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Data & Safety Monitoring Plans

Why does your study need a Data & Safety Monitoring Plan (DSMP)?

NIDDK requires that all grant applications involving human subjects (i.e., both clinical trials and observational studies) include a DSMP. The NIDDK has developed these guidelines for writing a DSMP to provide a uniform structure for all NIDDK grant applicants and grant recipients conducting human subjects’ research. See the decision tool (PPTX, <1 MB) to guide the selection of the monitoring options for your clinical study.

The study team should allocate appropriate budgetary funds to support safety activities, monitors, and monitoring board members as planned.

What is the approval process for a DSMP?

Prior to the conduct of human subject’s research, NIDDK staff must review and approve the DSMP. NIDDK may require a more detailed plan than was included in the grant application or approved by the Institutional Review Board (IRB). However, the final DSMP to be implemented must be both IRB and NIDDK approved, and this version must be documented in the grant folder at NIDDK. The investigator is required to adhere to the final IRB and NIDDK DSMP that was approved at the time of the initial award and may not implement any changes without the written prior approval of the revised DSMP by the NIDDK as well as the IRB. Investigators must update the Human Subjects Clinical Trials Information (HSCT) form with the approved version of the DSMP at the start of the study and with any approved revisions thereafter.

What type of monitoring is possible and required for NIDDK supported research?

Monitoring may be conducted by various individuals or groups and should be commensurate with the risk (including study interventions, procedures, and measurements), size, scope, and complexity of the study, and study population (including vulnerable populations and illness severity). Monitoring exists on a continuum from monitoring by the principal investigator with an independent safety monitor for low risk, small, and less complex studies such as no greater than minimal risk observational studies to the establishment of an independent data and safety monitoring board (DSMB) or observational study monitoring board (OSMB) for higher risk, complex, multi-center, or large studies, studies including vulnerable populations, and studies with more than minimal risk research assessments or interventions. In rare circumstances, the study investigator and research team alone may monitor the study. For example, the study investigator and research team may provide oversight of studies that conduct analyses on existing data and biospecimens but are designated as human subject research. Such studies require a DSMP with a focus on confidentiality. Please note that the determination of no greater than minimal risk is not up to the investigator, but is defined in 45 CFR Subpart A, Sec. 46.102 and designated by the IRB. Please reach out to your Program Officer if you would like guidance regarding your study’s risk level.

NIDDK sponsored collaborative agreements supporting observational or interventional studies (e.g., U01, UH3 awards) have an OSMB or DSMB appointed by NIDDK.

Independent Safety Monitor

The independent safety monitor is an independent scientist with relevant expertise in the health condition under study who advises the study investigators on safety and progress. If the trial or observational study is 'no more than minimal risk', it may be appropriate for the principal investigator (PI) to be involved with oversight of the study in conjunction with an independent safety monitor. In some cases, more than one independent safety monitor may be needed to monitor data and safety.

An independent safety monitor regularly reviews participant safety (including adverse events) and assesses study progress (including patient confidentiality, recruitment and retention, and data quality and management). The safety monitor must be free of any conflicts of interest, including any scientific, financial, or other conflict of interest related to the study so that independence and objectivity are maintained. (See Conflict of Interest section below) Written documentation attesting to absence of conflict of interest is required. Waivers may be granted by the NIDDK based on specific considerations and how conflicts will be managed. The independent safety monitor is proposed by the PI. However, the independent safety monitor and their qualifications must be approved by NIDDK.

Data and Safety Monitoring Board (DSMB) or Observational Study Monitoring Board OSMB)

A DSMB (for clinical trials) or OSMB (for observational studies) is an independent board of experts including scientists and biostatisticians that advise study investigators regarding the safety and progression of a study. Members should have the appropriate clinical and scientific expertise, including clinical trial design, and at least one biostatistician should be included. Additional members may include a patient advisor to provide patient perspectives as well as an ethicist for ethical considerations. The size of the Board will depend on the nature and complexity of the study but should consist of at least 3 members.

The DSMB/OSMB members should be free of conflicts of interest, including any scientific, financial, or other conflict of interest related to the study or investigators so that independence and objectivity are maintained. (See Conflict of Interest section below) Written documentation attesting to absence of conflict of interest is required. Waivers may be granted by the NIDDK based on specific considerations and specified management plans.

For NIDDK consortia under cooperative agreements (trials and observational studies) and some high-risk investigator-initiated trials, NIDDK will appoint the DSMB or OSMB and manage the meetings. For investigator-initiated studies that are not cooperative agreements or high risk, the PI will generally appoint the members of the DSMB or OSMB and manage the meetings. However, the composition and qualifications of the DSMB or OSMB must be approved by NIDDK as part of its review of the DSMP. The NIDDK program staff may request a copy of a proposed member’s CV as part of this review.

