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NIMH Clinical Research Toolbox

NIMH Clinical Research Toolbox

The NIMH Clinical Research Toolbox serves as an information repository for NIMH staff and the clinical research community, particularly those receiving NIMH funding. The Toolbox contains resources such as NIH and NIMH policy and guidance documents, templates, sample forms, links to additional resources, and other materials to assist clinical investigators in the development and conduct of high-quality clinical research studies.

Use of these templates and forms is optional; the resources can be used as-is or customized to serve study team needs. In cases where institutions provide research teams with institution-specific templates and forms for clinical research documentation, NIMH expects researchers to follow their institutional policies for document use. Nevertheless, the materials on this page can be consulted to assure that study teams are meeting NIMH expectations.

Clinical Research Start Up

Protocol Templates

NIMH encourages investigators to consider using one of the protocol templates below when developing a clinical research protocol. In cases where an institutional review board (IRB) has a recommended or required protocol template, reviewing the documents included below is still suggested as there may be sections that a study team may opt to include in an effort to develop a comprehensive research protocol.

NIH has developed a Clinical e-Protocol Writing Tool to support the collaborative writing and review of protocols for behavioral and social sciences research involving humans, and of phase 2 and 3 clinical trial protocols that require a Food and Drug Administration (FDA) Investigational New Drug (IND) or Investigational Device Exemption (IDE) Application.

This clinical trial protocol template is a suggested format for Phase 2 and 3 clinical trials funded by NIH that are being conducted under a FDA IND or IDE Application.

Investigators for such trials are encouraged to use this template when developing protocols for NIH-funded clinical trial(s). This template may also be useful to others developing phase 2 and 3 IND/IDE clinical trials.

This clinical trial protocol template is a suggested format for behavioral or psychosocial clinical trials funded by NIH. Investigators for such studies are encouraged to use this template when developing protocols for NIH-funded clinical trial(s). This template may also be useful to others developing behavioral of psychosocial research studies.

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Protocol Associated Documents

This template provides a recommended structure for developing consistent instructions on study procedure implementation and data collection across participant and clinical site activities. It details the study’s organization, operations, procedures, data management, and quality control.

This template provides a recommended structure for a plan to conduct internal or independent review of Good Clinical Practices (GCP), human subject safety, and data integrity throughout the lifecycle of a study.

Informed Consent Materials

Often study teams will be provided with informed consent form templates and guidance on requirements for the informed consent process by their institutions. Below is additional guidance and materials to support a thorough informed consent process.

The NIMH Data Archive (NDA) receives de-identified human subjects data collected from hundreds of research projects across many scientific domains, and makes these data available to enable collaborative science. This NDA sample informed consent language for data sharing can be adapted when using one of the NDA platforms.

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Regulatory Documents and Associated Case Report Forms

Regulatory Document Checklists by Study Type
The following checklists are intended to help the investigator community identify a set of core documents to be organized within a single study specific folder, either electronically, hard copy, or a mixture of both formats. NIMH encourages study teams to verify what additional documents, or alternative formats of the documents in the checklists, their institution and IRB require.

Study teams can use this checklist to compile essential documents for the conduct of a NIMH-funded study that does not meet the NIH definition of a clinical trial and is research on human subjects.

Study teams can use this checklist to compile essential documents for the conduct of a NIMH-funded NIH defined clinical trial that does not involve an investigational drug or device.

Study teams can use this checklist to compile essential documents for the conduct of a NIMH-funded NIH defined clinical trial with an investigational drug or device that is not under a FDA IND or IDE.

Study teams can use this checklist to compile essential documents for the conduct of a NIMH-funded NIH defined clinical trial or non-clinical trial with an investigational drug or device under a FDA IND or IDE.

Necessary Documents for Reportable Events

This document provides a log template for documenting reportable events. The types of events that require reporting may vary by institution, IRB, sponsor, state, and other factors.

This document provides a log template for tracking all protocol deviations/violations across a study.

This document provides a log template for tracking subject-specific protocol deviations/violations. If captured electronically, subject-specific deviation logs can be exported into a study-wide deviation log.

This document provides a log template for tracking all adverse events (AEs), including serious adverse events (SAEs), across a study.

This document provides a log template for tracking adverse events (AEs), including serious adverse events (SAEs), for each subject. If captured electronically, subject-specific AE logs can be exported into an electronic study-wide AE log.

Necessary Documents for Studies with Pharmacy/Investigational Product

This FDA form should be signed by the investigator prior to study initiation to provide certain information to the sponsor, and assure that he/she will comply with FDA regulations related to the conduct of a clinical investigation of an investigational drug or biologic.

This document provides a sample standard operating procedures (SOP) template to document how investigational product (IP) will be received, stored, monitored, labeled, dispensed, and destroyed.

