A report conducted by Science magazine has raised red flags about a possible conflict of interest among the experts charged with advising the Food and Drug Administration (FDA) on whether a medication should be granted marketing approval. Specifically, investigators uncovered a concerning trend of compensation flowing from pharmaceutical companies to drug advisory panel members.
FDA Advisory Committees provide the agency with independent advice from outside experts – typically physicians and researchers, but also industry experts, consumers and occasionally a patient representative – on issues related to human drugs, vaccines and other biological products, and medical devices. Committee members review and discuss preclinical and clinical trial data detailing the drug’s safety and efficacy profile, then vote whether to recommend the drug for approval. The FDA isn’t required to follow the advice of the committees, but it usually does.
To identify suitable panel members, the agency first uses a well-established system to flesh out potential committee members with possible conflicts of interest that includes requiring them to reveal potential existing conflicts of interest such as details of investments, contracts, research support, or other payments from drug companies. But a loophole in this system allows prospects to keep mum about any support they may receive between the appointment to the committee and the actual panel meeting, as well as any financial incentives received after the committee votes to approve or reject a drug.
“The people who are asked to weight this evidence impartially often stand to gain tremendously in their further professional careers from a positive relationship with the (drug) company,” Vinay Prasad, hematologist-oncologist with Oregon Health & Science University Portland, told Science. Prasad studied financial conflicts in drug approvals and said that there may not be a spoken agreement between the panel member and the drug company, “but you don’t have to evoke that to be very concerned. It’s in their best interest to play nice with these companies.”
Follow the money
The evidence is in the data, which Science pulled from physician disclosures in publications and Centers for Medicare & Medicaid Services records from 2013 to 2016 posted on the federal Open Payments website. The analysis focused on direct payments to physicians from companies whose pharmaceuticals were voted on as well as payments from companies selling competing drugs or researching drugs from the same class for the same indication. The analysis also looked at “associated research” funding by a drug company to an FDA advisor either directly or through their institution typically for research funding. These payments are vital to a scientist’s career advancement and compensation.
What the analysis revealed was startling. During the four-year study period, 40 of the 107 physician advisors received more than $10,000 in earnings or research support from the drug companies whose drugs they voted to approve or from competing firms. Twenty-six received more than $100,000, and seven were given more than $1 million each.
The vast majority (94 percent) of the $26 million in personal payments or research support paid by the drug industry to the top 17 earning advisors came from manufacturers of drugs that advisors had either reviewed or from their competitors.
Furthermore, most of the top earners received payments from the same drug companies while they were serving on the committee or the year prior to serving. But the FDA never disclosed this information. Science obtained it through scholarly journals.
Weeding out bias
Genevieve Kanter, a University of Pennsylvania economist who has studied conflicts of interest in FDA drug evaluations, told Science that the FDA system for evaluating possible conflicts of interest could be strengthened in order to protect against possible bias.
But Carl Elliot, a medical ethicist at the University of Minnesota, suggested that, “Even in the best of circumstances, disclosure is a remarkably weak way of controlling conflicts of interest. A better way would simply be for the FDA to say, ‘We are not taking anybody with any kind of conflict on an advisory committee.’”
It can be done. In fact, the European Medicine Agency (EMA), which holds a similar regulatory role in the United Kingdom as the FDA in the United States, prohibits the appointment of advisory committee members having any relationships with pharmaceutical companies three years prior to their service.