Cost effectiveness of a 92-gene assay for the diagnosis of metastatic cancer

Objectives:

To estimate the clinical and economic trade-offs involved in using a molecular assay (92-gene assay, CancerTYPE ID) to aid in identifying the primary site of difficult-to-diagnose metastatic cancers and to explore whether the 92-gene assay can be used to standardize the diagnostic process and costs for clinicians, patients, and payers.

Methods:

Four decision-analytic models were developed to project the lifetime clinical and economic impact of incorporating the 92-gene assay compared with standard care alone. For each model, total and incremental costs, life-years, quality-adjusted life-years (QALYs), incremental cost–effectiveness ratios (ICERs), and the proportion of patients treated correctly versus incorrectly were projected from the payer perspective. Model inputs were based on published literature, analyses of SEER (Surveillance Epidemiology and End Results) data, publicly available data, and interviews with clinical experts.

Results:

In all four models, the 92-gene assay increased the proportion of patients treated correctly, decreased the proportion of patients treated with empiric therapy, and increased quality-adjusted survival. In the primary model, the ICER was $50,273/QALY; thus, the 92-gene assay is therefore cost effective when considering a societal willingness-to-pay threshold of $100,000/QALY. These findings were robust across sensitivity analyses.

Conclusions:

Use of the 92-gene assay for diagnosing metastatic tumors of uncertain origin is associated with reduced misdiagnoses, increased survival, and improved quality of life. Incorporating the assay into current practice is a cost-effective approach to standardizing diagnostic methods while improving patient care. Limitations of this analysis are the lack of data availability and resulting modeling simplifications, although sensitivity analyses showed these to not be key drivers of results.     

Cost effectiveness analysis of a next generation risk assessment score for cardiovascular disease

Objectives:

The goal of this study is to determine the cost-effectiveness of MIRISK VP, a next generation coronary heart disease risk assessment score, in correctly reclassifying and appropriately treating asymptomatic, intermediate risk patients.

Study design:

A Markov model was employed with simulated subjects based on the Multi-Ethnic Study of Atherosclerosis (MESA). This study evaluated three treatment strategies: (i) practice at MESA enrollment, (ii) current guidelines, and (iii) MIRISK VP in MESA.

Methods:

The model assessed patient healthcare costs and outcomes, expressed in terms of life years and quality-adjusted life years (QALYs), over the lifetime of the cohort from the provider and payer perspective. A total of 50,000 hypothetical individuals were used in the model. A sensitivity analysis was conducted (based on the various input parameters) for the entire cohort and also for individuals aged 65 and older.

Results:

Guiding treatment with MIRISK VP leads to the highest net monetary benefits when compared to the ‘Practice at MESA Enrollment’ or to the ‘Current Guidelines’ strategies. MIRISK VP resulted in a lower mortality rate from any CHD event and a modest increase in QALY of 0.12–0.17 years compared to the other two approaches.

Limitations:

This study has limitations of not comparing performance against strategies other than the FRS, the results are simulated as with all models, the model does not incorporate indirect healthcare costs, and the impact of patient or physician behaviors on outcomes were not taken into account.

Conclusions:

MIRISK VP has the potential to improve patient outcomes compared to the alternative strategies. It is marginally more costly than both the ‘Practice at MESA Enrollment’ and the ‘Current Guidelines’ strategies, but it provides increased effectiveness, which leads to positive net monetary benefits over either strategy.     

The staff-working height and the designing-regulation height for patient beds as possible causes of patient falls

The staff-working height and the designing-regulation height for patient beds used in acute care wards might be possible causes leading to patient falls. Empirical data show the differences among the average height for home beds, staff-working height, and the designing-regulation height for patient beds. This evidence suggests an overlooked cause of patient falls.     

Cost effectiveness of oseltamivir treatment of influenza: a critique of published methods and outcomes

Objective: The objective of this review was to determine, from a systematic assessment of published data, the cost effectiveness of the neuraminidase inhibitor antiviral medication oseltamivir in comparison with usual care (i.e. over-the-counter medication such as analgesics and antipyretics for symptomatic relief) for the treatment of influenza. How the findings of each of the studies considered related to the methods used for each analysis and the assumptions made were specifically reviewed.

Results: The online search found 80 individual articles, 66 of which did not meet the pre-defined screening criteria. The 14 studies remaining reported cost, cost-effectiveness and cost-utility analyses for oseltamivir treatment in various groups: healthy adults and adolescents, children, elderly, and individuals at increased risk.

