Cost Effectiveness of a Human Papillomavirus Vaccine in reducing the risk of cervical cancer in Ireland using a transmission dynamic model. Cara Usher 1, Lesley Tilson 1, Cathal Walsh 2, Jens Olsen 3, Martin Rudbeck Jepsen 4, Michael Barry National Centre for Pharmacoeconomics, Dublin, Ireland. 2. Dept. of Statistics, Trinity College Dublin, Ireland. 3. University of Southern Denmark, Odense, Denmark. 4. Statens Serum Institut, Copenhagen, Denmark.

Aim To evaluate the cost effectiveness of a combined primary (vaccination) and secondary (screening) approach to managing pre-cancerous and cancerous lesions vs A population-based cervical cancer screening programme alone in Ireland.

Human Papilloma Virus (HPV) More than 100 different types of HPV infection have been characterised: –High risk – most common are HPV 16, 18, 45 and 31. –Low risk- include HPV types 6, 11. Cause ~70% of cervical cancers Cause ~ 90% of anogenital warts

Two vaccines currently developed: 1.Gardasil ® – protects against HPV types 16, 18, 6 and Cervarix ® – protects against HPV types 16 and 18. Efficacy demonstrated for up to 5.5 years after vaccination. Requirement for booster dose at later time not established. Routine cytology screening still required, as vaccines do not protect against all oncogenic types of HPV. Human Papilloma Virus (HPV) Vaccine

Natural history of HPV Normal Cervix Infection Clearance HPV infected Cervix (CIN 1) Progression Regression CIN 2/3 Cancer

Methods Framework Scope of analysis agreed with economic modelling group in Denmark and EAG in Ireland. Comparator Population-based cervical cancer screening programme Perspective Healthcare payer

Model Structure Transmission modelCost Effectiveness Model Simulated infection caused by HPV 16&18 only, using sexual behaviour patterns 1. HPV type-specific prevalence -Artistic trial 2. Calibration: Estimates CIN1-3, CC incidence 1.Layte et al, Kitchener et al, Outputs from transmission model combined with resource use and cost data Incremental effects ( incidence CIN 1-3, CC) Incremental costs (costs of vaccination vs no vaccination)

Model Inputs Epidemiological data Sexual behaviour patterns HPV-type distribution Prevalence of HPV infection Incidence of premalignant and invasive CC Resource use data Vaccination costs Direct medical costs Unit cost data

Model Inputs Time Horizon 70 yrs (9 – 79 years) Outcome Measure Life Years Gained Vaccine Coverage 80% (based on Men C catch-up programme). Discounting 3.5% costs & benefits

ScenarioCoverage 12 yr old females 80% 12 yr olds + catch-up to 15 yrs 80% 12 yr olds + catch-up to 17 yrs 80% 12 yr olds + catch-up to 19 yrs 80% 12 yr olds + catch-up to 26 yrs 80% 30% (GP)

Model Inputs (Summary) Vaccine efficacy95.2% Duration of vaccine protectionLifelong Screening25-44 yrs, 80% screened every 3 yrs yrs, 80% screened every 5 yrs Proportion of CIN 1-3 caused by HPV 16 & 18 74% CC 50% CIN 2/3, 35% CIN 1 Cost of vaccine€100 Administration costs€30 (<19 yrs) €58 (>19 yrs) Direct Medical Costs CIN 1 CIN 2/3 Invasive cancer €617 €1,632 €18,160 Discount Rate3.5% (costs & benefits)

ParameterOne-Way SAProbabilistic SA Vaccine Efficacy88% - 99%Beta (35, 2) Duration of vaccine protection10 yrs/booster Bernoulli (0, 5) Vaccine Coverage60%Beta (20, 5) Screening62%Beta (20, 5) Proportion of CIN 1-3 and CC caused by HPV 16 / 18 60% CC 40% CIN 2/3 21% CIN 1 Beta (60, 20) CC CIN 2/3 in proportion CIN 1 Cost of vaccine (per dose)€80 - €120 N (100, 10) Administration costs (per dose)€15 - €45N(30, 7) truncated to be +ive Direct Medical Costs  20%  N (0, 0.1) Discount rate0 and 6%Triangular (0, 3.5, 6%)

Results (1) – Simulation Model

Results (2) – Cases Averted Health state Estimated total number of cases in 2004 Average annual number of cases averted due to HPV vaccination CIN 17,2592,245 CIN2/33,5151,435 Cervical cancer Deaths from cervical cancer 9352

Results (3) – Cost Effectiveness of the base-case vaccination programme (HPV vaccination & screening vs screening alone) Incremental costs (discounted) Incremental life years gained (discounted) ICER € 6,984, years€ 17,383 / LYG

Results (3) – Cost Effectiveness of catch-up vaccination programmes ICER €17,383/LYG ICER €18,893/LYG ICER €20,646/LYG ICER €22,038/LYG ICER €24,534/LYG 12 yr olds + Catch-Up to 15 yrs: ICER €52,968/LYG.

Results (4) – Sensitivity Analysis: Probabilistic 2.5 centile 97.5 centile

Results (5) – Sensitivity Analysis: One-Way €17,383/LYG

Summary Cost-effectiveness of base-case vaccination programme ICER €17,383/LYG Cost-effectiveness of catch-up vaccination programmes ICER €52,968/LYG (12-15 yr olds)

Strengths / Limitations Study framework, i.e. a collaborative approach to assessing cost-effectiveness of an intervention in a short timeframe. Uncertainty with data. cross-protection requirement for booster vaccine efficacy against types 6 & 11

Conclusions Epidemiological impact of vaccination Cost effective to vaccinate 12 yr old females Cost effective to vaccinate 12 – 15 yr old females

Minister for Health Approves Introduction Of Cervical Cancer Vaccination Programme 5 th August 2008 “It is clear the main priority now is to move to the introduction of the vaccination programme for 12 year old girls to commence in September 2009”.

Acknowledgements