Business Analysis: Overhaul urged for US food and drug watchdog

Trusted regulator torn apart by internal dissent

The United States' Food and Drug Administration used to be a regulator so trusted that when it waved through the introduction of genetically modified foods, there was little resistance from American consumers. Now, the body that oversees what the nation eats and takes as medicine is so bedevilled by criticism and self-doubt that even its own people are launching damning critiques of its methods.

The United States' Food and Drug Administration used to be a regulator so trusted that when it waved through the introduction of genetically modified foods, there was little resistance from American consumers. Now, the body that oversees what the nation eats and takes as medicine is so bedevilled by criticism and self-doubt that even its own people are launching damning critiques of its methods.

Last week, a senior scientist at the FDA, David Graham, issued a warning about the body to a Senate committee that had been called to investigate the withdrawal of the arthritis drug Vioxx from the market by its maker, Merck, because it increased the risk of heart attacks.

Mr Graham, a long-established employee of the FDA and a member of its office monitoring drug safety, said: "The FDA as it is presently configured is incapable of protecting America against another Vioxx. We are virtually defenceless."

The body was quick to respond that Mr Graham's views, which included warnings about other drugs on the market, including AstraZeneca's anti-cholesterol medicine Crestor, were "junk science". But with the share price of drugs companies tumbling, and US politicians taking an increasing interest in what is going on within the corridors of the FDA, there is little doubt the regulator will need to reform itself, or will find change imposed from outside.

According to its critics, the FDA is as much to blame for the continued sale of Vioxx despite signs that it harmed some patients' hearts as was Merck itself.

That is because the structure of what was once seen as the gold standard of regulators is flawed, some say. Indeed, the respected Journal of the American Medical Association argued yesterday that the monitoring of Vioxx and Baycol, made by Germany's Bayer, was flawed. "It is unreasonable", editors of the influential journal wrote, to expect the body which is responsible for approving a drug to "also be actively committed" to acting on evidence that the decision might have been wrong and that the drug should be withdrawn.

In the eyes of Charles Grassley, the Republican senator who chaired the Vioxx hearing, the current set-up makes the regulator "too cosy" with the drugs companies it monitors. This is a criticism which has grown in currency in the past 10 years since the Prescription Drug User Fee Act (PDUFA) was introduced, which put funding costs for drug applications on to the industry, and as a consequence increased pressure on the regulator to speed up approvals.

If it is open season on the FDA in the US, this is a situation that is beginning to have echoes on this side of the Atlantic, where there has been criticism of the UK's regulator, the Medicines and Healthcare Products Regulatory Agency (MHRA).

Campaigners against Seroxat, GlaxoSmithKline's antidepressant, who say the drug can lead to suicidal behaviour, have turned their fire on the MHRA. They say the agency overlooked vital safety data for more than a decade. There have also been questions over the independence of its scientists, who often come from or leave for jobs in the industry.

The UK Government, to forestall further criticism, has promised to tighten the rules on MHRA officers holding outside interests and increase lay and expert oversight of its decisions.

The answer proposed for the US, as propounded by the American Medical Association and senators, is for a new, entirely independent, safety body to be set up to make it easier for decisions to be reversed. This would also counter accusations that the FDA's current office of drug safety is less powerful than its office of new drugs, which is responsible for approving products.

It would also tackle the lack of clarity about the FDA's priorities. Most agree its primary role is to protect the safety of the public. But many believe drugs with dangerous side effects can be put on the market if they are intended for very ill patients, where the risk is justified by the reward.

The difficulty of getting the balance right has led, according to the FDA's defenders, to the body being in an almost impossible position. Some say it has been too cautious in approving potentially life-saving drugs, while others accuse it of being in the pocket of big companies.

It does seem that there has been a pendulum effect at the FDA. The body has swung from an increased flow of approvals in the wake of PDUFA in 1992, to a backlash led by consumer groups against blockbusters such as Pfizer's Rezulin, whose sales were stopped in 2000.

AstraZeneca, after having its blood-thinning drug Exanta turned down, went as far as saying "regulatory medicine" had got out of line with "clinical medicine", with the consequence that useful drugs were not available. It was an extraordinary critique of the FDA, a body the industry had once been paranoid about upsetting.

The FDA has also been beset with a huge amount of upheaval at the top. Lester Crawford, the acting commissioner, who is dealing with the uproar about Vioxx, took over from Mark McClellan, a scientist from whom great things had been expected before he departed in March after only 14 months in the job. Before Mr McClellan, the FDA had not had a permanent commissioner since January 2001. One of George Bush's most difficult tasks is to find a new permanent head of the FDA. Whoever ends up in this deeply political job is almost certain to lead an era of tougher regulation, with increased regulatory costs for the industry, and the likelihood that more new products will fail to meet the necessary hurdles.

Stewart Adkins, of Lehman Brothers, said: "If the FDA is going to become more scrupulous in its oversight, that raises the probability that investors will continue to express their reluctance to pay for the pipeline until the products are actually approved." In other words, this could lead to more downward pressure on pharmaceutical company shares.