Guidelines for Reporting to a Safety Officer

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November 13, 2014

The Safety Officer (SO) is an independent individual, most often a physician, who performs data and safety monitoring activities in low-risk, single-site clinical studies. The SO advises the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Program representative and Principal Investigator (PI) regarding participant safety, participant risks and benefits, scientific integrity and ethical conduct of a study.

I. Appointment of the Safety Officer

Appointment of the SO is the responsibility of the NIAMS. However, the study investigator(s) may have input into the selection of SO with the approval of the NIAMS program staff. The SO is usually a physician, with relevant study and disease-specific expertise. The PI submits the individual's name for review and approval by the NIAMS Program representative. The NIAMS invites the individual to serve as a study's SO. Once the invitation is accepted, the SO receives the manual of operating procedures, which typically contains the study protocol and safety monitoring plan, before study enrollment begins.

II. Independence of the Safety Officer

To remain objective, the SO must maintain independence from the study. Accordingly, the SO should not be directly involved in the conduct of the study and should not have scientific, proprietary, financial or other interests that may affect independent decision-making.

Current collaborators of the PI are not eligible to be SOs. The letter of invitation to prospective SOs states the requirement of independence. In addition, potential SOs must sign a Conflict of Interest Statement prior to the appointment. Annually, the NIAMS Program representative will seek reconfirmation that no conflict of interest exists. Such a statement may also be required prior to each review.

III. Executive Secretary

A NIAMS contractor, KAI Research, Inc., will serve as the Executive Secretary (ES) and will facilitate the distribution of reports. All communication between the study staff and the SO should be facilitated by the ES with the NIAMS Program representative copied on the correspondence.

IV. Safety Monitoring Plan

It is the policy of the NIH that clinical trial monitoring activities for studies supported by the NIH be commensurate with the risks, nature, size, and complexity of the study. For further information regarding developing a data and safety monitoring plan, see "Guide for Developing a Data and Safety Monitoring Plan for Clinical Studies Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)" at https://www.niams.nih.gov/Funding/Clinical_Research/guidelines_monitoring_plan.asp.

V. Safety Reports

At predetermined intervals (e.g. biannually), the study team will prepare safety reports to be reviewed by the SO. The adverse events are reported in aggregate or by masked treatment groups, as requested. Serious adverse events are reported in an expedited manner, as they occur.

The data and safety monitoring plan should specify how data are to be presented and triggers for presenting safety data in an unmasked manner. In addition, the safety monitoring plan should specify the process for reporting safety concerns among the Institutional Review Board (IRB), the SO, the NIAMS and, if appropriate, the Food and Drug Administration (FDA).

The NIAMS has developed report templates for studies with data and safety monitoring oversight. These templates can be located at https://www.niams.nih.gov/Funding/Clinical_Research/NIAMS_guidelines.asp#3.

VI. Roles and Responsibilities of the Safety Officer

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 SOs 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 once the objectives of the study are met, outcome differences are detected or 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.