Clinical Research Study Investigator’s Toolbox
The purpose of the NIA Clinical Research Toolbox is to provide a Web-based informational repository for investigators and staff involved in clinical research. The Toolbox contains templates, sample forms, guidelines, regulations and informational materials to assist investigators in the development and conduct of high quality clinical research studies.
- Study Startup
- NIA Guidance on Clinical Trials
- Forms and Templates
- Glossary of Terms
Data Safety and Monitoring
As depicted in the NIA Guidance on Clinical Trials, NIA is responsible for overseeing the data and safety monitoring of the clinical research it supports. Data and safety monitoring of a clinical trial is commensurate with the risks posed to the study participants and with the size and complexity of the study.
Applicants requesting support for any intervention study must complete "PHS Human Subjects and Clinical Trials Information" form of the SF424 (R&R), describe a data and safety monitoring plan (DSMP), which discusses the need for an independent data and safety monitoring body or justifies why such a body is not needed to monitor the study and proposes an alternative safety monitoring mechanism. For example, for a single-site, low risk study, the PI may propose a local safety monitor, while a multi-site, higher risk study might propose a Data and Safety Monitoring Board (DSMB).
- Data and Safety Monitoring Plan (DSMP) Template and Guidelines (MS Word, 37K) and DSMP Checklist (MS Word, 43K) were developed to assist investigators in preparation of a sound data and safety monitoring plan. All clinical trials require study-specific monitoring procedures to ensure participant safety and data integrity. The DSMP outlines procedures that investigators and study staff will follow when implementing a clinical trial. Investigators submitting grant applications for clinical trials are required to include a general description of the DSMP as part of the research grant application.
- Guideline for Budgeting for Data and Safety Monitoring Activities (MS Word, 25K) aids investigators in budgeting for an independent DSMB or a Safety Officer when preparing the budget section of a grant application.
The National Institutes of Health (NIH) advocates making available to the public the results and accomplishments of the activities that it funds. NIH assures that research resources developed with public funds become readily available to the broader research community in a timely manner for further research, development, application, and secondary data analysis. The expectation is that this will lead to products and knowledge of benefit to public health. To ensure that future research can build on previous efforts and discoveries, the National Institutes of Health (NIH) has developed a data sharing policy effective October 1, 2003, for applicants seeking NIH funding of $500,000 or more in direct costs in any one year. The policy expects final research data, especially unique data, from NIH-supported research efforts be made available to the investigators. The NIH policy on data sharing applies to:
- Basic research, clinical studies, surveys, and other types of research supported by the NIH.
- Human subjects and laboratory research.
- Data not produced with NIH funding but used in an NIH-supported activity in some instances.
Investigators are expected to include in their grant application a brief description of how final research data will be shared, or explain why data-sharing is not possible (for example: human subject protection concerns). Please see NIH’s Example Plan (MS Word, 55K) for a template you may modify to fit the data you plan to share.
Initial Proposal Concept Form (MS Word, 39K) - This form should be used to advocate for an initiative by the Division of Geriatrics and Clinical Gerontology (DGCG) for a clinical trial or trials that exceed $2 million in direct costs in any year of funding. DGCG Clinical Trials Advisory Panel, a task force of the National Advisory Council on Aging (NACA), will evaluate the concept proposals in October – November of each Fiscal Year and will provide its recommendations to DGCG, NACA, and to the NIA Director on initiatives for large clinical trials.
The clinical protocol is a document that describes how a clinical study will be conducted by detailing the objective(s), design, methodology, statistical considerations and organization of a clinical study, and describes methods used to ensure the safety of the study participants and integrity of the data collected.
Protocol (MS Word, 93K) - The Clinical Intervention Study Protocol Template outlines a clinical study protocol and provides guidance on important content to include in each section. The template can be downloaded as an MS Word file for adaptation by the study investigator.
Manual of Procedures
A Manual of Procedures (MOP) is a handbook that details a study’s conduct and operations as well as facilitates consistency in protocol implementation and data collection across study participants and sites. It operationalizes the study protocol and describes each step of the study and how it is to be executed. A copy of the MOP should be provided to each member of the Study Team. Ideally, the MOP would contain an adequate amount of detail that any individual(s) at any site(s) could run the study consistently with only the information contained in the MOP and its appendices.
The NIA recognizes the importance of a MOP and has developed documents to assist principal investigators in writing their study MOP. Investigators with a multi-site study are required to submit a MOP, while single-site study investigators are strongly encouraged to review the MOP and determine which sections are necessary in order to ensure the study procedures are performed as intended. The Guidelines below provide details on each section of the MOP, while the MOP Outlines are an overview listing the sections that are most relevant in those types of studies.
- Manual of Procedures (MOP) Outline – Multi-Site (MS Word, 30K)
- Manual of Procedures (MOP) Guidelines – Multi-Site (MS Word, 179K)
- Manual of Procedures (MOP) Outline – Single-Site (MS Word, 27K)
- Manual of Procedures (MOP) Guidelines - Single-Site (MS Word, 170K)
The following documents can also be found within the MOP template:
- Screening Log provides documentation of all individuals who were evaluated for participation in a research study. The log typically contains a unique identification number for each person screened along with individuals’ initials, age, gender, race and ethnicity, screening date, and eligibility status.
- Schedule of Events presents the activities that take place at each contact with the participant.
- Protocol Deviation Log provides participant-specific documentation of missed visits and other actions that deviate from the protocol.
