Data and Safety Monitoring for Clinical Research

All clinical investigations involving greater than minimal risk to participants are, at a minimum, required to develop a data and safety monitoring plan to assure the safety and welfare of the research subjects.

In addition, the IRB Chair retains the right to require a monitoring plan for a clinical investigation involving no more than minimal risk, should it be determined appropriate based on the type of risk involved in the study.

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 should be developed and included as part of the 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

  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.

Data Safety Monitoring Plan (DSMP)

Data Safety Monitoring Board (DSMB)

What is a DSMP:

  • A DSMP describes how the Lead Researcher plans to oversee the research participant’s safety and welfare and how adverse events will be characterized and reported.

When is a DSMP required:

  • A DSMP is required when the research meets the definition of a clinical investigation.
  • Generally the study involves greater than minimal risk.
  • The IRB has the authority to request a DSMP for other clinical research studies with appropriate justification.

A DSMP should consider:

  • The size,
  • Complexity, and
  • Types of potential of risk involved in the research.

The DSMP must include:

Composition and Responsibilities:

  • Identification of a monitor or DSMB, if applicable;
  • A description of how risks are minimized;
  • A description of how risks are reasonable in relation to anticipated benefits;
  • A description of the plan to monitor progress and safety;
  • Depending on the complexity of the research, the plan may include assessments of
    data quality, timeliness, participant recruitment, accrual and retention.
  • A description of the plan to assure compliance with reporting of adverse events and/or unanticipated problems involving risk to participants or others.
    This may 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, Research Coordinator, Research Nurse, etc.);
    • Specification of who will be notified of an adverse event (e.g., IRB, NIH, FDA, LR, etc.);
    • A reporting plan indicating the timing of reports; and
    • A plan for annual reporting of adverse events if the study will go on longer than
      one year.

What is a DSMB:

  • A DSMB describes how a formally appointed independent group will conduct interim monitoring of accumulating data from research activities to assure the continuing safety of research participants, relevance of the study question, appropriateness of the study, and integrity of the accumulating data.

When is a DSMB required:

  • A DSMB may be required for some research projects based on the degree of risk involved in the research

A DSMB should be considered when:

  • The study is intended to provide definitive information about the effectiveness and/or safety of a medical intervention;
  • Prior data suggests that the intervention under study has the potential to induce a potentially unacceptable toxicity;
  • The study is evaluating mortality or another major endpoint, such that inferiority of one treatment arm has safety as well as effectiveness implications; or
  • 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.

The DSMB must include:

Composition:

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

Responsibilities:

  • Conduct initial review of the proposed research to assure quality study conduct;
  • Review procedures to assure quality of study conduct including data management and quality control procedures;
  • Evaluate the quality of ongoing study conduct by evaluating the study accrual, compliance with eligibility, participant adherence to study requirements, and accuracy and completeness of data;
  • 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;
  • Recommend early termination based on efficacy results;
  • Recommend termination due to unfavorable benefit-to-risk or inability to answer study questions;
    • Recommend continuation of ongoing studies;
  • Consideration of overall picture; primary and secondary analysis;
  • Modify sample sizes based on ongoing assessment of event rates; and
  • Review final results.

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