Conclusion: Despite the range of values assumed for key probabilities such as the diagnostic certainty of influenza among people presenting with influenza-like illness, and how much work time is lost due to illness in healthy adults, base-case analyses consistently showed oseltamivir treatment to be cost effective or even cost saving for the four population groups studied, a conclusion that is in-line with previous reviews on this topic. However, clarity was frequently lacking in the published data in terms of various model assumptions and results, particularly with regards to the exact distributions of the constituting elements of savings and of quality-adjusted life years gained.     

Cost effectiveness of memantine in Alzheimer's disease in the UK

Objective: This analysis assesses the cost-effectiveness of memantine for the treatment of moderate-to-severe Alzheimer's disease (AD) in the UK.

Methods: This cost-utility analysis was based on a Markov model. The model simulated 5-year progress of patients with AD until they need full-time care (FTC), defined as a patient becoming either dependent or institutionalised. Transition probabilities were based on a predictive equation, derived from the London and South-East Region epidemiological study. Resource use, utilities and mortality were obtained from the same study. Memantine efficacy was based on a meta-analysis of six large trials. The model compared memantine to its alternative in the UK, i.e. no pharmacological treatment or background therapy with acetylcholinesterase inhibitors.

Results: Memantine was found to delay the need to FTC by 6 weeks compared with current practice in the UK. It was associated with increased quality-adjusted life-years and cost savings to the healthcare system (probability of this outcome was 96%). The projections were made assuming that benefits from the 6-month treatment were sustained over time, which is regarded as the main limitation. The model underwent extensive sensitivity analyses, which confirmed the base-case findings.

Conclusions: The model suggests that memantine delays the need for FTC and decreases cost. It can be regarded as a cost-effective choice in the management of moderate and severe AD.     

Cost effectiveness of tiotropium for chronic obstructive pulmonary disease: a systematic review of the evidence

Abstract

Background:

Tiotropium has been shown to reduce exacerbations and improve quality of life for patients with chronic obstructive pulmonary disease (COPD), a lung disease characterized by a persistent and progressive airflow limitation.

Objectives:

To present a systematic literature review of the cost effectiveness of treatment with tiotropium compared with other currently used treatments for COPD.

Methods:

A systematic search was performed via PubMed, the Cochrane database, and EMBASE from 2002 to 2009. Methods and results by study design and by country were compared.

Results:

Seventeen studies were included in the review. Study designs were characterized as follows: modeling based on clinical trial data, and empirical analysis based on either clinical trial or observational data. Comparing monotherapy regimens (12 studies), all study designs found that treatment with tiotropium was associated with lower costs for hospitalisation and other non-drug services. Total costs, including the costs of maintenance drugs, were lower with tiotropium in some, but not all, of the studies. Tiotropium was shown to be cost effective based on commonly accepted benchmark values. Limitations of the review included the wide variety of outcome measures used in different studies, the limited number of observational database studies for monotherapy, and limited data for combination therapy regimens.

Conclusions:

The main conclusions of the economic evaluations derived from clinical trial data at the time of product approval and from later observational data reflecting clinical use are similar: use of tiotropium monotherapy is associated with lower hospital and other non-drug costs and better health outcomes and is either cost saving or cost effective compared with other maintenance monotherapies.     

Cost effectiveness of posaconazole in the prophylaxis of invasive fungal infections in acute leukaemia patients for the French healthcare system

Abstract

Background:

Acute myeloblastic leukaemia (AML) patients are at high risk of suffering from invasive fungal infections (IFI). Posaconazole demonstrated higher efficacy than standard azole agents (SAA) in the prophylaxis of IFI in this population.

The authors estimated the cost effectiveness of posaconazole versus SAA in France.

Methods:

A decision-tree model was developed to compare posaconazole with SAA with the results of a published clinical trial. Clinical events were modelled with chance nodes reflecting probabilities of IFI, IFI-related death, and death from other causes. Medical resource consumption and costs were obtained from results of the clinical trial and from a dedicated survey on the costs of treating IFI using a retrospective chart review design.

