A study has determined, using research on Duloxetine ( Cymbalta ) for major depressive disorder as an example, if there are inconsistencies between protocols, clinical study reports, and main publicly available sources ( journal articles and trial registries ), and within clinical study reports themselves, with respect to benefits and major harms.
Data on primary efficacy analysis and major harms were extracted from nine randomised placebo controlled trials of Duloxetine ( total 2878 patients ) submitted to the European Medicines Agency ( EMA ) for marketing approval for major depressive disorder.
Clinical study reports fully described the primary efficacy analysis and major harms ( deaths [ including suicides ], suicide attempts, serious adverse events, and discontinuations because of adverse events ).
There were minor inconsistencies in the population in the primary efficacy analysis between the protocol and clinical study report and within the clinical study report for one trial.
Furthermore, researchers found contradictory information within the reports for seven serious adverse events and eight adverse events that led to discontinuation but with no apparent bias.
In each trial, a median of 406 ( range 177-645 ) and 166 ( 100-241 ) treatment emergent adverse events ( adverse events that emerged or worsened after study drug was started ) in the randomised phase were not reported in journal articles and Lilly trial registry reports, respectively.
Researchers have also found publication bias in relation to beneficial effects.
In conclusion, clinical study reports contained extensive data on major harms that were unavailable in journal articles and in trial registry reports.
There were inconsistencies between protocols and clinical study reports and within clinical study reports.
Clinical study reports should be used as the data source for systematic reviews of drugs, but they should first be checked against protocols and within themselves for accuracy and consistency. ( Xagena )
Maund E et al, BMJ 2014;348:g3510