What are the problems with paediatric trials, and how can we make the evidence base in child health bigger, more reliable, and more relevant? That was the ambitious task set by the StaR Child Health group , which convened recently in Amsterdam. The group aims to “enhance the quality, ethics and reliability of pediatric clinical research by promoting the use of evidence-based standards or guidance for clinical studies with children”. Triallists, paediatricians, regulators, editors, and representatives from the pharmaceutical industry contributed towards assessing which standards might be relevant in child health, and what we need to do (at least initially) to work towards developing them.
The US Food and Drug Administration and the European Medicines Agency have both recently developed policies aimed at promoting the development of medicines for children. However, evidence put forward by Terry Klassen of the Alberta Research Center for Health Evidence, and the StaR Child Health Executive Board, clearly showed that although numbers of clinical trials in adults have increased dramatically over recent decades, the numbers of clinical trials in child health have remained static.
Increasing the amount of evidence is one challenge, but equally important is improving the relevance and quality of that evidence. One set of standards on the “priority list” for StaR Child Health is that of appropriate outcomes assessment in paediatric trials.
Research already done by Ian Sinha and colleagues from the University of Liverpool, which was published in PLoS Medicine has revealed that few studies have been carried out in paediatric specialties to assess the appropriate choice of outcomes for trials in children. Future work in this area might parallel that of the OMERACT group, a consensus group that establishes appropriate outcome measures in rheumatology. At StaR Child Health, Maarten Boers set out the challenges in achieving such consensus, and the criteria for appropriate outcome measures: a measure needs to be truthful, to discriminate well, and to be feasible. Standardised outcome assessment in children are likely to focus on measures which can accurately reflect important elements of health within different domains: disease activity, functional status, and quality of life.
Over ten years ago, Doug Altman (University of Oxford) commented that “Huge sums of money are spent annually on research that is seriously flawed through the use of inappropriate designs, unrepresentative samples, small samples, incorrect methods of analysis, and faulty interpretation”. It seems that this still applies to paediatric trials, and specifically the difficulties of doing adequately powered research in child health. Many speakers presented the problem of appropriately designing a trial when no prior good evidence exits to inform a proper sample size calculation; in addition, how does one even choose a comparator when efficacy is unknown? A key area that the StaR child health group hopes to target is that of designing studies with adequate sample sizes, and the role of data monitoring committees in protecting child safety.
Clearly, the group has set itself an challenging agenda, but a worthwhile one. To find out more, and to contribute to the initiative, go to http://www.ifsrc.org/.