Learn the NIAMS guidance and guidelines for studies that use internally-appointed monitoring for the oversight of NIAMS-funded clinical research.
TABLE OF CONTENTS
1.0 Internally-appointed Monitoring
For some interventional and non-interventional studies with low risk, the NIAMS may determine that the DSMP proposed by the PI, typically described in the grant application, is sufficient to ensure participant safety. In such cases, the NIAMS allows the PI to appoint data and safety monitoring oversight for the study. In general, this type of monitoring only applies to low risk studies when the PI has demonstrated in the application that he/she can establish a DSM body, often at the institution. There may also be cases where the PI proposes in the grant application that they will be responsible for conducting the monitoring for the study themselves; however, the NIAMS may determine that separate internally-appointed monitoring is required with individuals independent from the study. The NIAMS makes the final determination on the level of oversight and monitoring required for a study.
For studies where the PI selects, assembles, and manages the data and safety monitoring oversight process, the NIAMS refers to this as “internally-appointed monitoring” (rather than NIAMS-appointed monitoring, where the DSM body is appointed and managed by the NIAMS). For more information about NIAMS-appointed monitoring bodies, see sections 2.3.1, 2.3.2, and 2.3.3 of the DSM Guidelines for NIAMS-Funded Clinical Research. The oversight and management processes for internally-appointed monitoring vs NIAMS-appointed monitoring (or externally monitored) are different.
Internally-appointed monitoring allows minimal involvement in the management and oversight processes by the NIAMS. However, there are still certain requirements for oversight and reporting data to the NIAMS that must be followed by the PI. The NIAMS must be kept informed of ongoing study progress, safety events and decisions made by the PI’s DSM body on a routine basis. This process ensures the NIAMS is meeting its obligation for data and safety monitoring oversight for the studies it supports. The NIAMS’ determination for an internally-appointed DSM body includes factors including but not limited to, number of sites, risk to human subjects, number of participants, phase of study, study population, study complexity, type of intervention, and adequacy of the DSMP reviewed with the grant application.
A call (referred to as the initial PI call) will be set-up with the PI and any member(s) of the study team who is assisting the PI, the NIAMS, and the NIAMS Executive Secretary (ES) to review the NIH/NIAMS clinical trial requirements and to answer any questions on how to carry out the data and safety monitoring process.
Please note that all information shared with the NIAMS and the NIAMS ES related to data and safety monitoring oversight will be kept confidential.
1.1 Roles and Responsibilities of the PI
If the NIAMS determines internally-appointed monitoring is appropriate for the study, it allows the PI to take responsibility for establishing the DSM body. The PI may have decided that a DSM body similar to a DSMB/OSMB or SO/dual SO described in these guidelines (see sections 2.3.1, 2.3.2, and 2.3.3 of the DSM Guidelines for NIAMS-Funded Clinical Research) is required to provide safety monitoring, and the NIAMS will communicate with the PI to let him/her know that it is in agreement with the DSM body proposed.
Study materials are prepared by the PI and the study team. Please refer to section 6.1.3.a of the DSM Guidelines for further details.
The NIAMS requires that the DSM body selected by the PI must be independent of the study and members may not be in the same division as the PI and/or co-investigators. The NIAMS does not approve the DSM body members but does screen for conflict at the start of the study. The PI is responsible for vetting the DSM body members through the NIAMS via the NIAMS ES to ensure they are free of any conflicts. The PI and the study team should provide the name, affiliation, and curriculum vitae (if available) of the proposed DSM body member(s) to the NIAMS ES for a conflict of interest check to be conducted. If any member is found in conflict, the PI must propose others for vetting through the NIAMS.
The PI must establish a process for collection, assessment, and reporting of AEs, SAEs, UPs, and protocol deviations to the DSM body, IRB, and FDA (if applicable), and describe this process in the DSMP. The NIAMS requires the PI to report SAEs, UPs, and protocol deviations that impact participant safety to the NIAMS through the NIAMS ES in an expeditious manner. These events must be reported to the NIAMS within 48 hours of the investigator becoming aware of the event. For more information see the NIAMS Reportable Events Requirements and Guidelines for Investigators Conducting NIAMS-Funded Clinical Research Studies. Please note that the NIAMS expects to receive a copy of the internally-appointed DSM body’s final assessment of the event when it becomes available.
