Purpose

To provide grant applicants with guidance and information on the development of data and safety monitoring plans (DSMP) for NIH-defined clinical trials funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA).

Introduction

In June 1998, the National Institutes of Health (NIH) issued a policy on data and safety monitoring  requiring oversight and monitoring of all NIH funded clinical trials. This monitoring is to be commensurate with the risks, nature, size, and complexity of the trial. For purposes of this policy, NIH defines a clinical trial as a research study in which one or more human subjects are prospectively assigned  to one or more interventions  (which may include placebo or other control) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes . Interventions include drugs/small molecules/compounds; biologics; devices; procedures (e.g., surgical techniques); delivery systems (e.g., telemedicine, face-to-face interviews); strategies to change health-related behavior (e.g., diet, cognitive therapy, exercise, development of new habits); treatment strategies; prevention strategies; and, diagnostic strategies. Clinical trials are also used to determine whether new interventions are safe, efficacious and effective, and to evaluate the effects or impact of particular biomedical or behavioral interventions.  In June 2000, the NIH issued further guidance on data and safety monitoring for phase I and phase II trials. 

The NIAAA policy on data and safety oversight fulfills this mandate by ensuring that an appropriate monitoring structure is in place for all NIAAA-supported clinical trials (e.g., grants, contracts and cooperative agreements) and that NIAAA is informed in a timely manner of all recommendations that derive from monitoring activities. This policy is not intended to usurp the role of the local Institutional Review Board (IRB) or other regulatory and monitoring entities (e.g., Food and Drug Administration).  Release of funds for clinical trials is dependent upon compliance with this policy.

Data and Safety Monitoring Plan

A Data and Safety Monitoring Plan (DSMP) is required for all NIAAA-funded, NIH-defined clinical trials and optional for all other human subjects research. At a minimum, the DSMP must include the following critical elements as outlined below. In addition to NIAAA specific elements, this list includes the elements outlined in the current NIH SF424(R&R). Please ensure each element is addressed in the DSMP and include the DSMP in your grant application. If one of the elements does not apply to your study, please respond N/A.

1. A description of the individual or group responsible for monitoring the trial (e.g., PD/PI, Independent Safety Monitor/Designated Medical Monitor, Independent Monitoring Committee, Safety Monitoring Committee, Data and Safety Monitoring Board, etc.).
2. The overall framework for safety monitoring including a general description of the information that will be monitored.
3. The frequency of monitoring, including any plans for interim analysis and stopping rules.
4. Name of the responsible party (e.g., Principal Investigator, Study Physician if different than PI) who will a) distinguish a serious adverse event (SAE) from a non-serious adverse event (AE); b) provide an initial determination for potential Unanticipated Problems (UPs); and c) provide attributions (causality and severity). 
5. Confirmation that SAEs and UPs during the treatment and follow-up phases will be reported to the local IRB, DSMB, NIAAA within 48 hours of being notified and if under an Investigation New Drug application or Investigational Device Exemption, in accordance with the FDA reporting requirements of 21CFR312.32.
6. Description of how adverse events, SAEs, and UPs will be followed, the duration of follow-up, and by which staff member.
7. A statement confirming that all progress reports (e.g., annual RPPR, monthly, quarterly, etc.) will follow the terms outlined in the Notice of Award and at a minimum include the following: 1) a summary of all AEs, 2) confirmation of adherence to the NIAAA-approved DSMP, 3) a summary of any data and safety monitoring issues encountered since the prior reporting period, 4) a description of any changes in the research protocol or DSMP, 5) DSMB (or similar oversight committee, if applicable) meeting updates/minutes, and 6) new or continuing IRB approvals (if applicable).
8. A statement confirming that appropriately trained clinical staff will be present or on-call when study procedures take place, based on level of risk and consistent with approved protocol, policies, and guidance from the local IRB and/or other regulatory and monitoring entities. Examples include (but are not limited to) the administration of alcohol, other drugs and/or medications; invasive or other study procedures or testing; etc. The types of trained personnel (e.g., nurse, nurse practitioner, physician assistant, physician, etc.) should be stated.
9. For studies in which alcohol is administered, provide assurance that NIAAA guidelines for the administration of alcohol will be followed. These guidelines can be found here: Alcohol Administration Human Laboratory Studies.
10. Describe the plan for referral to treatment during follow-up phases for any research participant who may require additional intervention due to risks such as significantly increased alcohol consumption or serious psychiatric/medical symptoms.
11. Provide a statement indicating that IRB approval(s) of the study will be provided to NIAAA prior to screening study participants. IRB approval letter(s) should be submitted through the site’s Authorized Organizational Representative (AOR) to the NIAAA Grants Management Officer (GMO) before initiating a proposed clinical trial.   

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