w3.org/TR/REC-html40/loose.dtd"> <html><body><div class="box" data-nid="7649"> <p><a href="/funding/opportunities-announcements/clinical-trials-foas" data-entity-type="node" data-entity-uuid="2081f459-fc87-415e-a149-2c01c5305cf5" data-entity-substitution="canonical">Clinical Trials Funding Opportunity Announcements</a></p><a href="/funding/opportunities-announcements/clinical-trials-foas" data-entity-type="node" data-entity-uuid="2081f459-fc87-415e-a149-2c01c5305cf5" data-entity-substitution="canonical"><article class="media media--type-image media--view-mode-default"> <span class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <img loading="lazy" 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