Day 1 of the FDA Avandia Panel: Live Blogging the Afternoon

6:21: Kaul winds up to deliver a knock-out punch to the Nissen meta-analysis but Nissen pulls a judo move and turns the question around. Admitting his methodology and data are weak he asks: “who’s fault is it that there’s no better data?” After 11 years on the market GSK can only blame itself if there’s no better data, says Nissen.

6:00: Moritz will actually dare to present the same type of analysis for VADT that was just slammed for BARI 2D. He said he’s old and can take it. If you listen carefully you can hear Kaul and Fleming sharpening their knives. This is not going to be pretty.

5:38: Fleming really rips into the BARI 2D analysis. This type of analysis of BARI 2D is useless for understanding rosiglitazone, he said. “Not all sources of observational data are equally reliable, the conclusions are too strongly stated for a seriously biased study.” Sanjay Kaul completely agrees. Under withering attack Brooks gives up and waves the white flag. BARI 2D doesn’t really say anything about rosi, she agrees.

5:15: Now BARI 2D and VADT. I will monitor the proceedings but unless something important happens I’ll stop reporting.

4:32: Now Brad McEvoy gives the FDA pioglitazone metaanalysis and will compare it to the rosi metaanalysis. Slides here. Summary (from slides): “For pioglitazone the risk tended to be less compared to control overall, and across different trial groups. For rosiglitazone the risk tended to be greater compared to control overall, and across different trial groups.”

4:22: FDA meta-analysis finds significantly increased risk for rosi for serious myocardial ischemia, total myocardial ischemia, and CHF. Trends for increased risk of MACE, CV death, and MI, but not stroke.

4:07: Now, FDA’s Fiona Callahan presenting the agency’s Rosi meta-analysis of 52 trials. Slides here.

3:45: Graham: why is vitamin D and cancer in the study? OSE was stepped on. why is it there? to mask the bad deal” nature of the trial

3:42: TIDE is a “bad deal trial”. The people going into the trial: the best they can hope for is that they don’t get the trial drug.

3:39: Graham: No evidence of benefit for rosiglitazone. Doesn’t mean there is no evidence but aren’t we supposed to follow evidence-based medicine.

3:36: Graham: clinical trials were designed to show benefit. With TIDE we’re now talking about doing trials about drugs to see if they do harm.

3:34: Alicia Ault: Graham on #Avandia:  “If you don’t stay on a drug long enough to get a benefit, all you are buying is the risk.”

3:20: Victor Montori: Paul the octopus on stand by, expected to predict outcome of #FDA deliberations on #avandia any moment now…

3:17: Graham: before Nissen metaanalysis like “before the common era”— err, what does that make Nissen?

3:10: Here’s previous coverage on CardioBrief of Graham’s CMS study.

3:01: David Graham starts first of two talks. First on the CMS study. The second his “personal perfective on TIDE” His slides are here and here.

3:00: Kaul: was this a fishing expedition? Questions number of analyses and whether they were answering a prespecified hypothesis.

2:48: Gelperin: Overall,comparisons of rosiglitazone and pioglitazone for outcomes including acute myocardial infarction, congestive heart failure and all-cause mortality favor pioglitazone. No studies were identified in this review with results suggesting a protective cardiovascular effect of rosiglitazone compared to pioglitazone.

2:31: Now Kate Gelperin gives FDA’s systematic review of epidemiologic studies. Slides here.

2:29: Leibenhaut wouldn’t say it herself but FDA bosses want her to say that the audits were not concerning. But why won’t Leibenhaut say it?

2:24: Rosen: is this so complex that we can’t tell if we missed adverse events? I’d see angina pectoris on a case report but not on the SAE.

2:20 Question: was this a low or high number of violations? Leibenhaut: it’s not the number it’s the quality. So, what about the quality? Leibenhaut: typical of what we find. Ungar summed it up: there was a lot of ambiguity.

2:00: Now: FDA’s Susan Leibenhaut, reviewing FDA inspections of RECORD. Here are her slides.

1:50: Konstam asks Mahoney whether “anything you did can directly address or assuage the concern [raised by Marciniak] that a major degree of ascertainment bias” might have compromised the trial. Mahoney says she found no red flags.

1:36: Now comes David Hoberman’s statistical review of record. Here are the slides.

1:02: The FDA’s Karen Mahoney now discussing RECORD. Slides can be viewed here.

12:44: Before the panel resumes, here’s a thought about the morning. Many pundits pointed to the Marciniak analysis as the key weak point in the Avandia defense. It appeared that Ungar’s job was to discount or discredit Marciniak. (I don’t think too many people were fooled by his fulsome praise for Marciniak’s tenacity.) But near the end of his presentation Ungar blinked. Marciniak based his criticism of Marciniak’s analysis on the premise that the trial was so bad that all of the soft endpoints should be ignored. (Talk about damning with faint praise!) He then said that the one reliable endpoint is mortality, and that mortality in RECORD favored Avandia. But, near the end of the questioning, Ungar blinked, and admitted that even mortality in RECORD may not be reliable because of uneven and poorly documented followup of RECORD patients. So where does that leave the Avandia defense?

Here’s Matt Herper’s take on the morning in Forbes.

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  1. […] Day 1 of the FDA Avandia Panel- Live Blogging the morning Posted on July 13, 2010 by Larry Husten The afternoon will be blogged in a separate post. […]

  2. […] Blog of the 2 Day Panel (Part 1, Part 2, Part 3, Part 4) (July 13-14, […]

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