Very few studies have asked what the appropriate measurements are for assessing treatments in clinical trials in children, according to a systematic review of paediatric clinical research conducted since 1950. The review by Ian Sinha and colleagues from the University of Liverpool, published in this week’s PLoS Medicine, also shows that few studies have involved parents and none have involved children in the process to select which measurements to use to assess clinical trials.
Before conducting a clinical trial of a new drug, researchers choose several “outcomes.” These are measurements chosen in advance of the trial to ensure that as much information as possible is provided about the drug’s safety, effectiveness and its impact on the patients’ health and daily life. Children’s bodies handle certain drugs very differently to adults – it can’t just be assumed that drugs effective in adults simply need to be scaled down to work for children – and so paediatric clinical trials need to be designed with these differences in mind.
By using a search strategy and consulting experts in paediatric clinical research, the researchers identified all the studies since 1950 that have examined the selection of outcomes in clinical trials conducted in children. Their initial search was very wide to minimize bias, leading to the retrieval of 9,000 abstracts. Only twenty-five articles met the criteria established by the review and examined the selection of outcomes in clinical research in children. These studies came from thirteen groups researching different conditions – including asthma, Crohn’s disease and cystic fibrosis – but for many paediatric areas there has been no work done into the selection of appropriate outcomes for clinical trials in children.
Reaching agreement on standard outcomes for clinical trials in children is important because it enables researchers and clinicians to compare and combine the results of clinical trials. Standardization also helps avoid selectivity and bias in the conduct of research. Several of the studies reviewed by Ian Sinha and colleagues used methods that had previously been used to select outcomes in clinical trials in adults. These include a technique in which individual opinions are sought and fed back into a group discussion before a final consensus agreement is reached, as well as a technique that involves face-to-face discussion followed by a vote. But although the groups selecting the appropriate outcomes in these studies included clinical experts and specialists in a particular paediatric condition, only three groups asked parents about the outcomes that should be included to assess the clinical trials and none of them asked children directly. < /span>
In an accompanying perspective, Mike Clarke of the UK Cochrane Centre and Trinity College, Dublin - not involved in the systematic review - suggests the approaches identified should “make it easier to plan, appraise and use initiatives that have already attempted to standardize outcomes.” But as Ian Sinha and colleagues conclude, further research is urgently required to make this process easier and more uniform and to involve children and their parents in assessing which outcomes should be used in clinical trials.
Citation: Sinha I, Jones L, Smyth RL, Williamson PR (2008) A systematic review of studies that aim to determine which outcomes to measure in clinical trials in children. PLoS Med 5(4): e96.
IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050096
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-04-sinha.pdf
CONTACT:
Ian Sinha
University of Liverpool
Institute of Child Health
Alder Road
Liverpool, Merseyside L12 2AP
United Kingdom
+44 151 228 4811
i.sinha@liv.ac.uk
Related PLoS Medicine perspective:
Citation: Clarke M (2008) Standardising outcomes in paediatric clinical trials. PLoS Med 5(4): e102.
IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050102
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-04-sinha.pdf
CONTACT:
Mike Clarke
UK Cochrane Centre
NHS R&D Programme
Middle Way
Oxford, OX2 7LG
United Kingdom
+44-1865-516300
+44-1865-516311 (fax)
mclarke@cochrane.co.uk
THE FOLLOWING RESEARCH ARTICLES WILL ALSO BE PUBLISHED ONLINE:
Peripheral blood proteins as biomarkers for idiopathic pulmonary fibrosis
Naftali Kaminski (of the University of Pittsburgh School of Medicine) and colleagues find increased levels of specific proteins in the bloodstream of individuals with idiopathic pulmonary fibrosis, and suggest that these proteins may ultimately provide a biomarker for the disease.
The study is discussed in a perspective article by Peter Barnes of Imperial College London, who was uninvolved with the research.
Citation: Rosas IO, Richards TJ, Konishi K, Zhang Y, Gibson K, et al. (2008) MMP1 and MMP7 as potential peripheral blood biomarkers in idiopathic pulmonary fibrosis. PloS Med 5(4): e93.
IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050093
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-04-kaminski.pdf
CONTACT:
Naftali Kaminski
University of Pittsburgh School of Medicine
The Dorothy P. and Richard P. Simmons Center for Interstitial Lung Diseases,
Pittsburgh, PA 15261
United States of America
+1 412-647-3156
+1 412-647-7875 (fax)
kaminskin@upmc.edu
Related PLoS Medicine perspective:
Citation: Barnes PJ (2008) A blood test for lung fibrosis" PLoS Med 5(4): e98.
IN YOUR ARTICLE, PLEASE LINK TO THIS URL, WHICH WILL PROVIDE ACCESS TO THE PUBLISHED PAPER: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050098
PRESS-ONLY PREVIEW OF THE ARTICLE: http://www.plos.org/press/plme-05-04-barnes.pdf
CONTACT:
Peter Barnes
Imperial College London
National Heart and Lung Institute
Dovehouse St.
London, SW3 6LY
United Kingdom
+44 207 351 8174
+44 207 351 5675 (fax)
p.j.barnes@imperial.ac.uk
Journal
PLoS Medicine