Vaccine 27 (2009) 2954–2958 Contents lists available at ScienceDirect Vaccine journal homepage: www.elsevier.com/locate/vaccine Human papillomavirus immunisation of adolescent girls and anticipated reporting of immune-mediated adverse events Torbjörn Callréus a , Henrik Svanström b , Nete Munk Nielsen b , Sigrid Poulsen c , Palle Valentiner-Branth d , Anders Hviid b,∗ a Division of Vaccine, Statens Serum Institut, Denmark b Department of Epidemiology Research, Statens Serum Institut, Denmark c National Board of Health, Denmark d Epidemiology Department, Statens Serum Institut, Denmark article info Article history: Received 20 January 2009 Received in revised form 27 February 2009 Accepted 28 February 2009 Available online 13 March 2009 Keywords: Human papillomavirus Vaccines Adverse events 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 papil- lomavirus 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. © 2009 Elsevier Ltd. All rights reserved. 1. 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 embrac- ing 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 aid- ing 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 pop- ulation 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 reac- tions, 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) vac- cines [6], one of which will be administered within the Danish ∗ Corresponding author at: Statens Serum Institut, Artillerivej 5, 2300 Copen- hagen, Denmark. Tel.: +45 3268 3967; fax: +45 3268 3165. E-mail address: aii@ssi.dk (A. Hviid). 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 con- cerns 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 immunisa- tion 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 hos- pital contacts related to immune-mediated events in adolescent girls before the start in 2009 of the HPV immunisation program in Denmark. 2. Materials and methods The Danish Civil Registration System (CRS) contains compre- hensive demographic information on all citizens living in Denmark indexed by a unique personal identification number – the CRS num- ber [12]. The CRS number is used in all national registries and allows linkage of individual-level information. Based on the CRS we con- structed a cohort of all children born in Denmark in the 1980–1992 0264-410X/$ – see front matter © 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.vaccine.2009.02.106