Results:

IFI treatment costs were estimated using medical files from 50 AML patients from six French centres, with a proven and probable IFI, who had been followed-up for 298 days on average. Direct costs directly related to IFI were estimated at €51,033, including extra costs of index hospitalisation, costs of antifungal therapy and additional hospitalisations related to IFI treatment. The model indicated that the healthcare costs for the posaconazole strategy were €5,223 (€2,697 for prophylaxis and €2,526 for IFI management), which was €859 less than the €6,083 in costs with SAA (€469 for prophylaxis and €5614 for IFI management). A sensitivity analysis indicated that there was an 80% probability that prophylaxis using the posaconazole strategy would be superior.

Conclusion:

The findings from this analysis suggest that posaconazole use is a clinically and economically dominant strategy in the prophylaxis of IFI in AML patients, given the usual limits of economic models and the uncertainty of costs estimates.     

Evolving provider payment models and patient access to innovative medical technology

Objective:

To investigate the evolving use and expected impact of pay-for-performance (P4P) and risk-based provider reimbursement on patient access to innovative medical technology.

Methods:

Structured interviews with leading private payers representing over 110 million commercially-insured lives exploring current and planned use of P4P provider payment models, evidence requirements for technology assessment and new technology coverage, and the evolving relationship between the two topics.

Results:

Respondents reported rapid increases in the use of P4P and risk-sharing programs, with roughly half of commercial lives affected 3 years ago, just under two-thirds today, and an expected three-quarters in 3 years. All reported well-established systems for evaluating new technology coverage. Five of nine reported becoming more selective in the past 3 years in approving new technologies; four anticipated that in the next 3 years there will be a higher evidence requirement for new technology access. Similarly, four expected it will become more difficult for clinically appropriate but costly technologies to gain coverage. All reported planning to rely more on these types of provider payment incentives to control costs, but didn’t see them as a substitute for payer technology reviews and coverage limitations; they each have a role to play.

Limitations:

Interviews limited to nine leading payers with models in place; self-reported data.

Conclusion:

Likely implications include a more uncertain payment environment for providers, and indirectly for innovative medical technology and future investment, greater reliance on quality and financial metrics, and increased evidence requirements for favorable coverage and utilization decisions. Increasing provider financial risk may challenge the traditional technology adoption paradigm, where payers assumed a ‘gatekeeping’ role and providers a countervailing patient advocacy role with regard to access to new technology. Increased provider financial risk may result in an additional hurdle to the adoption of new technology, rather than substitution of provider- for payer-based gatekeeping.     

Cost effectiveness of transcatheter aortic valve replacement compared to medical management in inoperable patients with severe aortic stenosis: Canadian analysis based on the PARTNER Trial Cohort B findings

Abstract

Objective:

The only effective treatment for severe aortic stenosis (AS) is valve replacement. However, many patients with co-existing conditions are ineligible for surgical valve replacement, historically leaving medical management (MM) as the only option which has a poor prognosis. Transcatheter Aortic Valve Replacement (TAVR) is a less invasive replacement method. The objective was to estimate cost-effectiveness of TAVR via transfemoral access vs MM in surgically inoperable patients with severe AS from the Canadian public healthcare system perspective.

Methods:

A cost-effectiveness analysis of TAVR vs MM was conducted using a deterministic decision analytic model over a 3-year time horizon. The PARTNER randomized controlled trial results were used to estimate survival, utilities, and some resource utilization. Costs included the valve replacement procedure, complications, hospitalization, outpatient visits/tests, and home/nursing care. Resources were valued (2009 Canadian dollars) using costs from the Ontario Case Costing Initiative (OCCI), Ontario Ministry of Health and Long-Term Care and Ontario Drug Benefits Formulary, or were estimated using relative costs from a French economic evaluation or clinical experts. Costs and outcomes were discounted 5% annually. The effect of uncertainty in model parameters was explored in deterministic and probabilistic sensitivity analysis.

Results:

The incremental cost-effectiveness ratio (ICER) was $32,170 per quality-adjusted life year (QALY) gained for TAVR vs MM. When the time horizon was shortened to 24 and 12 months, the ICER increased to $52,848 and $157,429, respectively. All other sensitivity analysis returned an ICER of less than $50,000/QALY gained.

Limitations:

A limitation was lack of availability of Canadian-specific resource and cost data for all resources, leaving one to rely on clinical experts and data from France to inform certain parameters.

Conclusions:

Based on the results of this analysis, it can be concluded that TAVR is cost-effective compared to MM for the treatment of severe AS in surgically inoperable patients.     

