A version of this story, “The Yaz Men,” also appeared in Washington Monthly
The British Medical Journal, BMJ
10 January 2012
Jeanne Lenzer – New York
Keith Epstein – Washington, DC
At least four members of a key committee advising the US Food and Drug Administration on the safety of a top selling drug have had financial ties to its manufacturers, raising questions about the rigor with which the agency minimises potential conflicts of interest.
Court documents reviewed by the BMJ and Washington Monthly show that at least four advisers conducted research for Bayer AG or other manufacturers or licensees of drospirenone, the synthetic progestogen contained in several oral contraceptive pills whose safety was under review. Another adviser agreed to conduct research for the company but never did. The advisers served as paid key opinion leaders, researchers, consultants, or speakers for Bayer and other manufacturers of drospirenone.
Each of the advisers with ties to manufacturers told the BMJ that they fully disclosed their ties to the FDA, although the FDA declined to release advisers’ financial conflict of interest forms, saying that they are “confidential” and cannot be shared.
There is no reason to that think the advisers did not make the requisite disclosures. However, when asked whether the agency was aware of any financial ties between its advisers and manufacturers or distributors of drospirenone, the FDA spokeswoman Morgan Liscinsky said, “No waivers were issued.” Waivers can be issued to allow advisers with ties to industry to vote if the agency believes that their expertise is required and no suitable alternates are available. Waivers often serve as the only public signal that an adviser has a financial conflict of interest.
The committee met on 8 December to analyse the safety data of drospirenone, which is found in several branded oral contraceptive pills, including Yaz, Yasmin, Beyaz, and Safyral (all made by Bayer) and generic pills. Yaz and Yasmin were among the top sellers of the German based company. Over four million women worldwide use Yasmin alone, Bayer says.
The FDA ordered the review after three articles published in the BMJ found an increased incidence of venous thromboembolism among users of drospirenone (2011;343:d6423, doi:10.1136/bmj.d6423; 2011;342:d2151, doi:10.1136/bmj.d2151; 2011;342:d2139, doi:10.1136/bmj. d2139).
However, the committee did not see internal Bayer documents in which Bayer scientists determined that Yasmin’s rate of all serious adverse events was “10 fold higher than that with the other products” (BMJ 2011;343:d8104, 13 Dec, doi:10. 1136/bmj.d8104)
In a 15 to 11 vote the committee decided that the benefits of drospirenone outweighed its risks.
The first public sign that advisers may have had ties to industry came in a court filing by the former FDA commissioner David Kessler (http://bit.ly/yzYccr), who reviewed internal Bayer documents that are not available publicly but that, he says, reveal payments from Bayer. Dr Kessler is a paid expert witness for thousands of plaintiffs claiming harm from drospirenone.
The advisory committee’s acting chairwoman, Julia Johnson, professor of obstetrics and gynaecology at the University of Massachusetts Medical School, conducted four clinical trials, including one of drospirenone as hormone replacement, for Bayer or its subsidiary Berlex, a manufacturer of drospirenone. She said in an email, “The FDA is very vigilant on examining potential conflicts of interest and was aware of all my research.” When asked for an interview she wrote, “The US FDA states that I cannot speak about the meeting.”
Other advisers with ties to industry include Paula Hillard, a professor of obstetrics and gynaecology at Stanford School of Medicine who has served as a paid consultant to Bayer Schering. Asked about her ties to Bayer, Dr Hillard said that she had fully complied with all FDA disclosures and referred Washington Monthly and the BMJ to the FDA for further questions. The FDA declined to respond to any questions, citing the confidentiality clause of the Ethics in Government Act.
Elizabeth Raymond, senior medical associate at Gynuity Health Projects in New York, conducted studies funded by Barr Pharmaceuticals, now part of Teva, which has a licensing agreement with Bayer for generic versions of Yaz. Dr Raymond said that the FDA was “fully aware of all of my relevant current and past activities.”
Anne Burke, assistant professor of gynaecology and obstetrics at Johns Hopkins University in Baltimore, has received research funding from Bayer-Berlex and Duramed, which has a licensing agreement with Bayer for generic versions of Yaz and Yasmine. Dr Burke told the BMJ that she fully disclosed this to the agency.
According to Dr Kessler’s report, an internal Bayer document indicated that another adviser received payment from Bayer, but that adviser states that although she initially agreed to serve as a consultant to the company, the company never pursued the agreement. She said that FDA records indicated that she had ties to Bayer because of her disclosure about her agreement, but after she was nominated to the 8 December advisory committee she corrected the error.
Meanwhile a sixth adviser confirmed that he received consulting fees from a law firm representing Bayer in 2006. He told the BMJ and Washington Monthly that he did not disclose the information to the FDA because the FDA “did not require information for that timeframe for consulting unrelated to the meeting topic.
Bayer told the BMJ in an emailed statement, “Bayer had no input on who serves on the US FDA Advisory Committee panel as the FDA has its own process for selecting panel members. Furthermore, it is Bayer’s understanding that the FDA has a procedure for determining conflicts of interest for potential panel members.”
The Project on Government Oversight, a non-partisan watchdog group based in Washington, DC, plans to raise concerns about the FDA’s policies on conflicts of interest in a letter to the agency’s top official, Margaret Hamburg.
“It shouldn’t require a lawsuit and investigative journalism to learn about these kinds of conflicts,” said the group’s executive director, Danielle Brian. “The Yaz case puts FDA’s feckless ethics policy into stark relief. It also reveals the human impact of conflicts of interest and why we need an FDA that shuns even the appearance of such conflicts.”
The group intends to urge the FDA to routinely disclose advisers’ ties to industry and more aggressively determine whether an adviser has a conflict.
“Right now,” said Ms Brian, “the bar for considering whether an adviser has a conflict is too high.”
David Kessler’s expert report is at http://bit.ly/yzYccr.
Cite this as: BMJ 2012;344:e244 © BMJ Publishing Group Ltd 2012