PHARMALOT’S, Ed Silverman, from the Publishers of PharmaLive.com, examines the state of DRSP (DROSPIRENONE) birth control and the FDA Advisory Committee hearings of 12.8.11.
“Three months ago, an FDA advisory panel voted 15-to-11 that the benefits of the Yaz and Yasmin birth control pills outweigh the risks, and the drugs should remain on the market, albeit with added information about a risk of blood clots. The decision followed a long-running controversy - studies by Bayer, which sells the pills, found there is no risk, while other studies said risk is evident (see this).
But controversy also surrounded the meeting. Beforehand, the FDA yanked Sid Wolfe of the Public Citizen Health Research group from the panel due to an intellectual conflict of interest (read here). Afterwards, concerns were raised because four panel members held ties to Bayer, either as paid consultants or in the form of research funding, but the FDA did not disclose the conflicts, prompting the Project on Government Oversight, a watchdog group, to ask the FDA to convene an entirely new meeting (read this and this).
Now, a coalition of women’s health groups charges there were several irregularities that may well have altered the outcome. In a letter to FDA commish Margaret Hamburg, the coalition complains, in particular, that the key question panelists had to answer, which determined the outcome of the voting, was vague and confusing. And they maintain that several panelists who are practicing obstetricians and gynecologists may also have held intellectual conflicts that swayed their votes.
“Obviously, we can’t predict how people would have voted with different wording…,” the coalition wrote. “However, the vaguely (and, we believe, inappropriately) worded question and the difference in how conflicts of interest were handled raises very serious questions of bias.” The groups that signed the March 9 letter include the Jacobs Institute of Women’s Health, the National Research Center for Women & Families, the National Women’s Health Network and Our Bodies Ourselves.
The panelists were asked to vote on whether “the benefits of the DRSP-containing oral contraceptives for prevention of pregnancy outweigh their risks.” DRSP is drospirenone, which is a hormone contained in the Yaz and Yasmin pills. After voting, each panelist was asked to explain their vote, and the coalition noted that those who voted “no” explained that safer oral contraceptives were available.
However, the letter also notes that almost all of the 15 who voted “yes” indicated they voted on a comparison of risks and benefits compared to pregnancy, rather than on whether the risks and benefits of oral contraceptives containing DRSP outweigh risks and benefits compared to other oral contraceptives. These are two different issues, the coalition writes, the befuddled some panelists.
The coalition pointed to panelist Elaine Morrato, who voted “yes,” but said: “However, if the standard is to make a comparative, which… I just compared it in the absolute sense. I would agree that I didn’t see any benefit of the product that’s well demonstrated for Yasmin, perhaps for Yaz. And so if the regulatory standard would be that you’d have to demonstrate a comparative benefit, then I would vote no.” This would have changed the vote to 14-to-12.
Another panelist, Anne Burke, voted “yes,” and according to the letter, said: “I don’t think I was expecting it to be more effective than other pills on the market, and while I acknowledge that there does seem to be a moderate increased risk, it’s still lower than the risks of pregnancy. And like some other folks who have spoken, a no vote sounded like it would be - to take the product off the market. I’m not quite sure that’s necessary at this point.”
And panelist Julia Johnson voted “yes” and said: “I am significantly concerned regarding the most recent FDA study…I would like to see comparison with another U.S. study. I think that’s absolutely critical. I do not think there is one advantage for this pill over any other for use for women. If indeed there is truly an increased risk, then I would vote differently,” according to the letter. Both Johnson and Burke had ties to Bayer.
Meanwhile, seven other panelist are practicing OB/GYNs. “Given that practicing OB/GYNs routinely prescribe oral contraceptives, and that these physicians have likely made a decision to either prescribe or not prescribe/stop prescribing DRSP-containing OCs prior to the meeting, this certainly raises an intellectual conflict of interest as great as that attributed to Dr. Wolfe. Had they been ask to participate in the panel but not vote, as Dr. Wolfe was, this clearly would have resulted in a majority vote that the benefits do not outweigh the risks,” the coalition writes to Hamburg.
How so? Here is the math: If Wolfe voted no and at least one of the three panelist who expressed strong concerns voted “no” on the more specific question of whether the benefits outweigh the risks compared to other pills, the vote would have been 14 “no” and 13 “yes.” But if Wolfe and those with a financial conflict had not been allowed to vote, the final vote would have been 11-to-11. And if Morrato had been counted as a “no,” given her confusion, then the vote would have 12-to-10 against allowing the Bayer drugs to remain on the market, the coalition writes (here is the letter).
The coalition, however, stopped short of asking the FDA to hold a new meeting and, instead, wants Hamburg to review its policies “that resulted in biases” so a repeat does not occur. We asked the FDA, which previously indicated the POGO request for a new meeting would be reviewed, for a reply and will update you accordingly. [UPDATE: An FDA spokeswoman writes us to say the agency will respond directly to the coalition.]”
#JAAPA has published an article that examines some current literature on #DRSP #drospirenone pills entitled: “Do #Drospirenone Containing Oral Contraceptives Have a Higher Risk of #VTE?” Specifically, five (5) studies were reviewed and commented in in reaching an answer to the question posed by the title.
Combined oral contraceptives all have the potential to increase the risk of a #VTE or venous thromboembolism. This thoughtful analysis of current literature found that #DRSP pills should not be the first choice for most women. Rather, the author, Jennifer Hoffman Ribowsky, MS, RPA-C, concluded that it may simply be a reasonable choice for women with polycystic ovarian syndrome because of the antiandrogenic effects of #drospirenone. Existing data on the association between #VTE’s and #DRSP led the author to conclude it was not the choice for most women.
There are over 7,000 lawsuits arising out of the use of the #DRSP family of pills already pending in the US. Trials are scheduled in 2013 and alleged injuries include: death, strokes, pulmonary emboli, DVT, VTE’s, gallbladder removal, pancreatitis and related complications.
Gabriel F. Zambrano, P.A., is actively representing women that have suffered life altering injuries from the use of a #DRSP pill: #YAZ, #Yasmin, #Ocella, #BEYAZ & #SAFYRAL. Gabriel F. Zambrano, P.A., is the sponsor of this blog and commentary.