TRANSCRIPT: B: I'm Ben C. V: I'm Doctor V. The Medical Legal Guys.. Casual Guys! V: So yeah. So we're talking about, a recent decision by the FDA that goes to warning physicians and women about the dangers of Depo-Provera. And this is a big, big aspect of the litigation. And why is this FDA warning important as it relates to this litigation? B: So there's something called preemption, which basically is a legal concept that says if the federal government has preempted a state law, then you can't bring a case under that state law. And it's possible that preemption can result in the dissolution of coins. So that's basically the importance. But the argument was that, hey, if we had Pfizer, if we had told the federal government, the FDA that we wanted a warning, okay, then they may not have allowed us to have a warning. And they went a step further and they said, hey, we sought approval of a warning from the FDA. And the FDA said, no, okay, no warning. About a month ago, the FDA came out with a ruling, an order, and the FDA said, oh, yes, you must put a warning label on Depo-Provera about meningioma and indeed, there is one. So now, when they say it would be impossible to put a warning on because the FDA wouldn't allow it, they've allowed it. V: We're going to talk about the warning, and that the FDA has ordered Pfizer to change the label to notify physicians of the risk of meningioma. So Ben, do you want to read the sections from the warning? B: There are really two parts of the warning label the label change. Now, this is a 27 page document. We've talked about it before. And those are labels also called instructions for use or use instructions. And if you now look at what the FDA said, Pfizer must put under warnings and precautions. Meningioma discontinue Depo-Provera if meningioma is diagnosed. Monitor patients for signs and symptoms of meningioma. That's pretty straightforward. If if a doctor has a patient that has a meningioma, stop Depo-Provera. And there are reasons for that in the literature. And there's a second part of it and it's section 5.3. Let me get to it here. And that is 5.4. This is in the product insert the label, the packaging that goes with every injection of Depo-Provera. That doctor has that warning at their disposal. Meningioma cases of meningioma have been reported following repeated administration of medroxyprogesterone acetate. That's Depo-Provera, primarily with long term use. Monitor patients on Depo-Provera for signs and symptoms of meningioma. Discontinue Depo-Provera if a meningioma is diagnosed. So that's kind of going back up to the top of the warnings. What that's what part of this is about. The other part, though, is an indicator that cases of meningioma have been reported in the literature following repeated administration. And it says generally for a long term use or long term use in the pharmaceutical industry, long term use could be anything over six months. Be anything over a year. And these studies sometimes will use that short period of time, six months for a year to mean, okay, well that's a long term use, right. So so don't get the idea that they're saying generally takes five or 10 or 15 years. Long term use can be a pretty short period of time. Yeah. V: So when I look at this label, you know, I see some issues. We're way past reported. Okay. So and we're going to go through the history. B: Of recorded, if you read the British Medical Journal article that that came out last year, and if you read that study by Doctor Rowland and others, it's way more than a sort of a case study or a few reports here and there. They studied 108,000 women. And compared to women who took Depo-Provera or had the Depo-Provera injected in their bodies versus those who did not in, that's where they found close to a 600% more probability that a woman went on Depo-Provera is going to develop a meningioma than if she had not had the Depo-Provera. So that's as dark versus that a lot more than a reported case or two, which seems to be what, what the labels sort of suggesting the reports. Could it have been stronger? Yes. But is it something the company is required to warn about Depo-Provera and its association with meningioma? And the answer now is yes. V: So in my view it's kind of a weak, weak warning. So we're going to go over the literature that kind of built up to this change. So we're going back to 2006. Was the first in the 20 years ago first indication that progestin have a relative risk for causing meningioma and explain what why relative risk of two is important from a legal standpoint. B: So let me explain what relative risk is. So relative risk is the associated risk of being on a pharmaceutical like depo provera versus the risk as compared with someone that is not on the drug or has not taken the drug. If you have a relative risk that two or higher, then there's no question about its association. Relative risk of two means you're doubling the risk that it's a 100% increase in the risk. And if you got a 100% increase in the risk, then legally that is a an important distinction as opposed to just barely an association of pharmaceutical causing something. V: So so this article back in 2006 looked at birth control, types of birth control and their associations with gliomas, which is a type of brain tumor in meningioma and this article, 2006, showed that oral birth controls no increased relative risk of meningiomas, and when they combined the studies that looked at progestin that are embedded in IUDs and progestin that go underneath the skin and injections when they group those all together, that relative risk is two for prolonged use over five years. But the kicker is the IUD progestin. That dose is a lot less than Depo-Provera. B: Yes. V: So they have progestin in like Marina that are embedded in the IUD B: You call them, yes. V: So it's a form of birth control. So back in 2006, the pharmaceutical companies knew or should have known that progestins caused meningiomas. But if you look at the types, depo- Provera has a much higher dose of progestin than the other two forms, so it would have diluted the relative risk. B: I think what you're saying, doctor V, is that since we know there is a greater than two times risk of these other progestin, because Depo-Provera is a higher dosage, you would expect there to be a greater relative risk, right and right. V: So you're diluting the risk by having the two forms of birth control that don't cause meningioma. There's no Marina. There's no evidence that that causes meningeal. And then the underneath the skin progestin. We don't have the evidence that that causes meningioma. B: At this time. V: So they grouped both together. And the relative risk was still over two. That should trigger a study. That's right. You know you need to do something. And that's right. When the generics are getting rolled out, when generics are rolled out, the pharmaceutical liability goes way, way down. And explained why Pfizer when these medications were going generic, what would that do to Pfizer's liability? B: Well, there was a U.S. Supreme Court case some number of years ago that essentially said that a case involving a generic drug is really preempted. Okay. Talked about preemption earlier. And if it is a certain type of generic, okay, an unauthorized generic, we'll call it not authorized by the manufacturer or the founder, then there's no liability on the part of the manufacturers under certain circumstances. And generic manufacture under certain circumstances is seen as having no liability, essentially because they say, well, wait, we're just we're forced to use the same formula as the original manufacturer, right? In this case, when you get down to it for liability purposes, that would have been Pfizer. V: Yeah. So I'm thinking more of it that it's becoming generic. It's becoming a lot cheaper. It's being a more wide use because the price has gone down because it's going generic and Pfizer just sat there, looked at the data and did nothing. Okay. This is 2006. B: Yeah. You're talking about almost 20 years ago. V: 20 years ago, they could have studied. So then the next thing that really happened was 2015 study that identified the specific mutation that is associated with Depo-Provera. They didn't quite identify the link, but they identified the mutation that is most associated with Depo-Provera that causes multiple meningioma that tend to be on the skull base, which are the worst type of tumor.