Cost effectiveness of adding clostridial collagenase ointment to selective debridement in individuals with stage IV pressure ulcers

Objective: The purpose of this study was to determine the cost effectiveness (from a payer’s perspective) of adding clostridial collagenase ointment (CCO) to selective debridement compared with selective debridement alone (non-CCO) in the treatment of stage IV pressure ulcers among patients identified from the US Wound Registry.

Methods: A 3-state Markov model was developed to determine costs and outcomes between the CCO and non-CCO groups over a 2-year time horizon. Outcome data were derived from a retrospective clinical study and included the proportion of pressure ulcers that were closed (epithelialized) over 2 years and the time to wound closure. Transition probabilities for the Markov states were estimated from the clinical study. In the Markov model, the clinical outcome is presented as ulcer-free weeks, which represents the time the wound is in the epithelialized state. Costs for each 4-week cycle were based on frequencies of clinic visits, debridement, and CCO application rates from the clinical study. The final model outputs were cumulative costs (in US dollars), clinical outcome (ulcer-free weeks), and incremental cost-effectiveness ratio (ICER) at 2 years.

Results: Compared with the non-CCO group, the CCO group incurred lower costs ($11,151 vs $17,596) and greater benefits (33.9 vs 16.8 ulcer-free weeks), resulting in an economically dominant ICER of ?$375 per ulcer. Thus, for each additional ulcer-free week that can be gained, there is a concurrent cost savings of $375 if CCO treatment is selected. Over a 2-year period, an additional 17.2 ulcer-free weeks can be gained with concurrent cost savings of $6,445 for each patient.

Conclusions: In this Markov model based on real-world data from the US Wound Registry, the addition of CCO to selective debridement in the treatment of pressure ulcers was economically dominant over selective debridement alone, resulting in greater benefit to the patient at lower cost.     

The clearance rate as a measure of criminal justice system effectiveness

The validity of the clearance rate as a measure of either criminal justice system (CJS) effectiveness or of the probability of punishment for crime can be questioned on the grounds that the relationship between CJS effectiveness and observed clearance rates is mediated by the choice behavior of criminals. If the clearance rate is endogenous in that sense, then recent econometric results concerning the deterrence effect of punishment are fundamentally flawed. A model of criminal adaptation to changes in CJS effectiveness illustrates the basic problem.     

Cost effectiveness of tyrosine kinase inhibitor therapy in metastatic gastrointestinal stromal tumors

Abstract

Background:

Tyrosine kinase inhibitors (TKIs) such as imatinib mesylate have revolutionized the treatment of primary unresectable and/or metastatic gastrointestinal stromal tumors (GISTs), providing durable disease control and extended survival. Although most patients eventually progress on therapy, dose escalation has been shown to benefit some patients. Sunitinib, a multitargeted kinase inhibitor is effective against imatinib-resistant or intolerant GIST patients. Although the cost of TKI therapy in GIST is high, no other effective systemic treatment options exist.

Objective:

Review pharmacoeconomic studies to determine the cost effectiveness (CE) of 1st- and 2nd-line TKI therapies in GIST.

Methods:

A literature review using Medline and PubMed databases was conducted to identify published economic analyses of TKI therapy in GIST. Key results from these studies were analyzed.

Results:

Six pharmacoeconomic studies were identified, including three analyses of 1st-line imatinib and three analyses of 2nd-line sunitinib. These studies employed various time horizons and discount rates and modeled CE from a number of different perspectives. Most of the pharmacoeconomic studies reviewed used survival as their efficacy endpoint, projecting outcomes beyond available data to model CE. Analyses of 2nd-line sunitinib using survival additionally faced the challenge of adjusting for the effect of placebo crossover to active treatment in the pivotal phase III study. Most studies used Markov techniques with a range of transition probabilities.

Conclusions:

Published pharmacoeconomic studies of 1st- and 2nd-line TKI therapy for advanced GIST employ various time horizons, discount rates, and different CE models. Consequently, these differences make comparisons between studies difficult. Studies of 1st-line imatinib concluded that imatinib was cost effective in advanced, metastatic GIST. Likewise, based on data reviewed here, 2nd-line sunitinib appears to be cost effective in patients with advanced GIST who are intolerant/resistant to imatinib. Key limitations of this review included inconsistency among the studies evaluated with regard to methodologies, countries of origination (currency and healthcare systems), and patient demographics.     

