Put Drug Patents to Work for Everybody

Increasingly throughout my career as an internist, when I send a patient to a consultant, the patient was sent back to me with free samples and a prescription for the latest “me too” product entering this particular market. I felt cheated of the benefit of the consultant’s knowledge and experience because he seemed too influenced by a recent sales pitch and knew little more than I knew about the new drug.

Patients seldom felt cheated; they gained from the saved cost of free samples. But the reality is that the patient and his insurance company were actually cheated by the extra cost, over time, of a newly patented drug instead of an equivalent generic product, even though the generic had already been thoroughly proven safe by prolonged use.  The public not only pays for the much greater expense of the newly patented drug but also pays an additional cost due to the greater use of the newest drugs.  Some of these drugs will not survive post-marketing safety surveillance and would be dangerous to some users. The newest drugs should be used only on patients not doing well on previously available regimens, so the extra cost is worse than wasted.

Business as usual in our patent system entails seventeen years of patent protection. Much of that time passes before marketing. The result is very aggressive promotion immediately after approval by the FDA (Federal Drug Administration).  Patients who are already doing well on previously available treatments should not be the first to take new medications. Initial post-marketing safety surveillance should proceed more slowly.  Suggestion: stop the clock on patent expiration from the time of FDA approval of the new drug until sufficient time has elapsed for post-marketing safety surveillance, also stop all promotion except printed matter for physicians only.  Our patent system also fosters much drug development effort expended on “me too” drugs—just enough change in the structure of the new molecule to justify a new patent.  This is much easier and less useful to society than research to develop entirely new drugs that solve previously intractable therapeutic problems.  It does permit obtaining market share.  Frequently one of the first three or four “me too” versions of the new molecule is more effective than the original, so we need a patent system that rewards innovation much more generously than imitation.  This could result from giving drug manufacturers a choice in how they promote newly patented medications. The choice would be an additional long patent extension until the cost of bringing the new product from research to market had been recovered from profits. In return the manufacturer would refrain from promotion of that product directly to the public or to physicians by drug sales people who travel to physicians’ offices and hospitals to push the latest products.

A further incentive to induce most of the pharmaceutical industry to prefer the low cost, extended patent choice: Instead of business as usual, reward “breakthrough” drugs, those with a novel mechanism of action. A good way to accomplish this would be mandatory licensing with royalties paid to the “breakthrough” patent holder by those marketing “me too” drugs until the original drug’s development costs had been recovered.  All these changes would greatly reduce the adverse outcomes of new drugs that fail soon after approval because of rare, but very severe, effects not observed during testing before market approval.  Vioxx, withdrawn from the market in 2004, is the most recent highly publicized example.

Vioxx was developed for people who do not tolerate aspirin and similar drugs because of stomach symptoms; but, right from the start, it was promoted aggressively for all arthritis sufferers including direct to consumer advertising.  The beginning of this direct advertising of prescription drugs was by administrative rule change without public or legislative hearings, and it happened on Bill Clinton’s watch. New Zealand was the only other country to adopt this direct advertising, but only until 2006. The termination occurred as part of a comprehensive agreement with Australia to make the two countries compatible in the way they regulate drugs. Even so, the industry almost prevailed. Canada still prohibits advertising of prescription drugs to the public, but enforcement has been lax since our defection.  Vioxx was withdrawn from the market after tens of thousands of unnecessary deaths from cardiovascular disease were documented from its use.  Presumably Vioxx did not cause the cardiovascular disease—it merely precipitated premature death.  Ironically the proof did not specifically demonstrate that deaths in patients sensitive to aspirin were increased.  There are additional problems peculiar to patents of antibiotics.      

Antibiotics need special attention because of the conflict of interest to the owner of the patent in reserving the latest antibiotics for difficult infections not adequately treated by previously available agents. The introduction of a truly new antibiotic with a novel mechanism of action has become a rare event at least partly because of reduced incentives. Just like all other drugs faced with patent expiration, antibiotic manufacturers opt for very vigorous promotion immediately after FDA approval. The result has been the early emergence of resistant organisms too soon after discovery of each new antibiotic with a novel mechanism of action. This problem was even more severe a few years ago when antibiotics were promoted to enhance growth of livestock. The reality was that the antibiotics promoted growth by limiting infections—you might say, as a substitute for hygienic conditions.

This is how antibiotic resistant E coli 0157 became prevalent in hamburgers resulting in fatal human infections—more lethal because of antibiotic resistance. The germ was part of the steer’s intestinal flora and contaminated the meat during processing. The antibiotic resistance arose because of widespread use of antibiotics for “growth promotion” in most calves for several generations of calves. Of course, these calves acquired an intestinal flora resistant to these antibiotics and continued to harbor them until slaughter. Rare hamburger was most of the problem because it didn’t always get hot enough during cooking to kill germs and because the grinding dispersed the contamination, permitting more bacterial growth and larger doses of the infectious agent. Deaths caused by germs resistant to all available antibiotics are increasing—an emerging major public health problem.

A more prolonged stopping the clock on patent expiration of new antibiotics (ten or fifteen years or even longer, enough to cover development costs) would go a long way toward postponing the evolution of resistant organisms by making the economics of limited use of new antibiotics much fairer to the manufacturer. Almost all use of antibiotics with a novel mechanism of action should be limited to treatment of infections resistant to the previously available agents. All additional antibiotics with the same novel mechanism of action developed as “me too” drugs will have a very similar pattern of resistant organisms and should also be used circumspectly.  [note added in proof: China has had big problems with drug policy.  Until 2004 antibiotics were available over the counter; they popped them mindlessly as we do vitamin pills.  See China Takes Aim at Rampant Antibiotic Resistance by Mara Hvistendahl in Science for May 18, 2012 Page 795] 

Drug Costs:  Granting these long extensions of patent protection would result in substantial annual cost savings to the public: currently $3 billion a year is spent on direct to consumer advertising and considerably more for samples and salesmen visiting physicians: over $6 billion per year according to Jim Hightower’s LOWDOWN for May 2012 (hightowerlowdown.org).  In midcareer I stopped seeing drug salesmen to avoid participating in these unnecessary costs.  Now many physicians do not see drug salesmen in their offices. 

Finally, here is something good about drug salesmen: after I had stopped seeing them, they would occasionally track me down to ask why I wouldn’t talk to them about drugs (trout fishing, etc was OK).  My reply. “I cannot always remember where I heard things, so I am very careful about my sources.”  None of the salesmen seemed other than sympathetic.

Summary:  These extensions of patent protection would tend to get public and corporate benefits back in step. There is a precedent for this since an extra seven-year exclusive marketing privilege and other tax incentives were granted in 1983 for orphan drugs, which are useful only for rare diseases but are necessary nonetheless and deserving of incentives.

Patents really did originate to promote innovation for the benefit of inventors and society as a whole. So why not apply that logical thinking to life saving drugs.  Nature has been seldom wrong about processes she has fine-tuned for eons.  We are part of nature.  Patents are our creation.  Let us continue to fine-tune them.

John Frantz, MD
May 17, 2012