NIDDK requires monitoring by an independent DSMB or OSMB, typically comprised of external members for the types of studies listed below. Given the characteristics of these types of studies, they often require a high level of impartial scrutiny and safety monitoring. Exceptions should be discussed with the appropriate NIDDK program staff.

  • Phase 1 or 2 trials that involve masked interventions – These trials often require that clinicians involved in conducting the study remain blinded to outcome and safety data.
  • Phase 3 trials - These trials are often large, masked, involve multiple sites, and are intended to change medical practice or product labeling.
  • Multi-center clinical studies: These studies involve multiple institutions following the same protocol, which imposes a high level of complexity to ensure sites are conducting study procedures in a similar, uniform manner.
  • Clinical trials of higher-risk interventions or clinical studies where a study assessment is invasive or involves higher risk procedures: These may be trials testing higher-risk interventions such as gene transfer, drug with significant toxicities, major surgery or interventions with no or limited safety data or studies where the measured outcome or study procedure is used solely for research purposes, is invasive, and is greater than minimal risk.
  • Clinical studies involving vulnerable populations: The term “vulnerable populations” generally encompasses children, pregnant women, prisoners, elderly or terminally ill individuals, or those with diminished mental capacity. These groups have characteristics that may increase their risk of coercion, undue influence, or harm during research studies, requiring additional ethical and regulatory protections to ensure their safety and autonomy.

What are potential conflicts of interest?

Potential conflicts of interest for the Independent Safety Monitors or DSMB or OSMB members include: 1) financial conflicts; 2) publication or collaboration with study investigators in the last 3 years or currently planned; and 3) affiliation with the investigators and/or their institutions. Frequently, members are external to the investigator's department and institution, but this may not always be possible for investigator-initiated studies. If internal members are used, care must be taken to ensure that the members are independent of the investigators and can oversee the study in a rigorous and impartial manner. Members should NOT 1) be directly involved with the study in any way, including patient care for the study, 2) be a recent or active collaborator (within the previous 3 years) with any of the investigators in the current study, or 3) be under the investigators’ direct supervision or have a supervisory role over the investigators. Study investigators, including mentors on career development or training awards, should not be monitors or members.

What should be included in the Data and Safety Monitoring Plan (DSMP)?

The content of the DSMP should be designed to protect the health and safety of participants and ensure the validity and integrity of the study. DSMPs should therefore also allow for the appropriate termination of clinical studies for which significant benefits or risks have been uncovered or when it appears that the study cannot be conducted successfully. The DSMP should also specify all the details of what, how, when and by whom the data and safety monitoring activities will be conducted during the study.

NIDDK requires DSMPs to include a description of each of the following:

  • Potential risks to participants and approaches to prevent or mitigate risks
    • Adverse events/risks expected because of the underlying condition
    • Risks or known side effects of the intervention
    • Risks or complications of study procedures
    • Risks related to confidentiality and privacy, including any additional concerns related to the use of mobile devices in clinical studies
    • Actions to be taken to minimize or mitigate these risks including real time follow-up of clinically actionable events
  • Safety Reporting
    • What adverse events will be tracked, frequency of tracking, and how this will be accomplished.
    • How and by whom will adverse events be classified (for example, seriousness, expectedness, and relatedness).
    • Who has the responsibility for reporting adverse events and the roles and responsibilities of each person on the clinical study team who is involved in safety oversight and reporting.
    • A timeline for reporting of serious adverse events (SAEs) and targeted non-serious adverse events (AEs) to the entity doing the monitoring, the IRBs, NIDDK, and the FDA, if applicable. Information about investigational new drug (IND) safety reporting is available on the FDA website.
      • For all clinical studies (including low risk trials where routine program review is based on the annual progress report (RPPR), unexpected SAEs should be reported to the NIDDK Program Officer at the same time that they are sent to the IRB (e.g., within 7 calendar days of the initial receipt of information for fatal or life-threatening suspected unexpected, serious adverse events, and within 15 calendar days of receipt of information for non-fatal, non-life-threatening suspected unexpected, serious adverse events).
      • Investigators involved in multi-center clinical studies must ensure that a summary of the DSMB’s review of AEs be distributed to all site IRBs (see NOT 99-107) after each meeting.
      • Any substantive DSMB concerns, changes to the DSMP or IRB-mandated/approved actions, including changes to the protocol or informed consent, must be sent to NIDDK by the Institutional Official in real time. Otherwise, the annual RPPR should, at a minimum, provide dates of meetings and action items from all DSMB, OSMB, or other safety monitoring meetings during the previous reporting period (if applicable), and any data and safety monitoring issues that have occurred since the previous reporting period. Terms and conditions of the award may specify that full meeting minutes must be sent as an official communication in real time.
  • Safety Monitoring
    • Who or what groups of individuals is (are) responsible for study monitoring.
    • The frequency of monitoring (e.g. in real time for SAEs, and/or annually or more frequently for meetings/reports as appropriate to level of risk of the study, etc.) and how that monitoring will occur (e.g. in person or virtual/teleconference meetings and/or email communications).
    • The rationale for the proposed clinical study monitoring, considering the risk, size, and complexity of the study. (See related information above)
    • The approach to the selection of the monitors, e.g., independence, how conflict of interest will be ascertained, tracked, averted, or managed, including cases where the PI or study team serve as the only monitors.
    • For masked studies, the plan should make clear how masking is maintained and under what circumstances unmasking would occur as well as who would be unblinded.
  • Quality Assurance
    • The approach to monitor and ensure adherence to the protocol including the quality/fidelity and consistency to the intervention(s) implementation, visit completion, the quality of the data and laboratory measures (completeness/missingness and out of range values), and plans for handling any deficiencies that are uncovered.
    • How and how frequently participant accrual and retention data will be monitored, including any tracking by sub-group (e.g., age, sex, race/ethnicity). For multi-site studies, plans should be made for monitoring by site and in aggregate.
    • The approach to ensuring participant confidentiality and privacy.
  • Statistical Analysis
    • Power calculation(s) to demonstrate clinically meaningful effect estimates and feasibility.
    • Discussion of planned interim analyses for clinical trials, including adjustments for spending “alpha” on “multiple looks.” where applicable.
    • Stopping rules should also be specified where applicable. Generally, stopping rules reflect one of the following conditions: 1) there is clear evidence of harm; 2) there is no likelihood of demonstrating treatment benefit (futility); 3) there is overwhelming evidence of the benefit of treatment.
  • Conflict of Interest of Investigators
    • How any investigator conflict of interest will be handled or managed where applicable.

