(034) Scoping Review of the Use of Post-marketing Database Studies (PMDS) as an Additional Pharmacovigilance Activity of Risk Management Plans in Japan

Background: Post-marketing studies, usually observational studies with primary data collection, have long been implemented to monitor safety and effectiveness objectives listed in RMPs in Japan. A regulatory revision by the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan in 2018 acknowledged the potential advantages of PMDS using health claims data, electronic health records, or patient registries, and encouraged their use to address elements of the RMP. We investigated the characteristics of PMDS included in RMPs across all therapeutic areas in Japan.

Objectives: To summarize the characteristics of PMDA-accepted PMDS listed in RMPs in Japan.

Methods: Two researchers systematically and independently reviewed all RMPs listed in the PMDA website from April 2013 to December 2023. PMDS contained in RMPs were identified, reviewed, and summarized per therapeutic area by study design, objectives (safety and/or effectiveness) and data sources being utilized.

Results: Among 648 RMPs retrieved and reviewed, 85 PMDS were identified from 63 RMPs. Common target therapeutic indications of PMDS were “Neoplasms” 17 (20.0%), “Endocrine, nutritional and metabolic diseases” 13 (15.3%), and “Diseases of the musculoskeletal system and connective tissue” 9 (10.6%). Safety objectives were markedly more common than effectiveness objectives (81 vs 5 studies, 1 study investigated both). Cohort studies were the most frequent study design (n=74, 87.1%) whereas nested-case control studies (n=2, 2.4%) and other designs (n=1, 1.2%) were rare. The study design was not decided or described in 8 PMDS. The most frequently employed data source was the Medical Data Vision database, which includes inpatient and outpatient claims data from advanced hospitals (n=32, 37.6%), followed by the Medical Information Database Network, which contains electronic health records from 23 advanced hospitals (n=18, 21.2%). The data source was not decided/not described in 17 PMDS (20.0%).

Conclusions: PMDS offer potential advantages such as very large populations, rapidity, and low cost, and have particular utility in evaluating the occurrence of rare adverse events. In Japan, PMDS were limited to several specific therapeutic areas, and were usually cohort studies with targeted safety objectives. Increased sophistication in study design options and expansion of objectives to address questions around effectiveness could increase the applicability of PMDS to a wider range of therapeutic areas, and enhance the capability of RMPs to address regulatory concerns.