Data and Safety Monitoring for Clinical Research

Overview of Data and Safety Monitoring

All clinical investigations, including physiologic, toxicity, and dose-finding studies (phase I); efficacy studies (phase II); efficacy, effectiveness and comparative trials (phase III), involving greater than minimal risk to participants (i.e., full Committee review) are, at a minimum, required to develop a data and safety monitoring plan to assure the safety and welfare of the research subjects.

The method and degree of monitoring needed is related to the degree of risk involved. A Data Safety Monitoring Board (DSMB) is usually required to determine safe and effective conduct and to recommend conclusion of the trial when significant benefits or risks have developed or the study is unlikely to be concluded successfully. Risk associated with participation in research must be minimized to the extent practical.

Monitoring should be commensurate with size and complexity of the study. Monitoring may be conducted in various ways or by various individuals or groups, depending on the size and scope of the research effort. These exist on a continuum from monitoring by the Lead Researcher or a UCI-based DSMB for a small phase I study to the establishment of an independent DSMB for a large phase III clinical trial.

Data Safety Monitoring Plan

At a minimum, a Data Safety Monitoring Plan (Appendix S) should be developed and included as part of the electronic IRB Application. The Plan should contain the following information:

  1. An explanation of the plan to monitor progress and safety;
  2. Specific predetermined safety reviews to be conducted by an assigned board, committee or individual monitor;
  3. Depending on the complexity of the research, the plan may include assessments of data quality, timeliness, participant recruitment, accrual and retention.
  4. A description of the plan to assure compliance with reporting of adverse events and/or unanticipated problems involving risk to participants or others. This should include:
    • A description of the process for detecting and reporting serious and unexpected adverse events and/or unanticipated problems involving risk to participants or others;
    • A description of who will be monitoring and collecting the adverse events (e.g., LR, Coordinator, etc.);
    • Specification of who will be notified of an adverse event (e.g., IRB, NIH, FDA, sponsor, etc.)
    • A reporting plan indicating the timing of reports;
    • A plan for annual reporting of adverse events if study duration is longer than one year; and
  5. A description of the plan to assure data accuracy and protocol compliance.

In addition, various issues may be considered, as applicable;

  1. The assessment of individual events of particular concern,
  2. Changing the eligibility criteria if the risks of the intervention seem to be higher than anticipated,
  3. Altering the product dosage and/or schedule if the adverse events observed appear likely to be reduced by such changes,
  4. Instituting screening procedures that could identify those at increased risk of a particular adverse event,
  5. Requiring that current and future study participants are informed of newly identified risks via changes in the consent form,
  6. If applicable, assessing whether the study should be terminated earlier than planned, and
  7. The study data may also be reviewed for rates of recruitment, non-compliance, protocol violations and dropouts.

When a Data Safety Monitoring Board (DSMB) is required

The following research situations require the oversight of a Data Safety Monitoring Board (DSMB) rather than an individual monitor:

  1. The study is intended to provide definitive information about the effectiveness and/or safety of a medical intervention;
  2. Prior data suggests that the intervention under study has the potential to induce a potentially unacceptable toxicity;
  3. The study is evaluating mortality or another major endpoint, such that inferiority of one treatment arm has safety as well as effectiveness implications; or
  4. It would be ethically important for the study to stop early if the primary question addressed has been definitively answered, even if secondary questions or complete safety information were not yet fully addressed.

Composition of DSMB

The composition of a DSMB must include:

  1. Multidisciplinary representation, including physicians from relevant medical specialties and biostatisticians. This may include other experts such as bioethicists, epidemiologists and basic scientists.
  2. Members who are free of significant conflicts of interest (i.e., financial, intellectual, professional, or regulatory).
  3. The appropriate size depending on the type of study and types of expertise needed.
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