Cost effectiveness of rimonabant use in patients at increased cardiometabolic risk: estimates from a Markov model

Summary

Rimonabant, the first selective CB-1 receptor blocker, is expected to reduce cardiometabolic risk substantially. This study assesses the economics of such treatment in patients at elevated cardiometabolic risk.

A Markov model was developed using data from the Rimonabant in Obesity (RIO) trial, published risk equations, and UK cost and utility data. Patients begin either in a diabetic or a non-diabetic state and can transition to cardiovascular disease or to death (based on UK life tables). Transitions to diabetes and subsequent cardiovascular events are also counted. Resource use due to events and long-term management were translated to UK costs (2005 GBP). Tariffs for events and states were applied to age-dependent utilities. Extensive univariate and multivariate probabilistic sensitivity analyses were carried out.

Over 10 years, 8% will suffer a cardiovascular event with a loss of more than 1,000 quality-adjusted life years (QALYs) and a cost of more than £500,000 per 1,000 patients. Projecting risk for a lifetime, 1 year of rimonabant use is estimated to gain >65 QALYs at £8,574/QALY. In probabilistic sensitivity analysis, incremental cost-effectiveness ratios varied from £2,657 to £22,141/QALY.

Based on the metabolic effects seen in clinical trials, rimonabant should reduce cardiovascular risk in obese or overweight people at reasonable cost.     

Cost effectiveness of prophylactic HPV 16/18 vaccination in Finland: results from a modelling exercise

Objectives: the study aims to estimate the clinical-impact and cost-effectiveness value of adding human papillomavirus 16/18 vaccination against cervical cancer among women currently undergoing organised screening in Finland.

Methods: A Markov cohort model evaluating high-risk HPV infections and cervical cancer (CC) cases combined with screening has been customised to the Finnish setting. The model outcome for a cohort of 30,000 girls aged 10 years was calibrated to age-specific annual number of Pap smears, CC incidence and mortality.

Results: The observed age-specific incidence and mortality rates of CC closely match the data replicated by the model. The model predicts that with a 90% vaccine coverage rate, CC cases and mortality would be reduced by 70%. In the base-case analysis with a discount rate of 3% the incremental cost per quality-adjusted life-years (QALY) gained, from a healthcare perspective, was €17,294. Without discounting this value is €2,591/QALY gained.

Conclusions: The analysis suggests that implementing prophylactic CC vaccination within the current screening system would substantially reduce CC cases and deaths, as well as the overall disease burden expressed in pre-cancer lesions averted. Vaccination could be a cost-effective intervention in Finland despite the fact that the number of CC cases and deaths are currently relatively low. Conservative estimates of the cost effectiveness of the vaccination were provided since it was not possible to assess herd protection induced by vaccination using this Markov model.     

Cost effectiveness of palivizumab in children with congenital heart disease in Germany

Abstract

Objectives: To assess the cost effectiveness of palivizumab, a humanised monoclonal antibody, used as prevention against severe respiratory syncytial virus (RSV) infection requiring hospitalisation, in infants with haemodynamically significant congenital heart disease (CHD) in the German healthcare setting.

Study design: A decision-tree model was used to estimate the cost effectiveness of palivizumab for a hypothetical cohort of patients. The analysis was based on a lifetime follow-up period in order to capture the impact of palivizumab on long-term morbidity and mortality resulting from an RSV infection. Data sources included published literature, the palivizumab pivotal trials, official price/tariff lists and national population statistics. The study was conducted from the perspective of society (primary analysis) and the healthcare purchaser (secondary analysis).

Results: From the societal perspective, use of palivizumab results in an incremental cost-effectiveness ratio (ICER) of €2,615 per quality-adjusted life-year (QALY) without discounting, which increases to €9,529/QALY after discounting. From the perspective of the German healthcare purchaser, use of palivizumab results in an ICER of €4,576/QALY without discounting, which increases to €16,673/QALY after discounting. Probabilistic sensitivity analyses confirmed the robustness of the model. The study is limited by a number of conservative assumptions. It was assumed that palivizumab only affects the occurrence of RSV hospitalisation and does not influence the severity of the RSV infection. Another assumption was that international clinical trial data and data on utilities could be applied to the German healthcare setting.

Conclusion: This analysis showed that palivizumab represents a cost-effective means of prophylaxis against severe RSV infection requiring hospitalisation in infants with haemodynamically significant CHD.