What is a Data and Safety Monitoring Plan (DSMP)?
What is a Data and Safety Monitoring Board (DSMB)?
What are the responsibilities of a DSMB?
Are there regulations that apply to DSMBs?
What is a Data and Safety Monitoring Plan (DSMP)?
A Data and Safety Monitoring Plan (DSMP) describes how the Principal Investigator plans to oversee the human subject's safety and welfare. The IRB-HSR requires that all research protocols/protocol applications that are not exempt under Federal regulations contain a DSMP. The level of detail in the plan should be based upon the degree of risk to the subjects.
When you use Protocol Builder to create your protocol or protocol application a DSMP template is added to your protocol or protocol application. There are customized templates for different studies depending on risk level. As you answer questions using Protocol Builder the correct template is selected for you based on your responses. For instance, the DSMP template added for an expedited studies presenting minimal risk to subjects will be different from the DSMP added for a full board study presenting greater than minimal risk to subjects.
The DSMP includes:
- Definition of SAEs, Unanticipated Problems and Protocol Violations.
- Reporting timelines and guidelines including stopping rules as appropriate
- Plans for monitoring the data and safety information for the study, including who has overall responsibility and the frequency of the review.
- Assessment of potential risks for study subjects, including screening process and how it will be used to protect the subjects.
- Any specific procedures that are in place for activities such as monitoring and reporting in multisite trials.
What is a Data Safety Monitoring Board?
A Data Safety Monitoring Board (DSMB) is an independent group of scientists, physicians, statisticians and others that are not employees of the commercial drug company that are appointed to oversee the data and safety of subjects in the study. This group of experts advises the sponsor and the study investigators. The members of the DSMB serve in an individual capacity and provide their expertise and recommendations.
Other names for committees that monitor accumulating data are Data Monitoring Committee (DMC) and Data Safety Monitoring Committee (DSMC).
DSMBs provide ongoing evaluation of research date to assure participant safety and study integrity. They generally operate under a DSMB charter.
- A group of members of the study team who review data and safety do not meet the criteria of a DSMB. Study team members should not be on the DSMB. Remember DSMBs are INDEPENDENT of the study.
- Departmental groups who review data and safety for studies in their department do not meet the criteria for an independent DSMB
- Medical monitors from a commercial drug company are not a DSMB. The do provide critically important safety oversight function but are not a DSMB.
- Safety review committee within a commercial drug company also provide important safety oversight functions but do not meet the criteria for a DSMB.
- UVa Cancer Center Data and Safety Monitoring Committee is not meet the criteria for an independent DSMB
- A Site Monitoring Group or a Safety Oversight Committee of individuals hired by the sponsor to oversee site performance does not meet the criteria for a DSMB.
- The overall PI of a multi-site trial or a single individual who may serve as the medical monitor does not meet the criteria for a DSMB.
The DSMB should be comprised of individuals who are independent of the study, institution or commercial drug company. This independent group of scientists, physicians, statisticians and others are tasked with overseeing the data and safety of subjects in the study.
What are the responsibilities of the 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 in order to preserve the study credibility and facilitate the distribution and availability of timely and reliable findings to the broader research community including the sponsor, study investigators, and IRBs.
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 study per the DSMB Charter
- Provide to the sponsor a written report summarizing oversight activities and recommendations, and any concerns regarding subject safety. The sponsor is generally responsible for providing this report to the study team. Sponsors or study teams generally send these reports to the IRB.
Are there regulations that apply to DSMBs?
There is very little guidance in the regulations related to the operation of a DSMB.
In a 2006 guidance document, the FDA defined a DSMB/DMC as “a group of
individuals with pertinent expertise that reviews on a regular basis accumulating data from one or more ongoing clinical trials. The DMC advises the sponsor regarding the continuing safety of trial subjects and those yet to be recruited to the trial, as well as the continuing validity and scientific merit of the trial”.
https://www.fda.gov/regulatory-information/search-fda-guidance-documents/establishment-and-operation-clinical-trial-data-monitoring-committees. This document includes roles, responsibilities and operating procedures for DSMBs.
The DSMB is responsible for evaluating research data on an ongoing basis to assure participant safety and study integrity per regulations at 45 CFR 46.111 (a)(6).
While it is important to remember that all non-exempt HSR studies require a DSMP and careful safety monitoring, it is also important to know that not all studies require DSMB.
Some examples of studies that likely would not require DSMB oversight are:
- Studies with small numbers of subjects
- Studies in early phase non-randomized trials with limited safety concerns
- Studies where rapid enrollment and short term endpoints are not appropriate for DSMB oversight.
A DSMB may be needed.
- If there is there a large study population, or the study is multi-site.
- If the trial intended to provide definitive information about effectiveness and/or safety of a medical intervention? (Phase 2 or 3)
- Prior data suggest that the intervention being studied has the potential to induce unacceptable adverse events, toxicities or risks?
- Study is evaluating evaluate mortality or another major endpoint, such that inferiority of one treatment arm has safety and efficacy implications?
- Would it be ethically important for the trial 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?
A DSMB should be considered if any two or more criteria above questions are met.
In addition, if the study is being funded by the NIH, the IRB recommends checking with the center providing funding to determine if they require or perhaps provide a DSMB for this study.
Multi-Site Studies
A UVA investigator may conduct a multi-site study which includes non-UVA sites., also called relying sites.
The DSMP requirements are based on the role of the UVA investigator.
1. Multi-Site Trials where UVA investigator is the sponsor (IND/IDE is held by the UVA
investigator): The DSMP must include:
a) Promptly review safety information received from sites and analysis of reports for significance.
b) Plan for keeping all investigators informed of new observations re. drug or device, including information on safe use.
c) Plan for notifying FDA and investigators of reportable events.
d) Plan for reporting to the UVA IRB of UPs, terminations of the IND/IDE or termination of participation in the trial by a specific relying site investigator.
e) Robust monitoring plan that should include the following elements:
• Centralized monitoring:
o Example: study sites send source documents for comparison with
CRFs.
• On-site monitoring:
o Example: UVA sponsor or designated person visits site. Per FDA inspectors, a site visit must occur at least once a year or once during course of study if study duration is less than 12 months. CRO or independent monitor is a good option.
• Self-monitoring:
o Example: The UVA sponsor should provide a monitoring tool to be completed by site at prescribed frequency, with results
reported to UVA sponsor.
o Self-monitoring by site investigator alone is unlikely to pass FDA muster for adequate monitoring by UVA sponsor of multi-site
investigation involving non-UVA sites.
2. Multisite Trials where UVA investigator is ‘Coordinating Investigator’ (study is not
under an IND/IDE): The DSMP should specify:
a) UVA as coordinating site is only providing information to all investigators who each determine if event should be reported to their IRB.
b) Participating sites (or CRO) will promptly provide the coordinating site with
copies of adverse event reports that require expedited reporting to their local IRBs
c) Coordinating site (or CRO) will forward adverse events reports requiring
expedited reporting to participating sites
d) Coordinating/Lead investigator will review data summary reports of adverse
events on a regular basis, at least annually
e) Coordinating/ Lead investigator will submit data summary reports to the Data
Safety Monitoring Committee/Board for review as per their guidelines