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Optimiser l'évaluation des médicaments en néonatologie : l'exemple des médicaments anti-infectieux

Abstract : Neonates represent the most vulnerable paediatric population and probably the one with the greatest needs in medicines with regard to the specificities of neonatal diseases. Nevertheless, the off-label prescribing of drugs with no marketing authorisation, consequentlywithout information for their proper use, is widespread in neonatology. This situation is related to the difficulties of clinical research encountered in this population. The objective of this thesis is to analyse the different steps of drug development in neonates and to discuss the possible methods to optimize drug evaluation. To illustrate this development, we expose examples from the evaluation of anti-infective agents in neonatology. These drugs are very often concerned by a use outside their product licence in term and preterm neonates, despite the fact that they have been marketed for many years. This thesis includes studies concerning the different steps of their development illustrated by examples. 1) Evaluation of the specificities of the neonatal population and of drug prescribing. This was demonstrated by the results of a European survey on the use of ciprofloxacin and fluconazole in neonatal intensive care units. The surveys’ results underline the considerable variability in drug prescribing observed between different countries but also between units in the same country. 2) Analysis of available data, illustrated by the systematic review of the literature on ciprofloxacin use for the treatment of Gram negative neonatal infections, 3) Definition of optimal dosing. Use of modelling and data simulation approaches should be particularly favoured in neonatal drug research. Correct validation of models should be performed as illustrated by the external validation of vancomycin population pharmacokinetic models. 4) Design and implementation of clinical trials. This step has been illustrated by the clinical development of ciprofloxacin in neonatology. The review of all randomised controlled trials evaluating the therapeutic and prophylactic use of antibiotics in neonates showed that these trials are poorly designed, conducted and reported. Different methods of evaluation should be considered and further developed to circumvent the difficulties in drug evaluation and ensure the efficient and safe use of antibiotics.
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Submitted on : Friday, July 13, 2012 - 9:42:34 AM
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Florentia Kaguelidou. Optimiser l'évaluation des médicaments en néonatologie : l'exemple des médicaments anti-infectieux. Médecine humaine et pathologie. Université René Descartes - Paris V, 2012. Français. ⟨NNT : 2012PA05P605⟩. ⟨tel-00717477⟩



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