When Drug Treatments Fail

Bad data happen to good people.

Posted Sep 23, 2012

The Guardian
Source: The Guardian

In Britain yesterday, the Business section of The Guardian newspaper featured an article about the latest pharmaceutical scandal brewing in the UK that rocketed to the paper’s most-read spot, where it has stubbornly remained today. In “The Drugs Don’t Work—A Modern Medical Scandal,” by Ben Goldacre, a doctor and bestselling author who writes the paper’s excellent “Bad Science” column, U.S. readers will recognize issues of immediate importance to American doctors, psychiatrists, and their patients, even though the drug in question mercifully is unavailable over here.

With characteristic candor, Goldacre examines how, in both countries, “drugs are tested by their manufacturers, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that exaggerate the benefits. Unsurprisingly, these trials tend to produce results that favour the manufacturer.”

Exhibit A in his article is Reboxetine—also manufactured under the names Edronax, Vestra, Norebox, Prolift, Solvex, and Davedax—which is widely prescribed across Britain and other European countries—indeed, in sixty countries in total—for depression, panic disorder, and ADHD, though which in May 2001 was declined a license in the U.S., according to the Good Drug Guide, for reasons that “have not been officially disclosed...” In this case, the FDA deserves a nation's thanks for doing its job as pharma watchdog. In a distressingly large number of other cases, however, including that of Paxil (paroxetine), also the subject of Goldacre’s article, the same drug will be widely available in both the U.S. and across Europe, the same kinds of widespread “massaging” of clinical data takes place, and, alas no real surprise, the same kinds of side effects materialize in countless patients.

“I'd read the trial data before I wrote the prescription,” Goldacre writes of Reboxetine, for a patient for whom other drug treatments “had done nothing,” “and found only well-designed, fair tests, with overwhelmingly positive results. Reboxetine was better than a placebo, and as good as any other antidepressant in head-to-head comparisons. It's approved for use by the Medicines and Healthcare products Regulatory Agency (the MHRA), which governs all drugs in the UK. Millions of doses are prescribed every year, around the world. Reboxetine was clearly a safe and effective treatment. The patient and I discussed the evidence briefly, and agreed it was the right treatment to try next. I signed a prescription.”

“But we had both been misled,” Goldacre continues. “In October 2010, a group of researchers was finally able to bring together all the data that had ever been collected on reboxetine, both from trials that were published and from those that had never appeared in academic papers. When all this trial data was put together, it produced a shocking picture. 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. But six more trials were conducted, in almost 10 times as many patients. All of them showed that reboxetine was no better than a dummy sugar pill. None of these trials was published. I had no idea they existed.”

Readers of this blog will note the number of times this problem has surfaced as a widespread concern, with drug makers and researchers routinely withholding evidence they don’t like, either because it flatly contradicts results they are spending millions of dollars promoting or, in the case of researchers, because releasing such data can feel awkwardly close to biting the hand that feeds—in this case, the “hand” that's paying for the research in the first place.

Goldacre writes of his exasperation as a doctor implicated in such deception: “I did everything a doctor is supposed to do. I read all the papers, I critically appraised them, I understood them, I discussed them with the patient and we made a decision together, based on the evidence. In the published data, reboxetine was a safe and effective drug. In reality, it was no better than a sugar pill and, worse, it does more harm than good. As a doctor, I did something that, on the balance of all the evidence, harmed my patient, simply because unflattering data was left unpublished.”

“Nobody broke any law in that situation,” he concludes; “reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world.”

Goldacre’s article is an excerpt from his forthcoming book, Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients, available shortly in the UK and U.S. from Fourth Estate/HarperCollins. I recommend looking for the book here.

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