GxP Perspectives

Diabetics ask: What to do next? (see suggestions below)

Update 20 August 2010: The New York Times reported that GSK’s informational letter to researchers is questioned by FDA. As reported by Gardiner Harris:

NY Times Article on GSK

UPDATES: Avandia Advisory Committee, Day One and First Vote Day Two- End of Day Two: Advisory Committee votes 20-12 to keep Avandia on market

The FDA advisory committee meeting on the type 2 diabetes drug, Avandia, got off to a high profile start with Dr. Margaret Hamburg, FDA Commissioner, taking the unusual step of addressing a meeting of an advisory committee. One of the reasons is the deep divisions that exist among FDA staff. As the links to slides (below) indicate, some FDA scientists, including Dr. Thomas Marciniak and Dr. David Graham, are opposed to the drug due to safety concerns. Other FDAers don’t feel that Avandia is a risk for patients. GlaxoSmithKline remains adamant that their drug is safe and effective for treating type 2 diabetes.

Type 2 Diabetics are asking “what to do next.” On the Blogroll are several blogs with a focus on Diabetes. I have put them there as someone who is living with type 1 diabetes. Please look at each as they all have something to offer. I am recommending that diabetics and their loved ones think this through carefully. Is their physician current on treatments for diabetes? Do they have Nurse Practitioners, Diabetes Educators, and Registered Dietitians on staff? If not, you may look for a medical practice that is “full service” for the treatment of diabetes. I did that a year ago and it really made a difference in my life. Please let me know if you have additional comments, resources, or suggestions. I really want to know your comments! I am highlighting the link to:

Endocrine Today. I have found that they have the best direct suggestions to diabetics. Please let me know if there are other resources you know of in the comments section.

Here are five news articles in reverse chronological order that detail the Avandia saga: The first vote on Avandia on Day Two found that the drug increased risks for heart problems. Read Business Week on the vote to keep Avandia on market- Read the Washington Post Blog from Day two and MedPage blog from Day One:

L.A. Times: Aftermath- Diabetics Urged to Continue Avandia

NY Times: Final Wrap Up

Business Week: Advisory Committee Final Vote

Washington Post: First Vote Day Two

Avandia Day One: MedPage Today

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The FDA Advisory Committee meeting on Avandia on July 13-14 raises a number of questions about drug safety, the design of clinical trials, and FDA oversight. Three prominent critics of the popular type 2 diabetes drug Avandia, including two FDA scientific reviewers, are making presentations that will dispute the drug’s safety and whether it should keep FDA approval. However, there are a number of other presentations, including from FDA, that state the data are inconclusive or that the data from clinical trials show the drug is safe. The issue has been with us since 2007 and is complex in many ways. FDA has released the pre-meeting slides of each presentation to the upcoming advisory committee. One of the clearest reviews of the Avandia issue comes not from the press or the blogs but from the overview that will be presented by Dr. Mary H. Parks of FDA.

Avandia Pre-Meeting Slides- Overview

The Avandia critics are Dr. Steven Nissen, Chair of Cardiovascular Medicine at the Cleveland Clinic and Dr. Thomas Marciniak and Dr. David Graham, both of FDA. Dr. Nissen originally brought up safety concerns regarding Avandia in 2007 in an article he co-authored with Kathy Wolski, MPH, in the New England Journal of Medicine. Dr. Marciniak found a number of data integrity errors in his review of a post-market study ordered by the European Medicines Agency called RECORD. The RECORD study was an open-label phase IV clinical trial. Dr. Graham is an FDA scientist who testified to the U.S. Congress in 2004 that FDA was not effective in reviewing clinical trials for drugs safety.

There is strong interest in Dr. Marciniak’s presentation which calls into doubt the conduct of the RECORD clinical trial.

Dr. Marciniak’s Pre-Meeting Slides for Advisory Committee Meeting

There is also a very interesting presentation to be given by Dr. Susan Leibenhaut, Medical Officer/ Division of Scientific Investigations/Office of Compliance/CDER/FDA (DSI). She will present the results of FDA inspections of the RECORD study at the sponsor, GlaxoSmithKline (GSK), the contract research organization (CRO) Quintiles and three clinical sites. The slides detail the findings listed on the Form FDA 483s issued to GSK and Quintiles. Dr. Leibenhaut slides state that there were no systemic findings but three slides list the challenges that FDA faced when conducting sponsor/CRO/ monitor inspections, specifically of Avandia. It is the first time that I am aware of that FDA has conducted a sponsor, a CRO, and a clinical site inspection for a phase IV, post-marketing study (someone please correct me if I am wrong).

FDA Inspections of RECORD Trial – Pre-Meeting Slides for Advisory Committee Meeting

GSK is making a strong defense of Avandia:

GSK Pre-Meeting Slides for Advisory Committee Meeting

I receive a weekly digest of news from FDA each Sunday by email. “What’s New on the FDA Drugs Site” didn’t mention the Advisory Committee meeting and access to the slides is not that easy to find (transparency?). Here is a link to each presentation:

Review Each of the Pre-Meeting Presentations

The issue of Phase IV clinical trials that is raised by the RECORD study is discussed in the Nature Blog:

Nature Blog: IOM Weighs In on Ethics of Post-Market Studies

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This entry was posted on Sunday, July 11th, 2010 at 7:17 PM and is filed under FDA commentaries. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.