An absence of pediatric randomized controlled trials in general medical journals, 1985–2004

Abstract

Objective

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.

Study Design and Setting

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).

Results

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).

Conclusion

There may be significant barriers to the publication of high-quality pediatric RCTs in GMJs.

Introduction

Clinical trials have led to important changes in clinical practice and health outcomes for children. Some examples of this are the marked reduction in mortality from childhood acute lymphoblastic leukemia and from extreme prematurity as a result of well-conducted multicenter trials [1], [2]. However, pediatric practitioners and researchers commonly lament the lack of high-quality clinical trials in children [3]. This is particularly true of randomized controlled trials (RCTs), which are considered the “gold standard” of clinical trials, as they can provide unconfounded estimates of intervention effects when conducted appropriately [3], [4].

General medical journals (GMJs) are an important source of influential pediatric publications. They are widely read by both generalists and specialists and are widely cited. An assessment of pediatric studies referenced in the Cochrane Database of Systematic Reviews revealed that four out of the top six journals cited were GMJs [5]. All of these GMJs have a higher impact factor than any clinical pediatric journal. Some authors have argued that GMJs under-report studies of diseases of poverty or studies from resource-poor countries and thus poorly represent the global burden of disease [6], [7], [8]. Many of these conditions disproportionately affect children (e.g., gastroenteritis, meningitis, nonintentional injury), and it can therefore be hypothesized that there may be under-reporting of trials of important diseases of childhood in GMJs. The objectives of this study are to assess the quantity, trend over time, characteristics, and quality of RCTs involving children published in GMJs and to compare these with RCTs involving adults.