Evaluation of a complex intervention for prisoners with common mental health problems, near to and after release: the Engager randomised controlled trial.

BACKGROUND: Many male prisoners have significant mental health problems, including anxiety and depression. High proportions struggle with homelessness and substance misuse. AIMS: This study aims to evaluate whether the Engager intervention improves mental health outcomes following release. METHOD: The design is a parallel randomised superiority trial that was conducted in the North West and South West of England (ISRCTN11707331). Men serving a prison sentence of 2 years or less were individually allocated 1:1 to either the intervention (Engager plus usual care) or usual care alone. Engager included psychological and practical support in prison, on release and for 3-5 months in the community. The primary outcome was the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), 6 months after release. Primary analysis compared groups based on intention-to-treat (ITT). RESULTS: In total, 280 men were randomised out of the 396 who were potentially eligible and agreed to participate; 105 did not meet the mental health inclusion criteria. There was no mean difference in the ITT complete case analysis between groups (92 in each arm) for change in the CORE-OM score (1.1, 95% CI -1.1 to 3.2, P = 0.325) or secondary analyses. There were no consistent clinically significant between-group differences for secondary outcomes. Full delivery was not achieved, with 77% (108/140) receiving community-based contact. CONCLUSIONS: Engager is the first trial of a collaborative care intervention adapted for prison leavers. The intervention was not shown to be effective using standard outcome measures. Further testing of different support strategies for prison with mental health problems is needed.

Cost and health impact analysis of herpes zoster vaccination in Norway.

BACKGROUND: A decision analytic model was developed to estimate the cost-effectiveness of a national vaccination program against herpes zoster in Norway. METHODS: The model analyzed six vaccination scenarios that included the live-attenuated zoster vaccine under different target ages of vaccination (60, 65, and 70 years) compared with no vaccination. A catch-up program implemented in the first year of the vaccination was included in three of the scenarios. The model followed the population of Norway over a 40-year time horizon to estimate costs and outcomes associated with vaccination. Immunization costs, costs related to herpes zoster (both healthcare sector and non-healthcasre sector), the quality of life gains due to avoided cases of herpes zoster, and quality-of-life losses due to vaccine-related adverse events were estimated. RESULTS AND CONCLUSIONS: A national vaccination program would result in reduction of the number of herpes zoster cases and decreased burden of illness. Vaccinating adults at 65 years of age with catch-up up to 70 years in the first year of the program was the most cost-effective strategy with the incremental cost per quality-adjusted life-year gained at NOK (Norwegian Krone) 245,459 from the societal perspective and NOK 248,637 from the health care system perspective.

Cost-effectiveness analysis of cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplant recipients from a US payer perspective.

To evaluate the cost-effectiveness of letermovir versus no prophylaxis for the prevention of cytomegalovirus infection and disease in adult cytomegalovirus-seropositive allogeneic hematopoietic cell transplantation (allo-HCT) recipients. A decision model for 100 patients was developed to estimate the probabilities of cytomegalovirus infection, cytomegalovirus disease, various other complications, and death in patients receiving letermovir versus no prophylaxis. The probabilities of clinical outcomes were based on the pivotal phase 3 trial of letermovir use for cytomegalovirus prophylaxis versus placebo in adult cytomegalovirus-seropositive recipients of an allo-HCT. Costs of prophylaxis with letermovir and of each clinical outcome were derived from published sources or the trial clinical study reports. Incremental cost-effectiveness ratios (ICERs) in terms of cost per quality-adjusted life year (QALY) gained were used in the model. One-way and probabilistic sensitivity analyses were conducted to explore uncertainty around the base-case analysis. In this model, the use of letermovir prophylaxis would lead to an increase of QALYs (619) and direct medical cost ($1 733 794) compared with no prophylaxis (578 QALYs; $710 300) in cytomegalovirus-seropositive recipients of an allo-HCT. Letermovir use for cytomegalovirus prophylaxis was a cost-effective option versus no prophylaxis with base-case analysis ICER $25 046/QALY gained. One-way sensitivity analysis showed the most influential parameter was mortality rate. The probabilistic sensitivity analysis showed a 92% probability of letermovir producing an ICER below the commonly accepted willingness-to-pay threshold of $100 000/QALY gained. Based on this model, letermovir use for cytomegalovirus prophylaxis was a cost-effective option in adult cytomegalovirus-seropositive recipients of an allo-HCT.

