Data and Safety Monitoring for Human Subjects Research - PRO116
Procedure
Investigator Responsibilities - Describes the data and safety monitoring plan (DSMP), specifying the following patent features:
- Whether a Data Safety Monitoring Board (DSMB) will review the data (Note: Phase III federally funded trials require a DSMB.);
- Areas of expertise (e.g., biostatistician, experienced clinician, ethicist), relationship to study (i.e., internal, external, or independent) and qualifications of individual(s) performing the monitoring (Note: for DoD Component sponsored research see GUI339);
- Timing or basis of interim analyses, if any;
- Proposed endpoints (e.g., primary, secondary and stopping rules);
- Reporting mechanisms for communication of findings/determinations to federal agencies, sponsor, and IRBs (Note: Data and safety monitoring reports and communications must be forwarded to the IRB within 10 working days of receipt.);
- Protocol-specific information on reporting of adverse events to the IRB, and to the sponsor and FDA if applicable;
- Incorporation of UAB’s IRB policy and procedure on reportable problems (see POL006 UAB Policy to Ensure Prompt Reporting of Unanticipated Problems Involving Risks to Subjects or Others to the IRB, PRO106 UAB Procedure to Ensure Prompt Reporting of Unanticipated Problems Involving Risks to Subjects or Others);
- Includes the following information in the IRB Application eForm (FOR200) at the time of continuing review:
- Copies of all data and safety monitoring reports since the last review;
- Summaries of all UAB and non-UAB IRB-reportable adverse events and/or unanticipated problems since study inception.
- Submits any alteration to the DSMP to the IRB by using amendment procedures (see PRO148 Procedure for Review of Modifications to Previously Approved Research by the Convened IRB).
OIRB Responsibilities
Reviewing Staff: - At the time of initial review:
- Reviews and verifies that the IRB Application eForm (FOR200) submission contains sufficient information on data and safety monitoring to permit IRB review;
- Checks whether the submission is a Phase III federally funded study—if so ensures a DSMB is included for data and safety monitoring;
- Requests additional information to supplement the application if it does not adequately address the DSMP;
- Provides additional assistance to investigators when the research plan does not adequately address the DSMP.
- At the time of continuing review:
- Reviews the IRB Application eForm (FOR200), including copies of data and safety monitoring reports received since the last IRB review and a summary of all UAB and non-UAB reportable adverse events and unanticipated problems that have occurred since the inception of the study.
- Receives and reviews any modifications for any changes to the DSMP (see PRO148).
- Receives and reviews data and safety monitoring reports for completeness and determines whether they are unanticipated problems involving risk to subjects or others per POL006 UAB Policy to Ensure Prompt Reporting of Unanticipated Problems Involving Risks to Subjects or Others to the IRB.
- Receives and reviews all reportable adverse events and unanticipated problems (see POL006, PRO106).
- Refers all reports to the IRB Chair or designee for review.
- Schedules data and safety monitoring reports for convened IRB review, as determined by the Chair or designee.
IRB Responsibilities
IRB Chair or Designee: - Reviews all data and safety monitoring reports as they are received.
- Reviews reportable problems.
- Refers reports to the convened IRB.
Primary Reviewer(s): - Reviews and prepares to present at the time of initial review:
- DSMP in relation to the size, complexity, and level of risk for the research being performed;
- Whether the following criteria are met for imposing DSMB requirement:
- Phase III federally funded study; or
- Large study population;
- Multiple study sites when investigators enroll small fractions of the participants separately;
- Highly toxic therapies or dangerous procedures (e.g., gene therapy or gene transfer);
- High expected rates of morbidity or mortality;
- High chance of early termination (e.g., early stopping rules for significant evidence of benefit or harm).
- If the above criteria are not met, whether the following additional criteria are met for monitoring either by the investigator or independent individual(s):
- Low risk;
- Continuous, close monitoring with prompt reporting of toxicity information to IRB, FDA, and sponsor (e.g., Pilot, Phase I or II studies).
- Areas of expertise (e.g., experienced clinician, biostatistician, ethicist), relationship to study (i.e., internal, external, independent) and qualifications of individuals(s) performing the monitoring relative to the research being conducted;
- Summary of the oversight activities (e.g., timing or basis of interim analyses, endpoints, stopping rules, reporting mechanisms to oversight bodies, adverse event and unanticipated problem reporting);
- Whether the plan incorporates UAB policy and procedures for reportable problems (see POL006, PRO106);
- Reviews and presents to the IRB at the time of continuing review:
- Data and safety monitoring information received since the last review;
- Summary of all reportable adverse events and unanticipated problems that have occurred during the trial;
- Whether the DSMP remains adequate and appropriate in relation to the size, complexity, and level of risk for the research being performed.
IRB:
At the time of initial review and after presentation by the Primary Reviewer: - Discusses and determines whether the DSMP is adequate based on the following criteria:
- Description and qualifications of the monitor(s);
- Timing or basis of interim analyses, if any;
- Endpoints and stopping rules, if any;
- Reporting mechanisms to federal agencies, sponsor, and IRB (Note: Data and safety monitoring reports and communications must be forwarded to the IRB within 10 working days of receipt by the investigator.);
- Protocol-specific plans for reporting adverse events to the IRB, and to the sponsor and FDA if applicable;
- Incorporation of POL006, PRO106;
- Makes recommendations for additional enhancements for the safety and welfare of the participants involved in the research, including independent monitoring, if criteria are not met;
- Requests additional information, as deemed necessary, if criteria are not met.
At the time of continuing review and after presentation by the Primary Review Team: - Reviews and discusses data and safety monitoring reports and information received since the last review;
- Discusses summary of all reportable problems that have occurred during the trial;
- Determines whether the DSMP remains adequate;
- Receives and reviews data and safety monitoring reports referred by the Chair.
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