Saturday, May 26, 2007

GSK - Avandia: clinical trials, ain't they a bitch

A large clinical study meant to test the heart safety of the diabetes treatment Avandia may be in jeopardy as a result of recent reports of the drug’s risks, according to an executive at its maker, GlaxoSmithKline.

Dr. Ronald L. Krall, the medical director for GlaxoSmithKline, said in a telephone interview yesterday that some of the 4,450 patients enrolled in the drug trial, called Record, have dropped out this week because of safety concerns about Avandia.

Dr. Krall said he did not yet know how many patients have withdrawn, but said Glaxo was now worried about whether it could complete the drug trial, which has been scheduled to run through next year. The company has been counting on a successful outcome from the study to dispel widespread concerns that Avandia carries a higher risk of heart attacks than other diabetes drugs.

Now, though, the independent research committees overseeing the study “are concerned about the ability of the study to continue” and are “considering what to do to prevent people from dropping out of the trial,” Dr. Krall said.

The safety concerns were ignited by an analysis published Monday in The New England Journal of Medicine suggesting that Avandia, used to treat Type 2 diabetes, carries an increased risk of heart attack, estimated at 43 percent, compared with other diabetes drugs or placebos.

In response to the medical journal article, the Food and Drug Administration, issued a safety alert for Avandia and advised patients who take it to consult their doctors.

Avandia, which was approved by the F.D.A. in 1999, has been used by an estimated seven million people, six million of them in the United States.

Yesterday, the F.D.A. said its own recent analysis of more than 40 clinical studies of Avandia seemed to confirm the findings in The New England Journal of Medicine’s study, whose lead author was the influential Cleveland Clinic heart specialist Steven E. Nissen.

More at NYT

Insider's view: Record should have been started much earlier in the drugs' development.

One wonders why it wasn't.

In fact there is an argument to say that (as with the glitazar Pargluva, see here here and here) its results should have been a requirement for Avandia getting approval in the first place.

2 comments:

PharmaGuy said...

I agree -- first do no harm!

David J. Phillips said...

Nissen did disclose that he consults for, and receives research support to perform clinical trials through the Cleveland Clinic Cardiovascular Coordinating Center from Eli Lilly (LLY-$59.36) and Takeda—marketers of Avandia’s key (and only competitor) in the thiazolidinedione class, the $2.6 billion seller, Actos (pioglitazone).

That said, few—if any!—news outlets reported his potential conflict of interest, or any suspicion that the study was done in order to achieve a desired result.

Why did not one reporter mention that the interpretation of a meta-analysis is potentially subject to an author’s inherent bias? When an advocate of a particular position conducts a meta-analysis, it is more likely to be biased in concordance with the author's previously advocated opinion, rather than refute one’s prior conclusions. [It is well known within the pharmaceutical community that Nissen has been a vocal critic of Avandia for years.]

http://10qdetective.blogspot.com/2007/05/who-benefits-from-avandias-reported.html

Best--
David J. Phillips, Publisher
www.10qdetective.blogspot.com