Purpose:
A universal, publicly funded, school-based human papillomavirus (HPV) vaccination program in girls was initiated in Ontario in 2007, prompting an economic assessment of prevention programs.Method
: A cost-utility analysis of cervical cancer prevention from the healthcare payer perspective was performed based on linked HPV transmission and disease history models. The heterosexual network model of HPV transmission predicted age-specific incidence of infection over time by HPV type. The disease history model predicted HPV infection-related health outcomes (cervical cancer, mortality). Data on sexual behavior, disease history, quality of life, screening test performance, and vaccine effectiveness were obtained from the literature. Information on vaccination coverage and screening uptake was obtained from surveys and administrative data. Direct medical costs attributable to HPV infection, cervical intraepithelial neoplasia and invasive cervical cancer were estimated using Ontario population-based linked health administrative datasets. Interventions:Combinations of 2 vaccination scenarios (conservative and optimistic, based on coverage, vaccine effectiveness and duration of protection), and 900 screening scenarios (screening start age: 21-70 years, screening interval: 3-20 years; 1-year time steps). Current schedule: screening start age 21 years, screening interval 3 years. Primary outcomes:expected lifetime cost, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios and net benefit (NB) at λ=1xGDP/capita (~C$40,000/QALY). Analyses: (1) first vaccinated cohort (low herd-immunity), and (2) steady state, i.e. all cohorts were vaccinated (high herd-immunity).Result:
The NB of vaccination only was similar (conservative assumptions) or higher (optimistic assumptions) than screening only. Adding vaccination to the current screening schedule was highly cost-effective (<C$10,000/QALY). Delaying screening start and/or extending screening intervals reduced both expected QALYs and cost. Incidence of infection and disease is lower in steady state analysis and under optimistic vaccination scenarios, impacting optimal screening schedules. For first cohorts and steady state/conservative vaccination scenarios delaying screening start to 25 years increases NB; for the steady state/optimistic vaccination scenario delaying screening start to 30 years increases NB while maintaining 3 year screening intervals. However, given vaccination, differences in NB across screening scenarios are small and several screening scenarios increase NB.Conclusion:
Delaying screening start age and/or extending screening intervals in vaccinated cohorts is likely to be cost-effective. Consideration should be given to short-term implications of long-term health policy decisions, particularly for infectious disease interventions that require long time intervals to reach steady state.
Purpose: Vaccine cross-protection and the tendency to offer free-of-charge vaccination to older women demand a new evaluation of the cost-effectiveness of cervical screening and HPV vaccination in Italy.
Method: In Italy the non-mandatory vaccination is available free of charge to preadolescent girls. Each region has its own vaccination program in addition to the national one. We used our previously developed Markov model to describe the natural history of HPV infections and carcinogenesis of cervical cancer. The model was calibrated to fit to empirical age-specific HPV prevalence and incidence of cervical cancer observed in Italy. We simulated 10 million individual life histories using a Monte Carlo micro simulation. If the simulated woman undergoes a preventive strategies her life history can change. These changes represent the effects of the intervention. Strategies are defined by varying the type of first screening test, use of triage, the frequency of the screening program, screening age. Each scenario was evaluated without vaccination, with vaccination at age 11 years or 25 years. Vaccine assumptions: 100% coverage, 75.6% effective against HPV 16/18 infection, and 11% effective against high-risk HPV non 16/18. We compared alternatives strategies using incremental cost-effectiveness ratio (ICER). Discount rate was 3%.
Result: Vaccination at age 25 years was always dominated by strategies without vaccination.
| Preventive strategy | Vaccine | Screening frequency (yrs) | Screening age | ICER (EURO) |
| No screening, non vaccine | No | - | - | - |
| HPV DNA test+Pap test triage | No | 7 | 30 to 65 (to 50 for negative women) | 3269 |
| HPV DNA test+Pap test triage | No | 7 | 30 to 65 | 6581 |
| HPV DNA test+Pap test triage | Yes | 9 | 25 to 65 | 12656 |
| HPV DNA test+Pap test triage | Yes | 7 | 30 to 65 | 13617 |
| HPV DNA test+Pap test triage | Yes | 5 | 30 to 65 (to 50 for negative women) | 31982 |
| HPV DNA test+Pap test triage | Yes | 3 | 30 to 65 (to 50 for negative women) | 151732 |
Conclusion: Under the assumption that vaccination is ineffective in previous infected women, HPV vaccination in women aged 25 years is highly questionable and cost-ineffective. The prolongation of screening interval as well as narrowing the screening age range for women vaccinated at 11 years of age may be acceptable.
