A Review and Analysis of Economic Models of Prevention Benefits. A Review and Analysis of Economic Models of Prevention Benefits : Table 6


: Table 6

Abstracted informationChesson et al. 2011 The cost-effectiveness of male HPV vaccination in the United StatesChesson et al. 2008 Cost-effectiveness of human papillomavirus vaccination in the United StatesElbasha et al.  2007 Model for assessing human papillomavirus vaccination strategiesGoldie et al. 2004 Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 virusSanders & Taira 2003 Cost effectiveness of a potential vaccine for Human papillomavirusKulasingam & Myers 2003 Potential Health and Economic Impact of Adding a Human Papillomavirus Vaccine to Screening ProgramsJit et al. 2011 Comparing bivalent and quadrivalent human papillomavirus vaccines: economic evaluation bases on transmission modelCoupe et al. 2009 HPV 16/18 Vaccination to prevent cervical cancer in The Netherlands: Model-based cost effectivenessBergeron et al. 2008 Cost-effectiveness analysis of the introduction of a quadrivalent human papillomavirus vaccine in FranceGoldie et al. 2007 Cost-effectiveness of HPV 16, 18 vaccination in Brazil
PerspectiveSocietalSocietalSocietalN/SPayerN/SProviderN/SProvider & PayerSocietal
Target populationAmericansAmericansAmericansAmericansAmericansAmericansBritishDutchFrenchBrazilians
Study population (epidemiological)12 year old males or 12-26 year old females12 year old girls12 year old girls13 year old girls12 year old girls12 year old girls12 year old girls12 year old girls14 year old girls9 year old girls
Study population (economic)92 cohorts between ages 8 and 99 (inclusive), year one of program; 99 cohorts of incoming 8 year olds in years 2-100 of vaccine programCohort of girls starting at age 12Cohort of 12 year old girlsCohort of 100,000 adolescent girls starting at age 13Cohort of girls starting at age 12Cohort of girls starting at age 12Males and females from ages 12-75Cohort of 10,000,000 girls starting at age 12Cohort of girls starting at age 141,000,000 girls
Intervention(s)Quadrivalent HPV vaccine (protects against HPV types 6, 11, 16 and 18).   Strategies: (1) Vaccinating females aged 12-26 years (2) Vaccination of 12 year-old males and females (3) Vaccination of 12 year-old males and femalesHPV vaccination of 12 year old girlsAlternate strategies of administering prophylactic quadrivalent (types 6/11/16/18) HPV vaccine (3 doses) with current organized cervical cancer screening and HPV disease treatment practices: (1) routine vaccination of girls& boys at age 12; (2) routine vaccination of girls by age 12; (3) routine vaccination of boys and girls by age 12 years and catch-up vaccination for females age 12-24; (4) routine vaccination of boys and girls by age 12 and catch-up female and male vaccination for those aged 12-24Different cancer prevention policies: (1) HPV 16/18 vaccine (initiated at age 12); (2) cytologic screening (initiated at  18, 21, 25, 30, or 35 years); (3) combined vaccination and screening strategiesHPV Vaccine against high-risk HPV types (16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) - 3 injections in a school-based immunization program) with repeated booster shorts every 10 yearsThree strategies were compared: (1) Vaccination only (2) Conventional cytological screening only (3) Vaccination followed by screening   Two of the strategies incorporated a vaccine targeted against a defined proportion of high-risk (oncogenic) HPV types. Screening intervals of 1,2,3 and 5 years and starting at 18,22,24,26 and 30 years were chosen for the latter two strategiesVaccination program either to use quadrivalent or bivalent vaccine and screening (smear, if abnormal, followed by colposcopy); 12 year old girls in a school-based program and a catch up campaign up to age 18 staggered over 2 years3 HPV 16/18 vaccination doses to 85% of all 12 year old girls and cervical cancer screening once every 5 years between age 30 and 60.Quadrivalent HPV 6, 11, 16, 18 vaccination in conjunction with cervical screening program. Vaccination given at age 14 with screening strategy covering 20-69, at 55% screening coverage rate and a 3-year interval between two pap smearsScreening strategies targeting women at age 35 and 5-year intervals thereafter utilizing HPV DNA testing or cytology once, twice or three times a lifetime, may or may not be in combination with vaccination, and treatment for precancerous lesions or cancer depending on size and type
