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.

A discrete event simulation model of clinical and operating room efficiency outcomes of sugammadex versus neostigmine for neuromuscular block reversal in Canada.

BACKGROUND: The objective of this analysis is to explore potential impact on operating room (OR) efficiency and incidence of residual neuromuscular blockade (RNMB) with use of sugammadex (Bridion™, Merck & Co., Inc., Kenilworth, NJ USA) versus neostigmine for neuromuscular block reversal in Canada. METHODS: A discrete event simulation (DES) model was developed to compare ORs using either neostigmine or sugammadex for NMB reversal over one month. Selected inputs included OR procedure and turnover times, hospital policies for paid staff overtime and procedural cancellations due to OR time over-run, and reductions in RNMB and associated complications with sugammadex use. Trials show sugammadex's impact on OR time and RNMB varies by whether full neuromuscular recovery (train-of-four ratio ≥0.9) is verified prior to extubation in the OR. Scenarios were therefore evaluated reflecting varied assumptions for neuromuscular reversal practices. RESULTS: With use of moderate neuromuscular block, when full neuromuscular recovery is verified prior to extubation (93 procedures performed with sugammadex, 91 with neostigmine), use of sugammadex versus neostigmine avoided 2.4 procedural cancellations due to OR time over-run and 33.5 h of paid staff overtime, while saving an average of 62 min per OR day. No difference was observed between comparators for these endpoints in the scenario when full neuromuscular recovery was not verified prior to extubation, however, per procedure risk of RNMB at extubation was reduced from 60% to 4% (reflecting 51 cases prevented), with associated reductions in risks of hypoxemia (12 cases avoided) and upper airway obstruction (23 cases avoided). Sugammadex impact in reversing deep neuromuscular block was evaluated in an exploratory analysis. When it was hypothetically assumed that 30 min of OR time were saved per procedure, the number of paid hours of staff over-time dropped from 84.1 to 32.0, with a 93% reduction in the per patient risk of residual blockade. CONCLUSIONS: In clinical practice within Canada, for the majority of patients currently managed with moderate neuromuscular block, the principal impact of substituting sugammadex for neostigmine is likely to be a reduction in the risk of residual blockade and associated complications. For patients maintained at a deep level of block to the end of the procedure, sugammadex is likely to both enhance OR efficiency and reduce residual block complications.

EQ-5D™-derived utility values for different levels of migraine severity from a UK sample of migraineurs.

BACKGROUND: To estimate utility values for different levels of migraine pain severity from a United Kingdom (UK) sample of migraineurs. METHODS: One hundred and six migraineurs completed the EQ-5D to evaluate their health status for mild, moderate and severe levels of migraine pain severity for a recent migraine attack, and for current health defined as health status within seven days post-migraine attack. Statistical tests were used to evaluate differences in mean utility scores by migraine severity. RESULTS: Utility scores for each health state were significantly different from 1.0 (no problems on any EQ-5D dimension) (p < 0.0001) and one another (p < 0.0001). The lowest mean utility, - 0.20 (95% confidence interval [CI]: -0.27 - -0.13), was for severe migraine pain. The smallest difference in mean utility was between mild and moderate migraine pain (0.13) and the largest difference in mean utility was between current health (without migraine) and severe migraine pain (1.07). CONCLUSIONS: Results indicate that all levels of migraine pain are associated with significantly reduced utility values. As severity worsened, utility decreased and severe migraine pain was considered a health state worse than death. Results can be used in cost-utility models examining the relative economic value of therapeutic strategies for migraine in the UK.

Costs associated with outpatient, emergency room and inpatient care for migraine in the USA.

BACKGROUND: Data on the average US costs of an outpatient visit, emergency room (ER) visit or hospitalization for migraine are scant, with the most recent available values based on healthcare charges reported from 1994 data. METHODS: We estimated healthcare costs associated with outpatient and ER visits and inpatient hospitalizations related to migraine retrospectively obtained from the 2007 Medstat MarketScan Commercial Claims & Encounters database. Tabulated costs reflected payments from insurers, patients and other sources. All costs were adjusted to 2010 US dollars. RESULTS: The estimated mean cost (95% CI) for migraine-related care per outpatient visit (N = 680,946) was $139.88 ($139.35-140.41); per ER visit (N = 88,128) was $775.09 ($768.10-782.09); and per inpatient hospitalization (N = 5516) was $7317.07 ($7134.96-7499.17). The most frequently coded procedures at outpatient and ER visits were subcutaneous or intra-muscular injection, and for hospitalizations was computed tomography. Estimated annual US healthcare costs in 2010 for migraine associated with: outpatient visits were $3.2 billion, ER visits were $700 million, and inpatient hospitalizations were $375 million. CONCLUSIONS: Direct healthcare costs associated with patient visits and hospitalizations for migraine headaches have increased since previously published estimates. Further research is needed to understand the current overall healthcare cost burden per patient and within the US population.

