NIA Policies for Data and Safety Monitoring in OAIC-Funded Human Subject Studies

Background

NIA studies involving more than minimal risk should ensure that participants' safety is protected and that study results are likely to contribute meaningfully to scientific understanding. To achieve these goals, policies are needed for OAIC-funded studies, which do not undergo standard NIH peer review.

Definitions

A study involving more than minimal risk is one in which the probability and magnitude of harm or discomfort anticipated in the research are greater than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests (see 45 CFR 46). A study need not involve a clinical trial to be considered more than minimal risk. NIA will generally accept an IRB's assessment of a study's level of risk. In unusual cases, NIA may request a DSMP for studies not considered more than minimal risk by an IRB. 

OAIC-funded means a study that receives the majority of its funding through the OAIC. Such studies are typically supported by a Pilot/Exploratory Studies Core (PESC), Resource Core (RC), or Research Education Component (REC). OAIC-funded studies do not typically include External Projects of a Resource Core, which receive the majority of their funding from other sources and, therefore, are subject to the data and safety monitoring policies of those sources.

Data and Safety Monitoring Plan

Each OAIC-funded study involving more than minimal risk must have an NIA-approved Data and Safety Monitoring Plan (DSMP) prior to its initiation. A DSMP should include, at a minimum, descriptions of the items listed below. Investigators are encouraged to use the DSMP Template for OAIC-Funded Studies (MS Word, 22K).

1. BRIEF STUDY OVERVIEW
   1. Include title, principal investigator (PI), OAIC supporting component (i.e., PESC, RC, REC), expected start/end dates, inclusion/exclusion criteria, study design and procedures including any intervention(s), main outcomes, and analytic plan.
2. PARTICIPANTS' SAFETY
   1. Potential Risks and Benefits for Participants
      1. Describe the potential risks and benefits for study participants and society.
      2. Include a brief description of specific information collected from individual subjects that will be shared with them; e.g., abnormal test results, genetic information
   2. Study Staff Procedures for Collection, Assessment, and Notification of Serious Adverse Events (SAEs), Adverse Events (AEs), Unanticipated Problems (UPs), and Protocol Deviations
      1. Provide definitions of AEs and SAEs related to the study or studies covered by this DSMP. Assessment of AEs and SAEs should include classification of severity, expectedness, and relatedness to the study intervention(s). Refer to the NIA Adverse Event and Serious Adverse Event Guidelines (MS Word, 66K) for more information.
      2. Notification
         1. Studies satisfying the NIH definition of a clinical trial
            1. All unexpected SAEs should be reported to the OAIC Director(s), study principal investigator (PI), Safety Officer/DSMB, IRB, and NIA program official within 48 hours of the investigators becoming aware of the event, or sooner if required by the institution.
            2. The study PI should submit a summary of all other SAEs, AEs, UPs, and protocol deviations, along with any corrective plans to prevent recurrence, to the OAIC Director(s), Safety Officer/DSMB, and NIA program official in routine data and safety reports. (See Frequency below). Reporting to IRB should follow institutional policies.
         2. Studies not considered a clinical trial according to the NIH definition
            1. SAEs, AEs, UPs, and protocol deviations should be reported to the OAIC Director(s), study PI, Safety Officer/DSMB, and IRB according to institutional policies. The NIA program official need not be notified unless upon request.
   3. Protection Against Study Risks
      1. Describe how adverse events and other risks to participants in the study will be mediated. Specify any events that would preclude a participant from continuing with the study. Also include informed consent procedures and measures to protect participants against risk during the study. See Informed Consent Template (MS Word, 109K) and Informed Consent Checklist (MS Word, 54K) for more information.
3. PROCEDURES FOR DATA AND SAFETY MONITORING
   1. Individual(s) responsible for reviewing data and safety reports
      1. Reports should be reviewed by either an independent Safety Officer (SO) or a Data and Safety Monitoring Board (DSMB). NIA generally considers monitoring by study staff as an inadequate level of safety monitoring in studies involving more than minimal risk.
         1. The SO or DSMB members should not be directly involved in the conduct of the study nor have scientific, proprietary, financial, or other interests that may affect independent decision-making. The SO or DSMB members need not be external to the institution, except as indicated below.
         2. It is acceptable to establish a standing DSMB composed of members within an institution even though an independent SO would suffice.
         3. If studies are proposed that require expertise not already represented on a standing DSMB, NIA may require additional DSMB member(s) for such studies.
         4. If a study is proposed that is considered high risk, NIA may require a DSMB composed of members entirely outside the institution.
      2. Data and safety reports must also be reviewed by the OAIC Director(s) or a named designee authorized to act on behalf of the OAIC Director(s). In the yearly progress report to NIH, the OAIC Director and/or designee should certify that s/he has read all data and safety reports and that corrective actions have been taken where there were concerns, or that no concerns were noted.
   2. Verification of eligibility criteria
      1. Prior to study initiation, the SO/DSMB should verify that each study will have an inclusion/exclusion criteria checklist that is appropriate for the study and that will be used for each subject.
   3. Frequency of review of data and safety monitoring reports
      1. Reports should be reviewed at a frequency commensurate with risk, generally every 3-6 months. Unscheduled reviews may be conducted if necessary at the request of the OAIC Director, study PI, SO/DSMB, or NIA program official.
   4. Content of data and safety monitoring reports
      1. Reports should include, at a minimum, study status; descriptions of all SAEs, AEs, UPs, and protocol deviations; and any abnormal laboratory, imaging, and other test results. The study PI should attest that to his/her knowledge the list of SAEs, AEs, UPs, and protocol deviations is complete or that no SAEs, AEs, UPs, and protocol deviations occurred. Reminder: Enrollment of a subject who fails to meet eligibility criteria is a protocol deviation.

