The opportunity exists, in the next 10 years to change the status of children with respect to available therapeutic agents for improving their health. While in the past, children have been treated as ‘pharmacologic orphans’, recent legislative efforts have motivated an increased emphasis of purposefully studying therapeutic agents in children [1
]. This effort needs to develop into a direction that primarily supports gathering information for children to improve their health. While it provides incentive for drug developers to actively participate by studying all new agents developed for adults, there is a need to understand fundamental aspects of how children differ compared with adults in terms of their absorption, distribution and clearance of pharmaceutical agents. If this opportunity is managed well, then the next decade will provide a tremendously increased knowledge base for pediatric pharmacology that will allows drug developers to understand and predict how their compounds are likely to behave in children.
If this opportunity is not managed well, then there is the opportunity for drug developers to obtain increased marketing exclusivity for a number of individual agents without gaining the integrated knowledge that will be essential for adequately dosing therapeutic agents in children from neonates to adolescents. Which direction this will migrate is difficult to predict. The components are present for this effort to succeed, but only time will tell if this is indeed accomplished.
The role of modeling and simulation in this effort will be critical to extending information from sparse experiments into a context that allows broader understanding of how therapeutic agents behave in children. Owing to the limitations and constraints of pediatric clinical trials, developers have little choice than to use modeling and simulation efforts to their fullest in support of their pediatric drug development efforts. In doing so, it will be incumbent on the developers to engage in a dialogue with health authorities to understand and ratify modeling approaches taken in support of a regulatory submission for children [4
]. There must also be continual assessment and validation of simulation results with clinical outcomes as they emerge to assure that the models and gathered data converge. It will also be incumbent on the health authorities and clinical pharmacologists to work together with drug developers to efficiently study therapeutic agents with the greatest need and highest priority. This priority must be motivated by the need of children rather than the opportunity for adult therapeutics.
The opportunity exists to transform drug development for children and for all categories of patients who receive these therapeutic agents. In their forecasting report on the future of pharmaceutical development, the consulting firm PriceWaterhouseCoopers predict the movement of greater amounts of pharmaceutical research and clinical development towards in silico
approaches with the rapid approval in select populations for new chemical entities that ultimately can migrate into greater populations and clinical areas as need and indication develop [102
]. Although this is presented as a model for the future, in fact what is proposed is precisely the opportunity that is present in pediatric drug development. Through a number of opportunities, there is momentum, data and need to improve the process of understanding existing therapeutic agents used in children and in studying new agents as they emerge. With the committed effort from academics, drug developers and regulatory authorities, the chance to greatly improve drug development for children exists if these groups work together to optimize resources, energy and finances to answer the most important questions for pediatric clinical pharmacology. This can provide a framework for improving drug development in general by combining existing clinical pharmacology knowledge with quantitative modeling of drug behavior in vivo
and disease progression. Together, these factors can dramatically improve drug development, not only for pediatrics, but for all.
- Many pharmaceutical agents are used off-label in children without guidance to clinicians for dosage initiation or adjustment.
- The lack of dosing guidance stems from ethical, pharmacological, statistical and economic challenges to studying pharmaceutical agents in children.
- Current legislative efforts are changing this to increase efforts to study pharmaceutical agents in children.
- Increasing effort is needed to focus these efforts on understanding the most important characteristics that distinguishes pediatric from adult clinical pharmacology.
- Children differ dramatically with age and maturity from neonates to adolescents and dosing adjustment is required to match these changes.
- Modeling and simulation can provide significant insight into understanding how children differ from adults in clinical pharmacology.
- There is increasing acceptance of modeling and simulation efforts by health authorities combined with clinical data to support new compound submission.
- The opportunity exists to improve pediatric drug development efforts – and drug development efforts in general – through a collaborative interaction between academicians, drug developers and health authorities.