The average cost of conducting new studies with marketed drugs under the US Food and Drug Administration’s paediatric exclusivity programme shot up nearly eight-fold between 2000 and 2006, according to the Tufts Center for the Study of Drug Development.

The Tufts Center analysis, based on survey responses from 17 companies that had sponsored paediatric studies in response to a written request (WR) from the FDA, found that the average out-of-pocket cost (in nominal dollars) of completing a WR rose from US$3.93 million in 2000 to US$30.82 million in 2006. The reported costs of completing a WR ranged from US$0.5 million to US$20 million (a 40-fold difference) in 2000, when the Center conducted a similar survey, and from US$3 million to US$130 million (a 43-fold difference) in 2006.

These findings were consistent with general increases in the cost, length and complexity of drug development, the Tufts Center commented, citing an estimated annual clinical cost inflation rate of 10%. But the data contrasted sharply with a study recently published in the Journal of the American Medical Association, which concluded that the paediatric exclusivity programme was overcompensating blockbuster drugs. According to researchers from the Duke Clinical Research Institute in North Carolina, government and industry sources put US paediatric study costs in a range of US$1 million to over US$35 million, although a survey of pharmaceutical companies had produced an average cost of just US$3.87 million per written request.

One reason given by the Tufts Center for the ballooning cost of paediatric research was a 60% increase in the number of efficacy and safety studies conducted under the programme. While the cumulative number of paediatric studies completed since 1998 rose from 58 at the end of 2000 to an estimated 568 at the end of 2006, the proportion of efficacy/safety trials – the most time-consuming and expensive types of research, the Tufts researchers pointed out – went up from 25% to 40%.

Accordingly, the estimated time needed to complete paediatric studies nearly doubled over this period, partly reflecting the increased complexity and scope of the research. For example, the mean number of specific paediatric formulations developed in the course of these studies rose from one in 2000 to 1.67 in 2006. The mean number of patients per WR expanded by 178% over the same period, the Tufts analysis noted, while the mean number of studies per WR was up by 60%. Moreover, 33% of all paediatric programmes had to perform long-term follow-up studies of more than six months’ duration in 2006, compared with 17% in 2000.

The initiative has long been a bugbear for generic drug manufacturers, stymied by its liberal application of six months’ market exclusivity in return for paediatric data. The generics industry claims some manufacturers have abused the programme by conducting frivolous and/or low-cost paediatric studies of no intrinsic benefit to the target population. According to the Tufts Center, though, paediatric innovation is by no means in short supply. In 2006, 20% of written requests under the exclusivity programme were for new drugs in development, 40% for unapproved indications and only 40% for already approved indications.

The Best Pharmaceuticals for Children Act of 2002, which authorises the paediatric exclusivity programme, comes up for renewal in October 2007. US legislators will be looking for evidence that the programme is effective and not, as its critics claim, a windfall for research-based manufacturers. The Tufts Center itself has come under fire over its widely reported estimates for the average cost of bringing a new drug to market.

The Center’s associate director Christopher Milne said the Best Pharmaceuticals for Children Act “seems to be doing its job, which is to generate more paediatric studies”. Although the cost of completing these studies had soared, “drug companies are not letting that get in their way”, he commented.