Thursday, March 15, 2007

Making medicine safe for children
by Julie McKeel

Creating incentives for studies in children

The Pediatric Exclusivity Program to make drugs safer for children is up for renewal. Children often metabolize medicines in a different way from adults and sometimes experience unpredictable side-effects, but the children's drug market is not always big enough for companies to bother with trials needed to find out the details of such differences. The ten-year-old program offers a six-month patent extension on any product tested in appropriate child-focused trials.

[In 1997, Congress authorized the U.S. Food and Drug Administration (FDA) to grant 6-month extensions of marketing rights through the Pediatric Exclusivity Program if industry sponsors complete FDA-requested pediatric trials.]

Jennifer Li, MD, MHS

The scheme seems to have worked, with more than 300 studies completed resulting in 115 products that have had their instructions for use changed so that doctors can prescribe them to children with reasonable confidence. Still, the program is being questioned and will be debated in Congress next month. Some critics think the offer is too generous, and that the patent extension should be shortened or altered in some way.

A paper published last month in the Journal of the American Medical Association by the DCRI's Dr. Jennifer Li and her colleagues suggests the critics have a point. However, it concludes that altering the program could undermine its purpose--better health for children.

"Historically, only 25% of approved drugs marketed in the US have sufficient pediatric data to support approval of product labeling by the FDA for dosing, safety, or efficacy in children," Li states in the paper's introduction. "Inadequate dosing and safety information places children at risk for adverse events and denies them potential therapeutic benefits."

The point of Dr. Li's study was to quantify the economic return to industry for completing pediatric exclusivity trials. The team looked at one drug that had been granted pediatric exclusivity in each of nine categories (cancer, cardiovascular disease, psychiatry, etc.). The researchers were interested in the cost of conducting the tests required by the FDA for a drug to qualify for special treatment, and the benefits that resulted from the patent-extension.

The cost of performing each study was estimated. Then the three-year market sales were obtained and converted into estimates of after-tax cash inflows based on 6 months of additional market protection. Net economic return and net return-to-costs ratio for each product were then calculated.

In eight of the nine drug cases, the researchers concluded that there was a benefit to the company. (In the ninth case, the cost of the trials seems to have exceeded the value of the patent extension.) Likewise, the "labeling information" describing side-effects was changed to account for children's needs, so there was also a benefit to young patients, though the team did not quantify that benefit. They did, however, quantify the benefit to the companies--and they found an enormous range. In the most lucrative case the value of extra protected sales was about 74 times the cost of the trials, and it was more than 20 times the cost in three other cases.

While the team's results might argue in favor of less generous patent-extension terms, any alteration would complicate a program that is both clear and effective. In an era where fewer blockbuster drugs seem to be hitting store shelves, a change in this program might lead to fewer safety studies for children's medications.

According to the study authors, reducing marketing protection from 6 months to 3 months could reduce profit margins for some products, and thus those products may not be submitted for pediatric testing. Such products may include medications for conditions such as bacterial infections and hypertension, which have a profound public health importance for children.

"Clearly, however, the greatest return of the exclusivity program is the benefits derived in obtaining new information relevant and applicable toward the care of children,” stated Li, “and this benefit should not be compromised."

In addition to Li, other DCRI researchers involved in this study include E ric Eisenstein, DBA; Barry Mangum, PharmD; Kevin Schulman, MD; Robert Califf, MD; Daniel Benjamin, Jr, MD, PhD; and Elizabeth Reid.