Version Date: August 3, 2011
Guidance on developing a data safety monitoring plan
Federal regulations require that IRBs determine whether data and safety monitoring is necessary and, if so, whether the research protocol makes adequate provision for monitoring the data collected to ensure the safety of participants.
The HS-IRBs require that all studies involving more that minimal risk to subjects have a data and safety monitoring plan. In some cases, a formal data and safety monitoring board or committee may also be required.
Data Safety Monitoring Plans (DSMPs) vary depending on the nature, size, and complexity of the protocol; expected risks of the research; and population being studied. If the study involves a small number of participants, is conducted at only one site, and/or the range of possible study events having an important impact on risks and benefits to participants is narrow, the principal investigator (PI) or a group of investigators could perform the monitoring functions. However, if a study is larger, more complex, and/or higher risk, a monitor/monitoring group or Data and Safety Monitoring Board (DSMB) may be required.
When developing a data and safety monitoring plan, investigators should address the following:
What are the key elements of a DSMP?
A DSMP should describe the following:
- The type of data or events to be captured under the monitoring plan
- The name(s) of the person(s) who will be responsible for monitoring the data collected (i.e. study accruals, protocol deviations, protocol violations, unanticipated problems, adverse events) and their respective roles (e.g. investigators, research sponsor)
- The frequency of assessments/analysis of data or events captured by the monitoring plan (e.g. a periodic time interval or after a specific number of participants are enrolled)
- The time frame for reporting unanticipated problems, adverse events, protocol deviations, and protocol violations
- Definition of specific events or stopping rules dictating when some action is required. Stopping rules are predetermined guidelines used to determine that the study should be altered or stopped based on review of study-related events occurring during the conduct of the study, specific study endpoints, and the decisions prompted. For example, studies may be stopped when there is greater than expected morbidity or mortality rate or when the experimental arm in a comparison study is shown to be better or worse statistically than the standard care arm.
- Procedures and time frames for communicating outcomes of monitoring reviews to other participating sites, the IRB, study sponsor and/or indicated entities (e.g. NIH, FDA)
- Plans to monitor adherence to the IRB-approved protocol and assure the validity and integrity of data
When is a Data and Safety Monitoring Board or Committee necessary?
In general, a DSMB may be the most appropriate way to monitor data and safety for studies that involve:
- Large numbers of subjects where risk may be better assessed through statistical comparisons of treatment groups
- Blinded study treatment groups where the validity and integrity of the study may be adversely affected by having an individual or group associated with the design and conduct of the study break the blind
- Multiple clinical sites where there is a need for investigators to submit reports of adverse events to a central reporting entity, such as a coordinating center or statistical center, responsible for preparing timely summary reports of adverse events for distribution among the clinical sites, and to the IRBs
- High risk interventions where death or severe disability is a major risk of research participation
- Controlled trials with mortality or major morbidity as a primary or secondary endpoint where increased morbidity or mortality may be better assessed through statistical comparisons among treatment groups
More information can be found at the following links:
NIH Policy requires data and safety monitoring for all NIH funded clinical trials. The divisions within the Institute have each established policies, procedures, guidelines etc. to implement and comply with the general NIH policy. [See guidance for Data Monitoring Plans and Data Monitoring Committees
- NIH Policy for Data and Safety Monitoring
- NIH Policies and IC Guidance for Data and Safety Monitoring of Clinical Trials