The reputation of drug companies has taken a beating in recent years. Their prices have risen much faster than inflation (except for last year, when generics had some impact), makes them almost universally suspect. The industry’s claim that its fat margins are warranted by its investment in research doesn’t bear much inspection. 45% of drug R&D is government funded. Moreover, Big Pharma spends more on marketing than on research. Can you think of another business that is profitable enough to warrant in person selling to small businessmen, which is what most doctors are?
One would expect the major drug companies to be particularly image conscious these days. An industry on the defensive seldom takes pot shots at one of its main regulators. Yet that is precisely what Novartis has chosen to do. From the Financial Times:
The Food and Drug Administration has become over-cautious in its assessment of new medicines following political pressure arising from safety controversies, Dan Vasella, chief executive of Novartis, said on Friday.
Mr Vasella, the only chief executive from one of the big pharmaceutical groups to attend the three-day Clinton Global Initiative in New York this week, said the medicine regulator had gone too far in seeking to evaluate drugs on criteria beyond their safety and efficacy.
“The FDA has become subject to politics,” Mr Vasella said. “If they are assailed like they are now, the best thing to do is nothing.”
Novartis has felt the sting of the FDA’s increasing focus on safety that sprung partly from US drugmaker Merck’s withdrawal of painkiller Vioxx owing to heart risks three years ago. Two drugs in Novartis’s pipeline, Galvus for type II diabetes, and painkiller Prexige, have met significant regulatory delays with the FDA.
Both Prexige and Arcoxia, Merck’s successor to Vioxx, have been denied approval by the FDA in spite of receiving approval around the world. The US safety issue has shaped their assessment to include a broader discussion of their place in the market and alternative treatments.
“The discussion on what this [drug] brings over and above what’s on the market is a question that’s being asked. The FDA doesn’t seem to trust the physicians any more,” Mr Vasella said.
Novartis is taking an interesting gambit, in claiming that it is the true defender of consumer interests and (by implication) the FDA is a bad guy by withholding useful medicines. (I imagine that the FDA has come to regret its change in policy in 1997 to allow direct to consumer advertising, which has given drug companies another channel to influence public perceptions. Note that the US and New Zealand are the only two advanced economies that permit it).
But Vasella’s charges don’t stand up to scrutiny. in reverse order, the FDA shouldn’t trust physicians. This isn’t a matter of trust, but of findings in properly designed studies. In addition, your average MD doesn’t have the time to keep up on medical research. And very few have expertise in study design or methodology. That’s precisely why they can be manipulated by drug detailmen. So implying that physicians are in a better position to judge efficacy and safety than the FDA is bogus.
The grist of Vasella’s argument is that two drugs, his Prexige and Merck’s Arcoxia that have been approved “around the world.” The FT should have examined that claim rather than treating it as fact.
I didn’t have to look far to find problems with both drugs. I started with Australia and hit pay dirt.
Australia and New Zealand have banned Prexige. From the Australian announcement:
Prexige was withdrawn on 10 August 2007 by the Therapeutic Goods Administration because of a small number of cases of serious liver side effects. If you take Prexige, stop taking it immediately and see your doctor to discuss an alternative to this drug and to arrange any tests you may need.
New Zealand was slightly more forgiving, allowing use only in very low doses:
The New Zealand Ministry of Health’s medicine watchdog Medsafe has withdrawn the supply of 200mg and 400mg Prexige tablets.
The anti-inflammatory drug has been blamed for the deaths of two people and for two others requiring liver transplants in Australia.
Medsafe spokesman Stewart Jessamine said its medicines adverse reactions committee (MARC) discussed the overall risks and benefits of the use of Prexige with regulators in Australia, Singapore and the United Kingdom.
“This increased risk of liver damage for Prexige outweighs any of the potential benefits claimed for the 200mg and 400mg dose,” Jessamine said.
The 100mg Prexige tablets would stay on the market, though would be closely monitored.
Similarly, Australia did not approved Etoricoxib, the chemical name for Merck’s Arcoxia in its initial review in 2004, citing safety concerns. After the Vioxx scandal in the US, the Therapeutic Goods Administration decided that it would be approved only for very limited use:
It is proposed to greatly limit the approved uses of two other Cox-2 inhibitors which have not yet been marketed in Australia. They are etoricoxib and lumiracoxib. In both instances, ADEC was not sufficiently assured of the safety of these drugs for anything other than short term use in patients without increased cardiovascular risk.
So the idea that the US is tougher than other drug regulators is exaggerated. And by happenstance, a story in the New York Times yesterday depicts an FDA not only grossly understaffed in the area that oversees clinical trials, but also strongly inclined to downgrade any problems found:
In a report due to be released Friday, the inspector general of the Department of Health and Human Services, Daniel R. Levinson, said federal health officials did not know how many clinical trials were being conducted, audited fewer than 1 percent of the testing sites and, on the rare occasions when inspectors did appear, generally showed up long after the tests had been completed.
The F.D.A. has 200 inspectors, some of whom audit clinical trials part time, to police an estimated 350,000 testing sites. Even when those inspectors found serious problems in human trials, top drug officials in Washington downgraded their findings 68 percent of the time, the report found. Among the remaining cases, the agency almost never followed up with inspections to determine whether the corrective actions that the agency demanded had occurred, the report found.
“In many ways, rats and mice get greater protection as research subjects in the United States than do humans,” said Arthur L. Caplan, chairman of the department of medical ethics at the University of Pennsylvania.
So Vasella is 100% correct. Politics have a great deal to do with drug approvals. My FDA lawyer buddies tell me that the FDA enforcement area is understaffed precisely because its budgets have been cut by Congress.
But those politics already operate very much in favor of the drug industry.