GWEN IFILL: Next: the safety concerning -- concerns surrounding the diabetes drug Avandia.
This afternoon, an independent panel of experts recommended that it remain on the market with additional warnings, despite concerns over heart risks.
"NewsHour" health correspondent Betty Ann Bowser begins with this report. The Health Unit is a partnership with the Robert Wood Johnson Foundation.
BETTY ANN BOWSER: The decision came after the panel spent two days sorting through 700 pages of data, listening to more than 20 experts...
MAN: Continued marketing of rosiglitazone cannot be medically or ethically justified.
MAN: The rates of events in record is actually in line with other diabetes outcome studies.
BETTY ANN BOWSER: And these instructions from FDA Commissioner Dr. Margaret Hamburg.
MARGARET HAMBURG, Commissioner, Food And Drug Administration: Apply your sharpest scientific thinking and bring your best judgment to the questions facing the agency.
BETTY ANN BOWSER: Avandia has been one of GlaxoSmithKline's blockbuster drugs, used by millions of type 2 diabetes patients since 1999.
But new questions on Avandia's risks prompted the Food and Drug Administration to reexamine the drug's safety. The 33-member advisory panel of outside experts heard sharply conflicting opinions. Even FDA's own scientists came up with different analyses of a Glaxo study designed to look at Avandia's heart safety vs. other drug treatments.
Dr. Ellis Unger is the deputy director of drug evaluation.
DR. ELLIS UNGER, Office of New Drugs, Food and Drug Administration: The GSK analysis is very reassuring, a favorable trend on all-cause mortality.
BETTY ANN BOWSER: Dr. Thomas Marciniak works in the same FDA office and gave a stinging review of Avandia's safety trials.
DR. THOMAS MARCINIAK, Office of New Drugs, Food and Drug Administration: I don't believe you can find truth from these studies by superficially looking at the top-level data, without checking it thoroughly, without understanding it, and coming to any sort of truth.
BETTY ANN BOWSER: Glaxo officials insisted their product is safe.
Dr. Murray Stewart is vice president for drug research and development.
DR. MURRAY STEWART, Vice President for Drug Research and Development, GlaxoSmithKline: Overall, when used appropriately, rosiglitazone has a positive benefit/risk profile and should remain a treatment option for patients with type 2 diabetes.
BETTY ANN BOWSER: This isn't the first time the safety of Avandia, also known as rosiglitazone, has been called into question. In 2007, an analysis from a Cleveland Clinic cardiologist showed Avandia patients had a 43 percent increase in the risk of heart attacks and a 64 percent increase in the risk of death from cardiovascular causes.
In spite of that finding, an FDA advisory panel voted that same year to keep Avandia on the market, with the recommendation a stronger warning be added to the drug's label.
The Senate Finance Committee began investigating Avandia three years ago. And, yesterday, it released internal Glaxo documents showing the drug giant hid a 1999 study that revealed Avandia's heart risks.
A company executive wrote in an e-mail message dated March 29, 2001, "These data shouldn't see the light of day to anyone outside of GSK."
Even though Avandia's sales have dropped from $2.6 billion to about $1.2 billion over the past four years, two million prescriptions were filled last year. While the FDA often does not have to follow the panel's recommendation, it often does.
GWEN IFILL: We get two views now on today's FDA decision on Avandia's safety.
Dr. Harlan Krumholz is a cardiologist and professor of medicine at Yale University, and Dr. Hal Roseman is a cardiologist with a private practice in Nashville. For the record, he is also a paid lecturer for GlaxoSmithKline, the maker Avandia, and for other pharmaceutical -- pharmaceutical companies as well.
Welcome to you both, Doctors.
DR. HARLAN KRUMHOLZ, professor of medicine, Yale University: Thank you.
Dr. Roseman, describe for us, first of all, what it is that Avandia does.
DR. HAL ROSEMAN, cardiologist: Avandia makes insulin more effective. In diabetes, there's a condition that precedes diabetes called insulin resistance, in which fat basically causes changes in the way that insulin operates in the body.
And what Avandia does is actually corrects the defects that this fat has on the way that insulin works in the body.
GWEN IFILL: Dr. Krumholz, did the FDA panel recommendation today -- did they make the right recommendation?
DR. HARLAN KRUMHOLZ: Well, you know, it's -- time will tell about this.
But, you know, actually, I agree with the recommendation of the panel, because they said this drug should either be taken off the market or, if left on, the majority said it should have such severe restrictions that only certain doctors should be able to prescribe it, or, if patients take it, they should get special education about the medication, or doctors who prescribe it should have special education about the medication.
And I think the bottom line here is that, if you're going to leave it on the market, every patient who is taking this medication should understand that the FDA believes that there's increased risk associated with it, that there's evidence of increased risk of heart attack associated with it, and that the American Diabetes Association consensus statement last year said that they unanimously advise -- advised against the use of the drug.
So, you know, I think the panel did a good job. Twenty-two out of 33 voted to either take it off the market, or, if they're going to leave it on, it should have such severe restrictions, that only certain doctors should be able to use it.
GWEN IFILL: I want to ask you and then Dr. Roseman this as well. If -- with all those red flags, is that -- is that so -- too many red flags to be borne, which is to say, what are the risks you're asking patients and their doctors to take, the comparative risks, now?
DR. HARLAN KRUMHOLZ: Yes.
I mean, I think what patients need to know is that there are plenty of drugs that can control blood sugar, and this particular drug that controls blood sugar has a cloud over it. There's a strong probability that it's increasing the risk of precisely the things that you would hope to prevent in treating diabetes, that is, heart risk and stroke risk and cardiovascular disease.
