Cost-effectiveness of pembrolizumab + chemotherapy versus chemotherapy and pembrolizumab monotherapy in first line treatment of NSCLC in the US - updated analyses with additional trial follow-up.

OBJECTIVE: Pembrolizumab + chemotherapy substantially extends life expectancy for metastatic non-small cell lung cancer (NSCLC) patients. Its cost-effectiveness (CE) was previously evaluated based on interim trial analyses (follow-up ∼1 year). The present analysis describes CE incorporating additional follow-up based on protocol-specified final trial analyses (1-1.5 years additional follow-up), from a US healthcare payer perspective. METHODS: A partitioned survival model is used to compare pembrolizumab + chemotherapy vs chemotherapy using data from the KN189 (non-squamous patients) and KN407 (squamous patients) clinical trials. An indirect treatment comparison vs pembrolizumab monotherapy is made for patient subgroups with PD-L1 TPS ≥50% and 1-49% based on data from the KN024 and KN042 trials. Efficacy, treatment utilization, health utility, and safety data are derived from trials and projected over 20 years. Costs for drugs, non-drug disease management, and adverse events are also incorporated. RESULTS: Overall, versus chemotherapy alone, pembrolizumab + chemotherapy is projected to increase life expectancy by 1.12 years (3.35 vs 2.23) and 0.67 years (3.17 vs 2.50) in non-squamous and squamous patients, respectively. Resultant ICERs ($158,030/QALY and $178,387/QALY) are below a US 3-times GDP per capita threshold ($195,000/QALY). ICERs vs chemotherapy also generally fall below the threshold within PD-L1 sub-groups (except in squamous PD-L1 < 1%, which may have differed due to small sample size) while ICERs vs pembrolizumab monotherapy in PD-L1 ≥ 50% and 1-49% sub-groups generally exceed it (except in squamous PD-L1 1-49%); largely a result of the higher drug acquisition cost of pembrolizumab + chemotherapy relative to differences in life expectancy. CONCLUSIONS: Taken together, with longer-term trial follow-up and in the context of prior literature, in the US, one of the two options for pembrolizumab use (either pembrolizumab + chemotherapy or pembrolizumab monotherapy), represents a cost-effective treatment in virtually all non-squamous and squamous metastatic NSCLC patient populations and PD-L1 sub-groups evaluated.

Cost Effectiveness of PD-L1-Based Test-and-Treat Strategy with Pembrolizumab as the First-Line Treatment for Metastatic NSCLC in Hong Kong.

BACKGROUND: Pembrolizumab, a monoclonal antibody against programmed death ligand 1 (PD-L1), is approved by several regulatory agencies for first-line treatment of metastatic non-small-cell lung cancer (NSCLC) with a PD-L1 tumor proportion score (TPS) ≥ 50% and no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase genomic tumor aberrations. This study was conducted from the perspective of the Hospital Authority in Hong Kong and aimed to evaluate the cost effectiveness of a biomarker (PD-L1) test-and-treat strategy (BTS), in which patients with a TPS ≥ 50% received pembrolizumab and other patients received platinum doublet chemotherapy versus all patients receiving platinum doublet chemotherapy. METHODS: The model used a partitioned survival approach to estimate the incremental cost-effectiveness ratio (ICER) expressed as the cost per quality-adjusted life-year (QALY) gained. The clinical efficacy, utility and safety data were derived from the KN024 trial. Costs and health outcomes were projected over a 10-year time horizon and discounted at 3% per year. Costs for drug acquisition, PD-L1 testing, drug administration and disease management were used. Sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: The BTS approach led to an increase of 0.29 QALYs at an additional cost of Hong Kong dollars (HK$) 249,077 (US$31,933) compared with platinum doublet chemotherapy, resulting in an ICER of HK$865,189 (US$110,922) per QALY gained. This is lower than the World Health Organization cost-effectiveness threshold of three times the 2016 gross domestic product (GDP) per capita for Hong Kong of HK$1017,819 (US$130,490). Probabilistic sensitivity analyses showed a 59.4% chance that the ICER would be below this threshold. CONCLUSION: First-line treatment with pembrolizumab in a BTS to identify patients with NSCLC with PD-L1 TPS ≥ 50% can be considered cost effective in Hong Kong compared with platinum doublet chemotherapy based on a three-times GDP per capita threshold. However, local data on clinical efficacy and safety were not available to estimate overall survival (OS) and progression-free survival (PFS) specific to patients with NSCLC in Hong Kong. Further, uncertainty is inherent in the survival projections/extrapolation of PFS and OS beyond the trial period, and future research may help to further inform these parameters.

