{"id":36927,"date":"2013-05-31T13:34:39","date_gmt":"2013-05-31T17:34:39","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=36927"},"modified":"2013-06-03T21:28:04","modified_gmt":"2013-06-04T01:28:04","slug":"a-lot-better-than-this","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2013\/05\/31\/a-lot-better-than-this\/","title":{"rendered":"a whole lot better than this&#8230;"},"content":{"rendered":"<div align=\"justify\"><img decoding=\"async\" width=\"150\" hspace=\"4\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/bttf-2.gif\" \/>The SSRI era in psychiatry began with Prozac&reg; in 1987 and dominated the 1990s as a steady stream of new drugs were approved by the FDA. When it became apparent that they were only effective in approximately one third of the patients, the term <em>treatment resistant <img decoding=\"async\" width=\"150\" hspace=\"4\" border=\"0\" align=\"left\" src=\"http:\/\/1boringoldman.com\/images\/algo-land-1.gif\" \/>depression<\/em> came in vogue to describe the patients who didn&#8217;t respond, and a variety of strategies were proposed to increase their effectiveness [<em>algorithms<\/em>]. One such program was the Texas Medical Alogorithm Project [TMAP] which prescribed sequencing algorithms using expensive in-patent drugs for the huge Texas Public Mental Health systems. Director Dr. John Rush then was awarded a $35 M NIMH grant to study a <a href=\"http:\/\/1boringoldman.com\/images\/star-d-1.gif\" target=\"_blank\">sequencing algorithm<\/a> of antidepressants in a large cohort of subjects. It was called <strong><font color=\"#200020\">STAR*D<\/font><\/strong>.<\/div>\n<p>            <\/p>\n<div align=\"justify\">If you don&#8217;t know the story of how that study went, here&#8217;s my version:<\/div>\n<ul>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/03\/a-thirty-five-million-dollar-misunderstanding\">a thirty-five million dollar misunderstanding&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/04\/my-old-greek\">my old Greek&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/05\/a-slow-learner\">a slow learner&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/06\/recalculating\">recalculating&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/06\/still-recalculating\">still recalculating&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/08\/the-singapore-sojourn-ask-alice\/\">the singapore sojourn? ask Alice&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/09\/the-appearance-of-conflict-of-interest\/\">the appearance of conflict of interest&hellip;<\/a><\/div>\n<div align=\"justify\"><a target=\"_blank\" href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/10\/stard-too-important-to-ignore\/\">STAR*D: too important to ignore&hellip; <\/a>             <\/div>\n<\/ul>\n<div align=\"justify\"><img loading=\"lazy\" decoding=\"async\" width=\"200\" hspace=\"4\" height=\"216\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/star-d-2.gif\" \/>By any criteria, this was the clinical trial from hell. The idea was to start with one antidepressant [Celexa&reg;] and then treat nonresponders with another antidepressant, and continue for four iterations. The treatment algorithm was arbitrary. Nothing worked right and in the end, the dropout rate was so high that the results were immaterial, whatever they were. The extensive protocol called for the <strong><font color=\"#200020\">HDRS-17<\/font><\/strong>, [clinician administered] to be the primary outcome variable. Along the way, Dr. Rush developed another scale, the <strong><font color=\"#200020\">Quick Inventory of Depression Symptoms<\/font><\/strong> which came in three versions: <strong><font color=\"#200020\">QIDS-C<\/font><\/strong> [clinician rated]; the <strong><font color=\"#200020\">QIDS-S<\/font><\/strong> [a self administered version]; and the <strong><font color=\"#200020\">QIDS-S-telephone<\/font><\/strong> [a self administered version using an automated telephone call-in system]. <\/div>\n<p align=\"justify\">During the study, at each visit, a staff member administered the <strong><font color=\"#200020\">QIDS-C<\/font><\/strong>, available to the clinicians treating the subjects for treatment purposes. The patient later filled out a <strong><font color=\"#200020\">QIDS-S<\/font><\/strong> for the study. And subjects filled out a <strong><font color=\"#200020\">QIDS-S-telephone<\/font><\/strong> in the follow-up groups. There were to be <strong><font color=\"#200020\">HDRS-17<\/font><\/strong> at key end points. When the study was finally reported, the <strong><font color=\"#200020\">HDRS-17<\/font><\/strong> data was nowhere to be found [Primary Outcome Variable]. Instead, the QIDS values were used, and as best I could tell, the various versions were lumped together. When the <a href=\"http:\/\/ajp.psychiatryonline.org\/article.aspx?articleID=97282\" target=\"_blank\"><u><strong>study<\/strong><\/u><\/a> was published, the authors said: <\/p>\n<ul>\n<div align=\"justify\"><sup><strong>We  used the Quick Inventory of Depressive  Symptomatology&ndash;Self-Report  (QIDS-SR) as the primary measure to define  outcomes for acute and  follow-up phases because:<\/strong><\/sup><\/div>\n<ol><sup><strong><\/p>\n<div align=\"justify\">1. QIDS-SR ratings were available for all participants at each acute treatment clinic visit<\/div>\n<div align=\"justify\">2. <font color=\"#990000\">QIDS-SR and HRSD outcomes are highly related<\/font><\/div>\n<div align=\"justify\">3. the QIDS-SR was not used to make treatment decisions, which minimizes the potential for clinician bias<\/div>\n<div align=\"justify\">4. <font color=\"#990000\">the  QIDS-SR scores obtained from the  interactive voice response system, the  main follow-up outcome measure,  and the paper-and-pencil QIDS-SR16 are  virtually interchangeable, which  allows us to use a similar metric to  summarize the acute and follow-up  phase results.