The SO provides independent safety monitoring in a timely fashion to ensure patient safety and study quality.
At the beginning of a study, the SO will review the manual of operating procedures, containing the study protocol, study forms, and data and safety monitoring plan, for scope and comprehensiveness. The monitoring plan should delineate data preparation functions, the review process, and the role of the SO.
The monitoring plan also specifies the content and format of the reports, their frequency, and triggers for ad hoc reviews. Stopping rules, if appropriate, should outline the conditions under which a study may be stopped prematurely. The primary focus of the SO’s monitoring activity is participant safety. The SO may suggest modifications to the protocol, the monitoring plan and the reports that will routinely be prepared by the study statistician and study team, as appropriate. After completing his/her review of the study materials, the SO offers a recommendation to the NIAMS regarding study commencement.
All serious adverse events (SAEs) must be reported to KAI/NIAMS and the independent SO (through KAI) within 48 hours of the investigator becoming aware of the event. All adverse events (AEs), both serious and non-serious, must be reported at predetermined intervals to the NIAMS and the SO (through KAI).
The SO will notify the NIAMS if a pattern of events occurs and will suggest prevention measures (e.g., modifying the protocol to require frequent measurement of laboratory values predictive of the event).
For unexpected and/or related serious adverse events, the SO will contact the NIAMS Program representative. In addition, the SO may request individual patient records, including laboratory data, clinical records, and other study related data, to evaluate these events against the known safety profile of the study treatment and the disease. The SO may recommend actions including partial or complete unblinding, and/or modifying or terminating the study.
In addition to safety monitoring, the SO will review enrollment data, demographic information, retention status, and other reports prepared by the study statistician that describe study performance and progress. The SO will provide a report to NIAMS that describes study safety, progress and performance and provides recommendations regarding safe continuation or early termination of the trial.
The data and safety monitoring plan may require the SO to evaluate the general performance of the study, including periodic assessment of participant recruitment, accrual and retention, protocol adherence, and data quality and timeliness. The SO may also review interim analyses to ensure that if the objectives of the study are met, the outcome differences are detected, or if the stopping rule thresholds are reached, the study will conclude.
Confidentiality must be maintained throughout all phases of the trial, including monitoring, preparation of interim results, review, and response to monitoring recommendations. Thus, the SO should not receive patient identifiers, will maintain study confidentiality and will not share data.