Regulatory Focus™ > News Articles > Researchers: Need for More Neonate-Specific Clinical Drug Research

Researchers: Need for More Neonate-Specific Clinical Drug Research

Posted 29 October 2012 | By Alexander Gaffney, RAC

Researchers writing in the research publication Journal of Pediatrics (JP) are calling for the increased inclusion of neonates in pediatric drug trials, arguing that the sub-group is highly underrepresented, potentially to the detriment of newborn children.

The article, scheduled to be published this week, takes note of an oft-discussed problem: Pharmaceutical products are rarely studied in children to the same extent as adults, resulting in many of those products being used off-label. Though various pieces of legislation have been passed into law to confront the problem-the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act among them-parity remains an elusive hope for some research advocates.

The gap persists for various reasons, observed Henry Akibini, lead author of the study and an employee with the Cincinnati Children's Hospital Medical Center. Companies may be wary of the additional regulatory requirements, lack the financial incentives necessary to conduct additional-and expensive-testing, and the unique practical and ethical challenges associated with conducting testing on children. Akinibi said those challenges are compounded further when they are neonates-newborn children less than a month old.

In all, just 0.6% of trials registered with the National Institutes of Health (NIH) involve neonates, while just 3.4% of pediatric trials did, Akinibi found. Even when pediatric trials resulted in changes being made to the approved labeling of a product, just 6% of those changes ultimately impacted neonate prescribing.

The lack of neonate-specific information generated by clinical trials puts them at risk for receiving ineffective medications, incorrect doses and unsafe products, argued the researchers. And unlike requirements established under the BPCA, sponsors are not required to submit plans for neonate studies upon submission of an application. Just as results for children cannot be extrapolated from adults, they said, neither can results for neonates be extrapolated from children.

"In the current legislations and regulations, these two populations have always been lumped together," the authors wrote. "Yet, we recognize that premature infants are not just miniature children or adults. The inherent differences are a consequence of body composition, various physiologic adaptations, the evolving ontogeny of abundance and responsiveness of receptors, and the function of drug metabolizing enzymes and known transporters."

Even the differences between a six-month old child and a two-week old child are immense, they observed. A standard dosage of morphine has a half-life of nine hours in a two-week old neonate, but just 3 to 5 hours in a six-month old. Particularly for critically ill neonates, this difference can very well mean the difference between life and death, the authors argued.

Akinibi and colleagues raised several opportunities for increasing the number of clinical trials involving neonates.

"Inclusion of neonatologists and neonatal pharmacologists in study designs, and early in the drug development process, would make data generated from such studies more relevant and useful," observed Jason Wiles, a coworker of Akibini and a co-author of the study. "This multidisciplinary research approach would promote thoughtful anticipation, careful planning to identify and eliminate barriers, and utilization of novel investigative practices to maximize the yield of individual studies."

Ultimately, they conceded, it may be difficult to generate additional studies without either having US Food and Drug Administration raise its standards for what it requires from pharmaceutical companies or stronger government incentives-both of which were called for by the researchers.

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