Anyone out there who still believes that the system of drug safety regulation works and that the folks in the regulatory agencies have our best interests at heart ought to read the story of Lotronex and the US Food and Drug Association, as detailed i
Lotronex (alosetron hydrochloride) is an example of a new class of irritable bowel syndrome (IBS) drug called a 5-HT antagonist. The Lancet published a study in March 2000 hailing this drug as a "pharmacological breakthrough".
Lotronex's ascendency was short lived. The drug had been licensed by the US FDA in February 2000. Nine months later, GlaxoWellcome, its manufacturer, voluntarily took the drug off the market after reports of at least five deaths, 49 cases of ischaemic colitis and 21 cases of constipation so severe that some patients suffered an obstructed and ruptured bowel, often requiring surgery.
There are instances where side effects don't surface until the drug has been out on the market in some cases, for years. However, in this instance, the FDA had a few early warning signs. When the first cases of severe constipation and ischaemic colitis were reported, the FDA reviewed the latest studies of the drug. There in the clinical data were clear cases of potentially life threatening risk.
At this point, the FDA could have withdrawn the drug and asked for more evidence of safety. Instead, it allowed Glaxo to carry on. All it requested was the enclosure of a vague warning about stopping the drug if the patient experiences "increasing abdominal discomfort" the very symptom most IBS patients complain of.
The FDA supported a series of studies about the drug which were found to have serious flaws. Nevertheless, the one FDA scientist who attempted to blow the whistle on the tests was virtually ignored.
Indeed, certain scientists within the FDA were so concerned about the impossibility of weeding out women who would react to the drug that they concluded that it would be impossible to construct a "risk management plan" that would avoid "deaths, colectomies, ischaemic colitis and complications of treatment that were never seen previously in the management of IBS".
Once again, one would have thought that the action suggested by these unambiguous conclusions was decisive: immediate removal of the drug from the market. However, the FDA chose to take a conciliatory line with GlaxoWellcome and offered them several soft options, including voluntary withdrawal.
Public Citizen's Health Research Group has continued to record rising cases of serious side effects in patients.
Meanwhile, the FDA is now seriously considering allowing Lotronex to make a comeback. According to the Lancet, the FDA has worked with the company regarding the set up of the agency's advisory meeting and disclosed to Glaxo who will sit on its committee. The FDA scientists who have voiced so much concern over the drug have been ignored.
This kind of back door policy with industry is not surprising. A 1998 survey of FDA medical officers reported that, since 1992, when a government act allowed the FDA to accept $329 million from private industry to hire 700 medical officers, standards for drug approval have declined. The medical officers reported that they are often under pressure at the agency to approve a drug; many have received inappropriate calls from a drug's sponsor. Industry friendly officers are being appointed.
This story is not about a single drug escaping through the net. It is about what happens when a regulatory agency set up to protect the public interest becomes the handmaiden of industry. The Lancet is calling for an independent audit of the FDA's drug approval process. That a major publication in the medical industry now recognises how little integrity and independence remains in drug safety regulation is the first step forward.