Data and Safety Monitoring Guidelines
To assist grant applicants conducting or planning to conduct trials of behavioral or pharmacological interventions, human laboratory studies in which alcohol and/or drugs are administered, or human laboratory or clinical studies involving patients in alcohol treatment, the National Institute on Alcohol Abuse and Alcoholism (NIAAA) has developed guidelines for data and safety monitoring (DSM) plans, in accordance with NIH requirements. The purpose of the DSM plan is to ensure the safety of participants in these kinds of studies.
Grant applicants who plan to conduct a trial of a behavioral or pharmacological intervention, a laboratory study where human subjects will receive alcohol and/or drugs, or human laboratory or clinical studies involving patients in alcohol treatment must submit a DSM plan as part of the research grant application. The DSM plan must be approved by NIAAA before the study begins and should be included in its entirety in the grant application. The Scientific Review Group will review the DSM plan and any comments or concerns will be included in the summary statement. The responsibility for compliance with the DSM plan rests with the grant recipient.
These guidelines do not take the place of Institutional Review Board (IRB) guidelines, Food and Drug Administration (FDA) requirements, or special NIH guidelines.
In June of 1998, NIH issued a policy stating that "each Institute or Center (IC) in NIH should have a system for the appropriate oversight and monitoring of the conduct of clinical trials to ensure the safety of participants and the validity and integrity of the data for all NIH-supported or conducted clinical trials." According to this policy, data and safety monitoring is required for all types of clinical trials, including physiologic, toxicity, and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III); etc. It includes all types of intervention studies, whether medication or non-medication (e.g., behavioral, prevention, diagnostic) trials. Monitoring should be commensurate with the study risks. This policy provides each IC with the flexibility to implement the requirement for data and safety monitoring as appropriate for its clinical research activities (http://grants.nih.gov/grants/guide/notice-files/not98-084.html). As such, NIAAA also requires data and safety monitoring for human laboratory studies in which alcohol and/or drugs are administered and human laboratory or clinical studies involving patients in alcohol treatment.
Adverse events (AEs) are defined as any untoward medical occurrence that may present itself during treatment or administration of an intervention, and which may or may not have a causal relationship with the treatment. Serious adverse events (SAEs) are defined as any medical occurrence that results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; creates persistent or significant disability/incapacity, or a congenital anomaly/birth defects. Adverse events and serious adverse events may occur in medication and non-medication trials. In non-medication trials, for example, AEs may include suicidal ideation/attempts, drug or alcohol overdose/withdrawal, etc. Additional information about definitions and reporting of AEs and SAEs are available at:
Elements of a DSM plan
The overall elements and specifics of the DSM plan may vary depending on the potential risks, complexity, and nature of the trial. Research grant applications that involve trials of behavioral or pharmacological interventions, human laboratory studies in which alcohol and/or drugs are administered, or human laboratory or clinical studies involving patients in alcohol treatment, must include a detailed DSM plan. The PHS 398 application instruction indicates where to place this description.
At a minimum the DSM plan must include the following components:
The DSM plan must designate an experienced, qualified professional (usually the PI) who can distinguish a serious adverse event (SAE) from a non-serious adverse event (AE) and an unanticipated problem.
- This experienced, qualified professional may be the PI, an independent investigator, or a team of experts.
- The DSM plan must indicate that serious adverse events and unanticipated problems will be reported to the local IRB and to the NIAAA project officer within 48 hours
- The DSM plan must indicate that an annual report will be submitted to the NIAAA Project Officer summarizing all adverse events.
- The DSM plan must specify that female subjects who are pregnant, nursing, or not using effective methods of birth control will be excluded from studies involving the administration of alcohol and/or drugs.
- The DSM plan must indicate that trained personnel will be present or on call when human laboratory studies of alcohol or other drug intake are conducted.
- The DSM plan must indicate the follow up plans for serious adverse events and unanticipated problems.
- For studies in which alcohol is administered, the DSM plan must indicate that NIAAA guidelines for the administration of alcohol will be followed. These guidelines can be found at the following web address: http://www.niaaa.nih.gov/research/guidelines-and-resources/administering-alcohol-human-studies.
- If the study has a follow-up phase, there must be a specific plan for referral to treatment during follow-up of any patient requiring additional intervention due to significantly increased alcohol consumption or serious psychiatric/medical symptoms.
- The DSM plan must indicate that all adverse events and unanticipated problems during follow-up will be reported (SAEs within 48 hours) to the IRB and NIAAA.
- The DSM plan must briefly describe the procedures for data quality assurance and confidentiality.
- Phase III clinical trials must have an independent data and safety monitoring board. Phase I and II studies that have multiple clinical sites, are blinded or employ particularly high risk interventions or vulnerable subjects may require a DSMB at the discretion of NIAAA.
Review of DSM plans by NIAAA staff
The NIAAA Project Officer is responsible for reviewing and approving DSM plans. The review focuses on the quality of the process that the investigator plans have in place to ensure the safety of the participants and obtain reliable results. The review is based on the adequacy with which the plan covers the essential elements outlined above. Following review, specific recommendations are made for approval as is, approval with recommended changes, or disapproval. The NIAAA Project Officer assigned to the grant is available to assist the PI in revising and finalizing the DSM plan. In especially complex cases, the NIAAA DSM Panel may also convene to review the DSM Plans of an application. In this case, the committee will evaluate the areas described above while taking into account the unique aspects of the protocol.
According to NIH policy, the detailed monitoring plan must be included as part of the protocol and must be submitted to the local IRB and reviewed and approved by the funding Institute and Center (IC) before the trial/study begins. The responsibility for compliance with the DSM plan rests with the grant recipient. The Notice of Grant Award will not be issued or will be issued with restrictions until the DSM plan has been properly finalized and approved by the PI's Institutional Official. This approval can be done electronically if necessary.
For questions or comments please contact:
Raye Litten, Ph.D.
National Institute on Alcohol Abuse and Alcoholism
5635 Fishers Lane, MSC 9304
Bethesda, MD 20892-9304
Tel: (301) 443-0636