So, I mean, the question really is, how much proof do you need, when there are alternatives for patients, and how many of those two million people who are taking this drug know that there's a high probability of strong risk of heart disease associated with it?
GWEN IFILL: Well, let me pose that question to Dr. Roseman.
DR. HAL ROSEMAN: I think the data is extremely conflicting.
I think the analysis used by the FDA to substantiate the current committee's decision is one that is of inferior nature compared to some of the longer trials that we have.
GWEN IFILL: What do you mean?
DR. HAL ROSEMAN: We have six trials that have shown, in essence, that there's either no risk or actually some benefits. Those take priority.
It's a difference between just basically taking a hodgepodge of studies and essentially analyzing them and trying to make sense of them, or trying to have an orchestrated, well-processed study, in which there are boards that oversee the safety, oversee the definitions of the end points, such as whether someone has had chest pain, really did indeed have a heart attack, that is essentially important in terms of qualifying the value of these drugs.
GWEN IFILL: Explain something to me. Your understanding, then, of the board's decision today was that this is a question of insufficient study, not because of the underlying safety concerns about the drug?
DR. HAL ROSEMAN: No, the committee made the decision based upon the FDA's analysis, from my standpoint, of a large group of studies.
Those studies did not have the intent of really examining some of the end points that we really want to know as a physician. The more robust, the more significant type of data was really actually overlooked, when you hear the comments of the committee members.
And, in that respect, I think there are some problems. For example, the other speaker talks about stroke. There's -- there's a significant amount of evidence that both Avandia, as well as Actos, reduces stroke.
GWEN IFILL: Actos being the other drug we were talking about, the alternative.
DR. HAL ROSEMAN: Yes. That's correct.
And, in fact, in some of the trials, there was actually indications toward a trend, not statistically significant, of actually a reduction of mortality and a reduction of cardiovascular mortality. Now, keep in mind, what the committee actually ruled on was the issue around heart attacks.
And there certainly is a trend, from my standpoint not significant, of heart attacks related to this drug.
GWEN IFILL: Let me ask Dr. Krumholz about that, because he's talking about relative risk, I suppose.
DR. HARLAN KRUMHOLZ: You know what, Gwen? Let me just try to make this, I think, as clear as I can. You can try to cherry-pick the studies, but, when you take them all together, they suggest increased risk, a worrying increased risk.
When you take some of the best diabetologists in the country and you ask them to do a consensus statement on behalf of the American Diabetes Association, they look at the data in its totality and unanimously advise against the use of this drug.
You take a bunch of smart people on an FDA advisory panel who for two days are listening to testimony and facts and one study after another, 12 of the 33 say, my goodness, take this off the market. Another 10 say, if you leave it on, you must restrict it, such that, for example, only some people can prescribe it, or, in my opinion, if you leave it on, every patient should sign an informed consent, where they recognize that there are many doctors in this country that strongly believe it's going to increase their risks.
That is a major restriction. So, then you have got 22 out of the 33 people saying either take it off or highly restrict it. I think it's a strong message that's not just, leave it on the market. The message here is that things have to change. If you're going to leave it on, access has to be restricted, because, by leaving a label that most people ignore, you're still left with a billion-dollar drug and two million prescriptions a year.
And I think what the panel is saying is, we need to change the way that things are being done.
GWEN IFILL: Let me ask Dr. Roseman about that.
DR. HAL ROSEMAN: The absolute -- the absolute risk in this situation, if you look at the 52-study analysis that was done by the FDA that didn't include these longer, more robust studies, was point 0.3 vs. 0.4 percent in terms of M.I. rates.
GWEN IFILL: But with -- you're talking about myocardial infarction.
DR. HAL ROSEMAN: Myocardial infarction or heart attack rates.
GWEN IFILL: Heart attack rate.
DR. HAL ROSEMAN: That's insignificant.
GWEN IFILL: But what we have today is an actual decision. He's talking about the actual decision the FDA made, not the argument leading up to the decision.
DR. HAL ROSEMAN: Yes.
GWEN IFILL: So, based on the decision that they made today, is what Dr. Krumholz saying correct, which is that this -- a very strong warning has now been given to patients that they should, and to their doctors, that they should beware?
DR. HAL ROSEMAN: Well, first of all, the warning has not been given. There was a recommendation of the subcommittee to the FDA.
GWEN IFILL: Right.
DR. HAL ROSEMAN: Number two is, contrary to the -- to the -- to Dr. Krumholz's point, it turns out that the American Academy of Clinical Endocrinologists, as late as 2009, after reviewing all the data from 2007, actually still included Avandia as part of their algorithm of treatment for diabetic patients.
GWEN IFILL: I have to ask you both, very briefly, what do you tell patients now who are on Avandia?
DR. HAL ROSEMAN: I think, right now, there's a certain amount of uncertainty. From my standpoint, I still feel very convinced in the drug. I think both drugs have their risk, but the total risk/benefit analysis seems to favor the use of Avandia.
GWEN IFILL: Dr. Krumholz?
DR. HARLAN KRUMHOLZ: Yes.
Well, let me say, first of all, it's important to emphasize that, for diabetes treatment, lifestyle is the most important first step. When you come to drugs, you have many options. No reason to expose yourself to the potential risk of this drug, when there are other alternatives.
No one should be using this drug unless they know that there's a controversy about it, a cloud hanging over it, and that many people believe it should come off the market.
GWEN IFILL: Drs. Harlan Krumholz and Hal Roseman, thank you both very much.
DR. HAL ROSEMAN: Thank very much.
DR. HARLAN KRUMHOLZ: Thank you very much.