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Neonatal drug trials: impact of EU and US paediatric regulations
  1. Claudia Pansieri1,2,
  2. Maurizio Bonati2,
  3. Imti Choonara3,
  4. Evelyne Jacqz-Aigrain1,4,5
  1. 1Service de Pharmacologie Pédiatrique, AP-HP, Hôpital Robert Debré, Paris, France
  2. 2Laboratory for Mother and Child Health, Department of Public Health, IRCCS Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milan, Italy
  3. 3Academic Division of Child Health, Derbyshire Children's Hospital, University of Nottingham, Derby, UK
  4. 4Université Paris Diderot, Sorbonne Paris Cité, Paris, France
  5. 5INSERM, CIC1426, Hôpital Robert Debré, Paris, France
  1. Correspondence to Professor Evelyne Jacqz-Aigrain, Department of Paediatric Pharmacology and Pharmacogénétics, Hôpital Robert Debré, 48 boulevard Serurier, Paris 75019, France; evelyne.jacqz-aigrain{at}rdb.aphp.fr

https://doi.org/10.1136/archdischild-2013-305900

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    The rational use of medicines in neonates is limited by the lack of scientific evidence for their use, as most medicines used in neonates are either unlicensed or off-label.1 In order to improve this situation, legislation has been passed in Europe and the USA to encourage the pharmaceutical industry to study medicines in the paediatric and neonatal populations. In order to evaluate the impact of these paediatric regulations in the neonatal population, we analysed the drug trials registered in the Clinicaltrials.gov database.

    Among all (138 948) trials registered, 30 912 (22%) were paediatric trials, and only 288 (0.2%) involved neonates. The number of trials registered grew steadily over time. From 1999 to 2012 trials registered targeting the paediatric population increased fourfold, from 4328 to 16 275. Similarly, the number of neonatal drug trials registered increased sixfold, from 32 to 190. Furthermore, the number of neonatal trials located in Europe exceeded the number of those located in USA in 2011 and in 2012, probably due to a delayed effect of the Paediatric Regulation (figure 1).

    Figure 1
    Figure 1

    Number (N: right Y axis) and % (percentage: left Y axis) of neonatal drug trials registered per year between 1999 and December 2012 in Clinicaltrials.gov and distribution by participating countries.

    Most neonatal drug trials were classified as premarketing trials (84%), and were funded by non-profit organisations (58%). All therapeutic classes were represented, with a predominance for drugs targeting the nervous and cardiovascular systems, and for systemic anti-infectives. Around three quarters were randomised and just over half involved a comparison with a placebo, conducted mainly to evaluate a drug as adjunctive therapy or for the prevention of disease. The majority of trials were single centre-studies (164, 58%), and 81 of these were conducted in North America. Only 94 (33%) were multicentre studies. In all, the industry was sponsor in only 23% of trials, confirming the pharmaceutical industry's lack of enthusiasm for conducting clinical trials in this vulnerable population.

    The limitations of the legislation have been highlighted in relation to neonatal2 and paediatric trials.3 The pharmaceutical industry will study medicines where there is the greatest potential profit, not the greatest clinical need.4 The profit to be made from studying medicines in neonates is minimal. It is important therefore that publicly funded bodies such as the European Commission and the UK's National Institute for Health Research, continue to fund clinical trials in neonates. There is a danger that neonates will remain a group of patients without access to evidence-based therapy.

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    Footnotes

    • Contributors CP retrieved data, carried out the initial analyses, drafted the initial manuscript, reviewed and revised the manuscript, and approved the final manuscript as submitted. MB supervised the retrieving of the data and performed analyses, reviewed and revised the manuscript, and approved the final manuscript as submitted. IC critically reviewed and revised the manuscript, and approved the final manuscript as submitted. EJ-A conceptualised, designed and initiated the study, reviewed and revised the manuscript, and approved the final manuscript as submitted.

    • Funding This work is part of: the TINN network (Collaborative Project), supported by the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme (grant agreement no. 223614) and the GRIP network (Network of Excellence (GRiP), supported by the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme (Grant Agreement no 261060).

    • Competing interests None.

    • Provenance and peer review Not commissioned; externally peer reviewed.