Comparator(s)(1) No HPV vaccination (2) Female-only vaccination for 12-26 year-old females (3) Increased vaccine coverage of 12 year-old femalesCurrent cervical cancer screening practices in the United StatesCurrent practice (vaccinating girls before the age of 12 years)No interventionCurrent standard of care (pap smear every 2 years starting at age 16)See aboveSee aboveScreening alone (colposcopy/biopsy if smear test result is moderate or worse, or if borderline followed by a second abnormal smear)Screening alone (pap smear, colposcopy {with or without biopsy} or HPV DNA test)See above
Data sourcesVaccine trial data: FUTURE II Study Group, Villa et al. (2005), Garland et al. (2007), Munoz et al. (2009), Palefsky et al. (2008), Guiliano et al. (2008)Elbasha et al. 2007, CDC National Program of Cancer Registries, NCI Surveillance Epidemiology and End Results (SEER)US Census Bureau, Hughes et al. 2002, Oriel et al. 1971, Frega et al. 1999, Burchell et al. 2006, Myers et al. 2000, Winer et al. 2005, Castle et al. 2004CDC's Behavioral Risk Factor Surveillance System, NCI's Surveillance, Epidemiology, and End Results Program, US Bureau of Labor Statistics, Kim et al. 2002, Stratton et al. 2000, Krahn et al. 1998, Helms et al. 1999, CMS National Physician Fee, Shireman et al. 2001, National Center for Health StatisticsRichardson et al. 2002, Ho et al. 1998, Alexandrova et al. 1999, Liaw et al. 1999, HUI, CDC Surveillance, Epidemiology, and End ResultsKoutsky et al. 2002, Leigh et al. 1994, Cuzik et al. 1995, Ratnam et al. 2000, MEDSTAT, NAMCS, MedicareBritish Medical Association and the Royal Pharmaceutical Society of Great Britain, Department of Health, Jit et al. (2008), Gold et al. 1998), Myers et al. (No date) ,American National Health Interview Survey (NHIS), Institute of Medicine (IOM) expert panel valuation of HUI-2 instrument & EQ-5D questionnaire, Hospital Episodes Statistics (HES) database, Wolstenholme et al. 1998, De Rijke et al. 2002, Hu et al. (2008), Desai et al. (forthcoming), Hughes et al. (forthcoming), Curtis et al. (2009), Martin-Hirsch et al. (2007), Karnon et al. (2004), Brown et al. (2006), Klee et al. (2000), Korfage et al. (2009), Rogers et al. (2006), Woodhall et al. (ahead of eprint), Bishai et al. (2000), Howell-Jones et al. (2010), Chapman et al. (2011)  POBASCAM study, national registry, large screening trial: Bulkman et al. (2007), Coupe et al. (2008).; clinical cohorts: Nobbenhuis et a; (2001), Bulk et al. (2006), Nobbenhuis et al. (2001), Zielinski et al. (2001); costs: Berkof et al. (2006), van Ballgooijen et al. (2006)Securite Sociale reimbursement, French Official Journal, Elbasha et al. (2008), Myers et al. (2004)Primary data from Brazil, Goldie et al. (2005), WHO CHOICE 2007, Bigal et al. (2003), Department of Commerce, Goldhaber-Fiebert et al. (2006), International Center for Tropical Agriculture, International Labour Office, Miravitlles et al. (2003), Pinotti et al. (2000), World Bank
Valuation of health benefits ($, QALYs, LYS, cases averted)Quality-adjusted life years (QALYs)Quality-adjusted life years, costs avertedQuality-adjusted life years (QALYs)Quality-adjusted life years (QALYs)Quality-adjusted life years (QALYs)Life year gained, [QALYs in sensitivity analysis]Quality-adjusted life years (QALYs)Quality-adjusted life years (QALYs)Life years gained (LYG), quality-adjusted life years (QALYs); time trade-off techniques were used to elicit utilities in a population of 150 healthy female volunteersCancer incidence reduction, life expectancy
