Mar 23, 2012

Experts challenge FDA over approval for new dose of Alzheimerʼs drug

Although the drug improved cognitive symptoms, it did not improve overall functioning, which suggests that the cognitive difference was not meaningful. Furthermore, the new dose caused more side effects, including nausea and vomiting.

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Experts challenge FDA over approval for new dose of Alzheimerʼs drug | Alzheimer's Reading Room

Approval for a new dose of a best-selling Alzheimerʼs drug “breached the FDAʼs own regulatory standard” and has led to “incomplete and distorted messages” about the drug, warn experts on bmj.com.

In the first of a new occasional series, "not so", highlighting the exaggerations, distortions, and selective reporting that mark some news stories, advertising, and medical journal articles, Lisa M. Schwartx and Steven Woloshin challenge the claims made for the new 23 mg dose of donepezil.


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Experts challenge FDA over approval for new dose of Alzheimerʼs drug
Observations: How the FDA forgot the evidence: the case of donepezil 23 mg

Approval for a new dose of a best-selling Alzheimerʼs drug “breached the FDAʼs own regulatory standard” and has led to “incomplete and distorted messages” about the drug, warn experts on bmj.com.

In the first of a new occasional series, "not so", highlighting the exaggerations, distortions, and selective reporting that mark some news stories, advertising, and medical journal articles, Lisa M. Schwartx and Steven Woloshin challenge the claims made for the new 23 mg dose of donepezil.

Professors Lisa Schwartz and Steven Woloshin of the Center for Medicine and the Media at The Dartmouth Institute for Health Policy and Clinical Practice argue that the new dose was approved “only over the objections of the FDAʼs medical and statistical reviewers” and that it offers “no meaningful added benefit, just more harm.”

Donepezil was a blockbuster drug for Alzheimerʼs disease, with over $2bn in annual sales in the United States alone. Just before its patent expired, the US Food and Drug Administration (FDA) approved a new 23 mg dose for moderate to severe Alzheimerʼs disease, thereby extending its patent for three more years.

Previously, the drug was only available in 5 mg and 10 mg doses.

The FDA and the manufacturer agreed that the 23 mg dose would be approved only if it was shown to be superior to the 10 mg dose on both a cognitive and a global functioning measure.

Although the drug improved cognitive symptoms, it did not improve overall functioning, which suggests that the cognitive difference was not meaningful. Furthermore, the new dose caused more side effects, including nausea and vomiting.


Yet Schwartz and Woloshin point to “a stunningly erroneous statement” in an advertisement aimed at doctors which claims that patients on the 23 mg dose “experienced important clinical benefit on both measures [cognition and overall functioning].”

“Nowhere – not in the direct to consumer or the physician advertisements, nor even in the FDA approved label – are the great uncertainties about this drug acknowledged, uncertainties that led the FDAʼs own medical and statistical reviewers to recommend against approval of the 23 mg dose,” they argue.

Despite this, the drug was approved over the objections of the FDAʼs medical and statistical reviewers and government and private insurance programmes now cover the drug. It is now, or will soon be under consideration for approval in 16 countries in Asia and South America.

Alzheimerʼs is an awful disease, say the authors. “Sadly, the available drugs donʼt work well. But that is no excuse for manipulating vulnerable patients, desperate family members, and their doctors to use a product that is most likely to cause net harm.”

They conclude: “To make good decisions about drugs, doctors and patients need the evidence. The FDA should not forget to give it to them.”

New material recently obtained by the authors from the FDA acknowledge that they made an error in relation to the previous label, stating:
“The offending phrase was in the original label, and we donʼt recall how it slipped by, but we contacted the company as soon as it was brought to our attention, and they readily agreed to remove it. We are always inter­ested in improving the content and clarity of our labeling, and appreciate being informed of any misleading or inaccurate statements that anyone may notice.”
Interesting article on this topic in the New York Time -- Drug Dosage Was Approved Despite Warning

Source of information: The Dartmouth Institute for Health Policy and Clinical Practice

How the FDA forgot the evidence: the case of donepezil 23 mg

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