Criticism, a Long Time Coming
Despite its benefits, the Pediatric Exclusivity Program has faced criticism almost from the start.
Labeling Though FDA quickly reviews the data generated by pediatric testing, label changes—the necessary bridge to disseminate information
to doctors and parents—can come slowly. Some label changes, for example, took more than 1,000 days, according to a recent
GAO study. It's also important to note that not all studies led to label changes (though about 87 percent did, according to
the government report).
Richard Gorman, MD
Inability to enforce The Best Pharmaceuticals for Children Act of 2003 does not include adequate mechanisms to encourage pediatric testing of
off-patent drugs. After all, the program is voluntary for pharmaceutical companies. (In theory, the Pediatric Research Equity
Act of 2003 gives FDA the ability to require pediatric studies of an already marketed product when a company declines to perform
them under BPCA. In practice, as Sen. Hillary Clinton noted in introducing the Pediatric Research Improvement Act in March
2007, the provision is so complex that it has never been used.)
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.