Why Adjust The Dosage on A Useless Drug?

March 22, 2012

Professors Lisa Schwartz and Steven Woloshin of the Center for Medicine and the Media at The Dartmouth Institute for Health Policy and Clinical Practice are raising alarms about a recent Food and Drug Administration decision to approve a new dosage for the  best-selling Alzheimer’s drug Aricept (donepezil). The decision “breached the FDA’s own regulatory standard” and has led to “incomplete and distorted messages” about the drug, they warned in the latest British Medical Journal.

Aricept has become a $2 billion-a-year blockbuster in large part because people caring for elderly patients with dementia are desperate for something, anything to slow their loved ones’ inexorable decline. The original dose for the drug, which was approved in 1996, provided a short-term improvement in memory that faded to insignificance within six months. With its patent due to expire, the companies behind the drug — Eisai and Pfizer — went to the FDA with a clinical trial in 1,400 patients claiming a higher dosage showed better results. The FDA agreed, which gave the companies another three years of marketing exclusivity based on a use patent for that new, higher dose.

Here’s the medical problem with that higher dosage, according to Schwartz and Woloshin. While the clinical trial showed that patients did slightly better in cognition (like recognizing numbers), the drug had no impact whatsoever on their actual functioning in day-to-day life, at least none that their caregivers could notice. Yet the major side effects of the drug — nausea and vomiting — increased significantly. The article claimed that the FDA had said specifically to the trial sponsors that the higher dose had to have an impact that caregivers could notice to win approval. Schwartz and Woloshin charged the FDA with violating its own standards.

With approval in hand, the drug’s sponsors launched a major new advertising campaign featuring emotional scenes of people caring for spouses or parents with Alzheimer’s. The ads implied the drug improved cognition, which it did on tests, but didn’t mention anything about overall functioning, which did not improve. The ads, like all drug ads, warned about side effects, but gave no sense of their seriousness.  They did state that “side effects may get better after the patient takes Aricept for a while.”

The advertisements aimed at doctors were even more misleading, they charged.

It contains a stunningly erroneous statement in a large bold font: “Patients on Aricept 23 mg/day experienced important clinical benefit on both measures [cognition and overall functioning],” which is simply not true. In fact, this statement is directly contradicted by a statement in a smaller plain font that says that the results for global function “did not show statistical significance.”

As more blockbuster drugs come off patent, health care payers, including Medicare, can expect a desperate drug industry to deploy more such strategies like hiking doses to extend patent life of their billion-dollar blockbusters. At the least, the FDA must be a bulwark against using misleading science to accomplish those goals. It is also charged with policing misleading advertising. In this case, it appears to have failed at both of those tasks.

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4 Responses to Why Adjust The Dosage on A Useless Drug?

  1. Prof Donald Light on March 23, 2012 at 5:08 am

    In a set of detailed case studies spanning more than 30 years, Professor John Abraham has documented how the FDA has repeatedly violated its own standards for evidence so that it approves new drugs using weak or biased information about their effectiveness or dangers.

    Why is this work not better known, and why aren’t physician and patient groups calling for investigations of how the FDA falls short of protecting patients from relatively unsafe drugs?

    Why don’t the National Science Foundation and NIH fund grants like Abraham’s to research the organizational and scientific integrity of how new drugs get approved?

  2. Elizabeth Barbehenn on March 26, 2012 at 5:50 am

    Public Citizen petitioned the FDA to ban Aricept 23 on May 18, 2011 (http://www.citizen.org/hrg1950) using the similar arguments as Schwartz and Woloshin. FDA has not replied to our petition. Perhaps, this article will get more results.

  3. Julie Zito, PhD, Professor of Pharmacy and Psychiatry, University of Maryland, Baltimore on March 26, 2012 at 7:02 am

    A major point in this critique of research standards for psychopharmacologic agents is the emphasis on symptoms to the exclusion of functioning as primary endpoints. This is true of studies across the psychiatric spectrum and the DSM criteria have helped to create the imbalance. The situation makes a case for post-marketing outcomes of benefits and safety so that long-term drug use can be assessed–by an independent assessment agency.

  4. Mariel on March 26, 2012 at 1:19 pm

    Because I have a genetic ailment which makes me very sensitive to some drugs, I have a built-in rejection mechanism for bad drugs. The mechanism worked often, before I got a dx and knew why. I mainly take old tried and true drugs like Propanalol, which many others with Porphyria take, with only rare side effects, and lots of good help. It’s too bad, perhaps, that the drug companies must scramble for profits when patents run out. Should this law be changed?

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