Publication bias is known to be a major problem in the medical literature.[1,2,3,4,5] In general, studies with positive outcomes are more likely to be published than studies with negative outcomes. This finding also extends to the psychiatric literature. Negative outcomes are here defined as randomized clinical trials (RCTs) which fail to find statistically significant benefit with an active treatment as opposed to a control group in an adequate sample size. The nonpublication of negative outcomes in RCTs has been especially reported to occur in pharmaceutical industry-funded studies, as opposed to studies funded by governmental sources.[6,8,9,10,11,12] Recent controversies in varied medical disciplines have highlighted the importance of having access to such unpublished data; previously underappreciated unpublished side effect data have led to removal of certain agents, such as the anti-inflammatory agent rofecoxib, from the US market.[13,14] Marketing of other agents, such as gabapentin, for unproven treatment indications such as bipolar disorder despite initially unpublished studies showing absence of efficacy in that condition also has led to controversies and even malpractice lawsuits.[15,16] A recent review of antidepressant RCTs in unipolar depression in the Food and Drug Administration (FDA) database found that almost all negative studies were unpublished, leading to a false impression in the published literature that 93% of antidepressant RCTs had positive results; when unpublished studies were included, 51% of all RCTs were positive and 49% were negative. Thus, unpublished studies raise questions of concerns regarding both underreported risks and underreported limitations in efficacy.
In response to some of the above controversies, in 2002, the US lobbying group for the pharmaceutical industry (Pharmaceutical Research and Manufacturers Association; PhRMA) published its "Principles on the Conduct of Clinical Trials and Communication of Clinical Trial Results" (https://www.phrma.org/publications/policy_papers/phrma_clinical_trial_registry_proposal/) and committed to voluntarily registering all clinical trials at initiation, as well as providing access to the results of all study outcomes, positive or negative, via company-based (specific Web sites or www.clinicalstudyresults.org) or government-based Web sites (www.clinicaltrials.gov).
In this paper, we access those Web sites of companies with agents approved for the treatment of bipolar disorder, to examine the availability of study results with negative data, and then we focus on one of those agents with availability of negative data, lamotrigine, to examine the impact of those results on clinical interpretation of the utility of that agent in bipolar disorder.
Medscape J Med. 2008;10(9):211 © 2008
Cite this: Publication Bias and the Pharmaceutical Industry: The Case of Lamotrigine in Bipolar Disorder - Medscape - Sep 10, 2008.