A Hard Pill to Swallow

On a routine trip to the pharmacy to pick up a prescription last fall, I was informed that a medication I had been taking for many years was no longer available. Instead, the pharmacist substituted a new, more expensive drug made by the same company, supposedly containing the same active ingredient as the version to which I was so long accustomed.

The original pill was called Asacol, one of a number of commercially produced variants of the anti-inflammatory drug mesalamine. It came in a hard, reddish-brown caplet (in the photo below on the left). The new pill, Delzicol (in the middle photo), was a rather large capsule. After verifying with my doctor that the therapeutic value of Delzicol was much the same as Asacol, I proceeded to take it without much concern.

After a few weeks, curiosity got the better of me. I pried the two halves of a Delzicol capsule apart to see what it looked like inside. I expected to find a granular substance of some kind, but was simply amazed when what looked exactly like an Asacol capsule popped out (picture on right). The new pill was apparently just the old pill wrapped in a new coating.

Nice trick: turning drugs into gold

Now suspicion took hold. I went online and discovered that the patent for Asacol had nearly run out when the manufacturer, Warner Chilcott, released Delzicol. It wasn't hard to find any number of articles and chatter questioning whether the new drug was nothing more than an attempt by the company to protect its patent and prevent generic versions of mesalamine from coming onto the market. If patients and their insurance companies were now being forced to pay more, surely there had to be a good reason. Wouldn't the Food and Drug Administration have required the manufacturer to demonstrate that it had created a fundamentally new drug before giving it a new patent?

In a word, no. It seems clear from the FDA's own documentation that Warner Chilcott was not required to conduct new clinical trials to prove the value of its allegedly new delivery system. On the FDA website it says, "The data presented…are from clinical trials conducted with mesalamine delayed-release tablets. Delzicol is bioequivalent to these mesalamine delayed-release tablets." In other words, the manufacturer merely made reference to previous studies that demonstrated the efficacy of mesalamine, in its original delivery system. A newspaper in Oregon reported that, according to the FDA's own documentation, "no new safety or efficacy trials were conducted by the applicant using the proposed capsule product."

Even if we gave the drug maker the benefit of the doubt, and assumed that it was sincerely trying to reformulate Asacol in order to correct some known deficiency or address complaints from patients, it begs the question why it waited until just months before the expiration of its patent to introduce the new pill. If it knew that some patients were not getting the full benefit of the medication, or were perhaps even being harmed by it, what possible justification did it have to wait? It has been reported that the FDA asked Procter and Gamble (which manufactured Asacol before selling its product line to Warner Chilcott) to replace a plasticizer in the pill's coating, though without any data to suggest that it had ever caused anyone any harm. The new maker did so, and by adding the capsule was able to convince the FDA that it had produced a new drug entirely, without any known evidence to support its claim.

Suspicions seem further justified by the difference in price between the two drugs. Since I am among the fortunate Americans to have very good health insurance, this meant that my co-pay would "only" increase from $30 for a three-month supply of Asacol to $90 for Delzicol. Someone who had to pay the full retail price would see the cost per pill increase from about 80 to 85 cents (or about 50 cents for a generic Canadian version) to more than $3. Advertised discounts could bring the price down to about $2.40 per pill, which is still triple the original price for a drug that is virtually identical to its prior version. For someone taking a full daily dose, the price tag for Delzicol is in the range of $400-$500 per month, instead of $100-$150.

At the turn of the new year, I was notified by my insurance company that it would no longer pay for Delzicol at all. Clearly patients are not the only ones who are skeptical.

