Regulatory and HTA Considerations for Development of Real-World Data Derived External Controls.

Regulators and Health Technology Assessment (HTA) bodies are increasingly familiar with, and publishing guidance on, external controls derived from real-world data (RWD) to generate real-world evidence (RWE). We recently conducted a systematic literature review (SLR) evaluating publicly available information on the use of RWD-derived external controls to contextualize outcomes from uncontrolled trials submitted to the European Medicines Agency (EMA), the US Food and Drug Administration (FDA), and/or select HTA bodies. The review identified several key operational and methodological aspects for which more detailed guidance and alignment within and between regulatory agencies and HTA bodies is necessary.

Assessing the incidence of osteosarcoma among teriparatide-treated patients using linkage of commercial pharmacy and state cancer registry data, contributing to the removal of boxed warning and other labeling changes.

Background: Teriparatide, a recombinant human parathyroid hormone analogue, is associated with increased bone mineral density and a decreased risk of fractures. A dose-dependent increase in the incidence of osteosarcoma was observed in toxicology studies conducted in rats. The primary objective of this study was to estimate the incidence of osteosarcoma over a 10-year period among teriparatide-treated patients versus patients unexposed to teriparatide with osteoporosis and patients in the general population using national pharmacy dispensing data linked with data from participating state cancer registries (SCRs) in the US.

Real-world cohort study of adult and pediatric patients treated for hereditary angioedema in the United States.

There is limited real-world evidence on hereditary angioedema (HAE) patient characteristics and health-care resource utilization (HCRU); in addition, pediatric patients have been described in small cohorts. To describe patient characteristics, treatment patterns, and HCRU among adult and pediatric patients treated for HAE in a large U.S.

Awareness of, and Compliance with, Domperidone Revised Labeling After a Risk-Minimization Activity in Europe.

Background And Objective: Risk-minimization measures (RMM), including label revisions were implemented in Europe for domperidone because of evidence of increased incidence of cardiac arrhythmia and sudden cardiac death. In accordance with the guideline on good pharmacovigilance practices, the European Medicines Agency Pharmacovigilance Risk Assessment Committee requested to conduct two studies to evaluate the effectiveness of these risk minimization measures.

Methods: In Belgium, France, Germany, Spain, and the UK, surveys were conducted to assess physicians' knowledge on the updated domperidone labeling information, and a drug-utilization study (DUS) was conducted using healthcare databases to assess domperidone prescribing patterns before and after the RMM.