Cost-effectiveness of pembrolizumab versus chemotherapy as first-line treatment in PD-L1-positive advanced non-small-cell lung cancer in the USA.

Aim: This analysis aimed to evaluate the cost-effectiveness of pembrolizumab monotherapy as first-line treatment in advanced non-small-cell lung cancer patients with a programmed death ligand 1 (PD-L1) tumor proportion score ≥1% from a US payer perspective. Materials & methods: A partitioned survival model was developed using efficacy and safety data from the KEYNOTE-042 trial and projected over 20 years. Costs accounted for treatment, toxicity and disease management. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios were reported. Results: Pembrolizumab resulted in an expected gain of 0.60 life years and 0.49 QALYs compared with platinum-based chemotherapy. The incremental cost-effectiveness ratio was US$130,155/QALY. Conclusion: Pembrolizumab is projected to be cost-effective compared with platinum-based chemotherapy as first-line treatment for advanced non-small-cell lung cancer with PD-L1 tumor proportion score ≥1%.

Cost-effectiveness of pembrolizumab in combination with chemotherapy versus chemotherapy and pembrolizumab monotherapy in the first-line treatment of squamous non-small-cell lung cancer in the US.

Objective: To describe the cost-effectiveness of pembrolizumab plus chemotherapy (carboplatin and paclitaxel or nab-paclitaxel; P + C) in metastatic, squamous, non-small-cell lung cancer (NSCLC) patients in the US. Methods: A model comparing P + C versus C alone is developed utilizing partitioned survival analysis. Primary clinical efficacy, treatment utilization, health utility and safety data are derived from the KEYNOTE-407 trial and projected over 20 years. Costs for drugs and non-drug disease management are also incorporated. Additionally, the cost-effectiveness of P + C vs. pembrolizumab monotherapy (P) is evaluated via an indirect treatment comparison, for patient subgroups with PD-L1 Tumor Proportion Score (TPS) ≥ 50% and 1-49%. Results: Overall, P + C is projected to increase life expectancy by 1.95 years vs. C (3.86 versus 1.91). The resultant ICER is $86,293/QALY. In patients with PD-L1 ≥ 50%, 1-49% and <1 the corresponding incremental cost-effectiveness ratios (ICERs) are $99,777/QALY, $85,986/QALY and $87,507/QALY, respectively. Versus P, in the PD-L1 ≥ 50% subgroup, P + C appears cost saving; however, this result should be interpreted with caution as there is considerable uncertainty in the relative efficacy of these comparators. Conclusions: Across all eligible patients, the addition of pembrolizumab to chemotherapy is projected to approximately double life expectancy, yielding an extension to a point not previously seen in metastatic squamous NSCLC. Overall, and within all relevant PD-L1 subgroups, use of P + C yields an ICER below $100,000/QALY, and can be a cost-effective first-line treatment for eligible metastatic squamous NSCLC patients for whom chemotherapy is currently administered. In the PD-L1 ≥ 50% subgroup, additional follow-up within trials of pembrolizumab plus chemotherapy and pembrolizumab monotherapy are needed to better define cost-effectiveness between these comparators.

Cost-effectiveness of pembrolizumab in combination with chemotherapy in the 1st line treatment of non-squamous NSCLC in the US.

