Components of a Data Safety Monitoring Plan
The requirements for a data-safety monitoring plan must include four essential elements:
- plan for monitoring the progress of the trial and the safety and welfare of participants;
- plans for ensuring compliance with the reporting requirements for unanticipated problems involving risk to subjects or others (including but not limited to serious adverse events);
- plans for ensuring that any temporary or permanent suspension of the research will be reported to the IRB; and
- plans for ensuring the accuracy and security of the collected data and compliance with the IRB-approved protocol.
All studies require a data safety monitoring plan, even minimal risk studies whose only procedure is review of existing medical records. Many investigators only consider subject safety in their monitoring plan but a data-safety monitoring plan is incomplete without inclusion of the plans for ensuring the accuracy, integrity and security of the emerging data. Unless the data that is collected is valid and secure so that confidentiality is protected, valid conclusions will not be possible. Conclusions based on faulty, invalid data fail to contribute to scientific knowledge and will benefit no one.
Includes the methods for monitoring and ensuring the accuracy, security and validity of the data.
Includes the methods to ensure the safety of the subjects. The details and protections for this part of the plan should be calibrated to the likely harms associated with the research.
Requirements for an Adequate Data Safety Monitoring Plan
Studies that don't require a data monitoring committee
Phase I clinical trials and observational studies usually only require oversight by a single individual. Depending on the structure of the study, this could be either the principal investigator, the steering committee chair or the study medical monitor. Even though a formal committee is not required, the plan should be robust.
- Clear eligibility criteria that ensure enrollment of subjects with an appropriate level of risk to benefit.
- Establishment of baseline level of organ dysfunction (when appropriate)
- On-study safety evaluations and evaluation schedule appropriate for the detection of emerging safety concerns.
- Criteria and procedures for dose modification (drug trials) in the event of an adverse event or disease progression.
- Criteria for discontinuing or suspending enrollment or even the entire trial in the event of an emerging safety concern.
- Complete analytic plan for both efficacy and safety endpoints that ensures that the trial is adequately powered to achieve the state objectives.
Study Design and Implementation:
- Case report forms with sufficient detail to ensure capture of relevant details of adverse events.
- Clear directions for reporting unanticipated problems involving risk to participants to the relevant IRB(s), sponsor(s) and regulatory agency(ies).
- Adequate plan for data management that ensures that case report forms are submitted, entered, processed, summarized and monitored at an appropriate frequency
- Ongoing data and safety review procedures with clear delineation for reporting responsibilities
- Definitions of potential conflicts of interests for investigators, steering committee members, and DMC members (when applicable)
The guidance above is based upon the recommendations in Guidelines for data and safety monitoring for clinical trials not requiring traditional data monitoring committees Clin Trials 3: 314-319, 2008.
Requirements for an adequate data safety monitoring plan: studies that require a data monitoring committee
In addition to the criteria listed above, Phase II and Phase III randomized, blinded trials involving life-threatening diseases will always require an external Data Monitoring Committee (DMC) also referred to as a Data Safety Monitoring Board (DSMB). An internal data monitoring committee usually will suffice for Phase II or Phase III trials that are open-label.
Susan Ellenberg's book Data Monitoring Committees in Clinical Trials has the most thorough discussion of the various issues for developing data safety monitoring plans. The StAR initiative has recommendations for data safety monitoring specifically targeting pediatric clinical trials. Clinical trials and studies subject to NIH oversight need to comply with their requirements. Those conducting FDA-regulated studies should familiarize themselves with the FDA's guidance.
References: Data Safety Monitoring
- Ellenberg SS, Fleming TR, and DeMets DL. Data monitoring committees in clinical trials. Chichester, West Sussex J. Wiley; 2002.
- Ellenberg S, et al., and StaR Child Health Group. Standard 3: data monitoring committees. Pediatrics. United States; 2012;129 Suppl 3:S132-7.
- FDA. Guidance for Clinical Trial Sponsors; Establishment and Operation of Clinical Trial Data Monitoring Committees
- FDA. Guidance for Clinical Investigators, Sponsors, and IRBs: Adverse Event Reporting to IRBs: Improving Human Subject Protection
- NIH Policy for Data and Safety Monitoring
- (NIH) Further Guidance for Phase I and Phase II Trials
- Pocock SJ. Current controversies in data monitoring for clinical trials. Clin Trials. England; 2006;3(6):513-21
- Wilhelmsen L. Role of the Data and Safety Monitoring Committee (DSMC). Stat Med. England; 2002;21(19):2823-9.
- Fleming TR, Ellenberg S, and DeMets DL. Monitoring clinical trials: issues and controversies regarding confidentiality. Stat Med. England; 2002;21(19):2843-51.