Safety of Avandia

SAFETY OF AVANDIA -- (Senate - May 21, 2007)

Mr. GRASSLEY. Mr. President, I am here today to talk about another potential failure by the FDA that may have endangered the lives of millions of Americans. Avandia is a drug that was approved by the FDA in 1999. It is a diabetes drug and is used to lower blood sugar. This is important because lowering a diabetic's blood sugar can help prevent or at least postpone two of the biggest killers among diabetics: heart attacks and strokes.

But today, Dr. Steven Nissen, the chairman of Cardiovascular Medicine at the Cleveland Clinic and the immediate past president of the American College of Cardiology, and his colleague, Ms. Kathy Wolski, reported in the New England Journal of Medicine that there is a serious problem with Avandia. Avandia, according to Dr. Nissen and Ms. Wolski is increasing the likelihood that a diabetic will have a heart attack and maybe even die. I want everyone to pay attention to the fact that the New England Journal of Medicine accepted this analysis of Avandia on a ``fast track'' review. The New England Journal of Medicine did that because it was requested by the authors and because in its opinion, the analysis of adverse effects related to Avandia suggests serious patient health risks.

Dr. Nissen and Ms. Wolski based their finding on an analysis of 42 clinical trials.

FDA also decided to say something to the American people today in response to Dr. Nissen's analysis. Around 1 p.m. today, the FDA told the American people that they intend to call for an advisory board meeting to discuss Avandia and that they could not yet reach a ``firm conclusion'' on what to recommend to people taking Avandia. It was interesting to listen to the call because Dr. Dal Pan, who is the head of the Office of Surveillance and Epidemiology, didn't say a word, although he is in charge of postmarketing surveillance. I guess the FDA thinks that the decision to go to an advisory committee meeting takes the heat off what looks like another failed decisionmaking process. We will see.

Avandia has a long history. It has been on the market for about 8 years. Tens of millions of prescriptions have been written for Avandia, and Medicare and Medicaid have paid hundreds of millions of dollars for this drug.

There have been many clinical trials involving Avandia over the years and there have been numerous postmarketing changes to Avandia's label. I also understand that FDA has known about the possibility of problems with this drug since about October 2005. That is about 19 months ago.

The article appearing today in the New England Journal of Medicine raises a lot of serious questions for me about the real story behind the safety of Avandia. When I couple that article with the FDA conference call that ducked lots of questions I become very suspicious.

Over the last 3 years, my investigations into the FDA showed that the agency was too cozy with the drug industry and did not always put safety of the American people first. The FDA is supposed to regulate the drug industry, but in the case of Vioxx, just to name one debacle, American lives were endangered unnecessarily.

My question today is, Do we have another Vioxx on our hands with Avandia? I am not sure, but I intend to find out. In fact, today Senator Baucus and I sent out several document requests including one to the FDA and one to the drug sponsor. We want to understand what did FDA know about this drug, when did it know it, and what did it do about it?

The authors of the New England Journal of Medicine article report a 43 percent increase in the risk of myocardial infarction/heart attack and potentially a 64 percent increase in the risk of cardiovascular death. I need the FDA to tell me why a diabetic would take a drug that may increase the risk of the very thing they are trying to avoid--a heart attack. I also want to know why the FDA did not require the drug sponsor to conduct long-term safety studies instead of small, short-term trials that resulted in few adverse cardiovascular events or death. I want to know what the FDA has been doing for the last 18 months. We want to know the same from the drug sponsor.

Interestingly, in an editorial that accompanied the study, two other veterans of the Vioxx controversy--Dr. Bruce Psaty of the University of Washington and Dr. Furberg of Wake Forest University--write that: ``..... the rationale for prescribing rosiglitazone at this time is unclear.'' Additionally they call for the FDA to take regulatory action and note that bigger and better long-term studies of long-term treatments for conditions such as diabetes should be completed as soon as possible after a drug is approved.

Let me also say something else to all those FDA employees trying to do their job who probably know the answers to many of my questions: Please feel free to call the Finance Committee if you have any information about this drug and how the FDA handled the situation. You can also call or contact us anonymously if you want. If you want to fax information to me, here is my fax number: 202-228-2131. We welcome your help and insight because I know that many of you want to protect the American public first and foremost and sometimes that is not as easy as it should be at the FDA.

You will also remember that just a few weeks ago I came before the Senate several times to talk about drug safety. I told everyone then--as we were discussing S. 1082, a bill that was intended to dramatically improve postmarketing drug safety, that I was concerned that the bill would not do that. In my mind and in light of all the work I have done over the past 3 years on the FDA, I told everyone that the litmus test for me was whether or not the new drug safety bill would prevent another Vioxx.

My position has consistently been that S. 1082 did not go far enough and would not prevent another Vioxx. That was why I proposed and insisted on a vote giving joint authority between the office that approves new drugs for the market and the office that is responsible for postmarket safety. Forty-six Senators listened to what I had to say, but I was one vote short and the amendment did not pass.

Drs. Psaty and Furberg also said in their editorial, and I quote, ``On May 10, 2007, the Senate passed the Food and Drug Administration Revitalization Act. Although the Senate bill has many strengths, including the allocation of new authority to the FDA, none of its provisions would necessarily have identified the cardiovascular risks of rofecoxib or rosiglitazone in a timely fashion.''

The drug industry has brought us miracle drugs. These drugs have vastly improved the lives of millions throughout the world. At the same time, we all know that drugs have risks and benefits. Each of us tries to consider those risks and benefits when we consult with our doctors to make the best decision for ourselves or our family members as to whether we will take a particular drug. But we can't do what is best for ourselves or our family members if we don't know all the relevant information in a timely manner.

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