Over the years, this gap in available evidence has led to serious unintended harms: for example, the off-label paediatric use of paroxetine was associated with an increased risk of suicidal ideation and hostility, resulting in warnings by regulators that the medicine should not be used in children and adolescents. In one study, over 90% of surveyed paediatricians reported prescribing medicines off-label. Historically, information on the safety, efficacy, and appropriate use of new medicines in children has been lacking. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: TJH reports prior employment by Blackstone and Bain Capital, which have invested in healthcare companies. In addition, the paediatric investigation plans can be accessed through the EMA's public database at: įunding: FTB holds an Innovation in Regulatory Science award from the Burroughs Wellcome Fund. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: Relevant data are within the paper and its Supporting Information files. Received: OctoAccepted: JanuPublished: March 1, 2018Ĭopyright: © 2018 Hwang et al. PLoS Med 15(3):Īcademic Editor: Aziz Sheikh, Edinburgh University, UNITED KINGDOM The results for 85% of completed studies were published or publicly reported in a trial registry, at a median of 1.1 years after the completion date.Ĭitation: Hwang TJ, Tomasi PA, Bourgeois FT (2018) Delays in completion and results reporting of clinical trials under the Paediatric Regulation in the European Union: A cohort study.Overall, trials planned to be completed after marketing authorisation were associated with an 89% lower likelihood of completion compared to trials with planned completion before marketing authorisation.In addition, delays occurred due to changes in the planned completion date, with 50% of studies extending the completion date at the request of pharmaceutical companies. Most paediatric studies (76%) were not planned to be completed until after marketing authorisation.After a median follow-up of roughly 7 years, 38% of paediatric trials had been completed, and 17% of medicines had all paediatric requirements fulfilled.A total of 326 paediatric clinical trials were required for 122 medicines and comprised our study cohort. For all new medicines centrally authorised in the EU between 20, we identified those with paediatric trial requirements under the Paediatric Regulation.Limitations of this study include the potential lack of generalisability to medicines not authorised by the EMA and the possibility for more of these trials to be completed or published in the future. Among completed studies, the results were reported in a public registry or in the peer-reviewed literature for 85% (105/124) at a median of 1.1 years after study completion, and 60% (74/124) were published in a peer-reviewed journal. The rate of trial completion for paediatric studies planned to be completed after initial marketing authorisation was 23% (56/247), versus 86% (68/79) for trials planned to be completed before authorisation (adjusted hazard ratio 0.11 95% CI 0.06–0.19). Overall, 38% (124/326) of paediatric studies were completed as of 30 November 2017. The planned completion dates for 50% (162/326) were further postponed by a median of 2.2 years. In all, 76% (247/326) of paediatric studies were not planned to be completed until after the initial marketing authorisation. A total of 326 paediatric clinical trials were required for 122 novel medicines authorised by the EMA between 20. Cox proportional hazards regression models were constructed to examine factors associated with study completion. For our study cohort of paediatric clinical trials required for these medicines, we used internal EMA databases and publicly available trial registries to determine changes to the planned completion date or study design, rates of trial completion, time to trial completion, and results reporting (peer-reviewed publication or posting on trial registry). The European Medicines Agency (EMA) public database of paediatric investigation plans was searched for new medicines centrally authorised in the EU between 1 January 2010 and 31 December 2014 with at least 1 required paediatric study.
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