Fewer than half of the clinical trials conducted by pharmaceutical manufacturers under paediatric exclusivity provisions in the US have found their way into peer-reviewed journals. Moreover, the results of these studies are a good deal less likely to be published if they find the drug concerned is unsafe or ineffective in children.

The analysis by researchers from Duke University Medical Center and the US Food and Drug Administration (FDA) has raised concerns that vital information about paediatric label changes may not be reaching the medical community. As prescribing for children is often done off-label – based on what is demonstrably safe and effective in older patients – the outcome may be “beneficial, harmful or not effective, depending on how much information about use of the drug in the paediatric population is known”, noted lead investigator Dr Daniel Benjamin.

The research team, who published their findings in the 13 September issue of the Journal of the American Medical Association (JAMA), looked at the 253 studies submitted to the FDA between 1998 and 2004 under the paediatric exclusivity programme authorised by the Food and Drug Administration Modernization Act of 1997.

This provides six months of exclusivity from subsequent approvals for companies that conduct paediatric studies in response to a written request from the FDA. Uniquely – and gallingly, from the viewpoint of generic competitors – it may be used to extend other periods of market protection, such as the five-year data exclusivity for new chemical entities or the remaining patent term.

Results from just 113, or 45%, of the paediatric studies filed with the FDA in 1998-2004 were published in peer-reviewed medical journals, the researchers said. In the 100 cases where the paediatric trials led to “key” labelling changes – defined as a significant finding related to dosing, safety or efficacy that was particular to children – only 37 of the studies were published.

Where the paediatric data required dosing adjustments on labelling, only 49% of the studies were published in peer-reviewed journals, the analysis found. Just 43% of studies leading to a change to safety information were published; when the drug turned out to be ineffective in children, the publication rate dropped to 38%.

The researchers also categorised the resulting label changes as “positive”, meaning the studies established the drug’s safety and effectiveness in children; or “negative”, indicating, for example, that no meaningful clinical effect was seen in children or the drug was associated with a worse outcome than comparator therapy. They discovered that 54% of paediatric studies generating a positive label change were published, compared with 36% of studies leading to a negative adjustment.

The paediatric exclusivity programme has been “extremely successful in bringing about labelling changes where indicated, but additional efforts are needed to better inform the medical community about these changes and the studies behind them”, commented Benjamin. Physicians used peer-reviewed journals to keep abreast of medical developments, “so it makes sense to get this information in there”, he added.

While acknowledging that study publication in journals was the gold standard for disseminating new information, the US industry association, PhRMA, said data were often released at medical conferences or through online databases.

Labelling changes based on paediatric exclusivity studies are also posted on the FDA’s website, although detailed study descriptions or data are lacking.

The JAMA report will be welcome fuel to critics of the paediatric exclusivity programme, who consider it a windfall for research-based manufacturers. The generics industry claims some manufacturers have abused the exclusivity provision by conducting frivolous and/or low-cost paediatric studies of no intrinsic benefit to the target population.