An absence of pediatric randomized controlled trials in general medical journals, 1985-2004
ABSTRACT There are numerous potential barriers to conducting randomized controlled trials (RCTs) in children. The purpose of this study was to compare the quantity, trends over time, characteristics, and quality of pediatric RCTs published in general medical journals (GMJs) with adult RCTs.
We conducted an electronic search of adult and pediatric RCTs from 1985-2004 and a manual search of published RCTs in the year 2000 in five high-impact GMJs (New England Journal of Medicine, Journal of the American Medical Association [JAMA], the Lancet, British Medical Journal [BMJ], Canadian Medical Association Journal [CMAJ]). Linear trends were identified and the 1-year sample was analyzed for publication characteristics (location of recruitment, sample size, number of centers, funding sources, and results) and quality scoring (Jadad score, intention-to-treat analysis, and citation frequency since publication).
Adult RCTs increased by 4.71 RCTs/year (95% confidence interval (CI) 3.62-5.80; P<0.001), which was significantly higher (P<0.0001) than pediatric RCTs, which increased by 0.4 RCTs/year (95% CI -0.02 to 0.9; P=0.06). Adult RCTs were more likely to be hospital-based (P=.001) and to involve more centers in multicenter studies (P=0.02). Quality scores were similar, although adult RCTs were cited more frequently (P=0.003).
There may be significant barriers to the publication of high-quality pediatric RCTs in GMJs.
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ABSTRACT: This nationwide study is aimed at describing to what extent the European Paediatric Regulation has met therapeutic needs in children. Data for each drug substance in defined daily doses (DDD) were extracted from the national Danish data base. We evaluated if drug substances were used off-label and whether they had a paediatric investigation plan (PIP). This study did not include drug prescriptions for individual paediatric patients; thus, it was not possible to make use of all off-label categories previously used. Additionally, paediatric standard assortments (SA) were compared to the European survey on paediatric medicinal products. Thirteen percent of the 100 most used drug substances were determined as being used off-label, four of which had a PIP and one had a full waiver. Only one of the three drug substances used off-label most often, accounting for 85 % of such use, had a PIP. Neonates were included in one-third of PIPs and adolescents in 15. Nineteen out of 21 PIPs had a waiver and 14 PIPs were deferred. In line with the European survey, carbapenems, corticosteroids and proton pump inhibitors were frequent found in SAs. PIPs only cover a small proportion of the drugs found to be used off-label in this study. Despite waivers granted, drug substances were used nonetheless. Unmet regulatory needs are still considerable in some therapeutic areas in neonates as well as in children.European Journal of Clinical Pharmacology 01/2014; 70(4). DOI:10.1007/s00228-013-1626-1 · 2.70 Impact Factor
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ABSTRACT: To determine whether randomized controlled trials of pharmacologic interventions in children are more likely to be biased than similar trials in adults. Trials involving only children and published in MEDLINE between January 2008 and October 2009 (n = 100) were randomly selected and matched, by drug class and therapeutic area, with a similar trial completed in adults. The Cochrane risk of bias tool was used to compare the pediatric and adult trials. The characteristics of adult and pediatric trials included were similar, except that adult studies were more likely to be conducted in Europe and published in specialty journals. Two-thirds of all trials were single center, and 62% had 100 or fewer participants. Many trials had an unclear risk of bias for allocation concealment (65% adult, 52% pediatric). More pediatric trials had a low risk of bias for random sequence generation (59% pediatric, 41% adult, P = .002) and blinding of outcome assessment (63% pediatric, 48% adult, P = .04) than adult trials; however, a sensitivity analysis of trials published since 2008 (and so matched by year of publication) did not confirm this finding, suggesting year of publication was an important confounder. When randomized controlled trials are matched for drug class and therapeutic area, trials involving children display a similar risk of bias. Differences in the risk of bias between pediatric and adult trials are not caused by differences in the capacity of researchers to conduct and report trials of high quality.The Journal of pediatrics 05/2014; 165(2). DOI:10.1016/j.jpeds.2014.03.058 · 4.02 Impact Factor
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ABSTRACT: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. Conclusion: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.European Journal of Pediatrics 09/2014; DOI:10.1007/s00431-014-2398-z · 1.98 Impact Factor