The benchmark for using toxic medications in treatment is oncology where there is an understandable tolerance for high risk\/benefit ratios. Elsewhere in medicine, the risk\/benefit information is part of a much more complex decision process. In psychiatry the use of antipsychotic medications is such an area, hotly contested, particularly in children. While the issues in this controversy can spill outside the boundaries of simply risk\/benefit ratios, risk\/benefit itself is hardly a clear part of the equation – made even more confusing by the introduction of the second generation antipsychotics [SGAs] twenty years ago.<\/div>\n
While the article above is about that risk\/benefit data, a meta-analysis with the subtext question of bias in the literature, this post is really about my own acquired bias over the last several years. It’s in the journal, Pediatrics<\/strong>, not the psychiatric literature, and it was compiled by a group of Canadians from a variety of disciplines. I realized when I ran across it that I was looking it up expecting to trust what I read before I even read it<\/em> because it came from outside the danger zone<\/em> – the pharmaceutical industry, the psychiatric literature, my own country, and away from our halls of academia. I think it’s a sad commentary that I would have that reaction – looking outside my former reliable haunts<\/em> for the trustable information.<\/p>\nThe article itself didn’t disappoint. I liked this point in the
Methods<\/font><\/strong> at first glance: <\/div>\n\nQuality Assessment and Grading the Body of Evidence<\/font><\/strong><\/u>
Two reviewers independently assessed the methodologic quality of studies and resolved discrepancies through consensus. We evaluated trials using the Cochrane Collaboration Risk of Bias tool and cohort studies using a modified Newcastle-Ottawa Scale. The source of funding was recorded for all studies.<\/p>\n Two reviewers graded the strength of the body of evidence using the AHRQ GRADE approach. The evidence was graded separately for each comparison and outcome. Four domains were assessed: risk of bias, consistency, directness, and precision. Based on the individual domains, we assigned an overall strength of evidence [SOE] grade of high, moderate, low, or insufficient.<\/font><\/strong> When no studies were available for an outcome or the evidence did not permit estimation of an effect, we rated the SOE as insufficient.<\/p>\n To determine the overall SOE score, we first considered the risk of bias domain. RCTs with a low risk of biaswere initially considered to have a “high” SOE, whereas RCTs with high risk of bias and well conducted cohort studies received an initial grade of “moderate” SOE. Low quality cohort studies received an initial grade of “low” SOE. The SOE was then upgraded or downgraded depending on the assessments of the remaining domains.<\/sup><\/div>\n<\/ul>\n
This is a heavily truncated [by me] version of one of their tables to show the
Strength of Evidence<\/font><\/strong> in their efficacy assessments: <\/div>\n![](\"http:\/\/1boringoldman.com\/images\/sga-1.gif\")
<\/div>\n
And here’s a similarly truncated version of their
Adverse Reactions <\/font><\/strong>assessment:<\/div>\n![](\"http:\/\/1boringoldman.com\/images\/sga-2.gif\")
<\/div>\n
\n\n| Let me hasten to add that I’ve removed all the numeric data from both tables for fit only. That’s not to say that those numbers are unimportant. Anyone wanting to use this study for any scientific purpose should look at the tables in full. My intent is not to degrade this article, quite the opposite. I want to call attention to it because I think they did a fair and honest job of vetting a literature so suffused with opinion<\/em> and bias<\/em> that it has been almost impossible to interpret.<\/td>\n<\/tr>\n<\/table>\n There’s a whole lot of low Strength of Evidence<\/font><\/strong> in both efficacy and adverse effects. We’ve had almost two decades of controversy around this topic – studies, articles in medical journals, blogs, articles in newspapers, FDA\/Industry debates, suits in our courts, and this is the bottom line, "The evidence on the comparative benefits and harms of antipsychotics is limited.<\/font><\/strong>"<\/p>\nI said this blog post is about my own bias. Up front, I’m not thrilled about giving big medicines to little people, but I know that clinical situations arise where that becomes a real question. My point is that a doctor in those situations enters with very little in the way of solid risk\/benefit information to help make that kind of sticky decision, to give to parents to help them know what to do, or especially in situations like kids in foster care or institutions. That’s not the way things are supposed to work – not with potentially toxic drugs that have been around as long as these.<\/p>\n My other bias is where I started. I felt trusting of this study because it was from Canada in a non-psychiatric journal done by people who weren’t the usual suspects<\/em>. I’m outraged that I’ve been put in a situation where as an American doctor I don’t trust the American literature on this point, as a psychiatrist I don’t trust the psychiatric literature on this point, and that I automatically scan the list of authors, the funding sources, and the financial disclosures before I even read an article these days. That’s not the way things are supposed to work either…<\/div>\n","protected":false},"excerpt":{"rendered":"Antipsychotics for Children and Young Adults: A Comparative Effectiveness Review by Seida JC, Schouten JR, Boylan K, Newton AS, Mousavi SS, Beaith A, Vandermeer B, Dryden DM, and Carrey N. Pediatrics 2012 Feb 20. [Epub ahead of print] BACKGROUND AND OBJECTIVE: Despite increasing on-label and off-label use of antipsychotics, prescribing antipsychotics to children remains controversial […]<\/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_topic_count_hidden":0,"_bbp_reply_count_hidden":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-20340","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/20340","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=20340"}],"version-history":[{"count":27,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/20340\/revisions"}],"predecessor-version":[{"id":20384,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/20340\/revisions\/20384"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=20340"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=20340"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=20340"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}} |