Research Article: Children Are Not Just Small Adults: The Urgent Need for High-Quality Trial Evidence in Children

Date Published: August 12, 2008

Publisher: Public Library of Science

Author(s): Terry P Klassen, Lisa Hartling, Jonathan C Craig, Martin Offringa

Abstract: Terry Klassen and colleagues discuss a new study examining whether children and adults with drug-resistant partial epilepsy respond differently to antiepileptic drugs.

Partial Text: Children are often touted as being very important members of society because they represent our future. Optimizing their health outcomes has the potential for a huge impact on public health because children are at an early stage in the life trajectory. But it is often unclear how society allocates its resources or creates policies to ensure that it invests in children’s health. The under-investment in pediatric clinical trials is a good example of how our resource allocation may be insufficient.

History has shown that children may be exposed to serious unintended harms from medications if adequate research is not performed. Examples of such harm include the use of chloramphenicol for neonates producing the grey baby syndrome, the use of verapamil for treatment of infants with supraventricular tachycardia resulting in refractory hypotension and death, serious extrapyramidal dysfunction and bladder retention leading to hospitalization after domperidone, and many more [5–7].

A new study by Philippe Ryvlin and colleagues in this issue of PLoS Medicine makes an important contribution to the question of whether there are differences in treatments effects between children and adults [12]. In an effort to investigate whether children and adults with drug-resistant partial epilepsy respond differently to active treatment versus placebo, these authors performed a comprehensive search for methodologically rigorous RCTs evaluating antiepileptic drugs as add-on treatment for both children and adults. Overall, the treatment effect for their primary outcome (i.e., 50% responder rate) was significantly lower for children with a relative risk ratio of 0.67 (95% confidence interval 0.51–0.89), explained by the higher rate of response in the placebo arms of the pediatric trials (19% versus 9.9%, p < 0.001) [12]. We know that the lack of trial evidence goes beyond neurological diseases to other childhood areas, such as pediatric cardiology, neonatology, pediatric intensive care, and oncology [2,13]. If we use publication of RCTs in general medical journals as a marker, it would appear the gap is widening between the annual number of published pediatric trials and adult trials [14]. Furthermore, a recent review of studies published in six leading medical journals showed that “studies involving adults were significantly more likely than child studies to be randomized, controlled trials, systematic reviews, or studies of therapies” [15]. While more empirical evidence is needed to guide clinical practice for children, further research, such as the study by Ryvlin and colleagues, is important to inform the design and reporting of pediatric trials. Standards for the design and reporting of pediatric trials would contribute to the development of a methodologically strong and relevant evidence base for pediatric care. Moreover, adequate reporting will assist end-users in assessing the relevance and applicability of a study's findings ( Source:


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