Empirical evaluation of age groups and age-subgroup analyses in pediatric randomized trials and pediatric
Despina G Contopoulos-Ioannidis1, Iva Seto, Michele P Hamm
1Department of Pediatrics, Division of Infectious Diseases, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, California 94305, USA. dcontop@stanford.edu
Insights
Pediatric clinical research shows wide variation in child age ranges and subgroup analyses. Standardizing these criteria is crucial for improving trial conduct and data interpretation.
Area of Science:
- Pediatric clinical research
- Evidence synthesis
- Biostatistics
Background:
- Standardizing age criteria in pediatric trials is essential for improving research conduct.
- Defining optimal age subgroups for analysis enhances the validity of pediatric studies.
Purpose of the Study:
- To empirically evaluate age ranges and subgroup analyses in recent pediatric randomized clinical trials (RCTs) and meta-analyses.
- To identify variability in age inclusion and subgroup reporting in pediatric research.
Main Methods:
- Screened 24 RCTs from Pediatrics (2011), 188 RCTs from Cochrane Central Register (2007), and 48 meta-analyses from Cochrane Database (2011).
- Extracted data on age ranges, considered age subgroups, and reported age-subgroup differences.
Main Results:
- Significant variability observed in age ranges across pediatric RCTs and meta-analyses.
- Few studies (25% of Pediatrics RCTs, 28% of Cochrane RCTs, 23% of meta-analyses) reported age-subgroup analyses.
- Observed age-subgroup differences were often not statistically significant.
Conclusions:
- Considerable heterogeneity exists in age ranges and subgroup definitions within pediatric clinical research.
- Limited evidence of significant age-related differences in outcomes was found.
- Further investigation into the rationale for selecting specific age subgroups is warranted.
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 age-subgroups 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.
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