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.

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.

Reductions in human papillomavirus-disease resource use and costs with quadrivalent human papillomavirus (types 6, 11, 16, and 18) recombinant vaccination: the FUTURE Study Economic Evaluation.

OBJECTIVE: To examine the short-term impact of quadrivalent human papillomavirus (HPV) (types 6/11/16/18) recombinant vaccination upon HPV disease-related health-care resource utilization and costs among young women. METHODS: We analyzed data from a randomized clinical trial comparing quadrivalent vaccination to placebo, among women (N = 7861) primarily 16 to 23 years of age at enrollment. HPV disease episodes, health-care resource utilization and costs associated with cervical, vaginal, and vulvar precancers, and anogenital warts were analyzed over a period of 2.5 years among women, regardless of baseline HPV status. RESULTS: Overall, there was a 25.9% (P < 0.001) reduction in total HPV disease-related health-care costs among women receiving vaccine versus placebo (absolute reduction $3939 per 100 trial enrollees). We observed similar overall reductions in HPV-disease episodes and resource utilization. There was a statistically significant reduction in HPV 6/11-related disease episode costs of 65.1% ($1837 per 100), and a reduction of 51.4% ($1781 per 100) in HPV 16/18-related episode costs. CONCLUSIONS: Quadrivalent HPV vaccination can reduce HPV disease events, resource use and costs when administered to a broad population of young women 16 to 23 years of age. Prevention of HPV types 6 and 11 yielded similar value in terms of HPV disease cost offsets, compared to protection against HPV 16 and 18, during the years initially after vaccination. Over the short-term, costs of vaccination exceed cost offsets associated with prevention of HPV disease; however, quadrivalent HPV vaccination has previously been shown to be cost-effective in the longer term, when fully accounting for health benefits and cost offsets.

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.

Incidence and duration of cervical human papillomavirus 6, 11, 16, and 18 infections in young women: an evaluation from multiple analytic perspectives.

OBJECTIVE: To estimate the incidence and duration of cervical human papillomavirus (HPV)-6, HPV-11, HPV-16, and HPV-18 infections in a population of young American women. METHODS: The study population consisted of U.S. women who at baseline were 16 to 23 years of age, reported zero to five lifetime sexual partners, never having been pregnant, and never having had a prior abnormal Papanicolaou test and were enrolled in the placebo arm of a randomized multicenter clinical trial of a HPV-16 L1 virus-like particle vaccine. Women underwent type-specific endocervical/ectocervical swab HPV DNA testing at approximately 6-month intervals for up to 48 months of follow-up. To contribute person-time in the analyses of type-specific HPV incidence, a woman must have had at least three satisfactory swab specimens available and been negative for the relevant HPV type (HPV-6, HPV-11, HPV-16, or HPV-18) on her first two trial swabs. The duration of incident HPV infections was estimated using Kaplan-Meier survival analysis methods. RESULTS: Person-years of exposure ranged by type-specific analysis from 2,645 to 3,188, with an incidence rate per 100 person-years of 3.6 for HPV-6, 0.4 for HPV-11, 5.4 for HPV-16, and 2.1 for HPV-18. With censoring at the time of treatment for cervical intraepithelial neoplasia, where done, the mean duration of incident infections was 9.3, 8.4, 18.2, and 16.4 months, respectively, for HPV-6 (n = 103), HPV-11 (n = 13), HPV-16 (n = 142), and HPV-18 (n = 62). When the duration of HPV infections was truncated at the time of cervical intraepithelial neoplasia detection (any grade), where applicable, mean duration figures were 8.4, 8.1, 14.0, and 15.1 months for HPV-6, HPV-11, HPV-16, and HPV-18 infections, respectively. CONCLUSIONS: Previous studies of the mean duration of cervical HPV infection have been based on prevalent infections and/or featured relatively short duration of follow-up. This study tested women for HPV infection over a period of up to 48 months and observed a mean duration of incident HPV-16/HPV-18 infections approximately twice that of HPV-6/HPV-11.