CostsVaccination, administrative, vaccine wastage, HPV-related outcomes (CIN, genital warts, juvenile onset RRP; and cervical, vaginal, vulvar, anal, oropharyngeal, and penile cancers)HPV vaccine series, cervical cancer, CIN 1-3, genital wartsHPV vaccine, administrationVaccination, patient time, screening, conventional cytology, liquid-based cytology, HPV DNA test, office visitVaccine materials, personnel, administration, school-based vaccination program, booster shot, treatment (colposcopy, biopsy, cryotherapy, re-examination, pap tests)Conventional cytology, vaccine, booster, colposcopy and biopsy, CIN 1, CIN 2-3, cervical cancer (by stage)Vaccination, screening, treatment of anogenital warts, treatment of recurrent respiratory papillomatosisFirst smear, repeat smear, administration, vaccination (3 doses), booster dose, diagnosis, treatment for CIN0, CIN1, CIN2, CIN3, FIGO Stage 1, FIGO stage 1+, palliative careCervical screening, treatment of precancerous lesions and cervical cancer, vaccination program (no further specification)Screening HPV DNA test, screening cytology, colposcopy, LEEP (loop electrosurgical excision procedure), cold knife conization, simple hysterectomy, vaccination (doses, wastage support social mobilization, outreach), invasive cervical cancer (local, regional, distant), patient time (hourly wage, visits), transportation (screening, visits)
Time horizon100 years77 years100 yearsLifetimeLifetime73 years100 years88 yearsLifetimeLifetime
Discount rate (annual)costs and benefits 3%Costs and benefits 3%Costs and benefits 3%Costs and benefits 3%Costs and benefits 3%Costs and benefits 3%Costs and benefits 3.5%4% for costs, 1.5% for benefits3.5% for costs, 1.5% for benefitscosts and benefits 3%
Model design (static/dynamic)Dynamic (probabilistic sensitivity analysis)Dynamic (Markov)Dynamic (No further specification)Dynamics (Markov)Dynamic (Markov)Static (Markov)Dynamic (No further specification)Dynamic (No further specification)Static (Markov)Dynamic (stochastic)
Sensitivity analysis (parameters)One-way & multi-way: outcomes (e.g. genital warts were included); vaccine cost per person fully vaccinated; vaccine efficacy; health outcomes cost; number of QALYs lost per health outcome; incidence rates of health outcomes in absence of vaccination; percentages of health outcomes attributable to the HPV vaccine typesOne-way: herd immunity, cost of vaccine series, vaccine efficacy, cost per case of all HPV-related outcomes, discount rate, time horizon, incidence of health outcomes, genital warts, cancer rates, percentage of each health outcome attributable to HPV vaccine, QALYs lost for each HPV outcome Multi-way with 2+ of the aforementioned parametersOne-way on vaccine parameters (duration, degree, coverage, cost, target age), quality-of-life weights, discounting, and duration of natural immunity. Multi-way with duration of protection; vaccine coverage; health utility for genital warts; CIN 1, 2, 3; carcinoma in situ; degree of protection against HPV related disease. Also examined herd immunityOne-way: duration of vaccine efficacy, proportion of persistent HPV in older women, underlying frequency of cervical cancer screening, natural history parameters, cervical cancer mortality, costsOne-way on all variables.   Multi-way on selected variables (no further specification)One or multi-way not specified: for all variablesOne-way not specified. Multi-way: Drawing 10,000 samples from combinations of 2700 previously described scenarios for oncogenic HPV types and 900 scenarios for HPV types 6 and 11 representing combinations of assumptions about the natural course and epidemiology of HPV infection; probability distributions representing uncertainty in economic parametersOne-way: waning efficacy, cross-protection, screening compliance, disease parametersOne-way: duration of vaccine protection between 10 years and lifetime; vaccine efficacy from 80% to 100%; annual discount rate (0%, 3%, 5%); proportion of cervical cancer cases linked to HPV types 16 and 18 from 75% to 82%; treatment costs by +/-20%; duration of time spent in each state to elicit utilities. In addition, a scenario of a booster vaccine administered to 50% of female originally vaccinatedOne-way: vaccine efficacy, coverage, screening test performance (e.g. sensitivity), minimizing loss to follow-up, cross-protection existence, inclusion of other HPV-related cancer costs, invasive cervical cancer costs, cost per vaccinated women.   Multi-way: varied coverage for both vaccine and screening
