Merck removed Vioxx (brand of refecoxid), from the market early last fall because of reports of increased heart attacks among users. Vioxx is widely used for painful arthritis, For this “forthright” action Merck initially received some adulation. On November 19, 2004, The Wall Street Journal published e-mails from the Merck corporate files indicating that the company had known of the increased heart problems for four years. One of the documents was guidance for their salesmen when asked questions about side effects of Vioxx. The document was actually labeled “Dodge Ball Vioxx”.
For several years I have stayed friendly with the various detail men (drug salesmen) without discussing drugs. I divert the conversation to something else that interests them such as trout fishing. When pressed for an explanation of my reluctance to talk about their products, I reply, “I am so old that I cannot always remember where I learned something, so I have become very careful about my sources.” They almost uniformly indicate some tacit respect for my point of view (indicating that they are human beings first and salesmen second).
When new drugs are approved because they have been found safe and effective on preliminary trials, their safety is still in some doubt because rare side effects may show up only after much more extensive experience. Patent protection is limited to a few years resulting in aggressive promotion as soon as approval is granted by the FDA (Federal Drug Administration). In 1992 a new law provided for much of the FDA’s drug approval expense to be paid by license fees from the drug industry. The FDA’s Center for Drug Safety Evaluation exists within its Center for Drug Evaluation and Research (CDER) along with its Office of New Drugs. This creates a conflict of interest when the safety of a recently approved drug comes into question.
The FDA’s own investigators now estimate that from 1999 to 2003, 27,000 excess cases of myocardial infarction occurred in users of Vioxx. Clearly, some reforms are needed in the drug industry and in the FDA. Merck’s likely legal bill is $10 to $15 billion, perhaps too much for them to survive as a corporate entity. When the CEO of Merck retires prematurely, over what sort of terrain is he to be permitted to open his golden parachute? Australia might have been OK in British colonial times when they sent their prisoners there. To restore public trust in drug regulators and the industry will require some prompt and drastic reforms. For a start, the Office of Drug Safety needs to be insulated from the Office of New Drugs which collects the license fees.
In 1997 the US started permitting advertising prescription drugs to the general public. New Zealand is the only other country following this path. I sincerely believe the rest of the world’s reluctance is the correct attitude--time is wasted in talking about the advertisements during consultations and the costs materially increase drug prices. The costs of pell-mell promotion of brand new drugs before post-marketing surveillance thoroughly demonstrates their safety is totally wasted when they must be promptly withdrawn from further sale. Furthermore, such a massive experiment in risk assessment is unnecessarily hazardous to the public. Our policy about advertising prescription drugs was changed by administrative rule without legislative input or even public hearings.
Here is a reform that the pharmaceutical industry might find agreeable. Let us consider the consequences of a two stage approval process for new drugs. During the period of a few years between initial and final approval the clock would be stopped on patent expiration and in return the drug's commercial promotion would await the final approval. This would compensate the manufacturer for delaying intensive marketing. The public would benefit from obtaining necessary safety data with the risk falling on a more limited number of patients not fully responsive to previously available agents. Both the manufacturer and the public would benefit from the saved cost of not promoting new drugs that fail the post-marketing safety surveillance. Incidentally, a more prolonged stopping the clock on patent expiration of new antibiotics would go a long way toward postponing the evolution of resistant organisms by making the economics of limited use
of new antibiotics much more fair to the manufacturer. This type of extension of patent protection would tend
to get public and corporate benefits back in step. After all, patents originated to promote innovation for the public’s benefit.
The period of restrained use of new drugs would be an especially good time to promote and finance clinical research comparing the relative effectiveness of the old against the new remedies. I see no way to motivate business interests to finance such research. All attempts to privatize public health are similarly doomed to failure. To illustrate the point, the world’s pharmaceutical industry spends only 1% of its research budget on the diseases that cause 90% of the world’s disease burden, so support for these activities will have to come from sources such as universities, foundations and the NIH (National Institute of Health). An informed public can participate in these deliberations. This participation will enhance the important goal of restoring and preserving the public’s confidence in the FDA and the pharmaceutical industry.
See also: Vioxx, the implosion of Merck, aftershocks at the FDA, Lancet vol. 364: #9450, pg 1995, Dec 4, ‘04
John A. Frantz, M.D.
December 25, 2004