Verification of Decision-Analytic Models for Health Economic Evaluations: An Overview.

Decision-analytic models for cost-effectiveness analysis are developed in a variety of software packages where the accuracy of the computer code is seldom verified. Although modeling guidelines recommend using state-of-the-art quality assurance and control methods for software engineering to verify models, the fields of pharmacoeconomics and health technology assessment (HTA) have yet to establish and adopt guidance on how to verify health and economic models. The objective of this paper is to introduce to our field the variety of methods the software engineering field uses to verify that software performs as expected. We identify how many of these methods can be incorporated in the development process of decision-analytic models in order to reduce errors and increase transparency. Given the breadth of methods used in software engineering, we recommend a more in-depth initiative to be undertaken (e.g., by an ISPOR-SMDM Task Force) to define the best practices for model verification in our field and to accelerate adoption. Establishing a general guidance for verifying models will benefit the pharmacoeconomics and HTA communities by increasing accuracy of computer programming, transparency, accessibility, sharing, understandability, and trust of models.

The impact of losartan on the lifetime incidence of end-stage renal disease and costs in patients with type 2 diabetes and nephropathy.

INTRODUCTION: The RENAAL (Reduction of Endpoints in Non-insulin dependent diabetes with the Angiotensin II Antagonist Losartan) study demonstrated that, in hypertensive patients with type 2 diabetes mellitus and nephropathy, treatment with losartan plus conventional antihypertensive therapy (CT) reduced the relative risk of end-stage renal disease (ESRD) by 29% versus placebo over the time span of the study (mean patient follow-up of 3.4 years). The objective of this study was to project the effect of losartan compared with placebo on the lifetime incidence of ESRD and associated costs (from a US healthcare system perspective). METHODS: To estimate lifetime incidence of ESRD, we used a competing risks method to account for the risk of death without ESRD. We estimated the cost (US dollars, year 2002 values) associated with ESRD by combining the cumulative incidence of ESRD with the lifetime cost associated with ESRD. Total cost was estimated as the sum of the cost associated with ESRD, the cost of losartan study therapy and other costs (non-ESRD/non-losartan) expected for patients with type 2 diabetes. Survival was estimated by weighting the life expectancies with and without ESRD by the cumulative risk of ESRD. Costs and outcomes were discounted by 3% per annum. RESULTS: We projected a lower lifetime incidence of ESRD for losartan patients (66%) compared with placebo patients (83%). This reduction in ESRD resulted in a decrease in cost associated with ESRD of US dollars 31,803 per patient and a gain of 0.99 life-years per patient (0.70 discounted). After accounting for the cost of losartan and the additional cost associated with greater survival, we projected that treatment with losartan would result in a lifetime net saving of US dollars 24,632 per patient. CONCLUSION: Treatment with losartan plus CT in patients with type 2 diabetes and nephropathy reduced the within-trial incidence of ESRD and is projected to result in lifetime reductions in ESRD and associated costs, and increased survival, versus placebo.

Comparison of losartan and captopril on heart failure-related outcomes and symptoms from the losartan heart failure survival study (ELITE II).

BACKGROUND: Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors improves outcomes and symptoms in patients with heart failure (HF). We compared effects of losartan to captopril on mortality, morbidity, and functional status for patients in the ELITE II study. METHODS AND RESULTS: A total of 3152 patients, aged 60 years or older, with New York Heart Association (NYHA) classes II to IV HF and ejection fraction < or = 40% were assigned to receive losartan 50 mg once daily or captopril 50 mg 3 times daily. Outcome measures included all-cause and HF-related mortality, hospitalizations, and discontinuations; change in NYHA class; and quality of life (QoL). HF-related outcomes were not significantly different between therapies. Similar improvements from baseline (P < .01) in NYHA class were observed within both treatment groups. Among 1856 QoL participants, 1343 patients survived at least 1 year; the QoL for 1-year survivors improved in both treatment groups (P < .001 vs baseline) and did not differ between groups. CONCLUSIONS: In ELITE II, the effects of losartan on HF-related outcomes, NYHA class, and QoL were not superior to those of captopril. Although angiotensin-converting enzyme inhibitors remain the treatment of choice for patients with HF, the similarity of the findings in the present analysis supports a role for angiotensin-receptor antagonists in this patient population.

