Medical Matters:'Who owns the Food and Drug Administration (FDA) - the drug industry or the population?" was the question posed on a front cover of the British Medical Journal in September 2002, writes Muiris Houston
It flagged a number of inside stories highlighting concerns about how the US drug regulator had reapproved Lotronex, a drug for the treatment of irritable bowel syndrome, even though it was known to have caused 84 cases of bowel inflammation (colitis), 143 admissions to hospital and seven deaths.
The agency has continued to attract strong criticism for its modus operandi. Its failure to respond to concerns about the cardiac side effects of Vioxx and other Cox 2 anti-inflammatory drugs for seven years after safety questions were first raised is another indication that all is not well with the FDA.
But why should this be of immediate concern to patients in the Republic? Our drugs and medical devices are regulated by the Irish Medicines Board (IMB) and increasingly by the European Medicines Agency (EMEA).
Certainly I was not overly concerned until a recent conversation with Dr Garrett Fitzgerald, a distinguished UCD medical graduate and professor of medicine and chair of pharmacology at the University of Pennsylvania.
Dr Fitzgerald was one of the first to predict that Cox 2 drugs might cause serious heart side effects. He is a member of a high-powered committee that produced a report late last year, FDA Science and Mission at Risk, and has just given evidence to a US House of Representatives oversight and investigations committee who are examining the FDA report.
"The state of the FDA has global implications, bad and all as it is, because other agencies, including EMEA, rely heavily on its expertise," Fitzgerald says.
Apparently, the EMEA relies on the FDA to inspect pharmaceutical products both at their site of entry and at manufacturing locations around the world. As part of globalisation, bulk production of drugs has largely moved to China, with, for example, the majority of bulk aspirin for world supply made at a single site in China.
Given recent questions surrounding the quality of pharmaceuticals and foodstuffs made in China, clearly we Europeans must adopt a global approach to drug safety.
The FDA Science and Mission at Risk report did not pull any punches: "The agency suffers from serious scientific deficiencies and is not positioned to meet current or emerging regulatory responsibilities."
It said the demands on the food and drug regulator have soared "due to the extraordinary advance of scientific discoveries, the complexity of new products . . . the emergence of challenging safety problems, and the globalisation of the industries that FDA regulates".
In his testimony to the House of Representatives, Dr Fitzgerald said he and others were no longer confident that the FDA could safeguard the public and communicate informed and unbiased information about drug safety.
"There have been major scientific advances in drug discovery over the past decade, yet the way in which FDA reviews drugs and steers their development has not changed over half a century," he said.
Significantly, he called for the integration of drug evaluation carried out before and after marketing. "Our information about how a drug works and how safely it works is fragmentary at the time of approval; we must exploit enhanced mega databases of clinical information, assessed in real time by agency scientists to assess drug safety post approval."
The international drugs expert also pointed out that, at present, we approve drugs based on an ability to detect large average effects of benefit or risk in studies of large populations.
"People vary strikingly in their response to most drugs - differences determined by the interaction of factors within their environment and their individual complement of genes. What matters most to people is not whether there is an average effect in a population, but how a drug will work in them," he said.
Another recommendation from the expert group is that drug regulatory authorities build strong relationships with existing academic centres of excellence. It also recommends a doubling of the FDA's current budget and a 50 per cent increase in staffing levels.
But there is another key issue affecting drug regulation both in Europe and the US. The FDA and the IMB are all funded, to some extent, by the pharmaceutical industry. Drug companies pay substantial fees to regulators when they make an application for a drug licence. More than half of the FDA's drug review work is now funded directly by the pharmaceutical industry.
At the least, this creates a potential conflict of interest for regulators. And while there is absolutely no evidence of conflicting loyalties among staff at the IMB, one must ask how appropriate it is that a portion of their salaries are paid for by the drug firms they police?
It is time to either limit or abolish the funding of drug regulation by the pharmaceutical industry. That way we can be sure of the answer to: "Who owns the FDA, the EMEA and the IMB - the drug industry or the population?"
Dr Houston is pleased to hear from readers at mhouston@irish-times.ie but regrets he is unable to respond to individual medical queries.