Empirical Evaluation of Age Groups and Age-Subgroup Analyses in Pediatric Randomized Trials and Pediatric Meta-analyses

Abstract

BACKGROUND: An important step toward improvement of the conduct of pediatric clinical research is the standardization of the ages of children to be included in pediatric trials and the optimal agesubgroups to be analyzed. METHODS:We set out to evaluate empirically the age ranges of children, and age-subgroup analyses thereof, reported in recent pediatric randomized clinical trials (RCTs) and meta-analyses. First, we screened 24 RCTs published in Pediatrics during the first 6 months of 2011; second, we screened 188 pediatric RCTs published in 2007 in the Cochrane Central Register of Controlled Trials; third, we screened 48 pediatric meta-analyses published in the Cochrane Database of Systematic Reviews in 2011. We extracted information on age ranges and age-subgroups considered and age-subgroup differences reported. RESULTS:The age range of children in RCTs published in Pediatrics varied from 0.1 to 17.5 years (median age: 5; interquartile range: 1.8-10.2) and only 25% of those presented age-subgroup analyses. Large variability was also detected for age ranges in 188 RCTs from the Cochrane Central Register of Controlled Trials, and only 28 of those analyzed age-subgroups. Moreover, only 11 of 48 meta-analyses had age-subgroup analyses, and in 6 of those, only different studies were included. Furthermore, most of these observed differences were not beyond chance. CONCLUSIONS:We observed large variability in the age ranges and age-subgroups of children included in recent pediatric trials and meta-analyses. Despite the limited available data, some age-subgroup differences were noted. The rationale for the selection of particular age-subgroups deserves further study. Pediatrics 2012;129:S161-S184

In Children With Nonalcoholic Fatty Liver Disease, Cysteamine Bitartrate Delayed Release Improves Liver Enzymes but Does Not Reduce Disease Activity Scores

“…Evaluating response by age subgroups is commonly recommended for pediatric studies, especially those with a large age range such as we had in CyNCh 32 . Younger children have biological differences compared to adolescents including that they are more likely to be pre-pubertal or in early stages of puberty, and they tend to have fewer co-morbidities.…”

Do systematic reviews on pediatric topics need special methodological considerations?

“…Substantial differences exist between systematic reviews with respect to how infants, children, adolescents, and adults are defined. This difference may be due to the variation in age categories used in primary studies and insufficient attention to the importance of age groupings for public health relevance [18]. While PRISMA recommends to explicitly state the patient population being addressed and their defining characteristics such as disease and the setting of care considered, justifying the eligible pediatric age range and age group(s) selected for the systematic review, addressing potential age related differences in intervention effects are critical reporting elements in pediatric systematic reviews.…”

“…However, only 13% of the authors of pediatric relevant systematic reviews planned to conduct a subgroup analysis based on age, of which 60% (31/52) conducted the planned subgroup analysis [17]. Moreover the use of overlapping pediatric age subgroups has been reported [18]. In the “pediatric only reviews”, only 23% provided age sub-group analysis [18], and age categories used in these analyses varied substantially even for similar interventions and health conditions [17, 18].…”

“…Moreover the use of overlapping pediatric age subgroups has been reported [18]. In the “pediatric only reviews”, only 23% provided age sub-group analysis [18], and age categories used in these analyses varied substantially even for similar interventions and health conditions [17, 18]. While synthesising data increases statistical power and allows for more precise effect estimates of treatment comparison, a meta-analysis covering the whole of the pediatric population may be unsuitable when studies are too heterogeneous in terms of the pediatric age categories they include.…”

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“…Given the paucity of data, any age subgroup analyses (eg, infants, preschoolers) would be unable to detect any clinically significant differences. 40,41 Fourth, for some subjective harms (eg, pain), it is possible that children might underreport them, and this may affect the frequency of estimated discrepancies between adults and children for such end points. Fifth, we also considered mortality among the eligible end points, although death is often considered an efficacy outcome.…”