Cost effectiveness of losartan in patients with hypertension and LVH: an economic evaluation for Sweden of the LIFE trial.

OBJECTIVE: Evaluate the cost effectiveness of losartan compared with atenolol from a Swedish national health system perspective. DESIGN: The Losartan Intervention For Endpoint reduction in hypertension study (LIFE) was a double-masked, randomized trial of losartan versus atenolol in 9193 patients with essential hypertension and left ventricular hypertrophy (LVH) ascertained by electrocardiography. Losartan reduced the primary composite end point of cardiovascular death, myocardial infarction (MI), or stroke by 13% (P = 0.021) and reduced the risk of stroke by 25% (P = 0.001), despite a comparable degree of blood pressure control. METHODS: Life years gained was estimated by combining the absolute risk reduction in stroke with the life years gained by preventing stroke. Quality-adjusted life years (QALYs) gained was estimated by combining the absolute risk reduction in stroke with the QALYs gained by preventing stroke. QALYs were estimated by weighting life years by health-related quality of life (QoL), as measured with visual analogue scale (VAS) data collected in the trial. Net costs were defined as the total of study medication cost, stroke-related costs, and costs of increased survival. Costs are in 2003 Swedish prices. All costs and effects were discounted at a 3% annual rate. RESULTS: Prevention of a stroke resulted in a gain of 5.7 life years and 4.3 QALYs. As a consequence, losartan treatment resulted in a per patient increase of 0.092 life years [95% confidence interval (CI): 0.038, 0.146] and 0.069 QALYs (95% CI: 0.028, 0.109) as compared with atenolol treatment. Losartan reduced direct stroke-related cost per patient by 1141 euros due to a lower cumulative incidence of stroke for losartan at 5.5 years (4.9%) as compared with atenolol (6.5%) (95% CI of difference: 0.7, 2.5). The reduction in stroke-related cost offset 80% of the added cost of losartan drug therapy. After inclusion of study medication cost, net cost per patient was 289 euros higher for losartan than atenolol. The net cost per QALY gained for losartan was 4188 euros (37,813 SEK), which is well within common Swedish benchmark upper values (200-500,000 SEK) for accepted cost-effective interventions. CONCLUSION: Based on the results from the LIFE trial, treatment with losartan compared with atenolol, in hypertensive patients with LVH, is a cost-effective intervention.

Assessing the annual economic burden of preventing and treating anogenital human papillomavirus-related disease in the US: analytic framework and review of the literature.

The anogenital human papillomavirus (HPV) is estimated to be the most commonly occurring sexually transmitted infection in the US. Comprehensive estimates of the annual economic burden associated with the prevention and treatment of anogenital HPV-related disease in the US population are currently unavailable. The purpose of this paper is to (i) outline an analytic framework from which to estimate the annual economic burden of preventing and treating anogenital HPV-related disease in the US; (ii) review available US literature concerning the annual economic burden of HPV; and (iii) highlight gaps in current knowledge where further study is particularly warranted. Among eight US studies identified that describe the annual economic burden pertaining to one or more aspects of anogenital HPV-related disease, three met the review eligibility criteria (published between 1990 and 2004, examined multiple facets of annual anogenital HPV-related economic burden, and clearly articulated the data and methods used in the estimation process). All costs were adjusted to 2004 US dollars. Estimates of the annual direct medical costs associated with cervical cancer were comparable across studies (range 300-400 million US dollars). In contrast, there was a wide range across studies for estimates of the annual direct medical costs associated with cervical intraepithelial neoplasia (range 700 million US dollars-2.3 billion US dollars). Only one study reported direct medical costs for anogenital warts (200 million US dollars) and routine cervical cancer screening (2.3 billion US dollars). No studies examined direct medical costs attributable to HPV-related anal, penile, vaginal or vulvar cancers, or the work and productivity losses resulting from time spent receiving medical care, morbidity or mortality. Current economic burden estimates would suggest annual direct medical costs associated with the prevention and treatment of anogenital warts and cervical HPV-related disease of at least 4 billion US dollars. This figure would likely rise to at least 5 billion US dollars per year if direct medical costs associated with other disease entities caused by the sexual transmission of HPV were included, with further additions to the economic burden totalling in the billions of dollars if work and productivity losses were incorporated, a research priority for future studies.

