By Karen Outten, Merck
Patient safety is of paramount importance in clinical research and is a critical part of the clinical trial process. Robust collection and continuous monitoring of patient safety data in clinical trials protects patients from unnecessary risks and supports detection of important safety signals and the development of a robust safety profile, all of which contribute to the benefit-risk assessment and safety label information for a new drug, biologic, or device.
A cornerstone of safeguarding patient well-being and the quality of care in clinical research is the collection and reporting a serious adverse events (SAEs). According to the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), an adverse event is any unfavorable or unintended sign, symptom, or disease temporarily associated with the use of a medicinal product, whether or not the event is related to the product itself.1,2 The FDA considers an adverse event to be serious if it results in any of the following outcomes: death, a threat to the patient’s life, inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly or birth defect.3 Certain medical events may also be considered serious when they jeopardize the patient or require medical intervention to prevent one of the previously mentioned outcomes.1,3 These events would be reported as other medically important events.
Throughout the pharmaceutical industry, patient safety data collected during interventional clinical trials can vary widely across trial sponsors. While sponsors are required to follow the same health authority reporting regulations, there is a lack of standardization across the data fields included on SAE case report forms and SAE paper reporting forms. The resulting variation can create ambiguity for investigators working with multiple sponsors to conduct clinical trials, leading to delay and uncertainty in the process of collecting a patient safety data set that provides a complete clinical picture of the SAE. There is a clear opportunity to identify a set of core data fields for the purposes of SAE reporting to increase the quality and comprehensiveness of SAE reports and work with an industry standards-setting body to facilitate development of an industry standard.
To address that opportunity, TransCelerate launched the Common SAE Fields Initiative, which focused on the assessment of the common core data fields collected and reported after an SAE. The team consisted of subject matter experts from a variety of disciplines, including physicians, pharmacovigilance experts, clinical operations experts, and clinical trial reporting and data management experts.
In order to ensure the development of a core list of SAE fields that would be pertinent and valuable for stakeholders, the team used a multiphase approach to aggregate its core list of common SAE fields. First, the team conducted a regulatory landscape assessment to understand applicable current industry guidance and regulations.
Following the regulatory landscape assessment, each team member provided a third-party consultant with a copy of the SAE reporting form currently in use by their company. The consultant collected, blinded, and aggregated all data fields into a master list of 1,238 data fields. In other words, across the participating member companies, despite ostensibly collecting the same data to report to the same regulators, 1,238 differently named fields were utilized — an astounding result that shows the scale of the challenge. This not only highlighted the lack of consistency across trial sponsors but also the challenges facing investigators working with multiple clinical trial sponsors.
The team performed an SAE fields commonality assessment across the 1,238 data fields included in the master list. Once like data fields were grouped together, the team divided the data fields into nine categories. Data fields were assessed for commonality and relevance. For example, all data points related to collection of concomitant medications were grouped together.
At the end of this multiphase approach, the master list of 1,238 data fields became a list of 133 unique data fields to comprise the list of common SAE fields that would provide a complete clinical picture of a serious adverse event. The final list of 133 data fields was cross-referenced and compared to the industry guidance and regulations reviewed during the initial regulatory landscape assessment to ensure compliance with regulatory safety reporting requirements without sacrificing data quality or comprehensive data collection.
In August 2019, the TransCelerate Common SAE Fields Initiative team prepared for the transition of team deliverables to the Clinical Data Interchange Standards Consortium (CDISC) for purposes of having CDISC set industry standards for SAE data collection and reporting. The transition to CDISC was completed in October 2019. Five team members from the TransCelerate SAE Common Fields team also transitioned to the CDISC team as volunteers to serve as subject matter experts. CDISC’s Clinical Data Acquisition Standards Harmonization (CDASH) SAE Standard team has proceeded with the development of an industry standard surrounding SAE data collection, which is expected to be finalized in March of 2021. Eventually, this SAE standard will serve as an update to the existing CDASH SAE Supplement v1.0. As with any CDISC foundational standard, CDISC will continue to maintain and update the SAE standard as new industry guidance and regulations are released.
Developing and adopting an industry standard around SAE data collection is expected to add inherent value across patients, sites, sponsors, and health authorities. An industry standard is expected to optimize clinical trial safety data collection and provide efficiencies in the SAE data collection and reporting processes, including the potential to reduce the number of SAE case versions required to obtain a comprehensive SAE report. Earlier availability of high-quality comprehensive SAE reports will protect patients from unnecessary risks and support detection of important safety signals and the development of a robust safety profile.
Furthermore, these efforts underscore the importance of collaboration, where appropriate. The ability of pharmaceutical companies, investigators, and health authorities to work in partnership to bring new medicines to market for the benefit of patients and human health is a critical mission we can all stand behind. Development of a standard robust process for SAE reporting to support patient safety is one significant way to help achieve this goal.
- ICH E2A – Clinical safety data management: definitions and standards for expedited reporting https://www.ema.europa.eu/en/ich-e2a-clinical-safety-data-management-definitions-standards-expedited-reporting
- ICH E6 (R2) – Good clinical practice https://www.ema.europa.eu/en/ich-e6-r2-good-clinical-practice
- FDA 21 CFR 312.32 – IND safety reporting https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=312.32
About The Author:
Karen Outten is executive director, Clinical Trial Safety Reporting, within Global Clinical Safety and Pharmacovigilance (GCS&PV) at Merck Research Laboratories (MRL). She has over 20 years of experience in the pharmaceutical industry, including preclinical research, clinical research, and drug safety and pharmacovigilance. She has held leadership roles in both clinical research and drug safety. Today, Outten leads a global team of clinical safety scientists supporting clinical trial safety reporting across the Merck early and late stage clinical development portfolio. She holds a B.S. in medical technology and an M.S. in bacteriology. Outten was the team lead of the TransCelerate Common SAE Fields Initiative and has transitioned to the CDISC Clinical Data Acquisition Standards Harmonization (CDASH) SAE Standard team as a subject matter expert to support the development of an industry standard for SAE data collection.