A doctor consulting for the U.S. Food and Drug Administration on a controversial bowel pill claims the pressure of big money prompted the agency to let the drug back on the market after it was initially withdrawn over safety fears.
Dr. Paul Stolley, a retired professor from the University of Maryland, says he believes the FDA is too close to the drug companies it regulates. Under a 1992 law, pharmaceutical firms actually help pay the bill for regulators to review product applications. His experience with the bowel drug Lotronex, or alosetron, “is a perfect example” of how tightly industry and the agency are now linked, and how companies can use fiscal muscle to have their way over sound science.
“The FDA was in partnership with industry” in the Lotronex affair, Stolley says in this week’s British Medical Journal (BMJ). “It should have been negotiating, not in partnership. Why was it in partnership? Because it’s financially supported by industry.”
The author of the BMJ article is Ray Moynihan, a journalist with the Australian Financial Review. In a previous issue of the journal, Moynihan co-authored an article accusing drug companies of “disease mongering,” marketing generally minor problems into full-blown illnesses in order to sell medication.
One of these conditions, he said then, was irritable bowel syndrome, or IBS. IBS causes varying degrees of constipation, bloating, diarrhea and cramps in as many as 20 percent of American women.
In February 2000, the FDA approved Lotronex, from then-GlaxoWellcome, for the treatment of IBS marked by diarrhea. But over the course of a year, the agency began receiving reports of serious and even fatal, bowel trouble in some patients.
By November, the company withdrew Lotronex from pharmacies. As of last spring, the FDA said it had linked 84 cases of bowel damage and 113 cases of serious constipation to the pill, 137 of which required hospitalization. At least four, and possibly several more, proved fatal.
Patient groups with financial ties to industry, Moynihan argues were upset by the decision to withdraw the drug and pushed hard for its return. In December of last year, the company, now GlaxoSmithKline, asked the FDA to allow the drug back, which it did in June of this year.
The FDA stipulated that the company could sell Lotronex only under strict oversight to a select group of women with severe IBS marked by diarrhea who have failed to respond to other treatments. Of the 18.5 million people with IBS, about 185,000, or fewer than 5 percent, would qualify for the therapy, officials said at the time.
To prescribe the drug, doctors would have to notify the company that they were familiar with its risks and with the disease and would receive stickers in return. Pharmacies would be discouraged from filling prescriptions without first seeing a sticker.
Lotronex was also to carry a “black box” warning, the agency’s most stringent caution, and GlaxoSmithKline promised not to market the drug directly to consumers. [Officials said doctors could offer the drug to men with IBS, although it is not specifically approved for them.]
Yet, these precautions weren’t as stringent as those an FDA advisory panel recommended to regulators. The panel had in April 2002 urged the agency to narrow the physicians eligible to prescribe the drug to people with demonstrated and not merely avowed expertise with IBS.
And that is the guts of Stolley’s and Moynihan’s complaint.
“The FDA is not bound to take all the advice of its committees, but in this case several panel members were furious,” wrote Moynihan, who added that critics of the agency consider the outcome a “case study in regulatory capture.”
According to Moynihan, Stolley, who could not be reached to verify the account, felt that FDA officials turned a deaf ear to his concerns about Lotronex’s safety. Stolley also works for the advocacy group Public Citizen, which called on the FDA to withdraw Lotronex and keep it off the market. He alleges that an FDA official, Dr. Janet Woodcock, accused him of “brow-beating” other reviewers and that the pill was safe enough to return to market.
Woodcock, head of the Center for Drug Evaluation and Research, which was handling the Lotronex matter, in an interview Thursday denied Stolley’s charge. She said she remembers meeting with the consultant, but that the discussion didn’t involve his opinion of Lotronex.
Woodcock also rejected the notion that the 1992 user fee law has compromised the agency’s ability to review drugs objectively. “The FDA is not influenced by user fees in any individual decision about a drug. Period,” Woodcock said.
Dr. Brian Strom, a University of Pennsylvania epidemiologist who sits on the advisory panel whose advice was spurned, said he was angered by the FDA’s decision. Yet, he acknowledges that the agency was well within its rights to act as it did.
“We did think [Lotronex] should be back on the market, but under very strict limited conditions,” Strom said. The group felt that only IBS experts, some even said only bowel specialists should be allowed to prescribe the pill. They also believed that giving patients a consent form to fill out before receiving a prescription absolved both doctors and the company of responsibility for the harm that might ensue.
Strom, who is quoted in Moynihan’s article, said that perhaps just 2 percent of women with IBS would respond well to Lotronex. For this group, “it’s a good drug,” and the FDA should focus on serving these patients. The rest, he said, should probably not have access to the pill. “If [IBS] is sufficiently mild that they don’t need a gastroenterologist, they don’t need a drug that has a chance of killing them,” he said.
Woodcock defended the agency’s choice of risk plans, saying the panel was asked merely to consider a range of elements in such a system and recommend those it felt would be effective. Taken together, the litany of measures would have been “overwhelming as far as the burden on the health care system,” she said. The final version, she added, while somewhat looser than everything each of the panelists may have wanted, still provides more restrictions than govern the typical prescription drug.
In fact, some people familiar with the Lotronex debate said the drug might not be such a perfect case study in cash-over-conscience after all. Ramona DuBose, a spokeswoman for GlaxoSmithKline, in Research Triangle Park, N.C., noted that patient groups, not the pharmaceutical company, were the engine behind the pill’s return.
“When we took it off the market in November of 2000, it was our intention never to bring it back,” DuBose said. “But the outcry was so compelling” that the company decided to reconsider. DuBose said the firm then approached the FDA for help crafting a plan to give Lotronex a second, closely monitored chance.
DuBose said the company doesn’t expect Lotronex to make it much money, and that the cost of implementing and running the risk management system will be “substantial.” The pill will be available to patients by the end of the year.