<\/font><\/div>\n<p><\/strong><\/sup><\/ol>\n<\/ul>\n<div align=\"justify\">The change in primary outcome variable from a clinician administered <strong><font color=\"#200020\">HDRS-17<\/font><\/strong> to a <strong><font color=\"#200020\">QIDS-S<\/font><\/strong>\/<strong><font color=\"#200020\">QIDS-S-telephone<\/font><\/strong> is a no-no in Clinical Trials &#8211; particularly since it was a change <u>never<\/u> approved by the NIMH DSMB [<strong><font color=\"#300030\">Data Safety and  Monitoring Board<\/font><\/strong>]. Beyond that, particularly since the <strong><font color=\"#200020\">QIDS-S<\/font><\/strong> wasn&#8217;t really blinded [see <a href=\"http:\/\/1boringoldman.com\/index.php\/2011\/04\/09\/the-appearance-of-conflict-of-interest\/\">the appearance of conflict of interest&hellip;<\/a>]. They advertised publishing the HDRS-17 results later, but that has never happened. But all of this is old news. The new part of this story is that a British group interested in using a screening metric for depression in a primary care setting repeated Dr Rush&#8217;s testing of the <strong><font color=\"#200020\">QIDS-S <\/font><\/strong>against the <strong><font color=\"#200020\">HDRS-17<\/font><\/strong> [clinician administered]:        <\/div>\n<blockquote>\n<div align=\"center\"><a target=\"_blank\" href=\"http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/23419617\">Psychometric properties of the Quick Inventory of Depressive Symptomatology [QIDS-SR] in UK primary care. <\/a><br \/>                <sup><strong>by Cameron IM, Crawford JR, Cardy AH, du Toit SW, Lawton K, Hay S, Mitchell K, Sharma S, Shivaprasad S, Winning S, and Reid IC.<\/strong><\/sup> <br \/>                <strong><font color=\"#200020\">Journal of Psychiatric Research.<\/font><\/strong> 2013 47[5]:592-598.<\/div>\n<p>                 <\/p>\n<div align=\"justify\"><sup><strong>It is widely believed that severity of depressive disorder should guide treatment selection and many guidelines emphasise this factor. The Quick Inventory of Depressive Symptomatology [QID-SR16] is a self-complete measure of depression severity which includes all DSM-IV criterion symptoms for major depressive disorder. The object of this study was to assess the psychometric properties of the QIDS-SR16 in a primary care sample. Adult primary care patients completed the QIDS-SR16 and were assessed by a psychiatrist [blind to QIDS-SR16] with the 17-item Hamilton Rating Scale for Depression [GRID-HAMD]. Internal consistency, homogeneity and convergent and discriminant validity of the QIDS-SR16 were assessed. Severity cut-off scores for QIDS-SR16 were assessed for convergence with HRSD-17 cut-offs. Published methods for converting scores to HRSD-17 were also assessed. Two hundred and eighty-six patients participated: mean age = 49.5 [s.d. = 13.8], 68% female, mean HRSD-17 = 12.6 [s.d. = 7.6]. The QIDS-SR16 exhibited acceptable internal consistency [Cronbach&#8217;s alpha = 0.86], a robust factor structure indicating one underlying dimension and correlated highly with the HRSD-17 [r = 0.79] but differed significantly in how it categorised the severity of depression relative to the HRSD-17 [Wilcoxon Signed Rank Test p &lt; 0.001]. Using published methods to convert QIDS-SR16 scores to HRSD-17 scores did not result in alignment of severity categorisation. In conclusion, psychometric properties of the QIDS-SR16 were found to be strong in terms of internal consistency, factor structure and convergent and discriminant validity. <font color=\"#990000\">Using conventional scoring and conversion methods the scale was found not to concur with the HRSD-17 in categorising the severity of depressive symptoms.<\/font><\/strong><\/sup><\/div>\n<p>                 <\/p>\n<div align=\"center\"><img loading=\"lazy\" decoding=\"async\" width=\"297\" height=\"327\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/qids-s-0.jpg\" \/><\/div>\n<\/blockquote>\n<div align=\"justify\">Objectifying symptoms that are subjective is not something to be taken lightly, particularly since so much is made of small differences. The <strong><font color=\"#200020\">HDRS-17 <\/font><\/strong>has emerged along with the <strong><font color=\"#200020\">MADRS<\/font><\/strong> scale as the tried and true standard. And certainly, Clinician Rated scales have been the gold standard. I&#8217;m unaware of any other Clinical Trials that rely of Self Rating scales like the <strong><font color=\"#200020\">QIDS-S<\/font><\/strong>, and this <strong><font