Passing off "me too" drugs as new

 Between 1998 through 2002, 415 new drugs were approved by the FDA. Of those, only 14 percent were truly innovative and 9 percent were old drugs that had been significantly improved. The remaining 77 percent were all me-too drugs—drugs defined as being no better than those already on the market to treat the same condition. To pass muster with the FDA, the pharmaceutical companies are only required to show that the drugs are better than nothing. In fact, they can be approved even if they’re worse than drugs already on the market. (Incidentally, when new drugs are discovered, most are by researchers supported by the National Institutes of Health, not by drug company researchers.)

Sometimes the companies need to create a “new” drug to replace one that is going off patent, at which time it becomes generic and less profitable. So they change the old one enough to qualify for a new patent. For example, when Prilosec, a heartburn medicine with $6 billion in annual sales, was about to go off patent, the drug maker, AstraZeneca, took a patent out on just the active portion of the Prilosec molecule, making it a “new” drug, called Nexium, which became the most heavily advertised drug in the United States. (In their clinical trials, to prove it was better than Prilosec, they tested Prilosec at lower doses than Nexium, making Nexium look better.)

Similarly Prozac, an antidepressant made by Eli Lilly with annuals sales of $2.6 billion, not only lost its patent, but other companies began making similar drugs, such as Paxil and Zoloft. So Eli Lilly converted Prozac into a weekly dosage form, renamed it Sarafem, colored it pink and lavender, and marketed it for “premenstrual dysphoric disorder.” Same drug, but priced three and a half times higher than generic Prozac (which, if you want some, is called fluoxetine).

Companies also simply create their own versions of a competitor’s successful product. For example, five or more companies produce the highly lucrative statin (cholesterol-lowering) drugs. At comparable doses, these statins work about the same and are competing for the same market. In fact, most drugs that treat the same illness work about the same. For this reason, Robert Temple, the FDA’s associate director of medical policy offers this advice regarding me-too drugs: “I generally assume these drugs are all the same unless somebody goes out and proves differently. I don’t think you lose much if you just always use the cheapest drugs.” (My advice would be to avoid all drugs.)

Next week: How drug companies expand the market for me-too drugs

For an introduction to this blog, see I Just Say No; for a list of blog topics, click the Topics tab.

Manipulating research findings

Drug manufacturers use a variety of tactics to get positive results from their clinical trials. For example, they can compare their new drug with an existing drug at an inadequate dose or choose patients who are most likely to get better on the treatment. If they reach a point where results are looking good, they can stop the trial early. Or, when they see that the results of clinical trials are unflattering, they can choose not to publish them.

As to the last point—not publishing unflattering data—Dr. Ben Goldacre, in the UK, describes a particular instance in his medical practice. He had researched the medical literature looking for a drug that would help his patient with depression. Because he’d had no luck with a variety of drugs, he began looking at the literature for reboxetine. “I’d read the trial data before I wrote the prescription, and found only well-designed, fair tests, with overwhelmingly positive results. It looked like a safe and effective treatment.” Later, through a long process of investigation, a group of researchers finally brought together all the trials that had ever been conducted on reboxetine. “When all this trial data was put together it produced a shocking picture,” he recounts. “Seven trials had been conducted comparing reboxetine against a placebo. Only one, conducted in 254 patients, had a neat positive result, and that one was published in an academic journal for doctors and researchers to read” It turns out that six more trials had been conducted on almost ten times as many patients. All of these trials showed that reboxetine was no better than a sugar pill. None of these six trials was published. “I had no idea they existed.” Reboxetine is still on the market.

On September 30, 2004, Merck pulled its arthritis drug, Vioxx, from the market, following increasingly alarming data that the drug increased the risk of heart attacks and strokes. This was five years after discovering, in 1999, that people who took Vioxx were 2.4 times more likely to experience cardiovascular problems than those taking naproxen. Neither the company’s marketing materials nor articles published in the New England Journal of Medicine indicated the magnitude of this problem. In other words, Merck had withheld this data and also misrepresented safety information. By the time the drug was pulled, an estimated two million people were taking it, and yearly sales amounted to $2.5 billion dollars. Merck was finally moved to withdraw the drug when, in a later trial to test the effect of Vioxx on polyps, researchers found that people taking Vioxx were developing almost twice as many heart attacks, strokes, and blood clots as people taking placebos. (These results were in fact similar to those in its 1999 study, the results of which were withheld.) One of the FDA’s scientists estimated that Vioxx had been associated with more than 27,000 heart attacks or deaths. (Vioxx, by the way, had not been shown to alleviate pain any better than the older medicines.)

These are just a couple of examples. Given the lack of reliable information, how can doctors (or you) trust the drug companies?

Next week: Passing off “me too” drugs as new.

For an introduction to this blog, see I Just Say No; for a list of blog topics, click the Topics tab.

