An analysis of authors who published reports on GlaxoSmithKline’s Avandia diabetes pill shows that those with ties to the industry were more likely to conclude that the drug didn’t increase the risk of myocardial infarction compared with authors with no industry ties, according to a study presented at the American College of Preventive Medicine annual meeting, TheHeart.org reports.

The analysis, which was presented as a poster by Mohammed Hassan Murad of the Mayo Clinic,
reviewed 202 articles that addressed the possible association between MI risk and Avandia in diabetes patients. Articles selected for review addressed the findings of two studies, a meta-analysis of small trials and a subsequent larger trial, that contributed to the controversy, TheHeart.org writes.

Of the papers evaluated, 107, or 53 percent, included a conflict-of-interest statement and 90, or 45 percent, had a conflicting financial relationship. Among authors who concluded Avandia doesn’t increase the risk of MI, 91 percent had financial ties to makers of diabetes meds and 86 percent had relationships with Glaxo, TheHeart.org continues. Among authors of articles offering unfavorable reviews, only 25 percent had financial relationships with makers of diabetes meds and 18 percent had relationships with Glaxo that were disclosed in the papers.

Murad noted that in some cases, when an online search was conduced for some authors, they found some who listed financial conflicts in other publications that weren’t disclosed in their Avandia paper. “Disclosure rates of conflicting financial relationships were misleadingly low despite their clear and strong linkage with authors’ expressed views,” Murad noted. “These findings underscore the need for further progress in reform for the scientific record to be trusted. The quality of care patients receive is clearly affected by these findings.”

The study demonstrates the problem with pairing of researchers with financial interests in a company and studies involving that company’s product, according to David Katz of Yale University’s Prevention Research Center. “If the researcher has a direct financial interest in the item being studied, the researcher—who, unlike the funder, is responsible for interpreting the data—will share the funder’s bias,” Katz, who wasn’t involved in the analysis, tells TheHeart.org. “The trend in the literature indicates that most people do not adequately resist this inclination.”

A decade ago people were afraid of big the profit motives of Big Tobacco.  Today those fears no turn to the profit motives of Big Pharma. The story appearing in today’s NYT is frightening to say the least.

According to the NYT, “The reports, obtained by The New York Times, say that if every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.

“Rosiglitazone should be removed from the market,” one report, by Dr. David Graham and Dr. Kate Gelperin of the Food and Drug Administration, concludes. Both authors recommended that Avandia be withdrawn.

The internal F.D.A. reports are part of a fierce debate within the agency over what to do about Avandia, manufactured by GlaxoSmithKline. Some agency officials want the drug withdrawn because they believe there is a safer alternative; others insist that studies of the drug provide contradictory information and that Avandia should continue to be an option for doctors and patients. GlaxoSmithKline said that it had studied Avandia extensively and that “scientific evidence simply does not establish that Avandia increases” the risk of heart attacks.

The battle has been brewing for years but has been brought to a head by disagreement over a new clinical trial and a Senate investigation that concluded that GlaxoSmithKline should have warned patients earlier of the drug’s potential risks.

Avandia was once one of the biggest-selling drugs in the world. Driven in part by a multimillion-dollar advertising campaign, sales were $3.2 billion in 2006. But a 2007 study by a Cleveland Cliniccardiologist suggesting that the drug harmed the heart prompted the F.D.A. to issue a warning, and sales plunged. A committee of independent experts found in 2007 that Avandia might increase the risk of heart attack but recommended that it remain on the market, and an F.D.A. oversight board voted 8 to 7 to accept that advice.

Hundreds of thousands still take the medicine, although some top endocrinologists say they have sworn off the drug.

Since 2007, more studies have been done. In a December 2009 internal memorandum, Dr. Janet Woodcock, director of the F.D.A.’s drug center, wrote that “there are multiple conflicting opinions” about Avandia within the agency, and she ordered officials to assemble another advisory committee, expected this summer, to reconsider whether the drug should be sold.

“I await the recommendations of the advisory committee,” the agency’s commissioner, Dr. Margaret Hamburg, said Friday night. “Meanwhile, I am reviewing the inquiry made by Senators Baucus and Grassley and I am reaching out to ensure that I have a complete understanding and awareness of all of the data and issues involved.”

The bipartisan multiyear Senate investigation — whose results are expected to be released publicly on Monday but which were also obtained by The Times — sharply criticizes GlaxoSmithKline, saying it failed to warn patients years earlier that Avandia was potentially deadly.

“Instead, G.S.K. executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk,” concludes the report, which was overseen by Senator Max Baucus, a Montana Democrat, and Senator Charles E. Grassley, an Iowa Republican.

Mr. Baucus said of the report, “Patients trust drug companies with their health and their lives, and GlaxoSmithKline abused that trust.”

In response, GlaxoSmithKline said that it disagreed with the Senate investigation’s conclusions. The company said that it could not comment on internal F.D.A. documents but that “the official ruling from F.D.A. is that Avandia remain on the market.”

In the wake of the controversy, agency officials ordered GlaxoSmithKline to undertake a study comparing how many heart attacks, strokes and heart-related deaths occur among patients given either Avandia, Actos or a placebo. Studies suggest that Actos, made by Takeda, lowers blood sugar as well as Avandia but without hurting the heart as much.

But Dr. Graham and Dr. Gelperin, working in the F.D.A.’s office of surveillance and epidemiology, argued in two separate internal reports that the new GlaxoSmithKline study, called TIDE, is “unethical and exploitative” because patients given Avandia face far greater risks than those given Actos, with no promise of any additional benefit. The trial may include patients who have had heart attacks or chest pains even though some foreign drug authorities have warned against Avandia’s use by precisely such patients, the reports note.

“Although the proposed TIDE trial is motivated by a desire for definitive answers regarding the cardiovascular safety of the drug rosiglitazone, the safety of the study itself cannot be assured and is not acceptable,” one of the reports concludes.

These concerns, in internal reports dated October 2008 but not made public until now, were later overruled by other agency officials, and GlaxoSmithKline is currently enrolling patients in the TIDE trial. The trial is not expected to be completed until 2020, although the company is hoping to report some results to the F.D.A. by 2014. The company’s patent on Avandia expires in 2012, and generic versions will probably swallow most remaining profits.”

How much longer do we need to wait before Congress fixes this problem.  If an airplane dropped from the sky every month killing 500 people do you think  someone from Washington might do something about it?