color=\"#200020\">QIDS-S-telephone <\/font><\/strong>business is way off the beaten path. Looking at this study, no matter how you cut the cake, the <strong><font color=\"#200020\">QIDS-S <\/font><\/strong>and the <strong><font color=\"#200020\">HDRS-17 <\/font><\/strong>aren&#8217;t interchangeable in rating depression severity &#8211; not even close. So these statements from the <strong><font color=\"#200020\">STAR*D<\/font><\/strong> Report are not confirmed by this study. Another nail in the <strong><font color=\"#200020\">STAR*D <\/font><\/strong>coffin:<\/div>\n<ul><sup><strong><\/p>\n<div align=\"justify\"><font color=\"#990000\">2. QIDS-SR and HRSD outcomes are highly related<\/font><\/div>\n<div align=\"justify\"><font color=\"#990000\">4. the   QIDS-SR scores obtained from the  interactive voice response system,  the  main follow-up outcome measure,  and the paper-and-pencil QIDS-SR16  are  virtually interchangeable, which  allows us to use a similar  metric to  summarize the acute and follow-up  phase results.<\/font><\/div>\n<p><\/strong><\/sup><\/ul>\n<div align=\"justify\">Most people have forgotten <strong><font color=\"#200020\">STAR*D<\/font><\/strong> [even though it continues to generate superfluous journal articles at an amazing rate &#8211; filling resumes to overflowing]:<\/div>\n<div align=\"center\"><img decoding=\"async\" width=\"300\" border=\"0\" src=\"http:\/\/1boringoldman.com\/images\/star-d-8.gif\" \/>&nbsp;<\/div>\n<div align=\"justify\"><strong><font color=\"#200020\">STAR*D<\/font><\/strong> is unused and unusable, as is the follow-on NIMH study <strong><font color=\"#200020\">CO-MED<\/font><\/strong> in which combinations of antidepressants were tried [to no avail]. Dr. Rush&#8217;s partner, Dr. Trivedi, in <strong><font color=\"#200020\">STAR*D <\/font><\/strong>is still at it with <strong><font color=\"#200020\">EMBARC<\/font><\/strong>, yet another NIMH study aiming to improve antidepressant outcomes using genetic testing [doomed conceptually and in design in my opinion]. The whole enterprise of trying to improve antidepressant outcomes through the fantasy that treatment resistant depression represents something about the patients rather than simply reflecting on the heterogeneity of the diagnostic category [Major Depressive Disorder] and the weakness of the antidepressants involved has come to naught and wasted <u>millions<\/u> of NIMH dollars.<\/div>\n<p align=\"justify\"><img decoding=\"async\" width=\"240\" hspace=\"4\" border=\"0\" align=\"right\" src=\"http:\/\/1boringoldman.com\/images\/prefer-3.gif\" \/>TMAP was shut down in disgrace and resulted in large settlements against J&amp;J who financed the whole <strike>scheme<\/strike> scam. <strong><font color=\"#200020\">STAR*D<\/font><\/strong> was mismanaged, misreported. The report here just magnifies <strong><font color=\"#200020\">STAR*D<\/font><\/strong>&#8216;s worthlessness. Dr. Trivedi&#8217;s <strong><font color=\"#200020\">IMPACT<\/font><\/strong> study to computerize the algorithms never made it out of the gate because the doctors wouldn&#8217;t use his computers. The <strong><font color=\"#200020\">CO-MED<\/font><\/strong> study [combining antidepressants] was a decidedly negative study. And <strong><font color=\"#200020\">EMBARC<\/font><\/strong> is on its way to joining it as yet another hole in Texas into which the NIMH throws lots of money.<\/p>\n<div align=\"justify\">One has to ask why the State of Texas and the NIMH have tolerated this whole sequence of algorithmic studies. They have each been scientific embarrassments in their own right. Why hasn&#8217;t the NIMH insisted on publication of the STAR*D Primary Outcome variables? Why do they continue to fund these dead end studies of treatment resistant depression, itself a non-condition? This whole story deserves an investigation of its own, not just of the academics involved, but of the funding agencies. We can do a whole lot better than this&#8230;<\/div>\n","protected":false},"excerpt":{"rendered":"<p>The SSRI era in psychiatry began with Prozac&reg; in 1987 and dominated the 1990s as a steady stream of new drugs were approved by the FDA. When it became apparent that they were only effective in approximately one third of the patients, the term treatment resistant depression came in vogue to describe the patients who [&hellip;]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"closed","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_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[5],"tags":[],"class_list":["post-36927","post","type-post","status-publish","format-standard","hentry","category-opinion"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/36927","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=36927"}],"version-history":[{"count":58,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/36927\/revisions"}],"predecessor-version":[{"id":37035,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/36927\/revisions\/37035"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=36927"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=36927"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=36927"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}