Former FDA Reviewer & Avandia: In Her Own Words
3 CommentsBy Ed Silverman // July 13th, 2010 // 12:24 pm
By now, the name Rosemary Johann-Liang may sound familiar. She is the former FDA medical reviewer who left the agency three years ago amid controversy over her work on GlaxoSmithKline’s Avandia diabetes pill (background links here). Johann-Liang had pressed for stiffer warnings on the drug, but was rebuked and excluded from safety meetings. More recenty, she was deposed as part of litigation over cardiovascular risks associated with the drug.
The deposition was not included in a letter sent by the US Senate Finance Committee to FDA commish Margaret Hamburg yesterday in which new allegations were leveled at the drugmaker for failing to disclose a study that allegedly provided greater understanding of cardiovascular risks. However, it was not released publicly and we now have the deposition (start on page 19). [UPDATE We should note on page 172, it appears the Glaxo lawyer says that a jury was not supposed to hear most of the taped deposition because it conducted for a limited purpose]. And so here are some excerpts of what Johann-Liang had to say about inner agency workings, disclosure of trial data and other reflections.
For instance, she was asked about the black box warning placed on Avandia in 2007 and whether she felt vindicated, since she she sounded alarms about the drug much earlier. Her response: “I did not feel vindicated…Between the time it could have expeditiously gone to label, I believe that many people could have been - could be hurt by this adverse event that possibly would not have been hurt if they were alerted to this problem earlier.”
She was also questioned about whether it is important for the FDA to have been provided comparative safety info that Glaxo might have had about Avandia and the rival Actos pill. The question referred to what Glaxo dubbed Study 175, which examined Actos in order to determine whether to proceed with a head-to-head trial. The decision was not to proceed and this wasn’t shared with the FDA, but Johann-Liang testified this is something the agency should have been told.
“Any information pertaining to a serious adverse event, such as myocardial infarction, and especially death, is a high alert for any safety officer at the FDA. So any information, including something like this, because the lipid profile go to some biological mechanism by which maybe one drug may have more safety –adverse event than another within the same drug class, it would be extreme important information for someone in my position to consider.”
On page 149 of the deposition, Johann-Liang is asked about a memo, which appears on page 35 of the document and details various scenarios that could affect Avandia sales. One such scenario is impact if the “CV safety issue intensifies.” After examining the memo, she notes the hit to sales over a three-year period between 2003 and 2004 could total $600 million. “I don’t typically look at dollar figures. Thankfully, that’s not my role.”
And then there’s the questioning about John Jenkins, who headed the FDA’s Office of New Drugs. The deposition indicates he communicated with a Glaxo exec about the discussions held between the OND and the FDA’s Office of Drug Safety. Johann-Liang was asked what she thought of these communications. “I would not (have held those types of conversations), and FDA has a charge to regulate and I believe there are certain decorums one must abide by when one is regulating an application and deciding upon labeling and safety communication regarding that product.” When asked Jenkins’ discussions met with her decorum, she replied, “No.”
“This should not happen, and the fact that these kinds of things happen, I mean, I think people have to make a determination about the leadership at the FDA.”
My take
She seems like such a thoughtful person full of integrity and honesty who was shafted by the system. She stood up for what she thought was right and her career was ruined. It has happened so many times in Big Pharma as well. Good people get canned for trying to do the right thing.
Salmon
I was just on Senator Grassley’s website and did a search on the term Avandia.
The search provided the following link
http://grassley.senate.gov/news/Article.cfm?customel_dataPageID_1502=6817
Which included a July 23, 2007 letter from Senators Grassley and Baucus to FDA Commissioner Von Eschenbach regarding Dr. Johann-Liang.
What’s more troubling is that this letter also states the following:
Suppression of dissent at the FDA is terribly troubling to both of us. Today, we are writing regarding another FDA employee who was removed from the review of Avandia after voicing safety concerns related to that drug. During a recent interview with Finance Committee staff, a senior medical officer in the Office of New Drugs (OND), who at one point was the primary reviewer for Avandia, told staff investigators that s/he was told to stop participation in the review of potential cardiovascular safety problems associated with Avandia. Since 2005, the senior medical officer believed that there was enough evidence to support a black box warning regarding the risk of CHF.
Interestingly, the senior medical officer’s removal from the review happened at the same time that DDRE was recommending stricter labeling for Avandia, in particular a black box warning for CHF. What makes this allegation even more troubling is that numerous FDA employees told our investigators that this senior medical officer had the most experience with the drug class that includes Avandia. In fact, the senior medical officer had been looking at this particular drug class for about 6 years. It is our understanding that s/he was replaced by someone without experience in this drug class. The senior medical officer told our investigators, “It was the first time that this had happened to me, getting pulled off [a drug].” Another employee told our investigators, “OND does not like a black box.”
Given our July 10th discussion, this new allegation is especially significant and raises our level of concern about FDA interference in safety decisions regarding Avandia and the joint Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee (Advisory Committee) meeting scheduled for July 30 to discuss the safety of Avandia. We understand that OND has the lead responsibility for the upcoming advisory committee meeting instead of OSE and do not understand the logic behind this decision.
Is the above letter referring to Dr. Marciniak or another Sr. OND reviewer?
It’s also interesting that Glaxo just decided to settle a number of lawsuits over Avandia
Salmon
Anon
Dr. Jenkins appears to have adopted a pharma-friendly approach in his work at the FDA. The link below is to a video in which Dr. Jenkins discusses his views on FDA drug approval.
http://www.fda.gov/AboutFDA/Basics/ucm195693.htm
Dr. Jenkins considers the FDA’s current process to be the gold standard in approving drugs. He also states that FDA makes “population-based” decisions regarding the risk and benefits of drugs. The ultimate responsibility for determining the benefits verses the risk of a drug, according to Dr. Jenkins, conveniently lies with the patient and their doctor.
How is it that an individual physician or a patient is in a better position to know the risks of a particular drug than the manufacturer of that medication or the federal agency regulating it? When a model like the one Dr. Jenkins describes assumes choice, how, precisely, does it work with respect to drugs administered without the patient’s direct consent or in the case of mandated drugs? And, what risk is acceptable for consumers to assume when the product on the shelf isn’t the product they believe they are purchasing?