{"id":65684,"date":"2016-05-20T08:30:54","date_gmt":"2016-05-20T12:30:54","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=65684"},"modified":"2016-05-20T14:35:56","modified_gmt":"2016-05-20T18:35:56","slug":"publication-bias-ii-close-encounters-of-the-second-kind","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2016\/05\/20\/publication-bias-ii-close-encounters-of-the-second-kind\/","title":{"rendered":"publication bias II – close encounters of the second kind…"},"content":{"rendered":"\n

With the Paxil Study 329<\/a> paper, our problem getting it in print didn’t have to do with journal shopping<\/font>, it had to do with a tough love review process and a year of uncertainty that went with it. It was a top journal [British Medical Journal<\/font><\/b> Impact Factor<\/font> 17.445<\/font><\/b>] and I’m glad it’s there. The recent Citalopram paper<\/a> did have to do a lot of journal  shopping <\/strike> hopping<\/font> [see background notes<\/a>], moving from the Journal of Affective Disorders <\/font>[Impact Factor<\/font> 3.383<\/font><\/b>] to JAMA Psychiatry <\/font>[Impact Factor<\/font> 12.008<\/font><\/b>] to the Acta Psychiatrica Scandinavica <\/font>[Impact Factor<\/font> 5.605<\/font><\/b>] to the International Journal of Risk and Safety in Medicine <\/font>[Impact Factor<\/font> 0.86<\/font><\/b>]. Quite a journey.<\/p>\n

A few months back, I was writing about an elaborate KOL-rich campaign by Takeda and Lundbeck to get FDA Approval for Vortioxetine <\/font>[Brintellix\u00ae<\/font>] in Cognitive Dysfunction in Major Depressive Disorder [see indications\u2026<\/a> and more vortioxetine story…<\/a>]. I thought it was a commercially driven attempt [indication creep] and the science was woefully lacking. I was pleased that the FDA later agreed [a parable…<\/a>] and didn’t approve the indication. Prior to that, my only encounter with Vortioxetine <\/font>[Brintellix\u00ae<\/font>] was a industry-produced review article in the Journal of Clinical Psychiatry<\/font> [Impact Factor<\/font> 5.498<\/font><\/b>]: <\/p>\n

\n
An Overview<\/font> of Vortioxetine<\/a><\/div>\n
by Alan F. Schatzberg, Pierre Blier, Larry Culpepper, Rakesh Jain, George I. Papakostas, and Michael E. Thase.<\/div>\n
Journal of Clinical Psychiatry<\/font><\/b> 2014 75[12]:1411\u20131418.<\/div>\n
[full text on-line<\/a>]<\/div>\n

<\/p>\n

Six clinicians provide an overview of the serotonergic antidepressant vortioxetine, which was recently approved for the treatment of major depressive disorder in adults. They discuss the pharmacologic profile and receptor-mediated effects of vortioxetine in relation to potential outcomes. Additionally, they summarize the clinical trials, which demonstrate vortioxetine\u2019s efficacy, and discuss findings related to safety and tolerability that have high relevance to patient compliance.<\/font><\/b><\/i><\/div>\n<\/blockquote>\n
Speaking of KOL-rich, this was simply the worst article I’ve ever seen in a medical journal<\/font><\/b>. It’s hard to imagine that they published it, but I’ve had my say about that [see the recommendation?\u2026<\/a>]. While I was in the Vortioxetine neighborhood, I ran across an article that had been accepted but not yet published by Lisa Cosgrove and colleagues that looked interesting. I wrote them about it and they kindly sent me an advance copy:<\/div>\n
\n
Under the Influence: the Interplay among Industry, Publishing, and Drug Regulation<\/a>.<\/div>\n
by Lisa Cosgrove, Steven Vannoy, Barbara Mintzes, and Allen Shaughnessy<\/div>\n<\/blockquote>\n
Dr. Cosgrove was well known to me for running down the extent of Conflicts of Interest among members of the DSM-5 Task Force [see must be crazy…<\/a>] and as a coauthor of the recent book Psychiatry Under the Influence: Institutional Corruption, Social Injury, and Prescriptions for Reform<\/a><\/span>. In sending the article, she mentioned that they had a very difficult time getting it published. I thought it was an important article and made a note to blog about it later when it was published and fully available in Accountability in Research <\/font>[Impact Factor<\/font> 0.826<\/font><\/b>]. It includes a critical look at the Vortioxetine Clinical Trials that I’ll mention later. In the references, I found a meta-analysis of Vortioxetine published in the Journal of Psychiatry and Neuroscience <\/font>[Impact Factor<\/font> 5.86<\/font><\/b>]:<\/div>\n
\n
Vortioxetine: a meta-analysis of 12 short-term, randomized, placebo-controlled clinical trials for the treatment of major depressive disorder<\/a><\/div>\n
by Chi-Un Pae, Sheng-Min Wang, Changsu Han, Soo-Jung Lee, Ashwin A. Patkar, Praksh S. Masand, and Alessandro Serretti<\/div>\n
Journal of Psychiatry and Neuroscience<\/font><\/b>. 2015 40[3]: 174\u2013186. <\/div>\n
[full text on-line<\/a>]<\/div>\n