The PI and study team are required to provide to the NIAMS through the NIAMS ES monthly status updates regarding the progress of study activities during the start-up phase until the first participant is enrolled. The first update is due 30 calendar days following the initial PI call with the NIAMS and should include a milestone timeline table and a projected enrollment graph. Once the first participant is enrolled, the PI and study team should provide monthly enrollment reports. The NIAMS ES will be in close contact with the PI and study team to provide guidance and ensure these timelines are met.
1.2 Responsibilities of Internally-appointed Monitoring Body
The internally-appointed DSM body is responsible for data and safety monitoring oversight. The DSM body will be responsible for reviewing study data and progress in a timely fashion to ensure participant safety and data quality. The following are some examples of responsibilities a typical DSM body will have (but should not be limited to these) and should be well described in the DSMP:
- Review and provide comment/request clarification on specified study documents (e.g. protocol, informed consent documents, DSMP)
- Evaluate the progress of the study on an ongoing basis, as needed, including periodic assessments of data quality, participant recruitment, accrual and retention, participant risk versus benefit, performance of study site(s), and other factors that can affect the outcome
- Evaluate safety throughout the course of the study through the routine review of aggregated AE safety data, in addition to expedited review of UPs, SAE reports, and protocol deviations impacting participant safety
- Consider the impact of factors external to the study when new information, such as scientific or therapeutic developments become available and may affect safety of participants, their willingness to participate in the study or the ethics and conduct of the study
- Review the interim analyses and/or accumulating data at the specified interval(s) and as appropriate and make a recommendation to continue, terminate, or modify the study based on observed benefit or harm in accordance with the planned stopping rules
- Provide approval to start, continue, or stop the study
The PI may assign other responsibilities to the DSM body not mentioned above, and those should be documented in the DSMP.
1.2.a Internal Safety Monitoring Process
The PI is expected to prepare a study protocol, a MOP, informed consent/assent form(s), CRFs, a final DSMP, and DSM Report template(s) that will be used to report data to the DSM body. The NIAMS has helpful templates available that investigators can use to draft some of these documents, but it is not required that the NIAMS templates be used. The NIAMS templates can be found here: https://www.niams.nih.gov/grants-funding/conducting-clinical-research/trial-policies-guidelines-templates.
The NIAMS requests that all study materials mentioned above be submitted to the NIAMS through the NIAMS ES prior to study initiation. The NIAMS will do an administrative review of the study materials focused on quality to ensure all aspects pertaining to the data and safety monitoring oversight process are outlined clearly and consistently across all documents. Please note that this review is not focused on the scientific or methodological aspects of the study. It is acceptable for the PI to submit the materials to the NIAMS ES either before, after, or concurrently with the IRB; however, if any significant changes are requested by the NIAMS, it may require resubmission and approval of the updated materials to the IRB, or vice versa.
1.2.b Internal Review of Data and Safety Reports and Monitoring Body Meetings
The timeline and frequency of the review of reports and/or meetings by the internally-appointed DSM body is set by the PI and the DSM body. The NIAMS does not determine how often the internally-appointed DSM body should review data, but the PI can refer to the NIAMS-appointed DSM body guidelines as a guide (see Sections 6.1.2.c, 6.1.2.d and 6.2.2.b of the DSM Guidelines for NIAMS-Funded Clinical Research). Safety reports submitted to the DSM body must be shared with the NIAMS through the NIAMS ES, along with any feedback or recommendations from the DSM body immediately following the review of the reports or meeting. It is important for the NIAMS to be kept updated on the outcome of reviews conducted by the DSM body.
1.2.c Amended Materials
As the study progresses it is expected that there may be unanticipated changes to the study protocol that require updates to the study materials. Any changes to the study potentially impacting the budget must first be discussed with the NIAMS program staff. Amended materials include but are not limited to changes to the study’s protocol, MOP, DSMP, informed consent/assent form(s), and CRFs. All changes made to the study should be reviewed and approved by the internally-appointed DSM body and the IRB prior to implementing the changes. The NIAMS must be notified of these changes. All approved amended materials should be shared with the NIAMS through the NIAMS ES.