Olanzapine for schizophrenia: what do the unpublished clinical trials reveal?

Article type
Authors
Lawrence KA1, Beaumier J2, Wright J3, Perry, Jr. T1, Puil L1, Turner E4, Mintzes B5
1UBC Therapeutics Initiative, Canada
2Vancouver Coastal Health Authority, Canada
3University of British Columbia, Canada
4Oregon Health and Science University, USA
5University of Sydney, Australia
Abstract
Background: Selective reporting of data is a major obstacle to advancing and practicing evidence-informed medicine. Even with access to high-quality Cochrane Reviews, the true net benefit versus harm of an intervention cannot be established without inclusion of the data from unpublished clinical trials.
Objectives: To compare data on key outcomes from published randomized controlled trials (RCTs) and unpublished clinical trials concerning the antipsychotic olanzapine versus placebo.
Methods: Using Cochrane search methods and a trial search co-ordinator, all relevant, published RCTs were retrieved comparing olanzapine with placebo in the treatment of schizophrenia. Through the European Medicines Agency, all relevant clinical study reports submitted by Eli Lilly for olanzapine’s market authorisation for schizophrenia were requested and obtained. We will compare data on the following key outcomes in published and unpublished data, and will examine the effects of any discrepancies on results of meta-analyses: all-cause mortality, non-fatal serious adverse events, and quality of life. Additionally, methods descriptions in published and unpublished trial reports, and assessment of risk of bias, will be compared.
Conclusions: Accessing and including data from unpublished clinical trials may prove to create a more accurate assessment of benefit versus harm of a medical intervention. Although the volume of clinical trial data is large and the undertaking complex, this additional level of scrutiny may be required in order to produce the most accurate and unbiased Cochrane Reviews.