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Expert Rev Vaccines. 2016 May;15(5):573-84. doi: 10.1586/14760584.2016.1164045. Epub 2016 Mar 31.

Pandemic influenza vaccine & narcolepsy: simulations on the potential impact of bias.

Author information

1
a Department of Medical Informatics Erasmus MC Rotterdam , The Netherlands.
2
b Pharmacotherapeutic group IV, Medicines Evaluation Board , Utrecht , The Netherlands.
3
c Department of Statistics and Quantitative Methods, Division of Biostatistics, Epidemiology and Public Health, Laboratory of Healthcare Research and Pharmacoepidemiology , University of Milano-Bicocca , Milan , Italy.
4
d Sleep Medicine Center Kempenhaeghe , Heeze , The Netherlands.
5
e Department of Neurology , Leiden University Medical Center , Leiden , The Netherlands.
6
f Sleep Wake Center SEIN Heemstede , Heemstede , The Netherlands.
7
g Brighton Collaboration Foundation , Basel , Switzerland.
8
h University Children's Hospital , Basel , Switzerland.
9
i Center for Global Health, Cincinnati Children's Hospital , Cincinnati , OH , USA.

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.

KEYWORDS:

Bias; Narcolepsy; Pandemic Influenza; Pandemrix; Simulation; Vaccine Safety

PMID:
26967200
DOI:
10.1586/14760584.2016.1164045
[Indexed for MEDLINE]

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