This document provides a log template for recording the daily temperatures for investigational product (IP).

This document provides a log template for capturing all investigational product (IP) dispensed to and returned by participants for the duration of the study.

This document provides a log template for capturing all investigational product (IP) dispensed to an individual participant and returned by that participant. This log is typically placed in each subject’s study binder (study blind is maintained, if applicable).

Screening and Enrollment Logs and Materials

This document provides a log template for all potential participants who have completed initial screening procedures (i.e. phone screens or internet screening surveys; typically, prior to signing written informed consent). This log should capture the number of participants eligible for an official screening visit, as well as the number ineligible with the reasons for ineligibility listed.

This document provides a log template for chronologically documenting the participants who have been enrolled in the study.

This document provides a sample checklist to customize according to protocol-specific eligibility criteria. A qualified and appropriately-delegated study team member should sign and date to confirm eligibility once all criteria have been assessed. If criteria are assessed on different visit dates, this checklist should be reformatted to reflect which criteria are assessed on which visit dates, and who is responsible for assessing them.

This document provides a sample form template for documenting the informed consent process.

Additional Participant Tracking Logs and Materials

This document provides a log template for recording each participant’s medications throughout the study. This log is typically reviewed at all subject study visits and is located in each participant’s study binder.

This document provides a log template for tracking the collection and storage of research samples.

Staff Training and Administrative Tracking Logs and Materials

This document provides a log template for documenting completion of Good Clinical Practice (GCP) training requirements. Note: all NIH-funded investigators and staff who are involved in the conduct, oversight, or management of clinical trials should be trained in Good Clinical Practice (GCP), consistent with principles of the International Conference on Harmonisation (ICH) E6 (R2). Individual institutions may require GCP training regardless of funding source or clinical trial status.

This document provides a log template for documenting staff trainings for study-specific procedures (i.e., trainings for diagnostic interview administration, study protocol adherence, phlebotomy, outcomes measures, OSHA Bloodborne Pathogens, etc.).

This document can be used to record all study staff members’ significant study-related duties, as delegated by the Principal Investigator (PI). Most studies opt to use a log format, such as the Delegation of Authority log, because it captures study staff on one page and includes space to document the addition or removal of specific study tasks for individual staff members.

This document is typically completed by the clinical site monitor to document dates and purpose of clinical site monitoring visits.

This document provides a sample template for generating notes-to-file, which are written to acknowledge a discrepancy or problem with the study’s conduct, or for other administrative purposes (such as to document where study materials are stored).

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On-Site Monitoring

Even though it is the NIMH’s expectation that grantees will provide adequate oversight of their clinical research, NIMH Program Officials may require additional levels of on-site monitoring conducted by NIMH staff. Clinical monitoring helps ensure the rights and well-being of human subjects are protected; the reported clinical research study data are accurate, complete, and verifiable; and the conduct of the study is in compliance with the study protocol, Good Clinical Practice (GCP), and the regulations of applicable agencies.

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).

To promote clinical research that is compliant with GCP and human subject regulations, the CREST Program includes phone conversations, email consultation, and/or site visit(s) from NIMH staff, as needed, to assess and provide written feedback and recommendations on planned or ongoing clinical research protocols. Documents relating to the conduct of the clinical research, such as current IRB approved protocols, informed consent documents, source documents, and drug accountability records, as applicable, may be reviewed for compliance with applicable Federal regulations, and institutional and IRB policies.

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 serious adverse events; see NIMH Risk-Based Monitoring Guidance); a study intervention under a 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 study lifecycle, although projects are generally identified and selected for the program at the initiation of the grant.

Clinical Research Education, Support, and Training (CREST) Program Overview

This page provides a description of the NIMH CREST Program’s purpose, process for inclusion, and operating procedures.

Site Visits

This document provides a sample matrix of regulatory documents for drug/device studies that CREST monitors look at on site.

This document provides a sample matrix of regulatory documents for non-drug/device studies that CREST monitors use on site.

This document provides a sample site initiation visit agenda to be customized by the Principal Investigator (PI) and site monitor prior to the visit.

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Human Subjects Research

This section provides resources, including policy and guidance documents related to the conduct of human subject research. The resources included below represent those frequently of interest to NIMH investigators, specifically: overviews of human subject research, data and safety monitoring, human subject risk, reportable events, and recruitment. There are numerous other NIH webpages devoted to human subjects research; see Research Involving Human Subjects, NIH Human Subjects Policies and Guidance, and New Human Subjects and Clinical Trial Information Form.

The Office for Human Research Protections (OHRP) has developed graphic aids to help guide investigators in deciding if an activity is research involving human subjects that must be reviewed by an IRB under the requirements of the U.S. Department of Health and Human Services (HHS) regulations (45 CFR 46).