Losartan reduces the costs associated with diabetic end-stage renal disease: the RENAAL study economic evaluation.

OBJECTIVE: To evaluate the within-trial effect of losartan and conventional antihypertensive therapy (CT) compared with placebo and CT on the economic cost associated with end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS: The Reduction of End Points in Type 2 Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study was a multinational double-blind randomized placebo-controlled clinical trial designed to evaluate the renal protective effects of losartan on a background of CT (excluding ACE inhibitors and angiotensin II receptor agonists [AIIAs]) in patients with type 2 diabetes and nephropathy. The primary composite end point was doubling of serum creatinine, ESRD, or death. Data on the duration of ESRD were used to estimate the economic benefits of slowing the progression of nephropathy. The cost associated with ESRD was estimated by combining the days each patient experienced ESRD with the cost of ESRD over time. The cost of ESRD for individuals with diabetes was estimated using data from the U.S. Renal Data System. Total cost was estimated as the sum of the cost associated with ESRD and the cost of study therapy. RESULTS-We estimated that losartan and CT compared with placebo and CT reduced the number of days with ESRD by 33.6 per patient over 3.5 years (P = 0.004, 95% CI 10.9-56.3). This reduction in ESRD days resulted in a decrease in cost associated with ESRD of 5144 US dollars per patient (P = 0.003, 95% CI 1701 to 8587 US dollars). After accounting for the cost of losartan, the reduction in ESRD days resulted in a net savings of 3522 US dollars per patient over 3.5 years (P = 0.041, 143 to 6900 US dollars). CONCLUSIONS: Treatment with losartan in patients with type 2 diabetes and nephropathy not only reduced the incidence of ESRD, but also resulted in substantial cost savings.

Modeling the durability of ZOSTAVAX® vaccine efficacy in people ≥60 years of age.

Since 2006, the vaccine, ZOSTAVAX(®), has been licensed to prevent herpes zoster. Only limited clinical follow-up data are available to evaluate duration of protection, an important consideration when developing HZ vaccination policy recommendations. Four Poisson regression models were developed based on an integrated analysis of data from the Shingles Prevention Study and its Short Term Persistence extension to estimate the effects of years-since-vaccination and chronological-age on vaccine efficacy among people ≥60 years old. The models included number of HZ cases parsed into categories by chronological-age and time-since-vaccination as the dependent variable with different explanatory variables in each model. In all models, the interaction between vaccine-group and chronological-age was statistically significant indicating that vaccine efficacy decreases with the expected effects of advancing age but the interaction between vaccine-group and time-since-vaccination was not statistically significant indicating that much of the reduction in vaccine efficacy over time-since-vaccination can be explained by increasing age.

The health and economic burden of genital warts in a set of private health plans in the United States.

We estimated the prevalence of and costs associated with genital warts among privately insured individuals from the perspective of a private health plan in the United States. Health care claims data were derived from a sample of 3,664,686 privately insured individuals. The database was limited to cases of disease for which an insurance claim was generated, with costs reflecting inpatient, outpatient, and pharmacy payments from all sources. We identified 5095 cases of genital warts (1.7 cases per 1000 person-years) billed through the health plans during 2000. The prevalences of and health plan costs associated with genital warts were highest among women aged 20-24 years (6.2 cases and $1692 in costs per 1000 person-years) and men aged 25-29 years (5.0 cases and $1717 in costs per 1000 person-years). On average, individual episodes of care for genital warts involved 3.1 physician visits and incurred costs of $436. These are the first age- and sex-specific estimates of the prevalence and cost of genital warts for a US health plan.

