The last essential element of the safety monitoring plan is an adverse event reporting plan. All studies are subject to unique institutional adverse event reporting requirements. At a minimum, the DSMP should indicate who will be responsible for reporting adverse events at the institutional level. In addition, adverse events occurring in clinical trials involving investigational drugs or devices must be reported to the FDA by the sponsor in accordance with relevant federal regulations. In the case of multisite studies, the coordinating center is responsible for reporting and distributing safety information to participating sites.

Data monitoring. In contrast to safety monitoring, the purpose of the data monitoring plan is to ensure both adherence to the approved clinical investigative plan and the validity of the data collected. Its specific elements can include review of informed consent documentation, confirmation of subject eligibility, and verification of the accuracy of data transfer from source documents to case report forms.

Data monitoring should be scheduled at intervals sufficient to keep up with subject enrollment and/or the expected volume of subject information. Unlike the safety monitoring plan, qualified study staff (not necessarily the principal investigator), such as a research nurse or study coordinator, can be assigned responsibility for conducting and/or overseeing data monitoring. In many cases, the person responsible for data review reports on a weekly or monthly basis to a principal investigator.

Product accountability. In studies that involve an investigational product, a plan for product accountability should be in place to ensure that all study drugs, biologics or devices are accounted for. This plan should provide for a record of receipt, distribution, and disposal of the product, as well as an overall inventory accounting for all investigational products.

A person should be assigned responsibility for product accountability. Even if an institution-based research pharmacy assumes responsibility for these functions, the investigators are still ultimately responsible for product accountability and should still maintain records that document subject receipt of specified doses of the investigational product and return of any unused product. Devices can pose a greater challenge to research sites because the clinical research sites are typically required to manage accountability themselves.

Privacy and confidentiality. In addition to plans to protect subject safety and adherence to the protocol, sites should consider plans to protect subject confidentiality. Breaches in confidentiality have the potential to lead to unanticipated problems, ranging from embarrassment to socioeconomic impacts (e.g., loss of insurance or employment).

The HIPAA Privacy Rule, which took effect in April of 2003, requires that individually identified information (protected health information) created or collected during a study must be coded or de-identified.¹² Legal consequences associated with violation of the Rule include civil fines and criminal penalties.¹³

At a minimum, the DSMP should address how data will be protected, including how they are stored (password protected electronic records and/or paper files), who has access to the files, and what steps will be taken to prevent unauthorized access (e.g., contained in a locked office or large multistudy storage room). In addition, the plan may need to consider how investigators will protect subject privacy and confidentiality if the protocol calls for data or tissue samples to be shared with collaborators for the current or future research.

Implementation

To ensure compliance with FDA regulations, NIH policies, and GCP guidance, the QI Program developed a checklist that includes essential DSMP elements (Figure 1). Its main advantage for QI purposes lies in helping identify missing or underdeveloped DSMP elements when reviewing study protocols for study site initiated or IRB requested onsite review.¹⁴ Deficiencies can be easily detected, resulting in effective recommendations for corrective action.