Infection with human papillomavirus (HPV) is documented to be associated with several precancerous lesions (CIN, VIN and VaIN), cancer and genital warts. In this economic evaluation, we evaluated the cost-effectiveness of administering a catch-up vaccine to females aged 26 years or younger in addition to the current practice of vaccinating 12 year-old- girls compared to maintaining the current practice.
Currently, two vaccines are available in the Norwegian market with documented effect against HPV-infection: the quadrivalent vaccine, directed at HPV 6, 11, 16 and 18, and the bivalent vaccine, directed at HPV 16 and 18. In this report, we estimated the cost-effectiveness of the quadrivalent vaccine for the target population. The cost-effectiveness of the bivalent vaccine is nevertheless discussed in one of the scenario analyses we conducted.
The main results of the evaluation are the following:
- § From a public health budget perspective and given the current public price of NOK 1 010.9/dose of the quadrivalent vaccine, introducing a catch-up vaccine for the target population is cost-effective if one is willing to pay NOK 578 391 for a gained quality-adjusted life-year (QALY).
- § For a willingness-to-pay of NOK 578 391/QALY and from a public health budget perspective, the bivalent vaccine may be considered cost-effective if its price is no higher than approximately NOK 780/dose.
- § From a societal perspective, i.e. when costs to patients for time used under treatment and the work-related productivity costs due to disease are included, the catch-up vaccine is cost-effective if one is willing to pay NOK 553 691 per gained QALY.
The Norwegian Institute of Public Health is responsible for managing the publicly funded vaccination program against the human papillomavirus (HPV). Currently, this program covers the expenses of vaccinating 12-year-old girls with the quadrivalent vaccine (directed at HPV 6, 11, 16 and 18).
Catch-up vaccination programs for young women have been implemented in 10 out of the 29 EU/EEA countries ( 1 ). Due to this development and the interest shown by the Norwegian scientific community regarding this subject, the FHI commissioned the Norwegian Knowledge Centre for the Health Services (NOKC) an economic evaluation of administering a catch-up vaccine to those females aged 26 years or younger.
To evaluate the cost-effectiveness of administering a catch-up vaccine to females aged 26 years or younger in addition to the current practice of vaccinating 12 year-old- girls compared to maintaining the current practice.
We used an already published economic model consisting of a deterministic, dynamic population-based model that estimated the proportion of people in every future cohort infected with HPV 6, 11, 16 and/or 18.
The model was adapted to the Norwegian setting with respect to incidence rates of HPV-related outcomes, costs and health related quality-of-life (HRQoL). In addition, the model was modified in order to incorporate the findings on efficacy reported in our systematic review. Finally, the model was made probabilistic in order to assess the uncertainty around the results and to be able to perform Value-of-Information analysis.
The focus in our base case analysis was on evaluating the quadrivalent vaccine. We used the same vaccination coverage rates for the first dose reported for the Australian catch-up program, which on average were 54%.
Furthermore, the economic evaluation was performed from two different costs perspectives: a public health budget perspective focusing on costs to the National health system; and a societal perspective in which we also included the monetary value of patients’ spent time on receiving treatment for HPV-related outcomes (travelling and waiting time) as well as the monetary value of changes in time use after receiving treatment.
For each perspective, an Incremental Cost Effectiveness Ratio (ICER) in terms of NOK per quality-adjusted life year (QALY) gained was calculated. To determine whether the catch-up program was cost-effective, the resulting ICER was compared to a range of potential willingness-to-pay (WTP) values between NOK
250 000 - 1 000 000 per gained QALY. ICERs lower than the chosen WTP value typically supports the hypothesis that the catch-up vaccine is cost-effective and therefore yields good value for money, while ICERs above the chosen WTP value suggest the opposite.
We examined the uncertainty in our base case results and conducted value-of-information analysis by estimating the expected value of perfect information (EVPI).
The Norwegian Institute of Public Health is responsible for conducting open tender competitions regarding purchase of vaccine against human papillomavirus (HPV) for the Norwegian childhood immunization program. The current contract period is from 2013 through 2014, with the option of one to two additional years, and was awarded to Sanofi Pasteur MSD for its quadrivalent vaccine.
As the result of this tender process, the price per dose attained by the Norwegian Institute of Public Health may be lower than the public prices. We examined the cost-effectiveness of the quadrivalent vaccine in three different scenario analyses, using alternative prices of NOK 250, 500 and 750 per dose.
Finally, in addition to the price scenario analyses, we conducted a scenario analysis that excluded the effect on genital warts, in order to both estimate the cost-effectiveness of the only bivalent vaccine available in the market as of February 2014 (not protective against genital warts), and to ascertain the price level at which the bivalent vaccine achieved the same ICER as the quadrivalent vaccine.
In our base case analysis we assumed that approximately 54% of all girls and young women in the target population would get on average 2.78 doses of the HPV-vaccine. Furthermore, we assumed that the vaccine would only have effect on the health outcomes in the model as documented in our own systematic review. Finally, the price of the vaccine was set equal to the public price of the quadrivalent vaccine, currently NOK 1010.9/dose.
From a public health budget perspective, the base case results showed that a catch-up program for females aged 26 years or younger would lead to a discounted, incremental cost of NOK 335.7 million and an incremental health gain of 580.4 QALYs. This resulted in an ICER of NOK 578 391/QALY.
The scatter-plot of the ICER showed that both the incremental costs and the health gain were positive for all iterations. The expected value of perfect information (EVPI) curve reached a maximum of approximately NOK 38.6 million at a WTP equivalent to the program’s ICER 578 391/QALY. This means that if the expected costs of additional research are lower than NOK 38.6 million, then it is cost-effective to conduct further research given that the WTP is 578 391/QALY.
From a societal perspective the catch-up program had a lower ICER, NOK 553 691/QALY, mainly due to the large expected productivity costs associated with each case of cervical cancer and (to a lesser extent) conization-related, premature birth and late abortion.
Several scenario analyses were conducted in order to ascertain the impact on the base case results of both the vaccine price and the exclusion of the vaccine effect on genital warts:
- Using prices of NOK 250, 500 and 750/dose resulted in lower incremental costs and therefore lower ICERs of NOK 111 772/QALY, NOK 265 327/QALY and NOK 417 659/QALY, respectively.
- Excluding the vaccine effect on genital warts from the analysis resulted in both higher incremental costs and lower incremental health effect than in the base case. The ICER was NOK 704 308/QALY. Assuming these results apply to the bivalent vaccine, and that the price of the quadrivalent vaccine is equal to the public price of NOK 1010.9/dose, we estimated that the price of the bivalent vaccine had to be approximately 780 NOK/dose or lower in order to be as cost-effective as the quadrivalent vaccine.
Administering a catch-up (quadrivalent) vaccine at a price of NOK 1010.9/dose to females aged 26 years or younger may be considered cost-effective (regardless of perspective) for a willingness-to-pay value of NOK 578 391/QALY or higher.
The price of the bivalent vaccine should not be higher than approximately NOK 780/dose for it to achieve the same ICER as the quadrivalent vaccine.