AIMS: To describe cost-effectiveness of pembrolizumab plus platinum and pemetrexed chemotherapy in metastatic, non-squamous, NSCLC patients in the US. MATERIALS AND METHODS: A model is developed utilizing partitioned survival analysis to estimate the cost-effectiveness of KEYNOTE-189 trial comparators pembrolizumab + chemotherapy (carboplatin/cisplatin + pemetrexed) vs chemotherapy alone. Clinical efficacy, treatment utilization, health utility, and safety data are derived from the trial and projected over 20 years. For extrapolating survival beyond the trial, a novel SEER population-data approach is applied (primary analysis), with separate estimation via traditional parametric extrapolation methods. Costs for drugs and non-drug disease management are also incorporated. Based on an indirect treatment comparison, cost-effectiveness of pembrolizumab + chemotherapy vs pembrolizumab monotherapy is evaluated for patients with programmed death-ligand 1 (PD-L1) ≥ 50%. RESULTS: In the full non-squamous population, pembrolizumab + chemotherapy is projected to increase life expectancy by 2.04 years vs chemotherapy (3.96 vs 1.92), for an approximate doubling of life years. Resultant incremental cost-effectiveness ratios (ICERs) are $104,823/QALY and $87,242/life year. In patients with PD-L1 ≥ 50% and 1-49%, life expectancy is more than doubled (4.53 vs 1.88 years) and (4.87 vs 2.01 years), with a 32% (2.60 vs 1.97 years) increase in PD-L1 < 1% patients. Corresponding incremental costs/quality-adjusted life year (QALY) are $103,402, $66,837, and $183,529 for PD-L1 ≥ 50%, 1-49%, and <1% groups, respectively. Versus pembrolizumab monotherapy in PD-L1 ≥ 50% patients, representing current standard of care, pembrolizumab + chemotherapy increases life expectancy by 65% (4.53 vs 2.74 years) at an ICER of $147,365/QALY. LIMITATIONS AND CONCLUSIONS: The addition of pembrolizumab to chemotherapy is projected to extend life expectancy to a point not previously seen in previously untreated metastatic non-squamous NSCLC. Although ICERs vary by sub-group and comparator, results suggest pembrolizumab + chemotherapy yields ICERs near, or in most cases, well below a 3-times US per capita GDP threshold of $180,000/QALY, and may be a cost-effective first-line treatment for metastatic non-squamous NSCLC patients.

Cost-effectiveness Analysis of Golimumab in the Treatment of Non-Radiographic Axial Spondyloarthritis in Scotland.

INTRODUCTION: The aim of this study is to assess the cost-effectiveness of golimumab for the treatment of non-radiographic axial spondyloarthritis (nr-axSpA) vs. conventional therapy and other tumor necrosis factor inhibitors from the Scottish payer perspective. METHODS: A model comprising a short-term decision tree and a long-term Markov model was developed to compare cost-effectiveness (incremental costs per quality-adjusted life-year [QALY]) for patients in Scotland with nr-axSpA treated by conventional therapy, adalimumab, certolizumab pegol, etanercept, or golimumab for a lifetime period. A network meta-analysis (NMA) was conducted to identify clinical and safety data for treatments and synthesize the available evidence into relative treatment effects between comparators. The probability of patients achieving an Assessment of SpondyloArthritis International Society 20/40% response criteria (ASAS20/ASAS40) or a 50% improvement in Bath Ankylosing Spondylitis Disease Activity Index score (BASDAI50) at week 12 was obtained from the NMA for each of the comparators. Baseline health state utilities were based on the EQ-5D questionnaire collected in the golimumab GO-AHEAD study. The cost of treatment was calculated based on drug acquisition, drug administration, and initiation/monitoring costs. RESULTS: Golimumab resulted in an increase of 2.06 QALYs and additional cost of £39,770 compared with conventional therapy. Incremental cost per QALY gained was £19,280 for golimumab, which was lower than adalimumab (£19,737), etanercept (£20,089), and higher than certolizumab pegol (£18,710). Golimumab remained cost-effective throughout a range of sensitivity analyses where key assumptions were tested. CONCLUSIONS: From a Scottish perspective, golimumab was a cost-effective treatment for nr-axSpA compared with conventional therapy at a willingness-to-pay threshold of £30,000 per QALY. FUNDING: Merck & Co., Inc.

