[I]n 2010, seven medical researchers and one patient advocate gathered in a plush Marriott hotel in College Park, Maryland, to review a promising drug designed to prevent heart attacks and strokes by limiting blood clotting. The panel is one of dozens of advisory committees that vote each year on whether the Food and Drug Administration (FDA) should approve a therapy for the U.S. market. That day, panel members heard presentations on the drug’s preclinical and clinical data from agency staff and AstraZeneca…
By day’s end, the panel voted seven to one to approve. FDA, as usual, later signed off.
FDA… uses a well-established system to identify possible conflicts of interest before such advisory panels meet.
Before the Brilinta [AstraZeneca’s drug] vote, the agency mentioned no financial conflicts among the voting panelists, who included four physicians. As Brilinta’s sales took off later, however, AstraZeneca and firms selling or developing similar cardiovascular therapies showered the four with money for travel and advice. For example, those companies paid or reimbursed cardiologist Jonathan Halperin… more than $200,000 for accommodations, honoraria, and consulting from 2013 to 2016.
Brilinta fits a pattern of what might be called pay-later conflicts of interest, which have gone largely unnoticed—and entirely unpoliced.
In examining compensation records from drug companies to physicians who advised FDA on whether to approve 28 psychopharmacologic, arthritis, and cardiac or renal drugs between 2008 and 2014, Science found widespread after-the-fact payments or research support to panel members.
An analysis of pharma payments to 107 physicians who advised FDA on 28 drugs approved from 2008 to 2014 found that a majority later got money for travel or consulting, or received research subsidies from the makers of the drugs on which they voted or from competing firms.
Corporate payments and other support given to advisers before a drug review are widely acknowledged as troubling. When “a voting member of a committee demonstrably had financial associations with the company or the competitor prior to the meeting, and the FDA doesn’t flag it, then somebody’s dropping the ball on due diligence,” says Yale University physician Robert Steinbrook, editor at large for JAMA Internal Medicine.
Yet benefits that come later, even years after a drug approval vote—jobs, money, professional prestige, and influence —are also fraught, ethicists say.
They are a way of “postponing your reward,” says Carl Elliott, a medical ethicist at the University of Minnesota in Minneapolis who has persistently criticized the financial inducements pharma gives to researchers. “You do something positive for a company that you feel confident is going to pay you back for it later on. And they do.”
FDA declined interview requests about Science‘s findings.
Jacob Sitko enlisted in the U.S. Army in January 2008 and… [in] 2011, the private died in bed at his barracks at Fort Carson in Colorado, where he was being treated for posttraumatic stress disorder (PTSD).
Sitko, who was 21 and in good health other than his PTSD, had been killed by “mixed-drug intoxication.” Army doctors had been giving him a cocktail of medicines that included quetiapine, a top-selling antipsychotic from AstraZeneca sold under the name Seroquel. The particular mixture had been linked for years to sudden cardiac death, though no evidence has been made public that Sitko was told that.
“They sent his body home without his heart” and didn’t say why, [his mother] says.
Two years earlier, two panels of FDA advisers had considered whether to approve Seroquel for new conditions— schizophrenia and bipolar disorder in children, and depression in adults who are taking other medicines.
Seroquel was then known to be associated with sudden cardiac death when used with certain drugs, and several antipsychotics similar to Seroquel also had a record of cardiac fatalities. But AstraZeneca presented results from its clinical studies, which company representatives said showed, at worst, minimal risks.
In 2009, both panels voted by wide margins to approve Seroquel for the additional conditions. In the years afterward, several FDA advisers received significant financial support from AstraZeneca and the makers of competing drugs.
The next year, in 2010, AstraZeneca paid the government $520 million to settle lawsuits involving alleged improprieties in the company’s clinical trials and improper marketing of Seroquel for unapproved conditions. The company, which denied wrongdoing, pulled in more than $5 billion in revenues from the drug that year.
In recent years, FDA has fielded thousands of complaints about cardiac problems, including many deaths, tied to Seroquel.
FDA asks panel members who vote on recommending drug approvals to disclose in advance details of investments, contracts, or other payments from drugmakers. The agency uses those disclosures to determine whether pharma backing during or before a meeting should disqualify an adviser.
But the agency’s financial review process is primarily an honor system and seems to miss obvious conflicts. For the 17 physicians receiving the most compensation after a drug advisory vote, Science examined whether they also received industry compensation concurrent with or shortly before their FDA service.
Eleven physicians acknowledged support from competing companies on one or more drugs they reviewed. Five of those also received such funding from the makers of one or more of the drugs. Yet FDA publicly noted none of those apparent conflicts and issued no conflict waivers.
FDA would not discuss any individual adviser or detail what, if anything, the agency does to validate advisers’ disclosures.