<\/p>\n

Background<\/font><\/b><\/i>: Vortioxetine was approved by the U.S. Food and Drug Administration [FDA] in September 2013 for treating major depressive disorder [MDD]. Thus far, a number of randomized, double-blind, placebo-controlled clinical trials [RCTs] of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current understanding of the role of vortioxetine in the treatment of MDD.<\/div>\n
Methods<\/font><\/b><\/i>: We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression [HAM-D] and the Montgomery\u2013\u00c5sberg Depression Rating Scale [MADRS] from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D\/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment.<\/div>\n
Results<\/font><\/b><\/i>: We included 7 published and 5 unpublished short-term [6\u201312 wk] RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size [standardized mean difference [SMD]] of ?0.217 [95% confidence interval [CI] ?0.313 to ?0.122] and with odds ratios [ORs] for response and remission of 1.652 [95% CI 1.321 to 2.067] and 1.399 [95% CI 1.104 to 1.773], respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors\/agomelatine with regard to the SMD of the primary outcome measure [0.081, ?0.062 to 0.223] or for response [OR 0.815, 95% CI 0.585 to 1.135] and remission [OR 0.843, 95% CI 0.575 to 1.238] rates. Discontinuation owing to lack of efficacy [OR 0.541, 95% CI 0.308 to 0.950] was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events [AEs; OR 1.530, 95% CI 1.144 to 2.047] was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy [OR 0.983, 95% CI 0.585 to 1.650], whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group [OR 0.728, 95% CI 0.554 to 0.957].<\/div>\n
Limitations<\/font><\/b><\/i>: Studies examining the role of vortioxetine in the treatment of MDD are limited.<\/div>\n
Conclusion<\/font><\/b><\/i>: Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.<\/div>\n


Effect Size of the Primary Outcome Variable
[adapted for blog]<\/p>\n<\/blockquote>\n

I’ve obviously got two themes going in this post. One is the articles about the RCTs that lead the FDA to approve Vortioxetine <\/font>[Brintellix\u00ae<\/font>] <\/font>for the treatment of Major Depressive Disorder. The other has to do with what I’m calling publication bias of the second kind<\/font><\/i> – the difficulty getting contrarian articles about Clinical Trials published and into the general dialog. I’ll get to the Cosgrove et al article in detail in the next post, but for now just say that it is in the contrarian category. So, we have an industry created [incredible] review article in a journal with an Impact Factor of 5.498<\/font><\/b>, a credible meta-analysis in a journal with an Impact Factor of 5.86<\/font><\/b>, and the Cosgrove et al article that ended up in a journal with an Impact Factor of 0.826<\/font><\/b>. In my next post in this series, I’m going to continue both themes and claim that this disparity in journal ratings deserves our attention…<\/div>\n","protected":false},"excerpt":{"rendered":"

With the Paxil Study 329 paper, our problem getting it in print didn’t have to do with journal shopping, it had to do with a tough love review process and a year of uncertainty that went with it. It was a top journal [British Medical Journal Impact Factor 17.445] and I’m glad it’s there. The […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-65684","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/65684","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=65684"}],"version-history":[{"count":29,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/65684\/revisions"}],"predecessor-version":[{"id":65730,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/65684\/revisions\/65730"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=65684"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=65684"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=65684"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}