In this week's NEJM, (http://content.nejm.org/cgi/content/short/358/22/2344) Camilleri (of the Mayo Clinic) and comrades from Movetis (a pharmaceutical company) report the results of a study of Prucalopride, a prokinetic agent, for the treatment of chronic constipation. What is striking about this study is not the agent's relation to Ciaspride (Propulsid, an agent removed from the market a number of years ago because of QTc prolongation and associated cardiac risk) but rather the fact that this study was completed nearly a decade ago, and was only just now published. Such a delay is certainly worthy of concern as astutely pointed out by an editorialist (http://content.nejm.org/cgi/content/short/358/22/2402).
A colleague and I recently pointed out the unethical practice of witholding the results of negative trials from the scientific community (see http://ccmjournal.com/pt/re/ccm/fulltext.00003246-200803000-00060.htm;jsessionid=L2bQSl9ygT9BzlZq81qlnJGfyfG2Jh2f2qQvP4XTp0YqMQ1ZD3T1!195308708!181195628!8091!-1?index=1&database=ppvovft&results=1&count=10&searchid=2&nav=search#P6), but the Prucalopride trial takes the cake. Here, positive results were either intentionally witheld from that community or by happenstance were omitted from publication, delaying further study of this agent (if it is indeed even warranted) and undermining the altruistic basis of subjects' participation in the trial, which, ostensibly, was to advance science (unless they participated for financial incentives, which I might argue [as others already have] should be disclosed in the reporting of a trial - see http://content.nejm.org/cgi/content/extract/358/22/2316.)
I will leave it to other bloggers and commentators to speculate whether the profit or other motives were the impetus behind this delay and whether medical ghostwriting was in any way involved in the publication of this article. Suffice it to say that there are certain irregularities in the way a trial is reported (in addition to those with which it was conducted) that should give us pause. Prucalopride has now shown itself to be worthy of a bright spotlight of intense scrutiny.
Showing posts with label selective publication. Show all posts
Showing posts with label selective publication. Show all posts
Thursday, May 29, 2008
Friday, January 18, 2008
Have the Peddlers of Antidepressants (Big Pharma) been Successful in Suppressing Negative Trial Results?
Yes, according to this article in yesterday's NEJM:
http://content.nejm.org/cgi/content/short/358/3/252
Talk about publication bias. According to Erick H. Turner, M.D. and coauthors, the selective publication of only "positive" trials, in addition to publishing in a positive light studies that the FDA considered "negative" leads to a 32% increase in the apparent efficacy of antidepressant drugs, on average (range 11-69%). Once again, profit trumps science, safety, and patient and public health.
What can we do about it? First, reduce by one third the effect size of any antidepressant results you see in an industry-sponsored clinical trial. Next, carefully consider whether whatever [probably modest] effect remains is worth the side effects (e.g., increase in suicide), cost, and nuisance of the drug. Third, prescribe generic agents. Fourth, don't allow pharmaceutical reps to speak with you about new products. Fifth, consider alternative treatments.
I am reminded of a curious occurrence relating to a drug that I think is definately worth the cost, side effects, and nuisance associated with it: Chantix (varenicline) - Pfizer's smoking cessation drug. In JAMA in July 2006,
(http://jama.ama-assn.org/content/vol296/issue1/index.dtl)
two nearly identical articles described two nearly identical studies, which shared many of the same authors. What was the intent of this? Why not conduct one larger study? Was the intent to diversify the risk of failure and allow for selective publication of positive results? I'm very interested in any information anyone can provide about this curious arrangement, which appears to be without precedent. Please leave your comments below.
http://content.nejm.org/cgi/content/short/358/3/252
Talk about publication bias. According to Erick H. Turner, M.D. and coauthors, the selective publication of only "positive" trials, in addition to publishing in a positive light studies that the FDA considered "negative" leads to a 32% increase in the apparent efficacy of antidepressant drugs, on average (range 11-69%). Once again, profit trumps science, safety, and patient and public health.
What can we do about it? First, reduce by one third the effect size of any antidepressant results you see in an industry-sponsored clinical trial. Next, carefully consider whether whatever [probably modest] effect remains is worth the side effects (e.g., increase in suicide), cost, and nuisance of the drug. Third, prescribe generic agents. Fourth, don't allow pharmaceutical reps to speak with you about new products. Fifth, consider alternative treatments.
I am reminded of a curious occurrence relating to a drug that I think is definately worth the cost, side effects, and nuisance associated with it: Chantix (varenicline) - Pfizer's smoking cessation drug. In JAMA in July 2006,
(http://jama.ama-assn.org/content/vol296/issue1/index.dtl)
two nearly identical articles described two nearly identical studies, which shared many of the same authors. What was the intent of this? Why not conduct one larger study? Was the intent to diversify the risk of failure and allow for selective publication of positive results? I'm very interested in any information anyone can provide about this curious arrangement, which appears to be without precedent. Please leave your comments below.
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