Value of informationN/SN/SN/SN/SN/SN/SN/SN/SN/SN/S
Generalizability/scalability of findings            
Distributional or equity analysisN/SN/SN/SN/SN/SN/SN/SN/SN/SN/S
ResultsIn the 30% coverage scenario, the cost per QALY gained by female vaccination (compared to no vaccination) was $21,300 when including only cervical outcomes and $7200 when including all health outcomes in the analysis. In the 30% coverage scenario, the cost per QALY gained by adding male vaccination was $121,700 when including only cervical outcomes and $41,400 when including all health outcomes even if the increased female vaccination strategy incurred program costs of $350 per additional girl vaccinated.   The cost-effectiveness of male vaccination depended on vaccine coverage of females. When including all HPV-associated outcomes in the analysis, the incremental cost per quality-adjusted life year (QALY) gained by adding male vaccination to a female-only vaccination program was $23,600 in the lower female coverage scenario (20% coverage at age 12 years) and $184,300 in the higher female coverage scenario (75% coverage at age 12 years).Under base-case parameter values, the estimated cost per QALY gained by vaccination in the context of current cervical cancer screening practices in the United States ranged from $3,906 to $14,723 (2005 US dollars), depending on factors such as whether herd immunity effects were assumed; the types of HPV targeted by the vaccine; and whether the benefits of preventing anal, vaginal, vulvar, and oropharyngeal cancers were included.The ICER of augmenting this strategy with a temporary catch-up program for 12- to 24-year-olds was US $4,666 per QALY. Relative to other commonly accepted healthcare programs, vaccinating girls and women appears cost-effective. Including men and boys in the program was the most effective strategy, reducing the incidence of genital warts, cervical intraepithelial neoplasia, and cervical cancer by 97%, 91%, and 91%, respectively. The ICER of this strategy was $45,056 per QALY.The most effective strategy had an ICER of $58,500 per quality adjusted life year, which is combining vaccination at age 12 years with triennial conventional cytologic screening beginning at age 25 years, compared with the next best strategy of vaccination and cytologic screening every 5 years beginning at age 21 years.A vaccine with a 75% probability of immunity against high-risk HPV infection resulted in a life expectancy gain of 2.8 days or 4.0 quality-adjusted life days at a cost of $246 relative to current practice (incremental cost-effectiveness of $22,755/QALY). If all 12-year-old girls currently living in the United States were vaccinated >1,300 deaths from cervical cancer would be averted during their lifetimes. Vaccination of girls against high-risk HPV is relatively cost effective even when vaccine efficacy is low. If the vaccine efficacy rate is 35%, the cost effectiveness increases to $52,398/QALY.Vaccination only or adding vaccination to screening conducted every 3 and 5 years was not cost-effective. However, at more frequent screening intervals, strategies combining vaccination and screening were preferred. Vaccination plus biennial screening delayed until age 24 years had the most attractive cost-effectiveness ratio ($44,889 per life-year gained) compared with screening only beginning at age 18 years and conducted every 3 years. However, the strategy of vaccination with annual screening beginning at age 18 years had the largest overall reduction in cancer incidence and mortality at a cost of $236,250 per life-year gained compared with vaccination and annual screening beginning at age 22 years.The quadrivalent vaccine seems to be cost effective at threshold of £30 000 per QALY gained across all 12 of the scenarios considered. The incremental cost-effectiveness ratio of quadrivalent vaccination (compared with no vaccination) ranges from £12 000 (£11 000–£14 000) to £19000 (£17 000–£22 000) when protection against anal, penile, and oropharyngeal cancers is assumed, and up to £22 000 (£19000–£25 000) when only protection against licensed end points is assumed. The incremental