Budget impact analysis of multiple varicella vaccination strategies: a Mexico perspective.

A number of live-attenuated varicella vaccines are produced globally that provide protection against the varicella zoster virus. In Mexico, varicella vaccination is not included in the national immunization program and is recommended for use only in high-risk subgroups. We developed a budget impact model to estimate the impact of universal childhood immunization against varicella on the national payer system in Mexico. A scenario of no varicella vaccination was compared to scenarios with vaccination with a single dose at 13 months of age, in alignment with the existing program of immunization with the measles-mumps-rubella vaccine. Nine different vaccination scenarios were envisioned, differing by vaccine type and by coverage. Varicella cases and treatment costs of each scenario were computed in a dynamic transmission model of varicella epidemiology, calibrated to the population of Mexico. Unit costs were based on Mexico sources or were from the literature. The results indicated that each of the three vaccine types increased vaccine acquisition and administration expenditures but produced overall cost savings in each of the first 10 years of the program, due to fewer cases and reduced varicella treatment costs. A highly effective vaccine at 95% coverage produced the greatest cost savings.

Budget Impact Analysis of Afatinib for First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Exon 19 Deletions or Exon 21 Substitution Mutations in a U.S. Health Plan.

BACKGROUND: Afatinib is 1 of 3 tyrosine kinase inhibitors approved in the United States for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions (del19) or exon 21 (L858R) substitution mutations. In clinical trials, afatinib has demonstrated improvement in progression-free survival versus standard chemotherapy and gefitinib. OBJECTIVE: To analyze the impact of increases in afatinib treatment share on the cost and health outcomes in a commercial health plan in the United States. METHODS: A decision model was developed to evaluate the budget impact of increases in afatinib share for the first-line treatment of patients with metastatic NSCLC with EGFR del19 or L858R substitution mutations over a 5-year time horizon. The model compared the total annual costs for a health plan with 1 million covered lives in a scenario in which afatinib share increased 5 percentage points annually to one in which all treatment shares remained constant over time. The number of patients eligible for treatment was estimated using published incidence data. Therapies included in the model were afatinib, erlotinib, gefitinib, and the chemotherapy doublet, pemetrexed in combination with cisplatin. The mean time spent by patients in progression-free and progressive disease states was based on survival data from clinical trials and a network meta-analysis. Therapy-related costs included monthly drug acquisition and administration costs and costs of managing adverse reactions. Disease management costs were also assessed in the model. Scenario analyses were performed to assess alternative scenarios of afatinib treatment share. Additionally, a one-way sensitivity analysis was performed to test the robustness of the model, given parameter uncertainty. RESULTS: Using the base-case parameter assumptions and a 5-percentage-point annual increase in afatinib treatment share, we estimated the total budget increases in years 1 through 5 to be $1,606, $65,542, $140,564, $209,272, and $303,368, respectively. These budget increases translated to per-member-per-month increases ranging from $0.00 to $0.03 in years 1 to 5. The increase in afatinib use resulted in the proportion of the treated population (134 patients treated over 5 years) remaining in progression-free disease increasing from 23.7% to 26.2% at the end of year 5, versus if afatinib treatment share had stayed constant. CONCLUSIONS: Increasing the treatment share of afatinib in a health plan for the first-line treatment of NSCLC with EGFR del19 or L858R mutations was estimated to increase the proportion of treated patients remaining in progression-free disease, while having small budget impact to the health plan. DISCLOSURES: Boehringer Ingelheim Pharmaceuticals funded this study research and was involved in all stages of study conduct, including the analysis of data, and also undertook all costs associated with the development and publication of this manuscript. Graham and Earnshaw are employees of RTI Health Solutions, an independent contract research organization that has received research funding for this and other studies from Boehringer Ingelheim Pharmaceuticals. Lim and Burslem are employees of Boehringer Ingelheim Pharmaceuticals, which developed and produces afatinib, along with other pharmaceutical products.

