Federal regulations require the IRB to determine that research plans submitted provide adequate provisions for monitoring data collected in order to ensure the safety of subjects. Monitoring should be commensurate with risks and with the size and complexity of the trials. Phase III clinical trials generally require a data and safety monitoring board. Investigators involved in Phase I and II clinical trials must submit a general description of the data and safety monitoring plan as part of the research application and as part of the protocol submission to the IRB. The following template is provided for UMASS investigators as a guide to developing a data and safety monitoring plan.
I. Protocol Title
II. Oversight of this Investigation will be provided by person’s name, department, title, contact information
III. Purpose of the Study may use protocol abstract
IV. Assessment of Level of Risk
- Estimate risk level (minimal, moderate, high) and briefly discuss risk considerations relevant to your protocol.
- Adapt the monitoring plan based on the risk. Use the following information as guidance only. Check with the IRB for final risk assessment.
a) Minimal Risk: All protocols presenting the potential of risk to subjects, even minimal risk, should address how the investigator will monitor risk and report adverse events. A minimal risk study is defined as one where the probability and magnitude of harm and/or discomfort in the proposed research are not more than ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. Minimal risk studies may include non-therapeutic studies such as survey research, questionnaires, blood samples (venipuncture or intravenous catheter insertion), observational studies, DEXA scans, routine MRI scans, special diets, exercise testing, EKG’s, and anthropomorphic evaluations.
However: survey research and questionnaires may present more than minimal risk to subjects if they address highly sensitive information. inclusion of special populations (children, prisoners, pregnant women mentally disabled persons, or economically and/or educationally disadvantaged persons) who may be more sensitive or vulnerable to the risks posed by the research, regardless of the study, may increase the level of risk to moderate or high.
Monitoring Plan for Minimal Risk research does not require an independent Data and Safety Monitoring Board (DSMB). Monitoring is the responsibility of the investigator.
b) Moderate Risk: Moderate risk studies exceed the minimal risk, but constitute less risk to the subject than studies with the potential for serious risks to subjects. Moderate risk studies may include phase I, II or phase III multi-institutional trials, studies using drugs for their indicated use, studies that use invasive hemodynamic monitoring with arterial lines, and studies in which blood and tissue specimens are stored. Studies in which blood is drawn for genetic studies, either real time and/or stored for later use are also deemed to present risk to subjects.
Monitoring Plan for Moderate Risk will, in most cases, require independent safety monitoring. For some strictly genetic studies, in targeted populations, the investigator may serve as the monitor. For small, moderate risk studies, monitoring might be performed by an independent investigator who is an expert in the agent being studied and the patient population.
c) High Risk: Protocols presenting the potential for serious risks and adverse events may include clinical trials using investigational agents, gene transfer studies, studies using FDA-approved agents for non approved indications; Phase I clinical trials; studies requiring investigator-initiated IND’s (investigational new drug) or IDEs (investigational devices); and some Phase II clinical trials.
This category may include studies involving procedures in which there is a high risk for adverse events such as conscious sedation or interventional radiology. Studies in which some or all subjects are at risk of death or severe morbidity because of existing illness or disease are also considered high risk.
Monitoring Plan for High Risk research may require a DSMB. For example, in large, blinded studies involving high risk or special populations a DSMB should be constituted. For some high risk studies, monitoring might be performed by a single, independent investigator who is an expert in the agent being studied and the patient population.
V. Plan for Monitoring Safety/Confidentiality
- Specify the name and contact information of the individual responsible for monitoring the safety environment of the participants (PI, or additional monitoring personnel)
- Specify any conditions that would necessitate early termination of the study (i.e. some clinical trails require documentation of stopping rules that might be used if the participants are found to be exposed to excessive risks in relation to anticipated benefits).
Specify what you will monitor, for example:
- State that only subjects who meet the study eligibility criteria are enrolled.
- The informed consent process will be conducted appropriately and that informed consent will be obtained prior to proceeding with any study procedures. Monitor any problems with informed consent.
- Data will be collected and analyzed as specified in the protocol.
- Adverse events will be reviewed promptly and reported as required (see Section VII below).
- Discuss how privacy and confidentiality of subjects will be maintained. Indicate your plan to protect the private health information from improper use and disclosure (e.g. assign study numbers, de-identification process, locked storage, etc.).
- Documentation of dropouts.
- Evaluation of primary and secondary endpoints.
VI. Plan for Data Management
- Indicate who is responsible for collection and storage of data.
- Describe how data will be organized, managed, and stored. Security measures used to protect study data from loss or inappropriate use (password protection, restricted access to database, database backup etc.).
- Include a description of how often interim data will be reviewed and by whom.
- Indicate who will perform aggregate analysis of data and adverse events, if applicable.
VII. Adverse Event
- Describe the anticipated adverse events listed in the Consent Form for this protocol.
- Indicate that you will follow the Adverse Event guidelines and the Significant Adverse Event Report Form, and, in so doing, will report to the UMASS IRB and to NIH as required.
- Indicate how adverse events will be identified, for example, interviewing subjects, physical exams, laboratory results, safety test etc.
- Include the scale that will be used to grade the severity attribution of adverse event. The Common Toxicity Criteria (CTC) scale below is typically used:
0 = No adverse event or within normal limits
1 = Mild AE, not requiring treatment
2= Moderate AE, resolved with treatment.
3= Severe AE, resulted in inability to carry on normal activities and required professional medical attention
4= Life threatening or disabling AE
5= Fatal AE
- Attribution of Adverse Events Categories : Indicate a scale to be used to attribute the relatedness of the experience to the study procedures/interventions. The following is a common reference:
Probably not related
Definitely not related
VIII. Protection of Human Research Participants-Computer Based Training
- Specify that all key research personnel have completed the required human subjects training course. Key personnel include all individuals responsible for the design and conduct of the study.
The University of Massachusetts Amherst Institutional Review Board will approve this plan, with the project protocol, prior to implementation of the study.