cost effectiveness ratio of bivalent vaccination (compared with no vaccination) ranges from £16000 (£14 000–£18 000) to £25 000 (£21 000–£28 000) with protection against all cancer end points, and up to £41 000 (£34000–£45 000) with protection against licensed end points only. Hence when making pessimistic assumptions about duration of protection and range of end points prevented, bivalent vaccination may not be cost effective at £84.50 per dose.The discounted costs per QALY were € 19,500/QALY (range € 11,000 to € 25,000/QALY) and lied near the cost-effectiveness threshold of €20,000/QALY used in The Netherlands. Cost-effectiveness was stable, but was most sensitive to the discount rate used for costs and benefits.The incremental cost-effectiveness from screening plus vaccination versus screening along was €12,429 per life-year gained (third-party payer perspective {TPP})and €20,455 per life-year gained (direct healthcare cost perspective {DCP}); and €8,408 per QALYs (TPP) and €13,809 per QALY (DCP).The incremental cost-effectiveness ratio of vaccination and screening (a two-visit HPV) is I$700-9,600 per year of life saved (YLS) depending of the cost of vaccination.   Provided the cost per vaccinated woman was equal to, or below I$ 50, screening three times per lifetime alone was dominated by vaccination alone. When the cost per vaccinated woman was I$ 25, vaccination alone was cost saving compared to no intervention, and vaccination plus screening (at ages 35, 40 and 45) ranged from I$ 200 to I$ 700 per YLS, depending on the choice of screening test.   When the cost per vaccinated woman was I$ 50, vaccination alone was I$ 300 per YLS, compared to no intervention. As the cost per vaccinated woman exceeded I$ 75, screening alone (with two-visit HPV DNA testing) was no longer dominated by vaccination alone, and had an incremental cost-effectiveness ratio of I$ 500 per YLS, compared to nonintervention. At all vaccine costs above I$ 75, vaccination plus screening (at ages 35, 40 and 45) dominated vaccination alone, although the incremental cost-effectiveness ratio rose with higher vaccine costs.
LimitationsAssumed 100% lifelong protectionCannot examine how changes in cervical cancer screening strategies will effect cost-effectiveness; does not examine strategies of vaccinating boys and men; adjustments for herd immunity were arbitraryLimited data on natural history of type-specific HPV infection; did not account for cross-immunity between HPV types; did not model coinfection after disease nor existence of CIN lesions; assumed equal access to healthcare; did not consider homosexual transmission; model limited to cervical diseases and genital warts; did not include death and productivity costs (lost wages)Parameter estimates; did not model natural history of multiple HPV infections; did not consider cross-protection; assumed older women infections were reactivated of latent or previously acquired HPV; cannot assess herd immunity since it does not account for viral transmission between men and women; long-term vaccine efficacy is uncertainBenefits of HPV vaccine on reduce other cancers is not included; does not consider vaccination of boysDid not model HPV as an infection due to the lack of data of transmission dynamics of HPVDifferent manufacturers of HPV vaccine; poor data on natural course of HPV related cancers in sites other than the cervix; representation of non-vaccine HPV types as a single composite type; assumed quadrivalent vaccination reduces the incidence of recurrent respiratory papillomatoses at the same rate as warts related to HPV 6/11Limited data on disease parameters and HPV typesWomen may be less likely to be screened if they have been vaccinated - suggest an education campaign for continued screening despite vaccination; choice of discount rate (same discount rate for both costs and benefits penalize preventive interventions relative to treatment interventions)Does not reflect herd immunity and thus its benefits; does not account for additional benefits from preventing other cancers; too many parameters varied simultaneously - difficult to know if search space was reached comprehensively