How the FDA forgot the evidence: the case of donepezil 23 mgBMJ 2012; 344 doi: https://doi.org/10.1136/bmj.e1086 (Published 22 March 2012) Cite this as: BMJ 2012;344:e1086
- Lisa M Schwartz, professor12,
- Steven Woloshin, professor12
- 1VA Outcomes Group, Department of Veterans Affairs Medical Center, White River Junction, Vermont 05009, USA
- 2Center for Medicine and the Media, The Dartmouth Institute for Health Policy and Clinical Practice, Lebanon, New Hampshire, USA
What is the difference between 20 and 23? If you said three, you are off by millions—of dollars in sales, that is—at least from the perspective of Eisai, the manufacturer of donepezil (marketed as Aricept by Pfizer).
A little context helps make the maths clearer. Donepezil, the biggest player in the lucrative market for Alzheimer’s disease treatments, was a blockbuster, with over $2bn in annual sales in the United States alone. But the drug, first approved in 1996, had reached the end of the road: the patent expired in November 2010. Investors call this “going over the cliff,” an anxious reference to plummeting sales as market share is lost to generic competitors. Necessity, however, is the mother of invention. Just four months before the expiry of the patent, the US Food and Drug Administration (FDA) approved a new dose for moderate to severe Alzheimer’s disease: donepezil 23 mg. Is 23 an odd number? Not really, when you consider that you cannot get to 23 mg using the 5 mg and 10 mg doses that were going generic. The “new” 23 mg product would be patent protected for three more years.
Now it was time for the marketing to begin. In addition to their sales force, the manufacturers deployed dedicated teams of “Aricept 23 mg clinical nurse educators” to reach prescribers. They focused particularly on “priority targets”—neurologists and high volume facilities for the long term care of people with Alzheimer’s disease—to promote the idea that “there are no ‘stable’ AD [Alzheimer’s disease] patients—therefore aggressive treatment is …