Procedures for Communicating DSMPs and related information

DSMPs and related information for all OAIC-funded studies involving more than minimal risk should be submitted to the NIA program official for approval prior to initiation of the study. Submission should occur in the following ways:

1. In the competing OAIC application
   1. Include a general DSMP in the Overall section of the application that describes general principles for data and safety monitoring that will be applied to all OAIC-funded studies involving more than minimal risk. Some items listed in the Data and Safety Monitoring Plan section above may not be applicable in a general DSMP.
   2. Additions or modifications to the general DSMP that are specific to an individual component as a whole should be included in those respective sections of the application. For example, if all studies supported by the PESC will entail additional or different DSMP provisions compared to those in the general DSMP, describe the PESC-specific DSMP in the PESC section of the application. Otherwise, simply refer to the general DSMP.
   3. Data and safety monitoring information specific to an individual study should be submitted as described in the next section.
2. After submission of the competing OAIC application and any time during the OAIC award
   1. For each proposed OAIC-funded study involving more than minimal risk, send an email to the NIA program official with the following items:
      1. Study-specific DSMP
      2. A curriculum vitae and conflict of interest/non-disclosure agreement for the SO or each DSMB member, if not sent previously
      3. IRB approval
   2. At any time after submission of the competing application, revisions to an OAIC's general DSMP or component-specific DSMP may be submitted to the NIA program official for approval.

OAICs can expect written notification from the NIA program official if the DSMP and SO/DSMB membership are approved.

Annual Progress Reports

Annual progress reports to the NIA should include the following information for all OAIC-funded studies conducted within the reporting period:

• Status of each study
• A statement by the OAIC Director certifying that s/he, or a named designee authorized to act on behalf of the OAIC Director, has read all data and safety reports and that corrective actions have been taken where there were concerns, or that no concerns were noted.

Additional Guidance

Investigators are encouraged to review the Clinical Research Study Investigator's Toolbox for additional information and suggested forms and templates.