Pediatric Versus Adult Drug Trials for Conditions With High Pediatric Disease Burden

Abstract

BACKGROUND AND OBJECTIVE: Optimal treatment decisions in children require sufficient evidence on the safety and efficacy of pharmaceuticals in pediatric patients. However, there is concern that not enough trials are conducted in children and that pediatric trials differ from those performed in adults. Our objective was to measure the prevalence of pediatric studies among clinical drug trials and compare trial characteristics and quality indicators between pediatric and adult drug trials. METHODS: For conditions representing a high burden of pediatric disease, we identified all drug trials registered in ClinicalTrials.gov with start dates between 2006 and 2011 and tracked the resulting publications. We measured the proportion of pediatric trials and subjects for each condition and compared pediatric and adult trial characteristics and quality indicators. RESULTS: For the conditions selected, 59.9% of the disease burden was attributable to children, but only 12.0% (292/2440) of trials were pediatric (P < .001). Among pediatric trials, 58.6% were conducted without industry funding compared with 35.0% of adult trials (P < .001). Fewer pediatric compared with adult randomized trials examined safety outcomes (10.1% vs 16.9%, P = .008). Pediatric randomized trials were slightly more likely to be appropriately registered before study start (46.9% vs 39.3%, P = .04) and had a modestly higher probability of publication in the examined time frame (32.8% vs 23.2%, P = .04). CONCLUSIONS: There is substantial discrepancy between pediatric burden of disease and the amount of clinical trial research devoted to pediatric populations. This may be related in part to trial funding, with pediatric trials relying primarily on government and nonprofit organizations.

Finding Better Ways to Fill Gaps in Pediatric Health Research

“…5 Previous analyses have shown a discrepancy between the pediatric disease burden and the amount of clinical trial research devoted to pediatric populations. 2 Our analysis confirms this finding for low-and middle-income countries but not for high-income countries (Table 1). However, in determining how much research is needed for an age group, disease burden is just 1 factor.…”

“…Methodological and ethical challenges associated with pediatric research increase the costs of running pediatric trials, and the market for pediatric products is relatively small. 1,2 The subsequent knowledge gaps and lack of child-specific product development have resulted in high off-label and unlicensed medication prescription rates in children. 2 The past decade has seen increased recognition of this problem, and both the United States and the European Union have implemented legislative measures to stimulate pediatric health research by providing incentives and funding for pediatric studies and by requiring pediatric studies for new drug applications when appropriate.…”

“…1,2 The subsequent knowledge gaps and lack of child-specific product development have resulted in high off-label and unlicensed medication prescription rates in children. 2 The past decade has seen increased recognition of this problem, and both the United States and the European Union have implemented legislative measures to stimulate pediatric health research by providing incentives and funding for pediatric studies and by requiring pediatric studies for new drug applications when appropriate. [1][2][3] Although these measures have led to an increase in the number of pediatric trials being conducted and to several knowledge gaps being addressed, 3 the trials remain driven largely by market incentives, and evaluations of the measures in the United States 1 and the European Union 3 show that other areas remain neglected.…”

“…2 The past decade has seen increased recognition of this problem, and both the United States and the European Union have implemented legislative measures to stimulate pediatric health research by providing incentives and funding for pediatric studies and by requiring pediatric studies for new drug applications when appropriate. [1][2][3] Although these measures have led to an increase in the number of pediatric trials being conducted and to several knowledge gaps being addressed, 3 the trials remain driven largely by market incentives, and evaluations of the measures in the United States 1 and the European Union 3 show that other areas remain neglected. Moreover, the majority of the global pediatric disease burden lies with populations in low-and middle-income countries, for whom the lack of health R&D remains a significant problem.…”

“…When summed, the numbers in the table exceed 100% because trials regularly recruited participants from multiple age groups and multiple regions. Burden of disease for the age group 15-17 y was calculated using the method of Bourgeois et al 2 CI, confidence interval; DALY, disability-adjusted life-year. a It matters how one defines a pediatric trial.…”