Budget-Impact Analysis of Alternative Herpes Zoster Vaccine Strategies: A U.S. HMO Perspective.

BACKGROUND: A herpes zoster vaccine has been approved by the FDA for use in prevention of herpes zoster in individuals who are aged 50 years or older. The Advisory Committee on Immunization Practices (ACIP) recommends vaccination only in individuals who are aged 60 years and older. OBJECTIVES: To (a) estimate the overall budget and health impact of either the introduction of a new vaccination strategy (individuals over the age of 50 years vs. individuals over the age of 60 years) within a hypothetical health plan or simply an increase in coverage within the population aged 60 years and over and (b) discern what effect copayments and changes to copayments have on the health plan's budget. METHODS: A decision-analytic economic model was developed to inform managed care decision makers of the potential effect on costs and outcomes associated with the use of the herpes zoster vaccine for prevention of herpes zoster (i.e., simple zoster or shingles). The model took a U.S. payer perspective. The number of eligible patients entering the model was estimated by considering the age distribution of the plan population and the percentage of patients contraindicated for vaccination (i.e., those who were immunocompromised or who had a history of anaphylactic/anaphylactoid reaction to gelatin, neomycin, or any other component of the vaccine). Eligible patients were vaccinated based on the projected uptake rates among the unvaccinated population in 2 possible vaccination scenarios: (1) a vaccination strategy in which only individuals over age 60 years can be vaccinated and (2) a vaccination strategy in which individuals over age 50 years can be vaccinated. Vaccination was assumed to reverse the age-related decline in immunity against zoster. The population vaccinated each year was estimated based on the uptake rates (percentage of the eligible unvaccinated that are vaccinated) required to reach a target annual coverage (percentage ever vaccinated). Patients could experience costs and outcomes related to vaccination or related to herpes zoster. Specifically, vaccination could cause adverse events that would require the use of health care resources. Patients who developed zoster could experience postherpetic neuralgia or develop nonpain complications that would require the use of health care resources. Vaccine costs, zoster cases (with and without postherpetic neuralgia or nonpain complication), and vaccine-related adverse events for the 2 vaccination scenarios were estimated for each budget year. RESULTS: For a managed care organization population of 5 million members, the model estimated that a vaccination program that included patients over age 50 years instead of a program limiting vaccination to those over age 60 years was associated with a decrease in the number of patients developing zoster (2,372-3,392 cases avoided over 5 years). Annual incremental per-member-per-month (PMPM) costs associated with this vaccination program change were estimated to range from $0.08 to $0.14. When the vaccination program was kept at age 60 years and over and coverage was increased, the model estimated that the annual incremental PMPM costs ranged from $0.04 to $0.06. Differences in costs were driven primarily by vaccination costs. The results of the scenario analyses showed that lower vaccination costs because of the application of copayments for a managed care organization reduced the magnitude of the total cost increase associated with the increase in uptake. CONCLUSIONS: Vaccinating individuals aged 50 to 59 years with the herpes zoster vaccine would likely have an impact on a health plan's budget because of the expected increase in the total number of individuals being vaccinated in the population, with limited cost savings because of fewer cases of herpes zoster. Higher coverage of vaccinations resulted in a greater increase in total costs each year. However, increasing coverage would also result in a decrease in the number of individuals developing zoster and associated postherpetic neuralgia and nonpain complications over the next 5 years. DISCLOSURES: Merck & Co. funded this study/research and was involved in all stages of study conduct, including analysis of the data. Merck & Co. also undertook all costs associated with the development and publication of this manuscript. Graham and Mauskopf (and/or their institutions) received research funding from Merck & Co. to develop the budget-impact estimates and for other research studies. Johnson, Xu, and Acosta are employees of Merck & Co. Kawai was employed by Merck & Co. during part of the time of this study. Graham and Mauskopf were primarily responsible for the design and programming of the economic model, identification and final selection of the input parameter values, interpretation of the study results, and preparation of the study report. Johnson, Kawai, Xu, and Acosta contributed to model design, input parameter estimation, interpretation of the results, and review of and revisions to the study report. All authors had access to the data, participated in the development of this manuscript, and gave final approval before submission. All authors have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Cost Utility of Omalizumab Compared with Standard of Care for the Treatment of Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) negatively impacts patient quality of life and productivity and is associated with considerable indirect costs to society. OBJECTIVE: The aim of this study was to assess the cost utility of add-on omalizumab treatment compared with standard of care (SOC) in moderate or severe CSU patients with inadequate response to SOC, from the UK societal perspective. METHODS: A Markov model was developed, consisting of health states based on Urticaria Activity Score over 7 days (UAS7) and additional states for relapse, spontaneous remission and death. Model cycle length was 4 weeks, and total model time horizon was 20 years in the base case. The model considered early discontinuation of non-responders (response: UAS7 ≤6) and retreatment upon relapse (relapse: UAS7 ≥16) for responders. Clinical and cost inputs were derived from omalizumab trials and published sources, and cost utility was expressed as incremental cost-effectiveness ratios (ICERs). Scenario analyses included no early discontinuation of non-responders and an altered definition of response (UAS7 <16). RESULTS: With a deterministic ICER of £3183 in the base case, omalizumab was associated with increased costs and benefits relative to SOC. Probabilistic sensitivity analysis supported this result. Productivity inputs were key model drivers, and individual scenarios without early discontinuation of non-responders and adjusted response definitions had little impact on results. ICERs were generally robust to changes in key model parameters and inputs. CONCLUSIONS: In this, the first economic evaluation of omalizumab in CSU from a UK societal perspective, omalizumab consistently represented a treatment option with societal benefit for CSU in the UK across a range of scenarios.

