Two U.S. senators are pushing for answers about a long-running series of private meetings between drug company executives and federal regulators, events that were held at expensive hotels and paid for by the drug firms.
The letter from Sens. Joe Manchin (D-W.Va.) and David Vitter (R-La.) cites concerns about the controversial new high-dose painkiller Zohydro, which was approved last year by the U.S. Food and Drug Administration.
The two sent a letter to Mark Taubman, dean of the medical school at the University of Rochester, asking for financial records on two groups connected to the university — one known as IMMPACT and the other ACTTION — that facilitated meetings between the drug makers and FDA officials.
"We are deeply troubled by allegations that the FDA gave manufacturers of prescription drugs the opportunity to pay thousands of dollars to the University of Rochester Medical Center for the privilege to attend private meetings with FDA officials," the senators wrote.
They cited an investigation by the Milwaukee Journal Sentinel/MedPage Today that chronicled email communications between federal officials and doctors who created the groups, including Robert Dworkin of the University of Rochester and Dennis Turk of the University of Washington.
Representatives from pharmaceutical companies — including Zohydro's initial manufacturer Elan — paid between $20,000 and $35,000 to send one representative to the meetings with staffers from FDA and the National Institutes of Health, raising questions about potential pay-to-play in the industry.
In interviews at the time, Turk maintained the meetings simply "answered some questions." But the meetings also birthed the concept of "enriched enrollment," which enables drug companies to weed out non-responders or patients who have adverse reactions to a drug from enrollment in clinical trials. Critics say the process stacks the deck in favor of the drug.
University of Rochester Medical Center spokesman Christopher DiFrancesco said Thursday his institution is preparing a response to the letter.
"The work of these groups is being misrepresented by an advocacy organization that is trying to pressure the FDA to change its approval decision on the drug Zohydro," he said. "We're looking forward to clarifying the work of IMMPACT and ACTTION, which we believe is scientifically sound and serves the best interest of patients."
DiFrancesco countered allegations that the meetings involved pay-to-play because participants couldn't talk about specific drugs and no drug was approved by the FDA because of the meetings.
He also said there were a broad range of participants from academia, industry and government, and that the group functioned as a typical public-private partnership, along the lines of a "working group."
Manchin and Vitter are requesting financial information on all meetings of IMMPACT, ACTTION and other pain conferences that have taken place since 2001.
They also want to know specifics on when and where the meetings were held, who was in attendance, how much each person was paid, food and beverage expenses, and other operational costs.
"We have expressed to FDA Commissioner Margaret Hamburg our dismay with these pay-to-play meetings and the role they may have played in FDA's failure to protect and promote public health through the regulation and supervision of prescription painkillers," they wrote in the letter. "The FDA's approval process should not compromise patient safety for financial gain."
The emails, which were obtained through an open records request and sent to reporters, showed that IMMPACT and ACTTION meetings usually took place over two days at high-end hotels in the Washington, D.C., area, with about 25 to 50 people at each event.
In addition to Zohydro's manufacturer, several drug makers with a stake in pain management sent representatives, including Purdue Pharma, maker of OxyContin, and Janssen, which has several pain products.
The interactions raised serious questions about the way in which federal regulators interact with the pharmaceutical companies they regulate.
Michael Carome, director of the health research group of the watchdog group Public Citizen, said in an interview at the time that the "whole picture is a troubling one and warrants an independent investigation."
The FDA's deputy director for regulatory programs, Douglas Throckmorton, said agency officials attended the meetings only to hear from the scientific community.
"Pay-for-play is just not the way the FDA operates," Throckmorton said. "That's not part of the culture of the FDA."
But experts say enriched enrollment may provide evidence to the contrary, since the approach makes it much more likely a drug will prove effective and possibly win FDA approval. It's also cheaper for drug companies to conduct trials this way, since it can result in smaller studies, shortened drug development time and lower development costs.
Critics are concerned that drugs tested via enriched enrollment won't reflect real-world use, turning up different results when a drug gets on the market and is prescribed for large numbers of people.
Zohydro clinical trials used the enriched enrollment methodology.
During its FDA advisory committee hearing, several experts expressed concerns about what would happen once the drug moved from trials into the real world because of that methodology.
In earlier interviews, an FDA representative said enriched enrollment follows the concept of personalized medicine in that it attempts to find those for whom a drug will be most effective: "Enrichment will not save a drug that is not safe or effective, but it will help find one that is."
Despite the advisory committee's concerns, which resulted in an 11-2 vote against approval of Zohydro, the agency approved the drug last October.
Since then, several efforts have been made to get the FDA to reconsider its decision. In December, attorneys general from 28 states sent a letter to Hamburg, the FDA commissioner, asking her to rescind approval. And on Wednesday, a coalition of more than 40 doctors and health advocacy groups repeated that request with a letter of their own to Hamburg.
All of these groups voiced concerns that the drug will be prone to widespread abuse. It packs a dose of opioid five to 10 times greater than what is available on the market in the form of products such as Vicodin and Lortab, which also contain acetaminophen.
Zohydro will be pure hydrocodone, and it will not have abuse-resistant technology, which means users will be able to crush or chew the capsules to unleash all of the opioid high at once.
John Fauber is a reporter for the Milwaukee Journal Sentinel. Kristina Fiore is a reporter for MedPage Today.