The consent process provides individuals with sufficient information for making informed decisions about participation in a clinical research study. The following documents are provided as a tool to assist NIA investigators for developing a comprehensive informed consent:
- Informed Consent Template (MS Word, 115K) provides a general outline of a study specific informed consent form (ICF). It is critical that investigators consult with their local IRB for any institution-specific templates and/or requirements regarding the format and content of the consent form.
- Informed Consent Checklist (MS Word, 55K) presents required and additional elements of the consent forms as set forth in Code of Federal Regulations.
- Informed Consent Version Tracker (MS Excel, 20K) provides a template with two examples of tools that sites may use to track informed consent versions; this helps minimize the use of expired versions and the occurrence of consent deviations.
Data Safety and Monitoring Boards
The Data and Safety Monitoring Board (DSMB) is an independent group of experts that advises the NIA Director and the study investigators. The members of the DSMB serve in an individual capacity and provide their expertise and recommendations. The need for DSMB oversight is based on assessment of the study’s overall risk. Investigators may propose a DSMB in their grant application, or NIA may require that a DSMB be established following consideration of review panel’s comments, NIA’s National Advisory Council on Aging (NACA) advice, and/or input from NIA staff.
- Sample Data and Safety Monitoring Board Charter (MS Word, 24K) The DSMB Charter describes the responsibilities of the DSMB to ensure ongoing, independent study review and assure the study is conducted according to the highest scientific and ethical standards.
- DSMB Conflict of Interest and Confidentiality Statement (MS Word, 20K) - All members of the DSMB are required to be independent of the studies being reviewed and need to certify this by signing a DSMB Conflict of Interest and Confidentiality statement.
- DSMB Reports Templates are provided as a guide to facilitate the development of comprehensive reports for submission to the DSMB. The DSMB typically approves the final content and format of the reports.
Additional Startup Tools
- Recruitment and Retention Tips (MS Word, 33K) describe approaches to recruitment and retention of older individuals from diverse ethnic and racial groups in clinical research studies.
- Data Management Tips (MS Word, 30K) help to ensure adequate data management processes and procedures in a clinical study. Investigators are encouraged to use Data Management Tips to describe how data will be handled in the study.
- Best Practices for Data Coordinating Centers– This Compendium, developed by the National Heart Lung and Blood Institute (NHLBI) provides helpful tips for clinical researchers and other stakeholders for developing large, multisite clinical trial programs.
Investigators must include in their application proposed adverse event (AE) and serious adverse event (SAE) definitions and discuss their monitoring and reporting. All clinical trials of drugs and biological products conducted under an Investigational New Drug Application (IND) must use definitions of adverse events and adverse reactions and follow the reporting requirements established by 21 Code of Federal Regulations (CFR) Part 312.32. Trials of medical devices conducted under an Investigational Device Exemption (IDE) must use the definitions and reporting requirements established by 21 CFR 812. All other interventional studies must propose their definitions of adverse events and their reporting procedures. See the NIA Guidance on Clinical Trials for additional information.
- Adverse Event Form ( MS Word, 38K or screen-readable PDF, 69K) provides a template for a study form for collecting information about adverse events that is reviewed by safety monitoring bodies.
- Serious Adverse Event Form ( MS Word, 31K or screen-readable PDF, 769K) provides a template for a study form for collecting information about serious adverse events. The form includes major components of the Food and Drug Administration (FDA) Form 3500.
- AE/SAE Process Flow ( MS Word, 79K or screen-readable plain text file, 4K) illustrates how adverse events and serious adverse events are handled within a study.
The NIA Safety Training Course (available below), an online training venue, provides an overview of human subject safety surveillance and reporting requirements in clinical research studies. The intent of the course is to help clinical study investigators and staff understand and implement NIA and regulatory requirements for safe, high quality clinical research. The topics covered include Good Clinical Practice (GCP), Human Subject Protections, Adverse Events and Unanticipated Problems, Safety Monitoring and Reporting Requirements, Safety Monitoring and Oversight: Data and Safety Monitoring Boards (DSMBs) and Safety Officers, Regulatory Requirements and Responsibilities of Principal Investigators, and Data and Safety Monitoring Plans. The course requires about 40 minutes to complete.
Forms and Templates
Site Signature Log - Delegation of Authority Log ( MS Excel, 47K or screen-readable PDF, 294K) A record of all study personnel and their specific responsibilities, signatures, and dates of involvement during the conduct of a clinical research study.
Note to File Template (MS Word, 20K) - Used by clinical site staff to document protocol deviations or other discrepancies identified during the conduct of the clinical research study and plans for resolution/prevention.
Sample Visit Flow and Schedule (MS Word, 25K) – The visit schedule tracks an individual participant’s progress through the study and helps to ensure that visits take place during the protocol-specified timeframe. The visit flow provides an overview of the activities that take place at each study visit, and may be customized for each study site.
Study Drug/Investigational Product Tracker (MS Excel, 12K) - Used to track study drug/investigational product disposition and accountability by the clinical research site. For multi-site studies under an investigational new drug (IND) application, this tracker could be used by coordinating centers to track the overall distribution of investigational product.
Study Drug/Investigational Product Compliance Log (MS Word, 30K) - Used to track study drug/investigational product disposition and accountability for each individual participant. This form may be used to track protocol adherence via amount dispensed and returned and is designed to be used in conjunction with the Study Drug/Investigational Product Tracker. May also be used to track study drug/investigational return or destruction.