Impact of tetanus, diphtheria, and acellular pertussis (Tdap) vaccine use in wound management on health care costs and pertussis cases.

BACKGROUND: The Advisory Committee on Immunization Practices (ACIP) recommends the use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine for routine wound management in adolescents and adults who require a tetanus toxoid-containing vaccine who were vaccinated ≥ 5 years earlier with tetanus toxoid, reduced diphtheria toxoid (Td) vaccine, and who have not previously received Tdap. OBJECTIVE: To estimate the overall budget and health impact of vaccinating individuals presenting for wound management with Tdap instead of Td vaccine, the current standard of care in practices that do not use Tdap for purposes of wound management. METHODS: A decision-analytic economic model was developed to estimate the expected increase in direct medical costs and the expected number of cases of pertussis avoided associated with the use of Tdap instead of Td vaccine in the wound management setting. Patients eligible for Tdap were aged 10+ years and required a tetanus-containing vaccine. Age-specific wound incidence data and Td and Tdap vaccination rates were taken from the National Health Interview Survey and the National Immunization Survey for the most recent available year. Age-specific pertussis incidence used in this analysis (151 per 100,000 for adolescents, 366 per 100,000 for those aged 20-64 years, and 176 per 100,000 for those aged 65+ years) used reported incidence rates adjusted by a factor of 10 for adolescents and by a factor of 100 for adults, based on assumptions previously made by ACIP to account for underreporting. Vaccine wholesale acquisition costs without federal excise tax were assumed in the base case. Efficacy of vaccination with Tdap in preventing pertussis was based on clinical trial data. Possible herd immunity effects of vaccination were not included in the model. Costs associated with vaccination and treatment of pertussis cases were reported as total annual costs and per-member-per-month (PMPM) costs for hypothetical health plans and for the U.S. population. Aggregate and incremental costs and pertussis cases avoided were presented undiscounted (as recommended for budget-impact analyses) annually and cumulatively over a 3-year time horizon in 2012 U.S. dollars. Scenario analyses were conducted on key parameters, including wound incidence, pertussis incidence, vaccine efficacy and waning protection against pertussis, uptake rates for Tdap, and vaccine prices using alternative data sources or alternative clinically relevant assumptions. RESULTS: For a health plan with 1 million covered lives aged < 65 years, vaccination with Tdap instead of Td was estimated to cost an additional $132,364 ($0.01 PMPM) in the first year and an additional $368,640 ($0.01 PMPM) cumulatively over 3 years. For a health plan with 1 million covered lives aged 65+ years, vaccination with Tdap instead of Td was estimated to cost an additional $201,165 ($0.02 PMPM) in the first year and an additional $549,568 ($0.02 PMPM) cumulatively over 3 years. For the U.S. population aged 10+ years, vaccination with Tdap instead of Td was estimated to result in protection against pertussis for an additional 2.7 million patients with wounds annually and was estimated to cost an additional $121,101,671 to avoid 42,104 cases of pertussis over the 3-year time horizon. Results were sensitive to input parameter values, particularly parameters associated with the number of patients with wounds vaccinated with Tdap (range 2.7 to 5.1 million patients). However, for all of the alternative scenarios tested, the expected increase in PMPM costs ranged from < $0.01 to $0.03. CONCLUSIONS: Vaccination of adolescents and adults with Tdap for wound management may result in an increase in PMPM costs for health plans of < $0.01 to $0.03. Given the potential reduction in pertussis cases at the population level, vaccination with Tdap for routine wound management could be considered as another strategy to help address the pertussis public health concern in the United States.

