I hope to stimulate debate in favor of an underrepresented group in clinical pharmacology research. Two decades ago, women were underrepresented, including even female rats. We've made real progress. The same is true for the elderly and racial minorities, although that challenge continues, as reflected in the
Children remain neglected by the industry. They are a vulnerable and inconvenient population for medical research, especially outside developed economies. This is a demographic that demands an individualized approach to therapy. Many children die of infectious diseases and malnutrition while others are permanently damaged.
Physicians often must guess on drug choice and dose, because there is limited supporting data and often no suitable formulation. Mixing portions of drugs with compatible (or not) "baby food" is common for parents and not well controlled. Adult formulations are often unsuitable for children in physical size, dose and substances used as a vehicle for the drug. Special pediatric formulations, such as liquids, require extensive regulatory review, including oral syringes for parents to use, which are then medical devices.
Self-administered protein-based drugs become more popular for adults, for example, using pumps. In children, this presents costly regulatory issues with labeling, instructions and compatibility with little hands and physical play.
There is opportunity, step by step, to reduce the art and increase the science. Pharmacophenomic progress can be made today, without any speculative drug discovery. Most approved drugs compatible with pediatric disease are generic, but few have been thoroughly studied in children.
Why are children not the focus of clinical pharmacology?
* Children are not small adults. They change rapidly from birth to their early 20s. This is inconvenient for scientists and statisticians alike.
* Children are generally healthy and thus represent a small market for new drugs. This is inconvenient for CFOs.
* The ethical challenges of clinical trials with children can be daunting. We don't do drug trials on healthy children, as we typically do for adults.
* The rate of change in children confounds clinical trials of any length.
There are good things to say about pediatric research:
* The return on investment in children's health promises to be much higher than the return in the health of elderly professors like me. Preventive medicine means a lot.
* Children as a rule have avoided some of the bad habits that make studies in adults inconvenient (smoking, alcoholism, drug addiction, french fries) and have not experienced the degenerative diseases of aging.
* Children have fewer drug-drug interactions or druginduced enzymes.
Scientists are making progress. My own team has developed a means of automatically sampling exquisitely small blood volumes in a preprogrammed, painless way that eliminates labor and reduces infection risk. This is especially important with respect to recruiting children for trials where parental approval is crucial.
Colleagues have further developed measurement technologies that are compatible with much smaller sample volumes than even a decade ago. Today, the required sample volumes and concentrations for quality measurements are both reduced by up to a million-fold compared to 1980.
Expertise in modeling and predicting, much of it developed from industrial engineering, is now coming into play. I encourage those working in drug discovery to consider pediatric applications early and often. Please also recall that many drugs used in this population were approved before the new tools became available.
When you consider estate planning, consider pediatric pharmacology. Let's lend children a hand now to reduce the cost of the downstream consequences of inadequate care.*