Chapter 11 228 REPORTING AND USE OF EXPANDED ACCESS DATA Reporting of expanded access data in peer-reviewed publications Expanded access has recently gained attention by the large number of compassionate use studies or case reports on treatments for SARS-CoV-2, such as remdesivir and convalescent plasma.16,17 Unpublished data from our group indicate that from 2000 to 2022 over 1300 expanded access studies have been published. In oncology an estimated 198 expanded access studies were published with several examples concerning rare diseases from 2013 through 2020.18 The median number of patients in publications that were not case reports (80%) was 153. This number ranged from N=7 in a publication reporting the experience of Austrian physicians using venetoclax to treat high-risk patients with acute myeloid leukemia refractory to standard therapy, to N=4,543 patients from over 50 countries in a report of the expanded access program for sunitinib to treat metastatic kidney cancer.19,20 Both sunitinib2 and venetoclax3 received orphan designation for these diseases by the EMA. Several drugs are associated with numerous publications flowing from expanded access, such as cabazitaxel, a chemotherapeutic for metastatic, castration-resistant prostate cancer.21 It is associated with at least 10 expanded access studies, separately reporting experiences in Spain, Australia, Germany, South-Korea, Naples, Italy, the Netherlands, Canada, United Kingdom, and Europe.22–31 The outcomes measured in these reports are heterogeneous, ranging from only safety data, to data on safety and quality-of-life, to data on safety and effectiveness, while others focus on prognostic modelling.22,27,29,31 The heterogeneous reporting of different outcomes, and the multiplicity of reports across countries indicates the lack of harmonization or best practices in this setting. Use of expanded access data in regulatory filings Regulators require the conduct of clinical trials to determine safety and efficacy before granting marketing authorization. For rare diseases, performing such trials can be slow due to low patient enrolment, or even unfeasible or unethical.32 Therefore, any evidence generated through expanded access patients should be harnessed to help clarify harms and benefits. Through 2018 and starting in 1955 (FDA) or 1995 (EMA), 49 drug-indication pairs were approved by either the EMA or FDA based in part or in whole on expanded access data, 31 (63%) of which had an ‘orphan designation’ to support the development and evaluation of treatments for rare diseases.33 This includes for example lutetium-177 oxodotreotide, a radioactive treatment for gastroenteropancreatic neuroendocrine tumors. Supplementary to the pivotal randomized 2 https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu305268 3 https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3161617
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