April 28,2010

Grassley Continues Case for Greater Independence in FDA's Post-market Review of Drugs

WASHINGTON --- Senator Chuck Grassley today testified before a House Subcommittee hearing chaired by Representative Rosa DeLauro regarding drug safety and the work of the Food and Drug Administration. 

Grassley has been conducting active oversight of the FDA since 2004, when a dissenting opinion from an FDA scientist about suicide risks for teenagers with anti-depressants was suppressed by the agency.  Grassley has called the FDA's relationship with the drug industry "too cozy" and sought greater independence and transparency from the agency.

Grassley described the need for a legislative reform, which he has twice introduced, to empower the office that monitors post-market drug safety at the FDA.  “There’s a lack of equality between the FDA office that decides whether to approve a drug, or not, and the FDA office that monitors a drug’s safety once a drug is on the market and being sold to patients, when much more information is available than can ever be achieved from pre-market samples.”  Grassley says the result is that the FDA physicians and scientists committed to post-market monitoring of drugs have sometimes been suppressed and even ignored.

Here is the full text of the prepared testimony Grassley gave this morning.

Statement of Senator Chuck Grassley
U.S. House Committee on Appropriations Agriculture Subcommittee
Wednesday, April 28, 2010
Avandia and Drug Safety

Chairwoman DeLauro, Ranking Member Kingston, and distinguished colleagues, thank you for inviting me to speak today at this hearing on drug safety. 

Far too often, we read press reports about partisan warfare and a “do nothing” Congress. 

So I am glad to see both the Senate and the House, Democrats and Republicans coming together to work to protect the American supply of pharmaceuticals.

As the Ranking Member of the Senate Committee on Finance, I have made it my job to look into various aspects of the health care industry. 

I do this to protect the public’s health and to guard their pocket book. 

As part of this duty, I have taken a keen interest in the Food and Drug Administration and the pharmaceutical and device industries.

Back in May of 2007, Senator Baucus and I opened up an inquiry into Avandia, a drug sold by GlaxoSmithKline to control glucose levels in diabetics. 

We started this inquiry because the New England Journal of Medicine published a study which found that Avandia may cause heart attacks. 

Obviously, this was bad news, because one of the things diabetics are most at risk for is a heart attack.

The Finance Committee staff spent over two years combing through hundreds of thousands of pages of documents.  Let me tell you a little of what they found:

Back in 1999 when Avandia first came on the market, executives at GSK intimidated a physician at the University of North Carolina. 

The physician was worried that Avandia might cause heart attacks. 

To suppress his comments, top officials at GSK called his superiors and had him sign a form that he would no longer criticize the drug. 

Senator Baucus and I released a report on this finding, and I would like to enter that document into the record at this time.

The 2007 study that first caught the Committee’s attention was submitted to the New England Journal of Medicine by Dr. Steve Nissen, a professor and cardiologist at the Cleveland Clinic. 

However, GSK got a copy of the manuscript before it was published.  One of the experts who was peer-reviewing the study for the New England Journal of Medicine leaked it to GSK. 

This allowed GSK to launch a PR campaign to undermine legitimate concerns that Avandia might cause heart attacks.

Then, last February, Senator Baucus and I published a Committee Staff Report on Avandia.  This report is about 15 pages long, and contains another 300 pages of attached internal documents, charts, and emails. 

With this report, we wanted to let the people of America know what the company knew, and when they knew it.

I would now like to tell you some of what we found:

Shortly after GSK got a copy of Dr. Nissen’s study, they had their own statistician dissect it. 

GSK’s statistician found the study to be scientifically sound. 

However, GSK immediately drafted talking points to undermine Dr. Nissen’s study. 

At times, these talking points run counter to legitimate concerns of Avandia’s safety that are raised in emails by GSK’s own scientists.

In an internal email, GSK’s head of research discussed “take home messages” of the research on Avandia.  If you look through the report that the Finance Committee released, you’ll find this email on page 163.  

In that email, GSK’s head of research pointed out that Avandia has an increased risk of cardiovascular death. 

Let me emphasize this—cardiovascular death.  Not heart attacks.  Not heart failure.  Death. 

Well, the American public never knew about this risk until the Committee released the Avandia report.  And you still can’t find any mention of “cardiovascular death” in the warning section of Avandia’s label.

There are other findings in this report, but I would also like to discuss some internal FDA documents that we came across during our inquiry.

When concerns were first raised about the safety of Avandia, the FDA responded by requiring GSK to do a safety study.

Well, some drug safety experts inside FDA looked at that study that GSK was doing with patients and wrote that it was “unethical.” 

Here’s the troubling thing about the study: the patients that enrolled in that safety study never learned that FDA’s own safety experts thought that the trial was unethical. 

At least, they didn’t know this until the Finance Committee made that internal FDA document public in February.

This is not the first time questions have been raised about whether or not a study sanctioned by the FDA was ethical. 

In 2006, I inquired about FDA’s decision to allow a study on a blood substitute, PolyHeme, to proceed without adequate prior informed consent from the potential study participants. 

I raised questions about FDA’s decision, especially in light of the fact that another office within HHS, the Office for Human Research Protections, disagreed with the FDA.

In particular, I was concerned that during this study, when subjects arrived at the hospital after being treated with the blood substitute and real blood became available, the real blood was withheld from the patients as part of the study protocol. 

To end, I would like to highlight what I feel we can all learn from the FDA’s handling of Avandia. Because I think that we all want to move forward and make this agency better.

The Avandia case is another example of why I twice introduced legislation to establish an independent office of drug safety at the FDA. 

The Center for Postmarket Drug Evaluation and Research would tackle the lack of equality between the Office of New Drugs (OND), which decides whether to approve a drug, and the Office of Surveillance and Epidemiology (OSE). 

OSE is the office that monitors a drug’s safety once it’s on the market and being sold to patients.

The imbalance between OND and OSE was apparent in the Vioxx controversy about six years ago, and we can see it today in the incidents involving Avandia.  

Individuals in the office responsible for post-market surveillance should be allowed to provide an independent opinion based on the best available evidence. 

FDA employees dedicated to post-market surveillance should be able to express their opinions in writing and independently without fear of retaliation, reprimand, or reprisal. 

Instead, the FDA physicians and scientists committed to post-market monitoring of drugs have sometimes been suppressed.  In the case of Avandia, it appears that they have been ignored.

Before I conclude my remarks, I would like to call to your attention another matter related to drug safety. 

As you may have seen in press reports over the last two years, FDA has been taking action against some unapproved drugs. 

The problem is—FDA does not have a complete and accurate list of all of the products sold on the US market, including unapproved drugs, so the agency can’t take appropriate enforcement actions. 

I hope that we can work together to ensure that FDA has the resources and tools to ensure that the drugs in our medicine cabinets are safe and effective and approved for use by the FDA.

This concludes my testimony, and I once again thank you for this invitation.

I look forward to working with you as you continue your oversight of our country’s pharmaceuticals which remain vital to public health. I appreciate your leadership in this area.