The Orphan Drugs Environment: from regulatory decision making to patients’ availability

This doctoral research explores the regulatory ecosystem governing access to medicines for rare diseases, focusing on the evolution and performance of orphan drug policies and the mechanisms shaping patient availability. Beginning with a historical analysis of pharmaceutical regulation, the study traces how key public health crises—from the 1937 sulfanilamide disaster to the thalidomide tragedy—prompted the creation of global safety frameworks. The research then examines the emergence of the orphan drug concept and the comparative development of incentive-based legislation across major jurisdictions, including the U.S. Orphan Drug Act (1983) and the European Regulation (EC) No. 141/2000. Through the evaluation of two original studies—the performance of the European Medicines Agency’s Accelerated Assessment and the review of medicines excluded from the WHO Essential Medicines List—the thesis highlights the tension between regulatory acceleration and evidentiary rigor. Accelerated pathways can shorten access timelines but increase uncertainty, while the WHO’s evidence-based selection ensures global health equity by prioritizing safety, efficacy, and cost-effectiveness. By comparing these contrasting approaches, the work demonstrates that innovation and prudence are not conflicting principles but complementary forces that sustain both rapid access and patient protection. The final discussion offers policy recommendations for improving transparency, harmonizing Health Technology Assessment (HTA) practices, and aligning orphan designation incentives with actual therapeutic value. Ultimately, the research underscores the need for balanced, evidence-driven regulation that promotes equitable and sustainable access to treatments for rare diseases across Europe and beyond.