tag:blogger.com,1999:blog-9143719926358099859.post5485907747249938045..comments2023-10-26T08:08:43.486-07:00Comments on Dr. Mintz' Blog: The Avandia Scare: Why it Matters, Who's Responsible, and What to DoDr. Matthew Mintzhttp://www.blogger.com/profile/01058182168282244996noreply@blogger.comBlogger7125tag:blogger.com,1999:blog-9143719926358099859.post-75612846079653813522010-02-26T10:38:38.892-08:002010-02-26T10:38:38.892-08:00Ironic, isn't it? I have had Type 1 diabetes ...Ironic, isn't it? I have had Type 1 diabetes for over 40 years and the simple logistics are, most diabetics will die from 1) diabetes itself, 2) heart disease, and/or 3) kidney failure. You already have a fractured equation when you consider that 33 to 40% of diabetics will have a heart attack anyway.Rhonda Minernoreply@blogger.comtag:blogger.com,1999:blog-9143719926358099859.post-52629279519315733512009-11-21T15:22:28.525-08:002009-11-21T15:22:28.525-08:00Given that Dr. Mintz is quick to insinuate that co...Given that Dr. Mintz is quick to insinuate that conflicts of interest are partly to blame for the Avandia scare, I think it is only fair that he disclose all potential conflicts that he may have. <br /><br />The Nissen meta-analysis may be flawed, but the RECORD trial is not conclusive either. Furthermore, the impact of lower Avandia usage on patient outcomes is merely speculation on Dr. Mintz's part, unless he has actual data (and not just extrapolations and assumptions) to support his viewpoint.Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-9143719926358099859.post-19782052969336121112009-07-22T09:55:26.153-07:002009-07-22T09:55:26.153-07:00The same thing--almost--happened in 2000, when &qu...The same thing--almost--happened in 2000, when "consumer activists" got Rezulin pulled from the market, to be replaced by Avandia (and Actos). We will never know the real benefit-risk profile of Rezulin, but at least we have more data now on Avandia.<br /><br />See my 2000 op-ed in the Wall Street Journal, "Rezulin Proves the System Works."<br />https://www.acsh.org/news/newsID.225/news_detail.asp<br />Gilbert Ross MD www.acsh.orgAnonymousnoreply@blogger.comtag:blogger.com,1999:blog-9143719926358099859.post-52789978710276323192009-07-20T13:27:37.255-07:002009-07-20T13:27:37.255-07:00I don't believe that the results of RECORD sup...I don't believe that the results of RECORD support your contention that the concerns about cardiovascular risks of rosiglitazone were a "false alarm," or crying wolf. <br /><br />In fact, RECORD had several problems that prevented it from proving that rosiglitazone does not elevate the risk of myocardial infarction (MI, or heart attack). These were:<br /><br />1. Possibly because RECORD was an "open-label," rather than a double-blind trial, patients in the rosiglitazone group received different co-interventions than patients in the control group. In particular, about 10% more patients in the rosiglitazone group (55.2% vs 46.0%) were receiving statins at the end of the trial than were patients in the control group. There is pretty good evidence that statins reduce the risk of coronary artery disease, and hence, of MIs. Thus, thiis version of co-intervention bias may have decreased the apparent rate of MIs in the rosiglitazone group.<br /><br />2. The RECORD trial suffered from a significant loss to follow-up. For 8.9% of patients, ascertainment of cardiovascular outcomes was incomplete. Since the rate of MIs in the whole group was less than 3% over 6 years of observation, it is possible that had all these cardiovascular outcomes been ascertained, the ratio of MIs in the rosiglitazone and control groups would have turned out quite differently, either indicating less, or more risk due to rosiglitazone.