[A large epidemiological study on human papillomavirus vaccine post-vaccination symptoms and healthy vaccinee bias].

Abstract

Objective　This study aimed to examine the existence of healthy vaccinee bias, a source of distortion in the evaluation of vaccine efficacy, through analysis without random assignment using real data on post-vaccination symptoms from the Nagoya Study, a large epidemiological study of human papillomavirus (HPV) vaccine post-vaccination symptoms.Methods　For three school years of individuals born in 1997, 1998, and 1999, as the HPV vaccine had a 2-year target period, 3,246 were first vaccinated at age 14 years and 3,961 were unvaccinated. The proportion of symptom onset in these 7,207 individuals during the unvaccinated period at age 13 years was compared by birth year to examine the presence of a healthy vaccinee bias.Results　Only four symptoms were significantly higher among unvaccinated participants, such as the proportion of "severe headache," which occurred in 2010 among those born in 1997, "hyperventilation," which occurred in 2011 among those born in 1998, "fatigue" and "sudden vision loss," which occurred in 2012 among those born in 1999. Healthy vaccinee biases are rarely observed.Conclusion　Underestimation of the odds ratio of HPV vaccination due to healthy vaccinee bias is limited, and the claim that the supposedly high odds ratio in the Nagoya Study was masked by a healthy vaccinee bias is invalid.