III.13

Data and Safety Monitoring Plans

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PURPOSE

1. The purpose of this policy and procedure is to describe the review of data and safety monitoring plans.

SCOPE

2. This standard operating procedure is applicable to investigators, CPHS members and ORSC Staff.

DEFINITION

3. Minimal risk: A research study is said to be minimal risk when the probability and magnitude of harm and/or discomfort are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Minimal risk studies generally include research involving surveys, questionnaires, blood samples, MRI scans, exercise testing in low risk populations, ECGs, and other such non-interventional studies.

POLICY

4. An appropriate data and safety monitoring plan is one of the regulatory criteria for approval. Research proposals should include adequate provisions for monitoring of data collected for scientific validity and safety of research subjects. The monitoring plan for a particular research study depends on the complexity of the research study and the possibility of potential harm to subjects.

5. For research involving no more than minimal risk, provisions for data and safety monitoring are not needed to protect research subjects. In general, research involving not more than minimal risk does not require a data and safety monitoring plan.

PROCEDURE

6. Submission: Data and safety monitoring plans are submitted by principal investigators (PI) at the time of protocol submission in iRIS.

7. Review of Data and Safety Monitoring Plans - During initial and continuing review of research, CPHS considers if a data and safety monitoring plan is required. CPHS considers factors such as the risk, size, and complexity of the proposed research to determine if a research study should have a formal data and safety monitoring board. The CPHS also reviews the composition and qualifications of the DSMB members and frequency of DSMB meetings.

7.1. Some studies must have a DSMB; the CPHS makes the final determination if a DSMB is required. Some of the factors that CPHS considers in making this determination are:

1. Phase IIb, Phase III and Phase IV studies – Phase IIb, Phase III and Phase IV studies that involve life-threatening or serious morbidity require an independent DSMB. Early trials of high-risk treatment studies and trials in vulnerable populations may require either a DSMB organized by the Sponsor or a UTHealth appointed DSMB. A DSMB may not be required if the study risk is low or if the duration of a study is too short to allow for proper DSMB monitoring.
   
   
2. Level of risk and complexity – The level of risk and complexity of the proposed research are considered when determining if a DSMB is required. Examples of factors that increase risk and complexity include: a large study population; multiple study sites where it may be difficult to recognize patterns of problems; highly toxic therapies; dangerous procedures; high expected rates of morbidity or mortality in the study population; and high chance of early study termination.

8. Who Performs Safety Monitoring - The Data Safety Monitoring Plan should state who will assume monitoring responsibility. This will depend on the type and risk of the research study and may include the investigator, experts within the department or institution, independent consultants, the sponsor or a combination of the above. Some examples include, but are not limited to:

1. Principal Investigator – For a research study involving moderate increase over minimal risk, it may be appropriate for the Principal Investigator to manage the data and safety monitoring. Continuous close monitoring by the Principal investigator may be an adequate and appropriate format for monitoring with prompt reporting of unanticipated problems involving subjects and others including serious adverse events to CPHS. For studies involving multiple sites, this function could be managed by the team of Principal Investigators for each site or the lead or overall Principal Investigator for the entire research study.
   
   
2. Independent Expert(s) – Data and safety monitoring may be performed by an expert or group of experts in the disease and familiar with the agent being studied. Using an independent expert or team of experts is particularly helpful in monitoring of unblinded data for a double blind research study as this will help ensure a meaningful review by independent experts while maintaining the blind amongst the research staff.
   
   
3. Data Safety Monitoring Board (DSMB)- DSMB is a committee that is established specifically to monitor data throughout the life of a research study to determine if it is appropriate, from both scientific and ethical standpoints, to continue the research study as planned. For high risk studies and for sponsor initiated large, blinded studies involving multiple sites, it is recommended that a formal DSMB be appointed.
   1. Sponsor organized DSMB – Sponsors may appoint an independent DSMB.
   2. UTHealth DSMB – PIs may utilize the institutional DSMB. The Regulatory Unit helps to set up internal DSMBs.
   3. Investigator established DSMB – Principal investigators (PIs) may establish their own DSMB.

9. Frequency And Extent Of Monitoring – The plan should state how often monitoring will be performed and who will perform monitoring. There are several possible options for frequency of monitoring. Monitoring may be planned at specific points in time, after a specific number of subjects have been enrolled, or upon recognition of harm. The plan should state what data will be reviewed for safety monitoring.

10. Communication – The plan should describe how outcome of data and safety monitoring is communicated to other participating sites and CPHS. Principal Investigators should submit Data and Safety Monitoring Board reports to CPHS as and when they are available.

10.1. The ORSC Staff schedules the report for discussion at the next convened meeting. The ORSC Staff assigns the report to the Chairperson of the Subcommittee that initially reviewed the research, if possible. If the Chairperson is not available, the ORSC Staff assigns the report to any other member of the subcommittee or any CPHS member. The assigned Reviewer presents a summary of the report at the meeting and makes a motion to continue approval for the research, request more information from the Principal Investigator, request changes to protocol or consent document, or any other action. The Chairperson of the IRB opens the item discussion followed by a vote.

10.2. ORSC Staff notify the Principal Investigator of the outcome of review in a timely manner via iRIS.

RESPONSIBILITY

11. PI Responsibilities – Principal Investigator is responsible for submitting the data and safety monitoring plan at initial review. The Principal Investigator is also responsible for submitting reports from DSMBs to CPHS via iRIS.

12. CPHS Responsibilities – CPHS is responsible for ensuring an adequate data and safety monitoring plan exists. The CPHS is also responsible for continuing review of DSMB reports and to determine if the research study should be continued as approved, changed, or terminated.

13. Regulatory Unit – The Regulatory Unit staff help to coordinate internal Data Safety Monitoring Boards. The Regulatory Unit staff also help investigators develop a data and safety monitoring plan.

Applicable Regulations and Guidelines

1. 45 CFR 46.111(a)(6)
2. 21 CFR 56.111(a)(6)

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