The effect of montelukast versus usual care on health care resource utilization in children aged 2 to 5 years with asthma.

BACKGROUND: Limited clinical data are available on the long-term effects of asthma controller therapy on the utilization of health care resources in pediatric patients with asthma. OBJECTIVE: The objective of this study was to compare the effects of long-term treatment with montelukast and usual care on health care resource use in children with asthma. METHODS: Pediatric patients aged 2 to 5 years with asthma who had completed a 3-month, double-blind, double-dummy clinical trial comparing montelukast 4 mg and placebo were asked to participate in an open-label, controlled extension study comparing montelukast 4 mg and usual care. Usual care was defined as cromolyn or inhaled corticosteroid therapy Health care resource utilization was measured in terms of oral corticosteroid use and numbers of physician visits, emergency department visits, and hospitalizations. RESULTS: Of 618 patients who completed the primary phase of the study, 516 (83.5%) participated in the extension study Data from 506 patients (302 without previous asthma maintenance therapy, 204 with) were included in the analysis. During the extension phase, patients who received montelukast and had not used previous asthma maintenance therapy were followed for a mean of 329.5 days; those who received usual care and CONCLUSION: In this open-label study, pediatric patients aged 2 to 5 years with mild to moderate persistent asthma receiving long-term therapy with montelukast had similar rates of asthma-related health care resource utilization compared with those receiving usual care with cromolyn or inhaled corticosteroids.

Cost effectiveness of ACE inhibitor treatment for patients with type 1 diabetes mellitus.

OBJECTIVE: Current guidelines recommend treating patients with type 1 diabetes mellitus with ACE inhibitors after the onset of microalbuminuria. Recent clinical trials have shown ACE inhibitors can affect the development of nephropathy when initiated prior to the onset of microalbuminuria. Our objective is to examine the cost effectiveness of treating adults aged over 20 years with an ACE inhibitor (captopril) immediately following diagnosis of type 1 diabetes versus treating them after the onset of microalbuminuria. DESIGN: Using a semi-Markov model, we calculated four main outcome measures: lifetime direct medical costs (discounted), QALYs, cumulative incidence of end-stage renal disease (ESRD), and number of days of ESRD over a lifetime. Medical costs are in 1999 US dollars. SETTING: All analyses were from the viewpoint of a single US payer responsible for all direct medical costs, including screening for microalbuminuria, ACE inhibitor treatment (captopril), management of major diabetic complications, and routine annual medical costs not specific to diabetes. METHODS: We applied the model to a hypothetical cohort of 10,000 persons newly diagnosed with type 1 diabetes. Distribution of sex and race/ethnicity within the cohort is representative of the general US population. RESULTS: We estimated that the incremental cost of early use of captopril for the average adult with type 1 diabetes is USD 27,143 per QALY. This level varies considerably with age and glycaemic level. When the age at onset of diabetes is 20 years and glycosylated haemoglobin (HbA(1c)) level is 9%, the cost-effectiveness ratio is USD 13,814 per QALY. When the age at onset is 25 years and HbA(1c) level is 7%, the cost-effectiveness ratio is USD 39,530 per QALY. CONCLUSION: This model, with its underlying assumptions and data, suggests that early treatment with captopril provides modest benefit at reasonable cost effectiveness, from the US single-payer perspective, in the prevention of ESRD compared with delaying treatment until diagnosis of microalbuminuria. Early treatment with other ACE inhibitors will provide similar cost effectiveness if they have equivalent efficacy, compliance and price per dose. Treatment may be considered among patients at age 20 years with new onset of type 1 diabetes. This conclusion is sensitive to the extent that ACE inhibitors delay onset of microalbuminuria. Other factors such as the patient's age and glycaemic level must be considered when deciding to initiate early treatment.

The burden of appendicitis-related hospitalizations in the United States in 1997.

