{"id":29485,"date":"2012-06-05T09:40:52","date_gmt":"2012-06-05T13:40:52","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&p=29485"},"modified":"2012-06-07T14:32:05","modified_gmt":"2012-06-07T18:32:05","slug":"data-drugs-and-deception-a-true-story","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2012\/06\/05\/data-drugs-and-deception-a-true-story\/","title":{"rendered":"Data, Drugs, and Deception \u2013 A True Story"},"content":{"rendered":"

The following guest post by Dr. David Newman is reprinted with permission<\/em>\u00a0from his website and blog,\u00a0Smartem.Org<\/a>.\u00a0Dr. Newman is an Emergency Physician and Director of Clinical Research at Mt. Sinai School of Medicine in the Department of Emergency Medicine.\u00a0\u00a0<\/em><\/p>\n

<\/em>Recently\u00a0The Lancet<\/em>\u00a0published\u00a0a meta-analysis of 27 statin trials<\/a>, an attempt to determine whether patients with no history of heart problems benefit from the drugs \u2014 true story. The topic is controversial, and no less than six conflicting meta-analyses have been performed \u2014 also a true story. But last week\u2019s study claims to show, once and for all, that for these very low risk patients, statins save lives \u2014 true story.<\/p>\n

Actual true story: the conclusions of this study are neither novel nor valid.<\/p>\n

The Lancet<\/em>\u00a0meta-analysis, authored by the Cholesterol Treatment Trialists group, examines individual patient data from 27 statin studies. Their findings disagree with\u00a0an analysis published in 2010 in theArchives of Internal Medicine<\/em><\/a>, and with analyses from two equally respected publications, the\u00a0Therapeutics Letter<\/a>\u00a0and the\u00a0Cochrane Collaboration<\/a>.* Despite this history of dueling data the authors of last week\u2019s meta-analysis, in a remarkable break from scientific decorum, conclude their report with a directive for the writers of statin guidelines: the drugs should be broadly recommended based on the new analysis.<\/p>\n

As an editorialist points out, if implemented, the CTT group recommendations in the United States would lead to 64 million people, more than half of the population over the age of 35, being started on statin therapy \u2014 true story.<\/p>\n

Where is the magic, you ask, in this latest effort? What is different? In some ways, nothing. Indeed just a year and a half earlier\u00a0The Lancet<\/em>\u00a0published\u00a0a meta-analysis of 26 of the same 27 studies<\/a>, with the same results, by the same authors (true story, and an odd choice on the part of the journal). So the findings aren\u2019t new. They are, however, at odds with other meta-analyses. Why? It is the way they calculated their numbers. This meta-analysis, like the earlier one from the same group, reports outcomes per-cholesterol-reduction. The unit they use is a \u201c1 mmol\/L reduction in low density lipoprotein (LDL)\u201d, in common U.S. terms, a roughly 40-point drop in LDL.<\/p>\n

That\u2019s the magic: each of the benefits reported in the paper refers to patients with a 40-point cholesterol drop. Voil\u00e1. One can immediately see why these numbers would look different than numbers from reviews that asked a more basic question: did people who took statins die less often than people taking a placebo? (The only important question.) Instead, they shifted the data so that their numbers corresponded precisely to patients whose cholesterol responded perfectly.<\/p>\n

Patients whose cholesterol drops 40 points are different than others, and not just because their body had an ideal response to the drug. They may also be taking the drug more regularly, and more motivated. Or they may be exercising more, or eating right, and more health conscious than other patients. So it should be no surprise that this analysis comes up with different numbers than a simple comparison of statins versus placebo pills. Ultimately, then, this new information tells us little or nothing about\u00a0the benefits someone might expect if they take a statin<\/em>. Instead it tells us\u00a0the average benefits among those who had a 40-point drop in LDL<\/em>.<\/p>\n

But LDL drop cannot be predicted. Some won\u2019t drop at all, some will drop just a bit, and some may drop more. Therefore the numbers here tell an interesting story about certain patients who took statins, but they have no relevance to patients and doctors considering statins. And yet, the latter group is the target of the study\u2019s concusions.<\/p>\n

True story: in prior meta-analyses that found no mortality benefit the investigators simply looked at studies of patients without heart disease and compared mortality between the statin groups and the placebo groups. No machinations, no acrobatics, no per-unit-cholesterol. They took a Joe Friday approach (just the facts, ma\u2019am), and found no mortality benefit.<\/p>\n

Perhaps never has a statistical deception been so cleverly buried, in plain sight. The study answers this question: how much did the people who responded well to the drug benefit? This is, by definition, a circular and retrospective question: revisiting old data and re-tailoring the question to arrive at a conclusion. And to be fair they may have answered an interesting, and in some ways contributory, question. However the authors\u2019 conclusions imply that they answered a different, much bigger question. And that is not a true story.<\/p>\n

Guideline writers, doctors, patients, journalists, and policy makers will all have to pay close attention to avoid the trappings of deceptive data, dressed up as a true story.
\n\u2014\u2014\u2014\u2014\u2014\u2014\u2013<\/p>\n

*The Cochrane Collaboration analysis reports an overall mortality benefit with statins (RR=0.86), however their summary suggests that statins should be used for primary prevention \u201cwith caution.\u201d In particular on p.12, after a discussion of the biases in many of the trials that led to their numerical finding, they clearly state that using statins for patients with anything less than a 2% per year risk of coronary events \u201cis not supported by existing evidence.\u201d This cutoff encompasses virtually all people that would be considered candidates for primary prevention.<\/p>\n","protected":false},"excerpt":{"rendered":"

A skeptic looks at a recent meta-analysis of trials of statins for primary prevention and concludes that the authors cleverly buried a statistical deception. The study may have answered an interesting question, but it did not answer a much different and bigger question.<\/p>\n","protected":false},"author":601,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[7],"tags":[665,584],"class_list":["post-29485","post","type-post","status-publish","format-standard","hentry","category-prevention","tag-primary-prevention","tag-statins"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/29485","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/601"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=29485"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/29485\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=29485"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=29485"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=29485"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}