Incident cervical HPV infections in young women: transition probabilities for CIN and infection clearance.

BACKGROUND: We describe transition probabilities for incident human papillomavirus (HPV) 16/18/31/33/35/45/52/58/59 infections and cervical intraepithelial neoplasia (CIN) 1 lesions. METHODS: Women ages 16 to 23 years underwent cytology and cervical swab PCR testing for HPV at approximately 6-month intervals for up to 4 years in the placebo arm of an HPV vaccine trial. The cumulative proportion of incident HPV infections with diagnosed CIN, clearing (infection undetectable), or persisting without CIN, were estimated. RESULTS: Most incident infections cleared, without detection of CIN, ranging at 36 months from 66.9% for HPV31 to 91.1% for HPV59. There was little variation in the 36-month proportion of incident HPV16, 18, and 31 infections followed by a CIN1 lesion positive for the relevant HPV type (range 16.7%-18.6%), with lower risks for HPV59 (6.4%) and HPV33 (2.9%). Thirty-six-month transition probabilities for CIN2 ranged across types from 2.2% to 9.1%; however, the number of events was generally too small for statistically significant differences to be seen across types for this endpoint, or CIN3. CONCLUSIONS: Some incident HPV types appear more likely to result in diagnosed CIN1 than others. The relative predominance of HPV16, vis-à-vis some other high-risk HPV types (e.g., HPV33) in prevalent CIN2/3, appears more directly associated with relatively greater frequency of incident HPV16 infections within the population, than a higher risk of infection progression to CIN2/3. IMPACT: Nearly all incident HPV infections either manifest as detectable CIN or become undetectable within 36 months. Some HPV types (e.g., 16 and 33) appear to have similar risk of CIN2/3 despite widely varied incidence.

Incidence, duration, and reappearance of type-specific cervical human papillomavirus infections in young women.

BACKGROUND: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection. METHODS: Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at approximately 6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type-specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods. RESULTS: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within approximately 3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance. CONCLUSIONS: Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection. IMPACT: The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance.

Incidence and costs of cervical intraepithelial neoplasia in a US commercially insured population.

OBJECTIVE: This study aimed to estimate incidence, cost per episode of care, and US population burden of cervical intraepithelial neoplasia (CIN). MATERIALS AND METHODS: For women continuously enrolled in a US health plan from January 1, 1999 to December 31, 2004, medical claims were used to identify potential CIN diagnosis. Presence and grade of CIN (CIN 1, CIN 2,3, or no CIN) were verified in medical records for a randomly selected subset (n = 254). Incidence, costs, and population burden were calculated. RESULTS: Annual incidence for CIN 1 and CIN 2,3 was 1.6 and 1.2 per 1,000 women, respectively. Incidence was highest among women aged 21 to 30 years (3.3 and 3.6 per 1,000) and women aged 31 to 40 years (2.9 and 2.7 per 1,000). Costs per episode of care were higher for CIN 2,3 ($1,634 vs $1,084). Estimated annual burden per 1,000 US women was $1,059 for CIN 1 and $1,803 for CIN 2,3. CONCLUSIONS: We estimate that 412,000 women in the United States are diagnosed with CIN annually, with an associated cost of approximately $570 million.

Assessing incidence and economic burden of genital warts with data from a US commercially insured population.

