@article{2b1b9d252dca4b62afe46fc8244e510e,
title = "Generating Evidence from Expanded Access Use of Rare Disease Medicines: Challenges and Recommendations",
abstract = "Patients with rare diseases often have limited or no options for approved treatments or participation in clinical trials. In such cases, expanded access (or “compassionate use”) provides a potential means of accessing unapproved investigational medicines. It is also possible to capture and analyze clinical data from such use, but doing so is controversial. In this perspective, we offer examples of evidence derived from expanded access programs for rare diseases to illustrate its potential value to the decision-making of regulators and payers in the European Union and the United States. We discuss ethical and regulatory aspects to the use of expanded access data, with a focus on rare disease medicines. The heterogeneous approach to expanded access among countries within the European Union leaves uncertainties to what extent data can be collected and analyzed. We recommend the issuance of new guidance on data collection during expanded access, harmonization of European pathways, and an update of existing European compassionate use guidance. We hereby aim to clarify the supportive role of expanded access in evidence generation. Harmonization across Europe of expanded access regulations could reduce manufacturer burdens, improve patient access, and yield better data. These changes would better balance the need to generate quality evidence with the desire for pre-approval access to investigational medicine.",
keywords = "compassionate use, drug regulation, expanded access, perspective, policy recommendation, rare disease, real-world data",
author = "Polak, {Tobias B.} and Cucchi, {David G. J.} and {van Rosmalen}, Joost and {Uyl-de Groot}, {Carin A.} and Darrow, {Jonathan J.}",
note = "Funding Information: CU-DG, JR, and TP work on a Dutch government grant from HealthHolland. For this grant, they research legal, ethical, policy, and statistical issues of evidence generation in compassionate use programs (EMCLSH20012). HealthHolland is a funding vehicle for the Dutch Ministry of Economic Affairs and Climate Policy that addresses the Dutch Life Sciences & Health sector. Funding Information: CU-DG has received unrestricted grants from Boehringer Ingelheim, Astellas, Celgene, Sanofi, Janssen-Cilag, Bayer, Amgen, Genzyme, Merck, Glycostem Therapeutics, Astra Zeneca, Roche and Merck. TP works part-time for expanded access service provider myTomorrows, in which he holds stock and stock options (< 0.01%). He is contractually free to publish, and the service provider is not involved in any of his past or ongoing research, nor in this reply. DC received payments for lectures for Takeda, all outside the submitted work. JD receives research support from Arnold Ventures, the Commonwealth Fund, Health Action International{\textquoteright}s ACCISS program, the Kaiser Permanente Institute for Health Policy, the National Institutes of Health, and West Health, and under a Novo Nordisk Foundation grant for a scientifically independent Collaborative Research Programme (grant NNF17SA0027784). Publisher Copyright: Copyright {\textcopyright} 2022 Polak, Cucchi, van Rosmalen, Uyl-de Groot and Darrow.",
year = "2022",
month = may,
day = "23",
doi = "https://doi.org/10.3389/fphar.2022.913567",
language = "English",
volume = "13",
journal = "Frontiers in pharmacology",
issn = "1663-9812",
publisher = "Frontiers Media S.A.",
}