DSMB or OSMB Responsibilities and Meetings

For studies that have a DSMB or OSMB, there should be a charter that describes its charge and responsibilities and operating rules. (A sample DSMB charter is provided in the Templates Documents section below.) In general, the overarching role of the DSMB or OSMB is to provide oversight and monitoring of the feasibility of the study (e.g., study enrollment, retention, and overall progress), fidelity of the study (e.g., data integrity, randomization and intervention fidelity to the protocol), and safety of participants and make recommendations to address any concerns as well as whether to continue the study.

To achieve this goal, the specific responsibilities of the DSMB or OSMB should include:

  • Review the protocol, informed consent documents, and data and safety monitoring plans (DSMPs)
  • Consider major changes to the research protocol, informed consent documents and DSMPs
  • Evaluate the progress of the study, including periodic assessments of data quality and timeliness, participant recruitment, accrual and retention, participant risk versus benefit, performance of the study sites, and other factors that may affect study outcomes
  • Review SAEs and other safety reports and make recommendations regarding protection of the safety of study participants
  • Assess data integrity and confidentiality
  • Review areas of concern regarding the performance of individual sites and provide comment on actions to be considered regarding sites that perform unsatisfactorily
  • Consider factors external to the study when relevant information becomes available, such as scientific or therapeutic developments that may have an impact on the safety of the participants or the ethics of the study
  • Make recommendations for study protocol modifications or possible early termination of the study because of attainment of study objectives, safety concerns, low likelihood of showing a benefit of the intervention (futility), or inadequate performance (such as enrollment and retention problems)
  • Review the interim analysis of efficacy for trials, if appropriate, in accordance with stopping rules as defined in the protocol
  • Provide input on the desirability of proceeding to the full-scale study at the completion of a feasibility phase, if appropriate
  • Assess the potential impact of ancillary studies on the integrity of the parent study; and
  • Monitor clinical ancillary studies unless an independent monitoring system is used.

The DSMB or OSMB should meet regularly and as appropriate to the level of risk of the study. These meetings will have an open session, which includes the PI and the study statistician. The open session generally focuses on study conduct (e.g., recruitment and retention; data quality; and safety) and allows the members to interact with study leadership and raise issues about the conduct of the study. Outcome data for clinical trials should not be presented in the open session. Following the open session, the members meet in closed session. For trials, the unmasked study statistician(s) will present outcomes data and answer questions. The executive session should allow the DSMB or OSMB to have time to deliberate without any study staff present. There should be a summary of each meeting, noting the date/time and means of communication (e.g., in-person, teleconference, etc.), participant list, and recommendations. The PI should communicate the deliberations of the DSMB to any other investigators involved with the study, the IRB, NIDDK, and, if appropriate, applicable regulatory agencies. The PI must notify NIDDK in real time of any actions taken by the IRB.

Template Documents

The documents below are meant to provide assistance for NIDDK grant applicants and are simply examples that can be customized and used as needed for each individual study. There is no requirement to use these particular documents, and investigators are free to use their own materials.

Training Resources

The following are training resources for investigators developing an OSMB or DSMB for their clinical research study or trial:

Last Reviewed October 2024