OBJECTIVE: This study examined the incidence of and healthcare costs attributable to genital warts within a large US commercially insured, geographically dispersed population. RESEARCH DESIGN AND METHODS: Using a retrospective cohort study design, this longitudinal analysis assessed administrative claims of integrated medical and pharmacy encounters from five Blue Cross Blue Shield health plans. Genital warts cases were identified using a methodology previously described by Insinga et al. MAIN OUTCOME MEASURES: Age- and gender-specific incidence of genital warts per 1000 person-years in 2004, and duration-of-episode attributable direct medical costs (2004 US dollars) and healthcare resource utilization of cases diagnosed in 2002. Overall outcome measures were age- and gender-adjusted to the 2004 US civilian population. RESULTS: Genital warts incidence in 2004 was 1.2/1000 females and 1.1/1000 males. Incidence was highest among females aged 20-24 (4.6/1000) and males aged 25-29 (2.7/1000). Projected overall incidence was over 340,000 cases in 2004. Mean duration-of-episode per incident case in 2002 was 95.4 days (males 116.3 days; females 69.7 days). Mean ambulatory visits per episode were 1.5 for females and 1.9 for males, with <1 drug prescription/episode. Mean costs were $647/episode ($745 males; $528 females). The 2004 estimated economic burden was $760 per 1000 individuals in the general population with the total exceeding $220 million. LIMITATIONS: Only those genital warts cases that sought evaluation or for which the treating provider was covered by the health plan were captured in the study. CONCLUSIONS: Genital warts represent a significant health and cost burden in the US. Adoption of novel healthcare technologies such as vaccines along with traditional interventions such as physician education of signs and symptoms, condom use and abstinence or limiting number of sexual partners may significantly help reduce the burden of genital warts.

Epidemiologic natural history and clinical management of Human Papillomavirus (HPV) Disease: a critical and systematic review of the literature in the development of an HPV dynamic transmission model.

BACKGROUND: Natural history models of human papillomavirus (HPV) infection and disease have been used in a number of policy evaluations of technologies to prevent and screen for HPV disease (e.g., cervical cancer, anogenital warts), sometimes with wide variation in values for epidemiologic and clinical inputs. The objectives of this study are to: (1) Provide an updated critical and systematic review of the evidence base to support epidemiologic and clinical modeling of key HPV disease-related parameters in the context of an HPV multi-type disease transmission model which we have applied within a U.S. population context; (2) Identify areas where additional studies are particularly needed. METHODS: Consistent with our and other prior HPV natural history models, the literature review was confined to cervical disease and genital warts. Between October 2005 and January 2006, data were gathered from the published English language medical literature through a search of the PubMed database and references were examined from prior HPV natural history models and review papers. Study design and data quality from individual studies were compared and analyses meeting pre-defined criteria were selected. RESULTS: Published data meeting review eligibility criteria were most plentiful for natural history parameters relating to the progression and regression of cervical intraepithelial neoplasia (CIN) without HPV typing, and data concerning the natural history of HPV disease due to specific HPV types were often lacking. Epidemiologic evidence to support age-dependency in the risk of progression and regression of HPV disease was found to be weak, and an alternative hypothesis concerning the time-dependence of transition rates is explored. No data were found on the duration of immunity following HPV infection. In the area of clinical management, data were observed to be lacking on the proportion of clinically manifest anogenital warts that are treated and the proportion of cervical cancer cases that become symptomatic by stage. CONCLUSION: Knowledge of the natural history of HPV disease has been considerably enhanced over the past two decades, through the publication of an increasing number of relevant studies. However, considerable opportunity remains for advancing our understanding of HPV natural history and the quality of associated models, particularly with respect to examining HPV age- and type-specific outcomes, and acquired immunity following infection.

Age-based programs for vaccination against HPV.

