The recent guest post by David Newman has prompted several thought-provoking comments. Since most readers will likely miss the comments, I’ve moved these comments to a separate post.
Statin Island May 27, 2012, 3:35 PM:
Thank you. Clearly, this important commentary raises questions about the integrity of Lancet as well as the authors of the study.
But what is most discouraging, and dangerous, is that this kind of deception occurs so frequently. Meanwhile, major news outlets, television channels, etc. have reported the results as the authors intended. And so the gravy train has left the station.
Lancet should publish a clarifying editorial and send it everywhere they can. They are an accessory to any harm that has resulted, to patients and to the credibility of medical science.
Michael V Holmes (@mvholmes) (May 28, 2012, 10:10 AM:
I disagree with this critique. The authors weighed each RCT by the LDL-C lowering to be able to provide a standardized comparison across the studies (it’s in the Methods of the paper). By doing so, they didn’t break the randomization, and shouldn’t have introduced confounding, as suggested by this commentary piece. And being able to say “for each 1 mmol/L LDL-C reduced, the RR of CHD is 0.79, 95% CI 0.77, 0.81″ is very helpful metric.
Larry Husten (May 28, 2012, 12:31 PM:
I don’t claim to be an expert in meta-analysis but I’m not sure that Holmes is responding to the fundamental flaw in logic in the Lancet paper raised by Newman. The Lancet paper– correctly, as Newman acknowledges– identifies a benefit for statins in people who respond to statins, but it says nothing about the broader primary prevention population, some of whom will not respond to statins. The conclusion reached by the CTT authors, that statins should be more widely used in this primary population, is therefore unwarranted.
I am hopeful that Dr. Newman will respond in more detail and discuss the technical issues raised by Holmes.
MDinSTL (May 30, 2012, 11:32 AM):
Within any randomized group, some will do better than others. When targeting a lower LDL, those who achieve and maintain the target do better than those who do not. This phenomenon has been called dose targeting bias.
What is key to understand though is that an intervention may have NO benefit, yet this relationship of better LDL lowering to better outcomes can still be observed.
Therefore if the trials show no net benefit between statin vs placebo, it is not necessarily true that the subgroup analysis the Lancet group employs means some people benefited.
This is easiest to see by considering this point: If the statin-treated non-CAD patients had no overall reduction in mortality, and the subgroup with a large LDL drop did have lower mortality, then those without a large LDL drop must have been harmed by statins to account for the lack of overall effect compared to the placebo-treated patients.
If investigators really believe some benefit from statins accrues to those without apparent CAD provided LDL falls at least 40 pts, then the answer is to perform a trial where entry criteria include an ability to show a 40 pt drop in LDL, then randomize pts to statin vs no statin. That ain’t gonna happen because 1. few seriously believe that, and 2. this message is really a marketing message intended to promote use of statins in the general population.
DH Newman(May 28, 2012, 5:08 PM:
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