Rewarding doctors to prescribe drugs

As I mentioned in last week’s post, an investigation by the San Jose Mercury News found that big pharma pays extra bucks to physicians who prescribe psychiatric drugs to foster children. In fact, they’re paid more than double the amount paid to typical California physicians, helping to increase the use of psychiatric medication by foster kids. Reporters found that frequent prescribers are rewarded the most. For those doctors who wrote more than 75 prescriptions to foster children in 2013, the pharmaceutical companies paid them on average almost four times (or about $10,000 more) than the lower prescribers. (Again, the payments are ostensibly to compensate doctors for speeches or for participating in drug trials.) In California, from 2010 to 2013, almost 30 percent of all California doctors averaged about $10,000 apiece over that four-year period, while the foster care prescribers received about $25,000 each.

Companies also reward doctors for prescribing drugs by giving them a good deal on price. For example, in the 1990s, the maker of Lupron, which is a prostate cancer drug, lowered the wholesale cost of the drug to beat a competitor’s prices. Because oncologists buy their anti-cancer drugs at wholesale prices directly from the drug companies but get insurance reimbursements at 80 percent of the retail price, doctors make a profit from the drugs. In the Lupron case, when the competitor’s drug came on the market, the company inflated the average retail price of Lupron to $500 a dose. But because doctors were able to buy it for as little as $350 wholesale, they were able to keep the difference between what they paid and the reimbursement payment from Medicare, which was based on the $500 price.

In 2013, Insys Therapeutics paid a pain specialist $67,000 in speaking fees, travel, and meals, to promote a powerful addictive painkiller called Subsys—a drug that is approved only for cancer patients who are already taking opioid painkillers. Even though the drug is approved only for cancer patients, just 1 percent of prescriptions for this product are written by cancer specialists. To increase profits, sales reps were encouraged to call on physicians who see patients with a wide range of ailments—not just cancer. This is called off-label marketing. All in all, Insys paid doctors $2.8 million in the final five months of 2013.

Genentech manufactures two drugs for macular degeneration: one, Lucentis, is $2,000 a dose and the other, Avastin, is $50 a dose. According to a large government-sponsored clinical trial completed in 2011, the two drugs are nearly equivalent. So Genentech had to figure out a way to encourage doctors to prescribe and promote Lucentis. As you might predict by now, Genentech does this by rewarding the doctors with speaking engagements and other rewards. Half of the 20 doctors who received the most money from Genentech to promote Lucentis in 2013 were among the highest prescribers of the drug in 2012, billing for higher amounts of Lucentis than 75 percent of their peers. In the meantime, physicians convince themselves that the more expensive drug is better. In 2011 the Office of the Inspector General for the Department of Health and Human Services determined that if all patients being treated with Lucentis had instead been given Avastin, the federal government would have saved about $1.4 billion.

Next week: Manipulating research findings

For an introduction to this blog, see I Just Say No; for a list of blog topics, click the Topics tab.

Rewarding doctors to promote drugs

Drug companies recruit physicians to promote their drugs by paying them to participate in speaker’s bureaus. Here’s an example, as recounted in Sandeep Jauhar’s book, Doctored: The Disillusionment of an American Physician: “…a sales representative of the pharmaceutical company Scios…invited me to join Scios’s speakers’ bureau and start giving paid talks using company slides to promote the drug Natrecor….Though the talks were obviously for marketing purposes, I didn’t think giving them would be sleazy or unethical, especially since Natrecor was a drug I prescribed and believed in. Moreover, and just as important, I needed the money….This started a series of talks I gave over the next two years. At first, I asked to use my own slides to maintain some semblance of objectivity, but the company wouldn’t allow it. I asked if I could modify the standard company slides with some of my own interpretations, but it wouldn’t allow that either. Typically, the talks took place at a fancy restaurant on Long Island or in Manhattan once or twice every couple of months. I’d get paid a thousand dollars or more for each talk.” After about two years, Jauhar quit the speakers’ bureau, noting that Natrecor was safe but “no more effective than existing, cheaper therapies.”

The pharmaceutical industry calls doctors like Juahar “Key Opinion Leaders” (KOLs). Juahar may have been in the KOL minor leagues, but some doctors are big league, as one pharmaceutical sales representative described a KOL by the name of Von Hoff: “He was a big KOL-kahuna physician on steroids who conducted more clinical trials for drug firms than nearly any other KOL. He collected advisory fees and perks from more than thirty pharmaceutical firms and sat on several companies’ boards. When I saw how many shares he owned in biotech and drug firms, my jaw dropped. A good word from Von Hoff could catapult a drug’s sales.”

In a story about doctors prescribing anti-psychotic drugs to foster children, the San Jose Mercury News reported: “One Sacramento doctor raked in more than $310,000 in four years to give promotional speeches.” But it’s not just the money that draws physicians into the ranks of KOLs, it’s the feeling of importance that comes from associating with other academic luminaries who've been recruited by drug companies. It’s like being admitted to a selective fraternity. As one KOL reported, "You get to hobnob with these mega-thought leaders and these aspiring thought leaders. They make you feel like you're special."

The pharmaceutical industry spends a third of its marketing budget on KOLs, a fact that adds to the cost of drugs. In 2001 consumers paid the 30% markup for sales promotion. The markup is probably higher now.

Next week: Rewarding doctors to prescribe drugs

For an introduction to this blog, see I Just Say No; for a list of blog topics, click the Topics tab.