Cost-effectiveness of prasugrel in a US managed care population.

OBJECTIVE: Decision-makers in the US may be interested in the applicability to their populations of cost-effectiveness results generated from clinical trial populations. METHODS: An economic model estimating the cost-effectiveness of prasugrel plus aspirin relative to clopidogrel plus aspirin for patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) was developed from a managed care organization (MCO) perspective. The model estimated 15-month cardiovascular events or bleeding-related outcomes, life expectancy, and costs for patients who received thienopyridine treatment during and after a PCI following a diagnosis of ACS. Post-ACS event rates for patients treated with clopidogrel were from an MCO. The relative risks of these events with prasugrel compared with clopidogrel were from a head-to-head clinical trial. RESULTS: The results of the base-case analysis indicated that, in an MCO population, use of prasugrel-based therapy rather than clopidogrel-based therapy at current prices resulted in cost-savings and fewer clinical events over the 15 months after an ACS diagnosis followed by PCI. At possible lower prices for generic clopidogrel-based therapy, the cost-effectiveness ratio for prasugrel-based therapy compared with clopidogrel-based therapy was between $6643 and $13,906 per life-year gained. The results were most sensitive to the relative costs of the two treatments and the cost for hospital stays. LIMITATIONS: Limitations of the study included lack of follow-up of patients disenrolling from the MCO before the end of the 15-month observation period, the assumption of equal relative risks of events in an MCO as in the clinical trial, and the lack of information on the ratio of cost to charges in the MCO database. CONCLUSIONS: Use of prasugrel-based therapy compared with clopidogrel-based therapy in ACS patients having a PCI resulted in cost-savings at current prices and favorable cost-effective ratios at likely generic prices for clopidogrel-based therapy because of offsetting savings in the costs of rehospitalization.

Cost effectiveness of glatiramer acetate and natalizumab in relapsing-remitting multiple sclerosis.

BACKGROUND: Disease-modifying drugs are a significant expenditure for treating multiple sclerosis. Natalizumab (NZ) has been shown to be effective in reducing relapses and disease progression. However, assessment of the cost effectiveness of NZ compared with other disease-modifying drugs in the presence of long-term data has been limited. OBJECTIVE: To assess the lifetime cost effectiveness from the US healthcare and societal perspectives of glatiramer acetate (GA) and NZ (both given with symptom management) relative to symptom management alone in patients with relapsing-remitting multiple sclerosis (RRMS) using evidence from long-term published studies. METHODS: A Markov model was developed with patients transitioning through health states based on Kurtzke's expanded disability status scale (EDSS). Patients were >/=18 years of age with RRMS, EDSS <6.0 and receiving treatment. Treatment effects were obtained from clinical trials for years 1 and 2 of therapy and long-term clinical assessments thereafter. Transitions were adjusted for discontinuation and persistent NZ antibodies. Patients incurred drug, other medical and lost worker productivity costs. Patient quality of life was considered in the form of utilities, which were taken from assessments of patients with MS. Costs were valued in 2007 $US, and costs and outcomes were discounted at 3% per annum. Various parameters and assumptions were tested in one-way sensitivity analyses, and scenario-based analyses were also performed. RESULTS: Remaining lifetime, direct medical costs for patients receiving GA or NZ versus symptom management were $US408 000, $US422 208 and $US341 436, respectively. Patients receiving GA or NZ benefited from increased years in EDSS 0.0-5.5 (1.18 and 1.09, respectively), years relapse-free (1.30 and 1.18) and QALYs (0.1341 and 0.1332). The incremental cost per QALY for GA or NZ compared with symptom management was $US496 222 and $US606 228, respectively, excluding lost worker productivity costs. GA was associated with a cost saving compared with NZ. The incremental cost per QALY results were sensitive to changes in time horizon, disease progression and drug costs. Improved QALYs for NZ were sensitive to changes in the clinical effect of NZ on disease progression and discontinuation over time. CONCLUSIONS: GA or NZ in RRMS patients is associated with increased benefits compared with symptom management, albeit at higher costs. Although year 1 and 2 disease progression and relapse rates were better for NZ than GA, long-term evidence may show GA to have similar, if not improved, clinical benefit.

