Elsevier

Vaccine

Volume 27, Issue 22, 14 May 2009, Pages 2954-2958
Vaccine

Human papillomavirus immunisation of adolescent girls and anticipated reporting of immune-mediated adverse events

https://doi.org/10.1016/j.vaccine.2009.02.106Get rights and content

Abstract

Determining incidence rates of potential adverse events before and after an immunisation programme is initiated, provides a useful framework for the evaluation of vaccine safety concerns. Human papillomavirus vaccination (HPV) of adolescent girls has recently been introduced in Denmark. Using a nationwide hospitalisation registry we estimated incidence rates of immune-mediated disorders before HPV vaccination in a cohort of 418,289 Danish girls aged 12–15 years. We further estimated the expected number of cases of immune-mediated disorders occurring in temporal relationship to a hypothetical HPV vaccination schedule purely by chance. Our results and analytical approach provides a framework for the evaluation of adverse event reports following immunisation of adolescent girls.

Introduction

In recent years, regulatory bodies have promoted a proactive approach to managing risks associated with pharmaceuticals and vaccines [1], [2]. Although there is some ambiguity, the concept of pharmaceutical risk management is often defined as embracing the identification and assessment of risk, risk minimisation and evaluation of risk minimisation activities [3]. With respect to risk identification and assessment, the International Conference of Harmonisation (ICH) E2E guideline has been instrumental in aiding industry and regulators in the planning of pharmacovigilance activities [4]. One of its central recommendations relates to the assessment of baseline rates of adverse events in the target population for a particular product. Availability of this information can assist in the evaluation of spontaneous reports of adverse events recorded after the launch of a particular drug or immunisation program.

Even if immunisations entail some risk of minor adverse reactions, there is solid evidence of the safety of vaccines currently used in large populations [5]. Up until now the same seems to apply to the recently authorized human papillomavirus (HPV) vaccines [6], one of which will be administered within the Danish childhood immunisation program. However, as can be expected for newly introduced vaccines, one safety signal has already emerged after use in large populations [7]. Furthermore, although the concerns appear to be mainly theoretical, it has been suggested that immunisation may induce allergy [8] and that new-generation vaccines could trigger autoimmune disorders [9]. Given that the incidence of immune-mediated diseases in the target population is not negligible [10], the implementation of the HPV immunisation program in Denmark is likely to generate spontaneous reports related to these disorders. It has been suggested that determining local health care resource use before and after an immunisation program is initiated, could be a useful approach to estimating baseline incidences of events of interest and thus provide rapid answers to vaccine safety concerns [11]. Hence, the objective of the present study was to determine the incidence rates of hospital contacts related to immune-mediated events in adolescent girls before the start in 2009 of the HPV immunisation program in Denmark.

Section snippets

Materials and methods

The Danish Civil Registration System (CRS) contains comprehensive demographic information on all citizens living in Denmark indexed by a unique personal identification number – the CRS number [12]. The CRS number is used in all national registries and allows linkage of individual-level information. Based on the CRS we constructed a cohort of all children born in Denmark in the 1980–1992 period. Using the CRS number we were able to link information on immune-mediated disorders to the children in

Results

A total of 418,289 girls (and 432,261 boys) who were at the age 12–15 years in the 1995–2005 study period were included in the cohort. During 941,405 person-years of follow-up among girls in the cohort, we identified 8,303 hospital contacts with immune-mediated disorders. A total of 1,828 girls were lost to follow-up as a result of death (N = 122), disappearance (N = 51) or emigration (N = 1655).

In Table 1, we present allergic disorder incidence rates among girls in the study period. The most common

Discussion

The HPV vaccines bring forth the hope of significantly reducing the incidence of cervical cancer [15]. However, uptake of vaccines may be tempered by public mistrust stemming from the occurrence of isolated cases of sudden deaths or regular reporting of cases of serious disease in relation to vaccination. A noteworthy example is the large scale programme in France in the 1990s that aimed at vaccinating a similar age group against hepatitis B virus (HBV) [9]. After a few years, reports of

Acknowledgements

Conflict of interest statement: We declare that there is no conflict of interest.

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