BACKGROUND: The risk of infection with human papillomavirus (HPV) increases with age. Answering the question of which age groups are appropriate to target for catch-up vaccination with the newly licensed quadrivalent HPV vaccine (types 6/11/16/18) will be important for developing vaccine policy recommendations. OBJECTIVES: To assess the value of varying female HPV vaccination strategies by specific age groups of a catch-up program in the United States. METHODS: The authors used previously published mathematical population dynamic model and cost-utility analysis to evaluate the public health impact and cost-effectiveness of alternative quadrivalent HPV (6/11/16/18) vaccination strategies. The model simulates heterosexual transmission of HPV infection and occurrence of cervical intraepithelial neoplasia (CIN), cervical cancer, and external genital warts in an age-structured population stratified by sex and sexual activity groups. The cost-utility analysis estimates the cost of vaccination, screening, diagnosis, and treatment of HPV diseases, and quality-adjusted survival. RESULTS: Compared with the current screening practices, vaccinating girls and women ages 12 to 24 years was the most effective strategy, reducing the number of HPV6/11/16/18-related genital warts, CIN grades 2 and 3, and cervical cancer cases among women in the next 25 years by 3,049,285, 1,399,935, and 30,021; respectively. The incremental cost-effectiveness ratio of this strategy when compared with vaccinating girls and women ages 12 to 19 years was $10,986 per quality-adjusted life-year gained. CONCLUSION;: Relative to other commonly accepted health-care programs, vaccinating girls and women ages 12 to 24 years appears cost-effective.

Human papillomavirus infections and vulvar disease development.

BACKGROUND: We describe the prevalence of 14 common types [human papillomavirus (HPV)-6/11/16/18/31/33/35/39/45/51/52/56/58/59] in vulvar intraepithelial neoplasia grades 1 to 3 (VIN 1-3) and HPV genotype-specific infection in relation to the development of VIN 1-3. METHODS: Data were analyzed from women enrolled in the placebo arms of three randomized double-blind trials. Anogenital examinations, including collection of labial/vulvar/perineal/perianal swabs, occurred at day 1 and every 6 to 12 months through 48 months. Lesions that were possibly, probably, or definitely HPV related or of unknown etiology were biopsied. Biopsies and swabs were HPV typed. Biopsies were read for endpoint determination (VIN 1-3) by up to four pathologists. RESULTS: Incident infection with HPV-16 was the most common (6.0/100 person-years). The mean time from incident infection to the development of VIN 1-3 was 18.5 months (95% confidence interval, 13.4-23.6). HPV-6 or -11 was observed in 64.5% of VIN 1 and 29.0% of VIN 2/3, whereas HPV-16 was observed in 6.5% of VIN 1 and 64.5% of VIN 2/3. CONCLUSION: A vaccine that includes both low- and high-risk types could prevent more than half of VIN 1-3 lesions, including the precursor lesions to HPV-related vulvar carcinoma. Understanding the incidence and duration of vulvar HPV infection and risk for progression to VIN 1-3 may inform therapeutic decisions for vulvar disease and mathematical models that assess the cost-effectiveness of vaccination.

The cost-effectiveness of a quadrivalent human papillomavirus vaccine in Taiwan.

BACKGROUND: A quadrivalent human papillomavirus (HPV 6/11/16/18) vaccine has recently received regulatory approval in Taiwan for the prevention of cervical carcinoma, high-grade cervical dysplasia (cervical intraepithelial neoplasia 2/3 [CIN 2/3]), low-grade cervical dysplasia (CIN 1), high-grade vulvar and vaginal dysplasia, and external genital warts. OBJECTIVE: To examine the potential long-term epidemiologic and economic consequences of a quadrivalent HPV (6/11/16/18) vaccination program in Taiwan. METHODS: A transmission dynamic model was used to estimate the long-term epidemiologic and economic consequences of quadrivalent HPV vaccination. Two vaccination strategies were evaluated in conjunction with current cervical cancer screening: 1) vaccination of 12-year-old girls and 2) vaccination of 12-year-old girls with a temporary 5-year catch-up vaccination of females aged 12-24 years (catch-up). RESULTS: From an epidemiologic perspective, both vaccination strategies reduce the overall incidence of HPV 16/18-related cervical cancer relative to no vaccination by 91% during year 100 following vaccine introduction. Likewise, both vaccination strategies reduce the incidence of CIN 2/3, CIN 1, and genital warts by approximately 90%, 86%, and 94%, respectively, at this time point. However, the catch-up program consistently achieves greater benefit earlier than the 12-year-old program. The catch-up strategy is both more effective and efficient than the strategy that vaccinates 12-year-old girls only, with an incremental cost-effectiveness ratio of New Taiwan dollars (NT$) 410,477 per quality-adjusted life-year gained. CONCLUSIONS: The results from this model suggest that in Taiwan, prophylactic HPV 6/11/16/18 vaccination of females can: 1) substantially reduce genital warts, CIN, and cervical cancer; 2) improve quality of life and survival; and 3) be cost-effective when implemented as a vaccination strategy that includes a temporary catch-up program.

