Paula Hillard, a professor at the Stanford School of Medicine, has become the subject of an ethics controversy following her involvement with and voting record on an FDA advisory committee. Hillard voted on the safety of two drugs that were created by a company she had extensive ties with, according to California Watch, an investigative journalism group founded by the Center for Investigative Reporting.
The FDA committee was convened to evaluate the significance of recent studies showing that Yaz and Yasmin, popular oral contraceptives manufactured by Bayer HealthCare Pharmaceuticals, statistically increased the risk of potentially dangerous blood clots. The elevated risk has been linked to the presence of drospirenone in the contraceptives.
Yaz, Yasmin and related contraceptives constituted Bayer’s second-best-selling franchise last year, with global sales of $1.6 billion. This portion of company’s market share has been falling recently, at least in part because of ongoing lawsuits against Bayer, citing deceptive marketing and harmful effects from its products.
Three studies, all sponsored by Bayer, suggested that the risks posed by Yaz or Yasmin, and other contraceptives not containing drospirenone, were comparable. Seven other studies, however, asserted that Yaz and Yasmin did indeed pose an elevated risk of harmful blood clots.
The committee voted 15 votes to 11 that the benefits of Yaz and Yasmin continued to outweigh the risks documented in the studies. The committee did, however, support a change in labeling to advise physicians of the higher risk.
The Project on Government Oversight (POGO), a watchdog group, was not happy with the result and has called on the FDA to throw out the verdict on the basis of committee members’ prior involvement with Bayer, citing the existence of multiple conflicts of interest.
Four committee members, including Hillard and the committee’s chair, had prior affiliations with Bayer or the manufacturers of similar generic contraceptives. All four voted in support of the contraceptives but denied any link to their prior ties to Bayer or the existence of any conflict of interest.
POGO’s Director of Investigations Nick Schwellenbach stated that the watchdog’s scrutiny was prompted by the small margin by which the contraceptives’ continued sale was approved. Without the four members’ affirmative voting, the committee would have been unable to reach a majority opinion on whether consumer welfare was unduly endangered by the contraceptives.
Schwellenbach noted that potential conflicts of interest are relatively common in the FDA’s advisory process and that there is often a correlation between members’ industry ties and their voting records.
Schwellenbach singled out Hillard, however, for the extent of her links with Bayer. A POGO open letter to the FDA cited consulting arrangements between Hillard and Bayer that continued up to 2010. Schwellenbach also emphasized the conflict of interest posed by internal Bayer documents identifying Hillard as a valuable advocate as early as 2003.
“Hillard had sufficient ties to Bayer, and those ties were sufficiently recent to question her objectivity,” Schwellenbach said.
Hillard acknowledged that she had periodically served as a consultant to Bayer and other pharmaceutical firms, but said that she had done no such work during the 12 months preceding the committee’s decision. She argued that she bore no responsibility for Bayer’s internal portrayals of her relationship with the firm.
Hillard emphasized that she had satisfied all requirements for the disclosure of potential conflicts of interest to the FDA, as well as making prior consulting affiliations available to the public through the medical school website.
“It was the FDA’s decision that I satisfied the process for reporting conflicts of interest,” Hillard said. “The FDA allowed me to sit on the committee… I’m in favor of disclosure of potential conflicts, and I feel that I can be objective.”
Hillard said that she had sat on several advisory committees in preceding years and had each time completed a confidential form regarding conflicts of interest for the FDA.
According to Hillard, her decision to support Yaz and Yasmin’s continued sale stemmed from flaws in some of the studies linking the contraceptives to a higher risk of clots. She said that the disproportionate inclusion in the survey of women diagnosed with polycystic ovary syndrome, which elevates the base risk of blood clots, likely distorted results.
This led Hillard to conclude that, while all contraceptives containing estrogen carried some risk, Yaz and Yasmin posed no more risk than other contraceptives and less than the risks posed by pregnancy.
Schwellenbach emphasized that POGO didn’t consider Hillard to have breached any existing legal or ethical restrictions and credited Hillard’s disclosure of industry affiliations through the University.
He suggested, however, that the FDA change its policy toward a more expansive and stringent interpretation of conflicts of interest and that information on potential conflicts of interest be made more apparent and accessible to the general public.