Pandemic influenza vaccine & narcolepsy: simulations on the potential impact of bias. (3rd May 2016)

• Record Type: Journal Article
• Authors: Wijnans, Leonoor; Dodd, Caitlin; de Ridder, Maria; Romio, Silvana; Weibel, Daniel; Overeem, Sebastiaan; Lammers, Gert Jan; Bonhoeffer, Jan; Black, Steve; Sturkenboom, Miriam
• Is Part Of: Expert review of vaccines. Volume 15:Number 5(2016)
• Page Start: 573
• Page End: 584
• Publication Date: 2016-05-03
• Subjects: Narcolepsy -- Pandemrix -- Bias -- Simulation -- Pandemic Influenza -- Vaccine Safety; Vaccines -- Periodicals; Vaccination -- Periodicals; 615.37205
• DOI: 10.1586/14760584.2016.1164045
• Languages: English
• ISSNs: 1476-0584

Abstract

ABSTRACT: Several studies have identified an association between Pandemrix TM, an AS03 adjuvanted pandemic influenza A(H1N1) vaccine, and narcolepsy, a rare and under-diagnosed sleep disorder with a median onset-to-diagnosis interval of ten years. This paper reviews potential sources of bias in published studies and aims to provide, through simulation, methodological recommendations for assessment of vaccine safety signals. Our simulation study showed that in the absence of an association between the vaccine and the outcome, presence of detection bias and differential exposure misclassification could account for elevated risk estimates. These may play a major role, particularly in alert situations when observation times are limited and the disease has a long latency period. Estimates from the case-control design were less inflated than those from the cohort design when these biases were present. Overall, these simulations provide useful insights for the design and interpretation of future studies.