Socioeconomic effects of establishing a new stroke center in Central Switzerland.

BACKGROUND: Establishment of dedicated Stroke Centers has shown to be effective on the outcome of patients with acute ischemic stroke, as well as mechanical thrombectomy (MTE) in acute large vessel occlusion. The cost-effectiveness of this treatment has also been proven in several countries, but so far not in Switzerland. METHODS: We compare the pathways and economic impact of patients with acute large vessel occlusions causing acute ischemic stroke before the establishment of the stroke center and MTE in 2016 with the time afterwards in the years 2016-2020. Local data from the Swiss Stroke Registry and hospital accounting as well as economic data from a healthcare insurance company was used for evaluation in an economic model. Both payer and societal perspectives were considered, and probabilistic sensitivity analysis was undertaken to explore uncertainty. RESULTS: Establishment of a new Stroke Center in Central Switzerland increased the absolute number of thrombectomies from 0 in 2015 to 55 in 2016 to 83 in 2020, as well as the percentage of MTE in large vessel occlusions (LVO) from 50.9% in 2016 to 58.2% in 2020. Over a 15-year horizon, predicted average additional costs of CHF 7,978 were associated with the establishment of a new stroke center, as well as 0.60 quality-adjusted life-years (QALY) per patient and an additional survival of 0.59 years per patient. The calculated incremental cost-effectiveness ratio was therefore CHF 13,297 per QALY gained. When societal costs were included, the new stroke care model was predicted to dominate the old care model. Robustness of model results was confirmed via probabilistic sensitivity analysis. LIMITATIONS: The results rely on data from a single stroke center and, therefore, cannot be generalized. CONCLUSIONS: Establishment of a new Stroke Center can be cost-effective and provide better outcomes in terms of functional independence as well as quality-adjusted life-years.

Cost-effectiveness of balloon kyphoplasty and vertebroplasty versus conservative medical management in the USA.

The cost-effectiveness of surgical versus conservative medical management of vertebral compression fractures in the US was analyzed in the context of inpatient versus outpatient treatment. Surgical intervention (balloon kyphoplasty and vertebroplasty) was found to be cost-effective relative to conservative medical management at a US willingness-to-pay threshold. INTRODUCTION: To date, only one published study has evaluated the cost-effectiveness (C/E) of balloon kyphoplasty (BKP) or vertebroplasty (VP) in US Medicare patients with osteoporotic vertebral compression fractures. This study further evaluates the C/E of surgical treatment vs. conservative medical management (CMM), expanding on prior modeling by accounting for quality-adjusted life-years gained. METHODS: A Markov microsimulation model of 1000 patients was constructed. Cost data were based on an analysis of Medicare claims payments, with propensity-score matching performed for BKP and VP vs. controls (CMM). Mortality inputs were based on US life tables, modified to account for age at initial fracture, presence of subsequent fracture(s), and relative risk of mortality by treatment. Separate incremental cost-effectiveness ratios (ICERs) were calculated for BKP and VP in inpatient and outpatient surgical treatment locations to account for individual clinical profiles presenting to each. RESULTS: The discounted ICER for inpatient BKP vs. CMM was $43,455 per QALY gained; for outpatient BKP vs. CMM, $10,922; for inpatient VP vs. CMM, $39,774; and for outpatient VP vs. CMM, $12,293. Probabilistic sensitivity analysis confirmed that both BKP and VP would be considered C/E vs. CMM at a US willingness-to-pay (WTP) threshold of $50,000/QALY in 80% and 100% of 500 model simulations, respectively. The most sensitive parameters included quality of life estimates and hazard ratios for mortality. CONCLUSION: While VP and BKP are more expensive treatment options than CMM in the short term, model results suggest interventional treatment is cost-effective, among patients eligible for surgery, at a US WTP threshold. This conclusion supports those from economic analyses conducted in EU-member countries.

The use of irinotecan, oxaliplatin and raltitrexed for the treatment of advanced colorectal cancer: systematic review and economic evaluation.