Purpose: To estimate the change in net health benefits of medication to prevent osteoporotic fracture if patients perceive a small disutility from having to take medication.
Methods: Fifty percent of those treated to prevent osteoporotic fracture stop the medication prematurely within one year. A significant subset of patients dislike taking medication even if they have no side effects due to a sense of being dependent on them, altered personal identity, and/or fear of harm from taking them. A substantial number of osteoporosis patients need to be treated to prevent one fracture. We hypothesized that even a small decrement in quality of life from taking medication would significantly alter the cost-effectiveness of fracture prevention therapy. We used a previously validated Markov microsimulation model using the patient perspective to assess the lifetime net health benefits and costs per QALY gained for five years of bisphosphonate therapy compared to no therapy for two 65 year old Caucasian women with a femoral neck T-score of -2.5; one with no history of fracture, and another with a history of a prior fracture. For the base case analyses, we assumed willingness to pay per QALY gained of $50,000, discount rates of 3%, yearly out of pocket drug cost of $60, that patients out of pocket costs for fracture care would be 10% of total costs, and previously published rates, costs, and disutility estimates for hip, clinical vertebral, morphometric vertebral, wrist, and other fractures. We ran several models varying the assumed disutility from taking medication from zero to 0.04 QALY. We repeated these model runs assuming a) discount rates of 15%, and b) disutility estimates for fractures one half that of the base case.
Results: With no disutility from taking medication, treatment was dominant over no treatment. Net health benefits are diminished with increasing disutility from taking medication (figure), and become zero with disutilities ranging from 0.008 QALY (no prior fracture, discount rates 15%) to 0.036 (prior fracture, discount rates 3%). 
Conclusion: Perceived disutility from taking medication even in the absence of actual medication adverse events could substantially alter the cost-effectiveness of fracture prevention medication. More research is needed to characterize the implicit utility function patients employ when deciding whether or not to take fracture prevention medication.
Purpose: New evidence from two recently-published studies was applied to reevaluate the cost-effectiveness of the 21-gene Recurrence Score (RS) assay (Oncotype DX) in the context of multifactorial decision making to guide the use of chemotherapy for node-negative, estrogen receptor–positive breast cancer in the United States from the societal and healthcare system perspectives.
Methods: In order to cross-classify hypothetical patients by clinicopathologic characteristics according to the Adjuvant! decision aid and 21-gene RS risk groups, we developed a probabilistic decision-analytic model to generate estimates of long-term costs, survival, and quality-adjusted survival for the RS-guided and non–RS-guided strategies. In addition to costs for the 21-gene assay, we assigned attributable costs for chemotherapy, hormonal therapy, monitoring for disease recurrence, and distant recurrence. For the societal perspective, we also considered incremental patient time costs. Costs and survival were discounted at 3% annually.
Results: With the RS-guided strategy, 40.4% of patients were expected to receive chemotherapy relative to 47.3% in the non–RS-guided strategy. Estimated rates of recurrence at 10 years were 6.8% with the RS-guided strategy and 8.9% with the non-RS guided strategy. Targeted use of chemotherapy in the RS-guided strategy was expected to increase survival by 0.19 years (95% CI, 0.09 to 0.32) and 0.16 QALYs (95% CI, 0.08 to 0.28). Lifetime direct medical costs were expected to be $2692 (95% CI, 1546 to 3821) higher with the RS-guided strategy. The incremental cost-effectiveness ratios (ICERs) were $14,059 per life-year saved (95% CI, $6840-$28,912) and $16,677 per QALY (95% CI, $7613-$37,219). When incorporating lower patient time costs of $950 per patient, the ICERs were $9095 per life-year saved (95% CI, dominant-$23,397) and $10,788 per QALY (95% CI, $6840-$30,265). In probabilistic sensitivity analysis, more than 99% of the ICERs were less than $50,000 per life-year saved and per QALY. Numerous sensitivity analyses were conducted to evaluate the impact of varying assumptions regarding the use of chemotherapy in lower-risk and higher-risk women and varying model parameters pertaining to costs, health utilities, and disease recurrence. Across sensitivity analyses, ICERs remained below $22,000 per QALY.
