The development of medicines for children. Part of a series on Pediatric Pharmacology, guest edited by Gianvincenzo Zuccotti, Emilio Clementi, and Massimo Molteni
European Assessment Unit - Agenzia Italiana del Farmaco (AIFA), via del Tritone 181, 00187 Rome, Italy.Pharmacological Research (Impact Factor: 4.41). 03/2011; 64(3):169-75.
The lack of availability of appropriate medicines for children is an extensive and well known problem. As a consequence off label or unlicensed administration of medicinal products in every day paediatric practice is frequent. A variety of obstacles hinder the development of paediatric indications for drugs primarily intended for the adult market. The barriers to proper research on children's drug development include several complex factors, such as the limited commercial interest, lack of suitable infrastructure and competence for conducting paediatric clinical trials, difficulties in trial design, ethical worries and many others. Medicinal products used to treat children should be subjected to ethical research of high quality and be explicitly authorised for use in children as it happens in adults. Conducting adequate clinical trials in children is challenging and demanding. Identification of paediatric medical needs, extrapolation from adult data, modelling and simulation, specific clinical trial methodology are important features in the development of drugs intended for children. Market forces alone have proven insufficient to stimulate adequate research aimed at specific authorisation of medicinal products for the paediatric population, and for that reason, following the US experience, the European Paediatric Regulation has been amended in January 2007 by the European Commission. The objective of the Paediatric Regulation is to improve the development of high quality and ethically researched medicines for children aged 0 to 17 years, to facilitate the availability of information on the use of medicines for children, without subjecting children to unnecessary trials, or delaying the authorisation of medicines for use in adults. The impact of the Paediatric Regulation reflects in an increase in the number of paediatric studies to be performed, even if a significant number of these studies have not started yet. The objective of this review is to describe the main regulatory and scientific features which play a role in the complex issue of paediatric drug development.
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ABSTRACT: Due to the challenges inherent in performing clinical trials in children, a systematic review of published clinical trials was performed to determine whether the efficacy of antiepileptic drugs (AEDs) in adults can be used to predict the efficacy of AEDs in the pediatric population. Medline/PubMed, EMBASE, and Cochrane library searches (1970-January 2010) were conducted for clinical trials of partial-onset seizures (POS) and primary generalized tonic-clonic seizures (PGTCS) in adults and in children <2 and 2-18 years. Independent epidemiologists used standardized search and study evaluation criteria to select eligible trials. Forest plots were used to investigate the relative strength of placebo-subtracted effect measures. Among 30 adjunctive therapy POS trials in adults and children (2-18 years) that met evaluation criteria, effect measures were consistent between adults and children for gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate. Placebo-subtracted median percent seizure reduction between baseline and treatment periods (ranging from 7.0% to 58.6% in adults and from 10.5% to 31.2% in children) was significant for 40/46 and 6/6 of the treatment groups studied. The ≥50% responder rate (ranging from 2.0% to 43.0% in adults and from 3.0% to 26.0% in children) was significant for 37/43 and 5/8 treatment groups. In children <2 years, an insufficient number of trials were eligible for analysis. This systematic review supports the extrapolation of efficacy results in adults to predict a similar adjunctive treatment response in 2- to 18-year-old children with POS.Neurology 09/2012; 79(14):1482-9. DOI:10.1212/WNL.0b013e31826d5ec0 · 8.29 Impact Factor
- Journal of pediatric gastroenterology and nutrition 09/2012; 55(5). DOI:10.1097/MPG.0b013e318272af1f · 2.63 Impact Factor
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ABSTRACT: Background A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice. Method A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses’ experiences and views. Results The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance. Conclusion Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children.BMC Pediatrics 05/2013; 13(1):81. DOI:10.1186/1471-2431-13-81 · 1.93 Impact Factor
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