We conducted a CBA to evaluate the impact of the HPV vaccines (in this case, bivalent and quadrivalent) for 9-14-year- girls compared to no vaccination in 2020 in Iran (societal perspective). CBA is the extensive economic evaluation method that measures all the costs and benefits in monetary units. We applied two approaches, willingness to pay (WTP) by discrete choice experiment (DCE) technique and cost-of-illness (COI) averted to estimate the economic benefits of vaccines. The economic costs only included the price of the vaccines (Fig. 1). The study had three main steps: 1- estimating the benefits of vaccination, 2- estimating the cost of vaccination and 3- cost-benefit analysis.
Estimating the benefits of vaccination
We used two definitions of economic benefits. First, the COI approach evaluates costs of cervical cancer prevented through vaccination; and second, the economic benefits based on the WTP approach by DCE technique.
Cost of illness (COI)
We used the COI method to estimate the economic burden of cervical cancer prevention by averting direct and indirect costs through vaccination. We considered only cervical cancer because we could not acquire robust data about genital warts incidence, whereas the incidence of other forms of HPV-associated cancers was low in Iran. Through adopting a societal lenses, we used a prevalence-based and bottom-up approach. We divided the costs into direct (medical and nonmedical) and indirect costs.
the diagnostic and treatment process extracted from the National Comprehensive Cancer Network (NCCN) guideline[21] in order to estimate the direct costs of cervical cancer based on the early (stages I and II) and advanced (III and IV) stages. The direct medical costs included the cost of visits, diagnostic procedures, surgery, chemotherapy, radiotherapy, brachytherapy, chemo radiation therapy, chemotherapy medications, and one-year follow-up costs included the cost of visits, Pap smear, and Magnetic resonance imaging (MRI). We calculated these costs by reviewing medical records for all patients who were treated (n=117) at Imam Khomeini Hospital in 2020. With 1000-beds, the Imam Khomeini Hospital is affiliated with the Tehran University of Medical Sciences (TUMS) and is the largest referral hospital in Iran. Since the tariff for public medical service is universal across Iran and this hospital admits patients form across the country, our results can be generalized nationwide. Since the costs of chemotherapy medications were not recorded in patients’ records, we calculated these costs according to the type of chemotherapy regimen. In this regard, we identified the performed chemotherapy regimen through interviews with specialists and from patient‘s medical records (cisplatin + paclitaxel, cisplatin and carboplatin + paclitaxel + cisplatin). The frequency of each regimen was determined based on the information obtained from medical records. Then, the average cost of each regimen was calculated according to the medications’ price and the prescription dose. We only calculated the transportation cost by using the clinical practice guidelines, literature review and expert's opinions to estimate the direct non-medical costs. To calculate the indirect costs, we used the human capital method and also calculated the costs of productivity loss because of disability and premature death [22]. A 3% discount rate was considered to convert the stream of lifetime earnings into a present value[23].
The HPV vaccine effectiveness[24] and prevalence of HPV types in Iran [25]were identified through literature review. We calculated the HPV vaccine effectiveness in Iran (vaccine effectiveness * prevalence of HPV types in Iran). We were obtained the lifetime risk of cervical cancer in Iran from IARC. Then, according to the average cost of cervical cancer estimated expected cost per person, We considered a 3% discount rate[26] to convert the expected cost into a present value and Finally, we estimated the average
benefit per person (the present expected costs cervical cancer * vaccine effectiveness in Iran)[7].
Willingness to pay (WTP)
Our main study elicited WTP to HPV vaccines per person in Iran[9]. This study used DCE to elicit mothers’ preferences and WTP for vaccinating in their 9–14-year-old daughters against HPV. Commonly used in health economics, DCE is a method to elicit individuals’ preferences and WTP by observing their selections within hypothetical choice scenarios. The study participants were 327 mothers who had at least one 9–14-year-old daughter and were referred to five hospitals affiliated with TUMS in the megacity of Tehran, whom were interviewed face-to-face in 2019. In our study, participants when express their preferences, considered time, so there was no need to use a discount rate.
Estimating the Cost of vaccination
According to the structured vaccination system in Iran and annual vaccination costs calculated in the health system, the cost of new vaccines can be overlooked. Therefore, we did not include HPV vaccination cost and only included the vaccine cost. We obtained the cost per dose HPV vaccines from the Ministry of Health and Medical Education (MoHME).
Cost-benefit analysis (CBA) and sensitivity analysis
We performed CBA for total costs and vaccination benefits compared with no vaccination. CBA was performed with two economic criteria: Net benefit and cost-benefit ratio (CBR) for the HPV vaccination program[27] (table1).
Table 1
Cost - benefit analysis criteria; B: Benefit vaccine, C: Cost vaccine.
Criteria
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Formula
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Cost benefit ratio (CBR)
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B/C>1
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Net benefit
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B-C>0
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We conducted one-way sensitivity analysis for both vaccines to investigate possible parameter uncertainty changes influencing the CBA results: (1) Double and a half incidence cervical cancer rates to 2040 according to the IARC reports[9]; (2) changing price of HPV vaccines (±20% of their base-case values) [28] [29].