Cost-effectiveness of four immunomodulatory therapies for relapsing-remitting multiple sclerosis: a Markov model based on long-term clinical data.

BACKGROUND: Before the introduction of the immunomodulatory therapies for multiple sclerosis (MS), treatment options for MS consisted of symptomatic management (physical therapy and pharmacological treatment for symptom management). Symptomatic management for MS has been supplemented in the past decade by 2 new classes of immunomodulatory therapies that have been approved as first-line treatments for relapsing-remitting multiple sclerosis (RRMS): subcutaneous glatiramer acetate (SC GA) and 3 beta-interferons: intramuscular interferon beta-1a (IM IFNbeta-1a), SC IFNbeta-1a, and SC IFNbeta-1b. OBJECTIVE: To estimate the economic outcomes of 5 treatment strategies: symptom management alone, symptom management combined with SC GA, IM IFNbeta1-a, SC IFNbeta1-a, or SC IFNbeta1-b in patients diagnosed with RRMS. METHODS: A literature-based Markov model was developed to assess the cost-effectiveness of 5 treatment strategies for managing a hypothetical cohort of patients diagnosed with RRMS in the United States--4 immunomodulatory drug therapies and symptom management alone. Health states were based on the Kurtzke Expanded Disability Status Scale (EDSS), a widely accepted scale for assessing RRMS (higher EDSS scores = increased disease severity). Baseline relapse and disease progression transition probabilities for symptom management were obtained from natural history studies. Treatment effects of the immunomodulatory therapies were estimated by applying a percentage reduction to the symptom management transition probabilities for relapse (27% reduction) and disease progression (30% reduction). Transition probabilities were subsequently adjusted to account for (1) the effects of neutralizing antibodies, specifically on relapse rates by assuming no additional therapy benefits after the second year of continuous therapy, and (2) treatment discontinuation. Therapy-specific data were obtained from clinical trials and long-term follow-up observational studies. Transitions among health states occurred in 1-month cycles for the lifetime of a patient. Costs (2005 US$) and outcomes were discounted at 3% annually. RESULTS: The incremental cost per quality-adjusted life-year for the 4 immunomodulatory therapies is $258,465, $303,968, $416,301, and $310,691 for SC GA, IM IFNbeta-1a, SC IFNbeta-1a, and SC IFNbeta-1b, respectively, compared with symptom management alone. Sensitivity analyses demonstrated that results were sensitive to changes in utilities, disease progression rates, time horizon, and immunomodulatory therapy cost. CONCLUSIONS: The pharmacoeconomic model determined that SC GA was the best strategy of the 4 immunomodulatory therapies used to manage MS and resulted in better outcomes than symptom management alone. Sensitivity analyses indicated that the model was sensitive to changes in a number of key parameters, and thus changes in these key parameters would likely influence the estimated cost-effectiveness results. Head-to-head randomized clinical trials comparing the immunomodulatory therapies for the treatment of MS are necessary to validate the projections from the pharmacoeconomic analyses, particularly since the results available today from the clinical trials do not account adequately for treatment dropouts.