A multi-type HPV transmission model.

A prophylactic quadrivalent (types 6/11/16/18) vaccine against oncogenic and warts-causing genital Human papillomavirus (HPV) types was approved by the US Food and Drug Administration in 2006. This paper presents a nonlinear, deterministic, age-structured, mathematical model of the transmission dynamics of HPV and disease occurrence in a US population stratified by gender and sexual activity group. The model can assess both the epidemiologic consequences and cost effectiveness of alternative vaccination strategies in a setting of organized cervical cancer screening in the United States. Inputs for the model were obtained from public data sources, published literature, and analyses of clinical trial data. The results suggest that a prophylactic quadrivalent HPV vaccine can: (i) substantially reduce the incidence of disease, (ii) increase survival among females, (iii) improve quality of life for both males and females, (iv) be cost-effective when administered to females age 12-24 years, and (v) be cost-effective when implemented as a strategy that combines vaccination of both females and males before age 12 vaccination with a 12 to 24 years of age catch-up vaccination program.

Structural differences among cost-effectiveness models of human papillomavirus vaccines.

In this article we compare previously published cost-effectiveness studies of human papillomavirus (HPV) vaccines along a defined subset of key model structural assumptions relating to HPV infection and disease, cervical cancer screening and HPV vaccination. For each structural aspect examined, we summarize assumptions from each study, provide a critical review and discuss the impact upon results. Considerable variation was observed across HPV vaccine cost-effectiveness models in a number of influential assumptions. Holding constant factors for which current data are lacking, the combined impact of assumptions made for the remaining parameters examined would appear to tend toward underestimation of the cost-effectiveness of HPV vaccination within existing studies. However, uncertainty concerning parameters, such as the duration of vaccine protection and acquired immunity following HPV infection, and the relationship between age and HPV virulence, complicates precise estimation of the cost-effectiveness of HPV vaccination and rigorous evaluation of the validity of existing modeling results.

Healthcare resource use and costs associated with cervical, vaginal and vulvar cancers in a large U.S. health plan.

OBJECTIVES: To estimate healthcare resource utilization and costs of cervical, vulvar and vaginal cancers in a large U.S. health plan. METHODS: We estimated incremental ambulatory visits, hospitalizations, prescription fills and healthcare costs for cancer cases relative to population controls. Data for cervical (n=2788), vulvar (n=621) and vaginal cancer (n=254) cases and an identical number of controls were obtained from a large U.S. health plan. Cases were identified via diagnostic codes on a healthcare claim and matched to controls. Incremental resource use was assessed using a two-stage regression method developed by Carides, with costs analyzed using Lin's regression method. RESULTS: Through 4 years of follow-up, cervical cancer patients had incremental resource use of 12.0 ambulatory visits, 0.6 hospital admissions and 7.0 prescription fills per case. Cumulative 4-year incremental healthcare costs per case ranged from $8236 for vulvar cancers to $18,799 for cervical cancers. When adjusted to cervical, vulvar and vaginal cancer excess mortality rates observed within the U.S. Surveillance Epidemiology and End Results program, estimated incremental costs were $29,649 for cervical, $11,356 for vulvar and $21,963 for vaginal cancers. There was a significant upward trend in costs with increasing age for cervical cancer, however trends were less consistent for vulvar and vaginal cancers. CONCLUSIONS: Direct medical costs associated with cervical, vulvar and vaginal cancers were observed to be substantial. These data can help inform evaluations of the economic burden and cost-effectiveness of prevention of these cancers, particularly for vulvar and vaginal disease, where such data have not been previously reported.

