RESUMEN
The University of Bari (Italy), in cooperation with the National Institute of Geophysics and Volcanology (INGV) (Italy), has installed the OTRIONS micro-earthquake network to better understand the active tectonics of the Gargano promontory (Southern Italy). The OTRIONS network operates since 2013 and consists of 12 short period, 3 components, seismic stations located in the Apulian territory (Southern Italy). This data article releases the waveform database collected from 2013 to 2018 and describes the characteristics of the local network in the current configuration. At the end of 2018, we implemented a cloud infrastructure to make more robust the acquisition and storage system of the network through a collaboration with the RECAS-Bari computing centre of the University of Bari (Italy) and of the National Institute of Nuclear Physics (Italy). Thanks to this implementation, waveforms recorded after the beginning of 2019 and the station metadata are accessible through the European Integrated Data Archive (EIDA, https://www.orfeus-eu.org/data/eida/nodes/INGV/).
RESUMEN
OBJECTIVES: The research and development process in the field of rare diseases is characterised by many well-known difficulties, and a large percentage of orphan medicinal products do not reach the marketing approval.This work aims at identifying orphan medicinal products that failed the developmental process and investigating reasons for and possible factors influencing failures. DESIGN: Drugs designated in Europe under Regulation (European Commission) 141/2000 in the period 2000-2012 were investigated in terms of the following failures: (1) marketing authorisation failures (refused or withdrawn) and (2) drugs abandoned by sponsors during development.Possible risk factors for failure were analysed using statistically validated methods. RESULTS: This study points out that 437 out of 788 designations are still under development, while 219 failed the developmental process. Among the latter, 34 failed the marketing authorisation process and 185 were abandoned during the developmental process. In the first group of drugs (marketing authorisation failures), 50% reached phase II, 47% reached phase III and 3% reached phase I, while in the second group (abandoned drugs), the majority of orphan medicinal products apparently never started the development process, since no data on 48.1% of them were published and the 3.2% did not progress beyond the non-clinical stage.The reasons for failures of marketing authorisation were: efficacy/safety issues (26), insufficient data (12), quality issues (7), regulatory issues on trials (4) and commercial reasons (1). The main causes for abandoned drugs were efficacy/safety issues (reported in 54 cases), inactive companies (25.4%), change of company strategy (8.1%) and drug competition (10.8%). No information concerning reasons for failure was available for 23.2% of the analysed products. CONCLUSIONS: This analysis shows that failures occurred in 27.8% of all designations granted in Europe, the main reasons being safety and efficacy issues. Moreover, the stage of development reached by drugs represents a specific risk factor for failures.
