Article type
Year
Abstract
Background: Therapeutic benefit is commonly extrapolated from adult clinical trials to children without conducting trials in children. It has been widely recognized that children cannot be provided with safe and efficacious drugs compared to those available for adults without involving them in clinical trials. To our knowledge, extrapolation of data from adults to children based on the results of randomized controlled trials (RCTs) has not consistently been explored.
Objectives: Our main objective was to see whether the therapeutic benefit observed in placebo controlled RCTs is different between adults and children.
Methods: We searched three electronic databases for meta-analyses that included double-blind, placebo–controlled RCTs with separate results for adults and children. The selected reviews were classified according to disease and drug used. The heterogeneity of treatment response between adults and children was measured using ratio of odds ratios (RORs).
Results: We selected 89 meta-analyses and calculated RORs for 124 drugs. Heterogeneity in the direction of the treatment effect was observed in one drug and heterogeneity in the quantity of the treatment effect in 13 drugs (Figure 1), indicating significantly different treatment effect in adults when compared with children. RORs were not significantly different from 1 for 110 drugs. For 36 of these drugs, the treatment effect was confirmed in both populations.
Conclusions: We found different treatment benefits estimated by clinical trials performed in adults compared with those performed in children for 14 out of 124 drugs. Our results also show the potential influence of pharmacokinetics and pharmacodynamics and the need to better report on the rationale of dose adjustments in RCTs. A better reporting of age range and dose adjustment would allow full exploration of possible sources of clinical and statistical heterogeneity, enabling the prediction of situations where there may be differences between adults and children.
Objectives: Our main objective was to see whether the therapeutic benefit observed in placebo controlled RCTs is different between adults and children.
Methods: We searched three electronic databases for meta-analyses that included double-blind, placebo–controlled RCTs with separate results for adults and children. The selected reviews were classified according to disease and drug used. The heterogeneity of treatment response between adults and children was measured using ratio of odds ratios (RORs).
Results: We selected 89 meta-analyses and calculated RORs for 124 drugs. Heterogeneity in the direction of the treatment effect was observed in one drug and heterogeneity in the quantity of the treatment effect in 13 drugs (Figure 1), indicating significantly different treatment effect in adults when compared with children. RORs were not significantly different from 1 for 110 drugs. For 36 of these drugs, the treatment effect was confirmed in both populations.
Conclusions: We found different treatment benefits estimated by clinical trials performed in adults compared with those performed in children for 14 out of 124 drugs. Our results also show the potential influence of pharmacokinetics and pharmacodynamics and the need to better report on the rationale of dose adjustments in RCTs. A better reporting of age range and dose adjustment would allow full exploration of possible sources of clinical and statistical heterogeneity, enabling the prediction of situations where there may be differences between adults and children.