A data and safety monitoring plan (DSMP) is meant to assure that each clinical investigation has a system for oversight and monitoring of the conduct of the clinical investigation. This oversight is intended to ensure the safety of the participants and the validity and integrity of the data. A DSMP should be commensurate with the risks. A DSMP can be as simple as the investigator reporting adverse event information or as complex as having a Data and Safety Monitoring Board (DSMB).

Clinical Trial Monitoring

A DSMP often includes clinical trial monitoring. Clinical trial monitoring refers to the methods used to oversee the conduct of, and reporting of data from, clinical investigations including appropriate clinical investigator supervision of study site staff. Monitoring activities include communication with the investigator and the study site staff; review of the study site’s processes, procedures and records; and verification of the accuracy of the data.

What to Include in a DSMP

A DSMP should include processes for handling the following (as applicable):

Monitoring the Progress and Safety of the Trial

• What are the potential risks and benefits for study participants?
• What is the screening process and how will it be used to protect participants?
• What are the measures to protect participants against risk?
• Who will monitor the trials, what type of information will be reviewed, what are the parameters for defining abnormal values and what is the periodicity of review?
• What are the stopping rules for the study?
• What procedures are in place for multicenter trials, if applicable?
• How will conflict of interest, or the perception of a conflict, be managed?

Reporting Unanticipated Problems

• What constitutes an unanticipated problem (include a definition, grading scale and “study relatedness” criteria)?
• What is the process for assuring that unanticipated problems are reported appropriately?
• What are the timelines for an unanticipated problem collection and reporting?

Reporting of Suspensions or Terminations

• Which actions will be reported and who ensures these actions are reported appropriately?

Assuring Data Accuracy and Protocol Compliance

• How are data accuracy and protocol compliance assured?
• What are the procedures to assure protocol adherence (i.e., protocol compliance checks, external data audits, regular data verification, etc.)?
• How are protocol deviations reported?
• How is noncompliance reported?

In addition to the principal investigator (PI), there may be other data and safety monitoring entities responsible for the DSMP.

For data monitoring, this may include the following:

• Data coordinating center or project PI (for multi-site studies)
• Commercial sponsor or contract research organization

For safety monitoring, this may include the following:

• Data safety monitoring board (DSMB)
• Medical monitor
• Cancer Center Data Safety Monitoring Council

Data and Safety Monitoring Board

A Data and Safety Monitoring Board (DSMB) is an independent group of experts that advises the study investigators. The DSMB reviews data for both safety and efficacy. The protections afforded by this review apply to both current and future research participants if the DSMB identifies the need to modify or even halt the trial. Primary responsibilities of a DSMB are to:

• periodically review and evaluate the accumulated study data for participant safety, study conduct and progress and, when appropriate, efficacy; and
• make recommendations concerning the continuation, modification or termination of the trial.

The DSMB considers study-specific data as well as relevant background knowledge about the disease, test agent or patient population under study.

Federal Regulations and DSMBs

Federal regulations provide minimal insight on DSMBs. The Code of Federal Regulations (45 CFR 46) indirectly addresses data safety monitoring, stating “When appropriate, the research plan makes adequate provision for monitoring the data collected to ensure the safety of subjects.”

The 2006 U.S. Food and Drug Administration (FDA) guidance document “Establishment and Operation of Clinical Trial Data Monitoring Committees” discusses the roles, responsibilities and operating procedures of DSMB. This document is helpful in determining whether a DSMB is needed and how it should function. 

Some government agencies that sponsor clinical research have required the use of a DSMB in certain clinical trials. Current FDA regulations, however, impose no requirements for the use in trials except under 21 CFR 50.24(a)(7)(iv) for research studies in emergency settings in which the informed consent requirement is excepted. Though it is not required, the FDA generally expects the use of DSMBs for randomized trials with mortality or major morbidity as primary endpoints.

• Federal Regulations for the Protection of Human Subjects in Research (45 CFR 46)
• Establishment and Operation of Clinical Trial Data Monitoring Committees

Responsibilities of a DSMB

The primary responsibility of the DSMB is to safeguard the interest of study participants. Therefore, the DSMB must approve the safety measures in the protocol to preserve the study credibility and facilitate the availability of timely and reliable findings to the broader clinical community. In addition, the DSMB should:

• Provide written documentation confirming review of the protocol and agreement with the study design and the data safety monitoring plan (DSMP)
• Review the progress of the study carefully and diligently. The DSMB should assure that all significant adverse events are reported according to policies and procedures
• Be available to the investigator for consultation concerning any adverse study events
• Consider the impact of newly published findings bearing on the safety profile of the study
• Provide written reports to be shared with reviewers that summarize oversight activities and recommendations, and any concerns regarding subject safety

Principal Investigators (PIs) must provide information about the DSMP and, if applicable, the DSMB in the study materials they submit for review by Brown’s Human Research Protection Program (HRPP) and Institutional Review Board (IRB) 

When a DSMB is established, the PI must submit to HRPP/IRB a description of the board; a list of DSMB members, including their affiliation and credentials; and the DSMB charter. The charter defines the responsibilities for the study PI and DSMB members and sets guidelines for the conduct of DSMB meetings. The charter is intended to be a living document. The DSMB may wish to review it at regular intervals to determine whether any changes in procedure are needed.

In addition, DSMB reports should be provided to HRPP/IRB for review as they are received.

DSMB Charter Template