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.

EuroQol (EQ-5D) health utility scores for patients with migraine.

PURPOSE: Previous studies have reported health utilities for migraine patients as generally measured between migraine attacks, but health utility data for within a migraine attack are unavailable. We evaluated within-attack health utilities among acute migraine patients experiencing different grades of headache severity. METHODS: We examined data for 330 20-65-year-old adults, in good physical health, who had 1-6 moderate/severe migraine attacks per month in the 2 months prior to the screening visit. Data were collected from a multicenter, double-blind study of a treatment for acute migraine in the United States. The EQ-5D system was used to measure generic health status at baseline and 24 h post-treatment within an acute migraine attack, and patients were also asked to rate their pain level at these time points (no, mild, moderate, or severe pain). The D1 time-trade-off scoring algorithm for the U.S. population was applied. Confidence intervals were estimated by bootstrap methods. RESULTS: The study population was 88% women and 78% white ethnicity, with 60% of subjects over age 40. The disutility of mild migraine pain was estimated to be 0.140 (95% CI: 0.0848, 0.1940), with a disutility for moderate migraine pain of 0.186 (95% CI: 0.1645, 0.2053) and for severe migraine pain of 0.493 (95% CI: 0.4100, 0.5654). CONCLUSIONS: Within-attack disutilities estimated for migraine in this study are much greater than those reported for migraine when evaluated as a chronic health condition (e.g., valuations collected at random time points). These data can be of value in adapting results from clinical trials of migraine interventions to cost-utility policy analyses.

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.

Incremental 1-year medical resource utilization and costs for patients with herpes zoster from a set of US health plans.

BACKGROUND: Nearly 1 million new episodes of herpes zoster (HZ) occur annually in the US, yet little is known about the medical resource utilization (RU) and costs associated with HZ and its complications. OBJECTIVES: To describe the medical RU and cost burden of HZ in the first 90 days and the first year after diagnosis from the health insurer perspective and to stratify this burden for patients diagnosed with post-herpetic neuralgia (PHN) and those who are immunocompromised. In addition, this study explores costs from the societal perspective as a result of work loss in the first year after diagnosis. METHODS: The medical RU and cost data were obtained from the MarketScan Research Database for the years 1998-2003. This database contains inpatient, outpatient and prescription drug data for approximately 14 million individuals of all ages, covered under a variety of fee-for-service and capitated provider reimbursement arrangements, including those with Medicare and private insurance. The work loss estimates were based on the MarketScan Health and Productivity Management Database. Claims for services incurred between 1 January 1998 and 31 December 2003 were screened to identify a cohort of HZ patients based on the presence of at least one International Classification of Diseases, 9th Revision (ICD-9) diagnosis code 053.xx. Each patient was assigned an index date based on the earliest observed occurrence of an HZ diagnosis. A cohort of PHN patients was identified as a subset of the HZ cohort with ICD-9 codes 053.12, 053.13, 053.19 or 729.2x in the period of 90 days to 12 months after the index date. Multivariable regression was used to compare HZ cases with matched controls after adjusting for demographic characteristics, insurance status, co-morbidities and medical expenditure in the 6 months prior to diagnosis for each of the endpoints. Separate regression models were developed, in which age and immune status were stratified. All costs were adjusted to March 2008 values using the medical care component of the Consumer Price Index. The average per patient cost of all HZ cases was $US605 in the first 90 days after diagnosis and $US1052 at 1 year. For the subset with PHN, the average per patient cost of HZ at 1 year was $US3815. For the subset with an immunocompromising condition, the average HZ cost at 1 year was $US1745. The majority of the costs were the result of outpatient visits and prescription drugs. The subset of HZ cases that had both absence hour and short-term disability (STD) records available had 26.5 absence hours and 2.9 STD days. Healthcare utilization, medical care costs and work loss all increased with age for all HZ cases. Based on the results from the present study, the direct medical cost burden of HZ in the US is high, exceeding $US1000 per HZ patient. This direct medical cost may be nearly twice as high in immunocompromised patients and four times as high in the subset of HZ cases with PHN. The direct medical cost burden of HZ may exceed $US1 billion annually in the US. The majority of medical RU and cost burden is incurred by the elderly. Although many people with HZ may no longer be in the workforce, HZ does contribute to lost work time.

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.

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.

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.

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.