<br /><br />3. The RECORD trial was too small to prove that rosiglitazone did not raise MI risk, possibly substantially. The 95% confidence interval for the risk of MI due to rosiglitazone was (0.80, 1.63). A somewhat crude way to interpret this is that the chances of rosiglitazone causing a risk of MI higher than 1.63 was less than 5%. On the other hand, the trial could not disprove that rosiglitazone raised the risk of MI by as much as 1.63 times. (Note that the point estimate of risk of MI was 1.14, meaning that the best guess of the effect of rosiglitazone on MI risk was that it raised it by 1.14 times, or 14%) <br /><br />Moreover, I do not see how you can justify your point that patients who discontinued Avandia were harmed. Can you show any evidence that the drug provides clinical benefits (that is, to do with outcomes that actually affect patients, not laboratory values they cannot feel) that outweigh its harms? In the absence of such evidence, how could a patient be harmed by withdrawing the drug (and perhaps substituting something else)? <br /><br />There may be some evidence that the drug improves diabetic control when added to other, older drugs. But it is not the only drug that can do this. Furthermore, I do not believe there is clear evidence that tight glucose control in Type 2 diabetes produces clinical benefits that clearly outweighs the risks of hypoglycemia. For example, VADT did not show a statistically significant decrease in the primary outcome, but did show an increase in hypoglycemic events in the intensive-treatment group. ADVANCE showed that intensive control reduced nephropathy (absolute decrease 1.1%) but increased severe hypoglemia (absolute increase 1.2%)<br /><br />Finally, shouldn't you disclose that you have served on an advisory board and the speakers' bureau of GlaxoSmithKline, the manufacturers of Avandia?<br />See: http://cme.medscape.com/viewprogram/6294 and<br />http://content.nejm.org/cgi/content/full/354/11/1206Roy M. Poses MDhttps://www.blogger.com/profile/00497209843184497847noreply@blogger.comtag:blogger.com,1999:blog-9143719926358099859.post-17571704551390360032009-06-17T14:40:53.361-07:002009-06-17T14:40:53.361-07:00This is really an excellent analysis, and I think ...This is really an excellent analysis, and I think its pretty close to the truth. I hope someone from a significant media source picks up on this and makes it public.<br /><br /> I really dont think anyone will investigate this at all... the primary parties are all too invested in it.<br /><br />GSK? They dont dare whistleblow on the FDA for fear of future reprisals. And all pharma has learned to never, ever cross Nissen.<br /><br />The ADA? The American Diabetes Association would never turn on David Nathan.<br /><br />Someone complain about Nissen? No drug company would complain about him. Look how many torpedoes he has fired and how many drugs he's sank. And Takeda loves him. Just watch his positive studies that will be done on Alogliptin and Actos. Heck, they even are naming their new drug after him...Anonymousnoreply@blogger.comtag:blogger.com,1999:blog-9143719926358099859.post-32826449633019153252009-06-17T13:52:04.388-07:002009-06-17T13:52:04.388-07:00thanks James, and excellent question. I am not exa...thanks James, and excellent question. I am not exactly sure why the NEJM "fast tracked" the publication, but I suspect it's because:<br />1. They knew what a stir the Nissen study would create, and more attention for the NEJM means more business.<br />2. They probably knew that the FDA had it's own meta-analysis and if word got out that the NEJM was going to release a similar one, the FDA would try to get the data out first so as not to look bad (which is what happened). NEJM probably realized that they needed to act fast before the FDA got wind, and likely bypassed some of its peer review policies. <br />3.Another possibility (which is complete speculation) is that there was some political pressure. Congressional hearings were called for immediately after the Nissen study hit the press, almost as if the congressmen knew about the study beforehand. If that's the case, maybe they leaned on the NEJM to get the story out ASAP.Dr. Matthew Mintzhttps://www.blogger.com/profile/01058182168282244996noreply@blogger.comtag:blogger.com,1999:blog-9143719926358099859.post-55708244015318352172009-06-17T13:40:43.284-07:002009-06-17T13:40:43.284-07:00I continue to be impressed with your through,thoug...I continue to be impressed with your through,thoughtful reviews and tireless effort in this regard.From the first I was skeptical that a single meta analysis should have stirred up so much trouble.My question is why did NEJM rush to judgment on this issue and publish so soon ? <br />I realize you have no special powers to discern motivations but I would be interested in your thoughts.james gaultehttps://www.blogger.com/profile/05537303135780186926noreply@blogger.com