Study Finds That Children And Adults Respond Differently To Placebo

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Main Category: Pediatrics / Children's Health
Also Included In: Clinical Trials / Drug Trials;  Epilepsy
Article Date: 12 Aug 2008 - 0:00 PST

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According to an article published in the open-access journal PLoS Medicine, children with drug-resistant partial epilepsy who are enrolled in trials tend to have a greater response to placebo than adults enrolled in such trials. Philippe Ryvlin (Hospices Civils de Lyon, France) and colleagues say in their systematic review of antiepileptic drugs that their findings should be considered when researchers are designing drug trials to be carried out with epileptic children.

Randomized controlled trials (RCTs) are the standard research methods used to test a drug against placebo. Most RCTs include samples of adult patients, and the results are assumed to hold true for children with the same disease if the dosage is scaled down. Using the results of adult studies for children has been a common approach to treating epilepsy - a common brain disorder in children in which disruptions in the electrical activity of part (partial epilepsy) or all (generalized epilepsy) of the brain cause seizures. Epileptic drugs have been quite successful in stopping seizures in most patients. Since adults and children respond differently to epileptic drugs, researchers sought to determine the general differences in treatment response between children and adults; future researchers could then allow for these differences when developing pediatric RCTs. Specifically, Ryvlin and colleagues analyzed published RCTs of epileptic drugs for partial epilepsy to look for age-dependent differences in drug response.

The authors searched through the existing RCT literature for trials that compared the effects of giving an additional antiepileptic drug with those of giving a placebo by asking what fraction of patients given each treatment had a seizure frequency reduction of 50% during the treatment period compared to some baseline period - the "50% responder rate". They found 32 such trials, five of them pediatric RCTs. Pooling the results of the studies to perform a meta-analysis, the researchers found that the treatment effect was significant lower in children than in adults. One reason for this difference, note the researchers, is that children responded to placebo more often than adults - about 20% of children had a 50% reduction in seizures after receiving placebo compared to about 10% of adults.

The findings suggest that children with drug-resistant partial epilepsy respond more strongly in RCTs to placebo than adults. However, results are limited by the small number of pediatric trials available. The researchers conclude by calling for additional studies that can explain this observation. They maintain that the differences between adults and children should be taken into account when developing pediatric RCTs for antiepileptic drugs and perhaps drugs for other conditions as well.

In an accompanying perspective article, Terry Klassen (University of Alberta) and colleagues write that, "This study again underscores the relatively weak evidence base informing medical care in children compared with adults". They conclude: "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."

Greater response to placebo in children than in adults: A systematic review and meta-analysis in drugresistant partial epilepsy
Rheims S, Cucherat M, Arzimanoglou A, Ryvlin P
PLoS Medicine (2008). 5(8): e166.
doi:10.1371/journal.pmed.0050166
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Children are not just small adults: The urgent need for high-quality trial evidence in children
Klassen TP, Hartling L, Craig JC, Offringa M
PLoS Medicine (2008). 5(8): e172.
doi:10.1371/journal.pmed.0050172
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About PLoS Medicine

PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit http://www.plosmedicine.org

About the Public Library of Science

The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit http://www.plos.org

Written by: Peter M Crosta
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