This NIMH webpage presents items which investigators should pay particular attention to when proposing to use human subjects in NIMH-funded studies.

Human Subjects Risk

This NIMH guidance aims to clarify risk level definitions and the NIMH’s monitoring expectations to mitigate these risks. This guidance will assist study teams in determining the level of data and safety monitoring that should be established for a study based on the probability and magnitude of anticipated harm and discomfort.

Data and Safety Monitoring for Clinical Trials

The policies, guidance and documentation in this section outline NIMH expectations for data and safety monitoring of clinical trials. For human subject research that does not meet criteria for NIH clinical trial designation, investigators still have an option of including a data and safety monitoring plan (DSMP; i.e., in studies that may have significant risk to participants). The initial links below apply to all NIMH-funded clinical trials, while the second section provides documentation for clinical trials under the oversight of a NIMH-constituted data and safety monitoring board (DSMB).

All Clinical Trials

This NIMH policy outlines NIH and NIMH expectations for data and safety monitoring of clinical trials. This policy also assures that the NIMH is notified by NIMH-funded researchers in a timely manner of all directives emanating from monitoring activities.

This guidance was created to aid investigators developing a data and safety monitoring plan (DSMP) to ensure the safety of research participants and to protect the validity and integrity of study data in clinical trials supported by NIMH. This guidance applies to data and safety monitoring for all NIMH-supported clinical trials (including grants, cooperative agreements, and contracts).

This policy establishes expectations for the monitoring of NIMH-supported clinical trials by Independent Safety Monitors (ISMs) and/or independent data and safety monitoring boards (DSMBs) to assure the safety of research participants, regulatory compliance, and data integrity.

Trials Reviewed by a NIMH-Constituted DSMB

The materials below are for studies designated for review by a NIMH-constituted DSMB. Study teams developing materials for a study-constituted independent DSMB may benefit from reviewing the data report template and the protocol amendment memo.

This letter provides an orientation to working with the NIMH Clinical Trials Operations Branch which supports study teams reporting to the NIMH DSMB.

This template may be used when submitting a study protocol or consent document amendment to the NIMH DSMB.

Reportable Events

This policy outlines the 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; non-compliance (serious or continuing); suspensions or terminations by monitoring entities (i.e., Institutional Review Board (IRB), Independent Safety Monitor (ISM)); and suspensions or terminations by regulatory agencies (i.e., Office for Human Research Protections (OHRP) or the Food and Drug Administration (FDA)).

(For associated documentation, see: Guidance on Regulatory Documents and Associated Case Report Forms)

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Recruitment

This policy is intended to support effective and efficient recruitment of participants into all NIMH extramural-funded clinical research studies proposing to enroll 150 or more subjects per study, and all clinical trials, regardless of size.

This policy outlines NIMH expectations regarding the establishment of recruitment plans and milestones for overall study enrollment, and as appropriate, recruitment plans for females and males, members of racial and ethnic minority groups, and children, as well as recruitment reporting.

This NIMH FAQ document provides responses to several of the most common questions surrounding RMR.

These “points to consider” are meant to serve as a resource as investigators plan a clinical research study and a NIMH grant application. It also outlines common barriers that can impact clinical recruitment and retention.

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Additional Resources and Trainings

Good Clinical Practice Training

Based on the NIH Good Clinical Practice (GCP) policy, all NIH-funded clinical investigators and clinical trial staff who are involved in the design, conduct, oversight, or management of clinical trials are requirement to be trained in GCP. Below are links to some GCP courses that meet NIH GCP training expectations.

The NIH Office of Behavioral and Social Sciences Research (OBSSR) offers a self-paced Good Clinical Practice (GCP) training course with nine video modules. Learners complete knowledge checks and exercises throughout the course.

NIAID has created a self-paced Good Clinical Practice (GCP) training course that includes four modules. These modules educate the learner on the history of human subject research, the regulatory framework, planning human subject research, and conducting human subject research.

This NDAT course includes 12 modules based on International Council for Harmonisation (ICH) Good Clinical Practice (GCP) and the Code of Federal Regulations (CFR) for clinical research studies in the U.S. The course is self-paced and takes approximately six hours to complete.

Data Sharing

The following notices and links present NIMH expectations and tools for data sharing.

This notice establishes NIMH’s data sharing expectations, including the request to include a detailed data sharing plan as part of grant applications.

This notice encourages investigators in the mental health research community to utilize data collection protocols using a common set of tools and resources to facilitate sharing, comparing, and integration of data from multiple sources.

The NIMH Data Archive is an informatics platform for the sharing of de-identified human subject data from all clinical research funded by the NIMH.

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Additional NIMH Links and Contacts:

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