The Pediatric Exclusivity Gambit

A little over a decade ago Congress gave drug manufacturers six months extra patent protection if they tested their drugs in children. Kids aren't little adults. Their bodies metabolize drugs differently so dosing isn't necessarily a straight line extrapolation based on weight or body size. And what works in mature bodies doesn't necessarily work in bodies that are still growing or with still developing immune systems. Testing drugs for safety and efficacy is kids in sorely needed.

But there are some obvious flaws in the incentive provided by Congress. Many if not most drugs used in children -- I'm thinking here about antibiotics and anti-cancer drugs -- are generic so the carrot of patent extension is irrelevant. And on the other side of the equation, some of the manufacturers who conduct the kid trials are more interested in getting another few billion in sales out of their blockbuster drugs, which usually don't have much use in youngsters anyway (Nexium, an acid reflux disease drug, and Celebrex, a minor painkiller, are typical of this genre).

The Food and Drug Administration has to issue a written request for the study, but manufacturers can amend the request and they often do. Not surprisingly, the results that come back are less than optimal. Of the 140 drugs granted additional patent life in the first ten years of the law, only 25 resulted in new or changed dosing labels and only 35 came up with new or enhanced safety data, and there may have been overlap between those two groups. Clearly, the protocols in the many of the trials being submitted by the manufacturers were inadequate for generating meaningful data.

To be fair, there's huge problems with conducting clinical trials in kids. What parent would give informed consent for their sick kid to participate in a clinical trial where the kid might get a placebo?

So at a meeting of the FDA's Pharmaceutical Science and Clinical Pharmacology committee (full disclosure: I'm a member), the FDA presented a model for using data from adult trials to design better kid trials. The hypothetical example given was for a blood pressure control medication. The committee gave its unanimous approval for the FDA to use such models in negotiating better trial protocols with the manufacturers when they seek additional exclusivity for their patented drugs.

I agreed that such modeling was better than nothing. But as the meeting wound down, I couldn't stop myself from complaining to the FDA about the mismatch between the rewards for manufacturers and the paucity of data generated by the trials. Why not ask companies to conduct two-arm comparative trials, I asked. One arm would be their on-patent drug and the other could be a generic. It would solve the kids-on-placebo problem. It could generate dosing and efficacy information for two drugs for the price of one. And, if properly designed, it might even let physicians know which of the two drugs was more effective in children.

Was there anything in the law that prevented the FDA from requesting such a trial from the manufacturers, I asked. No, the FDA staffers in attendance said.

Given the amount of health care dollars being poured into drug companies through this additional exclusivity, it seems like the least we can ask for. And if companies come in half way through the pediatric trials and ask for an amendment to their protocols, as has frequently happened in the past, the FDA should remember that they can say no to that, too.

Posted by gooznews at March 19, 2008 07:24 AM