BACKGROUND: Acute appendicitis is among the most frequent causes of surgical abdominal disease worldwide. METHODS: Data from the Nationwide Inpatient Sample of the Healthcare Utilization Project were used to estimate the prevalence and disease burden of appendicitis-related hospitalizations in the United States in 1997. The data are a representative sample of discharge records from community hospitals drawn from 22 states in the United States. RESULTS: In the United States in 1997, there were an estimated 252,682 (95% CI: 242,957-262,407) appendicitis-related hospitalizations. The mean length of stay and total charges for appendicitis-related hospitalizations were four days (95% CI: 3.4-4.6) and $11,645 (95% CI: $11,299-$11,992) per hospitalization, respectively. Appendicitis-related hospitalizations associated with post-operative infection, peritoneal abscess, or peritonitis had longer average lengths of stay and higher average costs when compared to hospitalizations associated with local appendicitis without post-operative infection. Appendicitis cases among very young and older patients were more likely to be associated with peritoneal abscess, peritonitis, or post-operative infection. CONCLUSIONS: In 1997, appendicitis-related hospitalizations accounted for 0.6% of all hospitalizations in the United States, resulting in approximately one million hospital days and $3 billion in hospital charges. Between 1984 and 1997, the rate of appendicitis hospitalizations in the U. S. population declined slightly, whereas the total number of hospital days remained unchanged.

Cost-effectiveness of pneumococcal vaccines for adults in the United States.

INTRODUCTION: In 2012, the Advisory Committee on Immunization Practices (ACIP) revised recommendations for adult pneumococcal vaccination to include a sequential regimen of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) for certain high-risk adults with immunocompromising conditions. This study, from a payer perspective, examined: (1) the cost-effectiveness of the new 2012 ACIP vaccine policy recommendation relative to the 1997 ACIP recommendation; (2) the cost-effectiveness of potential future pneumococcal vaccination policies; and (3) key assumptions that influence study results. METHODS: A static cohort model that incorporated costs, health outcomes, and quality-adjusted life-year (QALY) losses associated with invasive pneumococcal disease and non-bacteremic pneumococcal pneumonia (NBPP) was developed to evaluate seven pneumococcal vaccination strategies for a 50-year-old adult cohort over a 50-year period using incremental cost-effectiveness ratios (ICERs). RESULTS: For objective 1, the 2012 ACIP recommendation is the more economically efficient strategy (ICER was $25,841 per QALY gained vs. no vaccination). For objective 2, the most efficient vaccination policy would be to maintain the 2012 recommendation for PPSV23 for healthy and immunocompetent adults with comorbidities, and to modify the recommendation for adults with immunocompromising conditions by replacing PPSV23 with a sequential regimen of PCV13 and PPSV23 at age 65 (ICER was $23,416 per QALY gained vs. no vaccination). For objective 3, cost-effectiveness ratios for alternative pneumococcal vaccine policies were highly influenced by assumptions used for vaccine effectiveness against NBPP and accounting for the herd protection effects of pediatric PCV13 vaccination on adult pneumococcal disease. CONCLUSION: Modifying the 2012 recommendation to include an additional dose of PCV13 at age 65, followed by PPSV23, for adults with immunocompromising conditions appears to be a cost-effective vaccine policy. Given the uncertainty in the available data and the absence of key influential data, comprehensive sensitivity analyses should be conducted by policy-makers when evaluating new adult pneumococcal vaccine strategies.

Targeting human papillomavirus to reduce the burden of cervical, vulvar and vaginal cancer and pre-invasive neoplasia: establishing the baseline for surveillance.

BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias was obtained from high-quality national population-based registries. A literature review was conducted to define the fraction of these lesions attributable to HPV16/18, i.e., those that could be prevented by HPV vaccination. RESULTS: Among the four countries, the age-standardised IR/105 of cervical, vaginal and vulvar cancer ranged from 8.4-13.8, 1.3-3.1 and 0.2-0.6, respectively. The risk for cervical cancer was highest in women aged 30-39, while vulvar and vaginal cancers were most common in women aged 70+. Age-standardised IR/105 of cervical, vulvar and vaginal pre-invasive neoplasia ranged between 138.8-183.2, 2.5-8.8 and 0.5-1.3, respectively. Women aged 20-29 had the highest risk for cervical pre-invasive neoplasia, while vulvar and vaginal pre-invasive neoplasia peaked in women aged 40-49 and 60-69, respectively. Over 50% of the observed 47,820 incident invasive and pre-invasive cancer cases in 2004-2006 can be attributed to HPV16/18. CONCLUSION: In the four countries, vaccination against HPV 16/18 could prevent approximately 8500 cases of gynecological cancer and pre-cancer annually. Population-based cancer and vaccination registries are essential to assess the predicted public health effects of HPV vaccination.

The Cost-Effectiveness Analysis of a Quadrivalent Human Papillomavirus Vaccine (6/11/16/18) for Females in Japan.

OBJECTIVE: We assessed the epidemiological and economic impact of a quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for females in preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), cervical intraepithelial neoplasia grade 1 (CIN 1), and genital warts in Japan by using a transmission dynamic model. METHODS: A published mathematical model of the transmission dynamics of HPV infection and disease was adapted for Japan. Model inputs were used from Japan or the Asia/Pacific region when available; otherwise, the default values in the original model were used. The transmission dynamic model was used to assess the epidemiological and economic impact of a quadrivalent HPV (6/11/16/18) vaccine for females in preventing cervical cancer, CIN 2/3, CIN 1, and genital warts in Japan.Maintaining current cervical cancer screening practices, we evaluated two strategies: routine vaccination of females by age 12 years (S1), and S1 combined with a temporary (5 years) female catch-up program for age 12 to 24 years (S2). The vaccine coverage rate was 80% for the routine and 50% for the catch-up vaccination programs. RESULTS: Compared with no vaccination, both vaccination strategies significantly reduced the incidence of HPV 6/11/16/18-related disease. The most effective strategy was S2. By using this strategy over 100 years in the Japanese population, the estimated cumulative percentage reduction in incident HPV 6/11/16/18-related genital warts-female, genital warts-male, cervical CIN 1, CIN 2/3, and cervical cancer cases was 90% (2,113,723 cases), 86% (2,082,637 cases), 72% (263,406 cases), 71% (1,328,366 cases), and 58% (323,145 cases), respectively. The cost-effectiveness ratios were JPY 1,244,000, and JPY 1,205,800 per quality-adjusted life-year gained for S1 and S2 compared with no vaccination, respectively, over a time horizon of 100 years. CONCLUSION: We conclude that a quadrivalent HPV vaccination program for females can reduce the incidence of cervical cancer, CIN, and genital warts in Japan at a cost-per-quality-adjusted life-year ratio within the range defined as cost-effective.

Impact of vaccinating boys and men against HPV in the United States.

We assessed the public health impact and value of vaccinating boys and men with the quadrivalent HPV vaccine in the United States. We used mathematical population models, accounting for both the direct and indirect protective effects of vaccination. Inputs for the models were obtained from public data sources, published literature, and analyses of clinical trial data. Compared with a program of vaccinating girls and women only, including boys and men 9-26 years of age would further decrease the cumulative mean number of genital wart cases, cervical intraepithelial neoplasia 2/3 cases, cancer cases, and cancer deaths by 5,146,000, 708,000, 116,000, and 40,000, respectively, within 100 years. The mean cost-effectiveness ratio (2008 US $) of this strategy was $25,700 (range: 13,600-48,800) per QALY gained if vaccination protects against all HPV 6/11/16/18-associated diseases, and $69,000 (range: 37,700-152,300)/QALY if it only protects against diseases currently in the vaccine indication. Vaccinating boys and men age 9-26 against all HPV 6/11/16/18-associated diseases provides substantial public health benefits and is cost-effective at commonly cited thresholds.