Conclusions: Our updated cost-effectiveness estimates are supportive of the economic value of the 21-gene RS assay in the setting of node-negative, estrogen receptor–positive breast cancer.
Purpose: We assessed the potential cost-effectiveness of UGT1A1 genetic testing to inform choice of the initial protease inhibitor-containing regimen in antiretroviral therapy (ART)-naïve HIV-infected individuals. Homozygosity for UGT1A1*28/*28 (Gilbert's variant) has been reported to predict abnormal liver tests and mild jaundice (hyperbilirubinemia) associated with the protease inhibitor drug atazanavir and premature atazanavir discontinuation.
Methods: The Cost-Effectiveness of Preventing AIDS Complications (CEPAC) computer simulation model projected quality-adjusted life years (QALYs) and lifetime costs (2009 US dollars) for atazanavir-based ART with or without UGT1A1 testing, using the protease inhibitor darunavir rather than atazanavir when indicated. We assumed UGT1A1-associated atazanavir discontinuation rates as reported in the Swiss HIV Cohort study, a *28/*28 frequency of 14.9%, equal efficacy and cost of atazanavir and darunavir, and genetic assay cost of $107. Sensitivity analyses varied these inputs, hyperbilirubinemia impact on quality of life, and loss to follow-up (LTFU). Costs and QALYs were discounted at 3% annually.
Results: Initiating atazanavir-based ART among patients eligible for ART (<500 CD4 cells/mm3) without UGT1A1 testing had an average discounted life expectancy of 16.02 QALYs and $530,700 discounted lifetime cost. Testing for UGT1A1 increased QALYs by 0.49 per 10,000 patients tested, and was not cost-effective (>$100,000/QALY) in the base case. Testing for UGT1A1 was cost-effective (<$100,000/QALY) if assay cost was reduced to $10 (Figure) or if avoiding toxicity by UGT1A1 testing reduced LTFU by 5%. If atazanavir and darunavir differed in cost or efficacy, testing for UGT1A1 was not cost-effective under any scenario. 
Conclusions: Testing for UGT1A1 may be cost effective if assay cost is low and if testing improves retention in care, but only if the comparator regimens have the same drug cost and efficacy.
Purpose: Advanced hip osteoarthritis (OA) is a common chronic condition causing severe joint pain and loss of joint function. Since 2004,the Alberta Hip Improvement Project (HIP) has been prospectively collecting data on the effectiveness and safety of metal-on-metal hip resurfacing arthroplasty (HRA) and conventional total hip arthroplasty (THA) in younger hip OA patients. The most common hip resurfacing method used in Alberta is Birmingham hip resurfacing, and thus in this study we evaluate the cost-effectiveness of the Birmingham HRA compared to THA.
Methods: A probabilistic Markov decision analytic model was constructed to compare the quality-adjusted-life years (QALYs) and costs of HRA vs THA over a 15-year time horizon from a healthcare perspective. The base case cohort was 50-year old advanced hip OA patients. Data inputs were derived from HIP and the literature. Sensitivity analyses evaluated cohort ages for hip replacement, utilities, failure probabilities, and treatment costs.
Results: In the base case, HRA was less costly and associated with better outcomes, thus HRA dominated THA. THA remained dominated when either only males were assessed or the cohort age decreased to 40y from the base case value of 50y. When either only females were assessed or the cohort age increased to 60y, THA dominated HRA. Threshold analyses determined the percent change of selected variables needed for THA appear on the efficiency frontier rather than being dominated by HRA. Primary HRA surgery costs needed to increase 2.5% from the base case value of $14,746 to $15,115. HRA revision surgery cost or HRA revision probability needed to increase 44% from the base case values of $21,916 and 1.22% (1st y revision probability shown as example—revision probability changes per year) to $31,449 or 6.09%, respectively.
Conclusions: In a cohort of 50-year old patients THA is dominated by HRA. The results of this study, the first to use costs from an observational trial and the first Canadian study, confirm results reported in other studies that HRA is more cost-effective for males and younger patients.