Criticism, a Long Time Coming

Despite its benefits, the Pediatric Exclusivity Program has faced criticism almost from the start.

Richard Gorman, MD

Dissemination of information Another potential problem with the Pediatric Exclusivity Program was highlighted last September by Daniel K. Benjamin of Duke University, et al, in the Journal of the American Medical Association (JAMA). BPCA requires FDA to issue summaries of data submitted under the Pediatric Exclusivity Program, even if the data do not lead to label changes. (Compare that with the policy that requires FDA to keep data secret when a company applies for, but fails to obtain, a new indication for an existing drug.) However, publication in peer-reviewed journals is not a requirement of the Pediatric Exclusivity Program as currently constructed.

Benjamin and colleagues reviewed data submitted to the Food and Drug Administration as part of the Pediatric Exclusivity Program to assess the public dissemination of the data resulting from new clinical studies that tested drugs in children. They found that less than half—only 45 percent—of the 253 studies submitted to FDA for pediatric exclusivity between 1998 and 2004 were published in the peer-reviewed literature. That needs to change if one goal of the clinical-research enterprise is to broadcast this information to physicians and the public.

Incentive terms The most frequently cited objection to pediatric exclusivity is that it provides excessive incentives to some manufacturers. Because the program offers manufacturers a fixed incentive, products with a larger sales volume may yield returns to manufacturers that vastly exceed the cost of performing pediatric studies—regardless of the actual uses of these products in children. For example, several manufacturers have received exclusivity for products used mainly in adults, such as atorvastatin (Lipitor), pravastatin (Pravachol), celecoxib (Celebrex), and a variety of anticancer agents. Indeed, since the point of the program is to generate data rather than increase drug use, a product can gain the full six months of exclusivity even if pediatric studies demonstrate that the drug should never be used by children.

Deconstructing the Reward

Are the rewards of pediatric exclusivity too large? A recent article in the JAMA sheds further light on this important question. Jennifer S. Li of Duke University and colleagues examined the likely costs of clinical studies under the Pediatric Exclusivity Program. The researchers looked at 59 products submitted to FDA for pediatric exclusivity from 2002 to 2004. During that time period, 137 pediatric clinical trials were completed, and almost 23,000 children were included in these studies. The selected medications included drugs for depression and generalized anxiety disorder, high blood pressure, asthma and allergy, osteogenesis imperfecta, bacterial infection, gastroesophageal reflux, type 2 diabetes, attention-deficit hyperactivity disorder, and a medication used on difficult-to-treat tumors. About 22 percent of these medications were considered blockbusters, meaning that they had more than $1 billion in sales annually for both adults and children. Forty-eight percent of the drugs had sales between $200 million and $1 billion, and 30 percent of the drugs in the sample had sales of less than $200 million.