A systematic review of the prevalence and attribution of human papillomavirus types among cervical, vaginal, and vulvar precancers and cancers in the United States.

OBJECTIVES: To describe prevalence and estimated attribution of human papillomavirus (HPV) types in U.S. cervical, vaginal, and vulvar precancers and cancers. METHODS: U.S. studies reporting HPV typing for cervical intraepithelial neoplasia (CIN), vulvar intraepithelial neoplasia (VIN), and vaginal intraepithelial neoplasia (VaIN) and/or invasive cancers of those sites were gathered from the PubMed database (http://www.ncbi.nlm.nih.gov/sites/entrez/). Selected studies had PCR testing data for > or =10 cases for a disease endpoint. Analytic methods augmented prior reviews of cervical disease with an updated and expanded analysis (including vulvar and vaginal disease), new selection criteria for specimens, and adjustment for histologic type, where possible, among pooled cancer cases. In addition, for analyses of estimated attribution of HPV types, we incorporated accounting methods for lesions infected with multiple HPV types. RESULTS: Data from 22 U.S. studies meeting review eligibility criteria were tabulated. Following adjustment for the presence of multiple HPV types in a single specimen, the top two HPV types contributing to disease were CIN 1 (HPV 16/66; 15.3%), CIN 2/3 (HPV 16/31; 61.9%), cervical cancer (HPV 16/18; 79.2%), VIN 1 (HPV 6/11; 41.7%), VIN 3 (HPV 16/18; 84.0%), vulvar cancer (HPV 16/33; 55.5%), VaIN 3 (HPV 16/18; 65.1%), and vaginal cancer (HPV 16/18; 72.7%). CONCLUSIONS: The HPV type distribution and proportion of cases testing positive for any HPV type were observed to vary among U.S. cervical, vulvar, and vaginal neoplasias and by grade of disease. Adjustment for the presence of multitype HPV infections can have an important effect on the estimated attribution of HPV types to disease, particularly for types other than HPV 16.

Five-year routine cervical cancer screening rates and intervals in a US health plan.

OBJECTIVE: Cervical cancer screening with liquid-based cytology or concurrent HPV screening may decrease positive predictive value and specificity of screening results. Following changes to leading guidelines for cervical cancer screening, policy-makers may benefit from more detailed statistics to improve management of routine screening intervals. This paper reports annual cervical cancer screening rates, intervals between routine screenings, population cost burden of routine screening, and concurrent HPV screening rates in the medical claims database of a large US health plan between 2000 and 2004. RESEARCH DESIGN AND METHODS: Annual cervical cancer screening rates were reported for each calendar year between 2000 and 2004, plus intervals between routine screenings in a cohort enrolled for 5 years after a first routine screening. Interval estimates accounted for women not screened in the first year of the study period. Overall screening rates and intervals were adjusted to the US civilian female population, and costs were adjusted to 2004 dollars. This database research was exempt from IRB review. RESULTS: Annual routine screening rates during the 5-year period ranged from 33.7 to 37.2 tests per 100 enrollees. Among females with routine screenings, 68.8% were re-screened within 3 years, and 26.8% were not re-screened within 5 years. Concurrent HPV screening was 1.9 tests per 1000 routine screenings in 2000, and 27.9 per 1000 in 2004. The cost of routine screening per 1000 females was $31,282.00 in 2000 and $38,515.07 in 2004. CONCLUSION: More than a quarter of women with evidence of a routine cervical cancer screening were not re-screened within 5 years, while 43.4% were re-screened within a year. Triennial screening rates reported here are not comparable to traditional 3-year screening rates, and screening intervals were not reported separately by conventional and liquid-based cytology. Reducing rates of women receiving annual routine screening may offset the cost burden of newer screening technologies, but must be managed carefully to avoid decreasing 3-year screening rates. Clinicians should reinforce with their patients the need for routine screening at least triennially.