Lest we think this is an isolated case of the FDA falling down on the job, my internist told me a few weeks ago about another drug whose price soared after a pharmaceutical company was given approval for a "new" medicine that is identical to one that was already on the market. In this case the company is URL Pharma, and the drug is colchicine, a highly effective treatment for gout that has been prescribed by doctors for many decades, and whose use can be traced back to the 6th century. According to articles in the Wall Street Journal and elsewhere, colchicine was available until quite recently in generic form for about 10 cents a pill. Because its existence predated the establishment of the FDA, it had never received government approval for its use. About five years ago, the agency began a campaign to bring previously unapproved drugs under its regulatory authority. URL Pharma conducted clinical trials and came up with a "new" drug called Colcrys, which retails for $5 per pill. You are not reading that wrong: the price for this allegedly safer version is 50 times higher than for generic colchicine.

And the news gets worse: Since any company that performs clinical trials for a drug is given exclusive rights to market it for a period of years, URL Pharma promptly proceeded to sue generic makers of colchicine for infringement of its patent. Since the profit margin for a drug that sells for pennies was too low to tempt any of these other makers to conduct their own clinical trials, URL Pharma now has the field all to itself. My doctor tells me that generic colchicine is now nearly impossible to find on the American market. Patients and insurers — including the very government that inadvertently induced URL Pharma to drive generics off the shelves in the first place — now have to pony up for a vastly more expensive drug that has no more therapeutic value than the cheaper version that was used for centuries.

First, Do No Harm

In his memoir The Youngest Science, the late Lewis Thomas described what it was like to train as a physician at the very moment when the practice of medicine changed utterly. Just as he was completing medical school in the 1930s, antibiotics were discovered. He and his fellow Harvard students, who had been taught everything about how to diagnose illness and nearly nothing about how to treat it, watched in amazement as pneumonia patients who would almost certainly have died were thoroughly cured within days of being given the new miracle drugs. He recalled how his father, who practiced medicine in Flushing, Queens in the early years of the 20th century, regularly dispensed prescriptions of no therapeutic value whatsoever. The United States Pharmacopeia, a standard reference for practicing physicians and pharmacists, at that time contained a thousand pages of useless concoctions. Only a handful of medications were yet known to have any demonstrated usefulness, among them aspirin, morphine and digitalis. Yet every patient expected the doctor to prescribe something for every complaint, and any doctor who didn't risked losing all his patients.

The discovery of penicillin began a revolution in the research and production of useful drugs, and, concurrent with great advancements in surgical techniques, transformed doctors from largely helpless observers of the course of illness to proven healers (and also made many of them very wealthy). Ironically, in one important respect the expectations of the sick and injured have apparently not changed. When a patient goes to the doctor, he or she expects not only a diagnosis, but an effective treatment. "There's nothing I can do for you" has departed the doctor's lexicon forever. In the century after Dr. Thomas's father plied his trade, people are no longer given placebos to keep them occupied while the disease runs its natural course, and this is of course a great leap forward. But while beneficial drugs have unquestionably improved the lives of billions of people, the system of finding, approving and producing them leaves a lot to be desired. It is now so rife with corporate hucksterism, which is abetted by bureaucratic ineptitude and/or collusion, that we can no longer be as sure as we once were that the drugs coming to market are worth what we are made to pay for them. Any assertions that there is a free market at work in drugs and their dispensation are overwhelmed by evidence to the contrary. Slick advertisements for expensive new drugs to treat conditions that few people have ever even heard of do not exactly inspire confidence in the good intentions of drug makers or the critical oversight of regulators.

For a period of time in the second half of the last century, the family doctor was revered even beyond his actual abilities to treat his patients. For baby boomers, he was an omniscient and comforting presence. Since then, the decline in the public's confidence in medicine has run parallel with a general skepticism about the claims of science. A half century ago, the wonderful new worlds of biology and chemistry were supposed to usher in an unprecedented era of healthy living. Instead, they are widely blamed for befouling the planet and making us sicker. Even if these suspicions are exaggerated, the evidence that medicine is no longer as widely trusted as in the past can be found on the well-stocked supplements aisle of every drug store. We're still taking potions and tonics of unproven value, only now we are prescribing them for ourselves. With their obsession with profits and regulatory shenanigans, the pharmaceutical companies and their handmaidens in the government have only themselves to blame.