OBJECTIVES: To evaluate three technologies for the management of advanced colorectal cancer: (1) first-line irinotecan combination [with 5-fluorouracil (5-FU)] or second-line monotherapy; (2) first- or second-line oxaliplatin combination (again, with 5-FU); and (3) raltitrexed, where 5-FU is inappropriate. To examine the role of irinotecan and oxaliplatin in reducing the extent of incurable disease before curative surgery (downstaging). SOURCES: Ten electronic bibliographic databases covering the period up to August 2004. METHODS: Searches identified existing studies of the effectiveness and economics of the technologies and any studies that evaluated any of the indications outlined above were included. Data were extracted and assessed generic components of methodological quality. Survival outcomes were meta-analysed. RESULTS: Seventeen trials were found, of varying methodological quality. Compared with 5-FU, first-line irinotecan improved overall survival (OS) by 2-4 months (p=0.0007), progression-free survival (PFS) by 2-3 months (p<0.00001) and response rates (p<0.001). It offered a different toxicity profile and no quality of life (QoL) advantage. However, second-line irinotecan compared with 5-FU improved OS by 2 months (p=0.035) and PFS by 1 month (p=0.03), and provided a better partial response rate, but with more toxicities and no QoL advantage. Compared with second-line best supportive care, irinotecan improved OS by 2 months (p=0.0001), had a different toxicity profile and maintained baseline QoL longer, but with no overall difference. The addition of oxaliplatin to second-line 5-FU is associated with a borderline significant improvement in overall survival (p<0.07); a significantly higher response rate (<0.0001); and more serious toxicities. There is no evidence for a significant difference in QoL. Schedules with treatment breaks may not reduce clinical effectiveness but reduce toxicity. The addition of oxaliplatin to second-line 5-FU also saw no improvement in OS (p<0.07), better PFS (by 2.1 months, p=0.0001), an 8.9% higher response rate (p<0.0001), more toxicities and no QoL advantage. There was no significant difference in OS or PFS between first-line irinotecan and oxaliplatin combinations except when 5-FU was delivered by bolus injection, when oxaliplatin provided better OS (p=0.032) and response rates (p=0.032), but not PFS (p=0.169). The regimens had different toxicity profiles and neither conferred a QoL advantage. When compared to 5-FU, raltitrexed is associated with no significant difference in overall or progression-free survival; no significant difference in response rates; more vomiting and nausea, but less diarrhoea and mucositis; no significant difference in, or worse QoL. Raltitrexed treatment was cut short in two out of four included trials due to excess toxic deaths. 5-FU followed by irinotecan was inferior to any other sequence. First-line irinotecan/5-FU combination improved OS and PFS, although further unplanned therapy exaggerated the OS effect size. Staged combination therapy (combination oxaliplatin followed by combination irinotecan or vice versa) provided the best OS and PFS, although there was no head-to-head comparison against other treatment plans. In the only trial to use three active chemotherapies in any staged combination, median OS was over 20 months. In another study, the longest median OS from a treatment plan using two active agents was 16.2 months. Where irinotecan or oxaliplatin were used with 5-FU to downstage people with unresectable liver metastases, studies consistently showed response rates of around 50%. Resection rates ranged from 9 to 35% with irinotecan and from 7 to 51% with oxaliplatin. In the one study that compared the regimens, oxaliplatin enabled more resections (p=0.02). Five-year OS rates of 5-26% and disease-free survival rates of 3-11% were reported in studies using oxaliplatin. Alone or in combination, 5-FU was more effective and less toxic when delivered by continuous infusion. Existing economic models were weak because of the use of unplanned second-line therapies in their trial data: the survival benefits in patients on such trials cannot be uniquely attributed to the allocated therapy. Consequently, the economic analyses are either limited to the use of PES (at best, a surrogate outcome) or are subject to confounding. Weaknesses in cost components, the absence of direct in-trial utility estimates and the limited use of sensitivity analysis were identified. Improvements to the methodologies used in existing economic studies are presented. Using data from two trials that planned treatment sequences, an independent economic evaluation of six plans compared with first-line 5-FU followed on progression by second-line irinotecan monotherapy (NHS standard treatment) is presented. 5-FU followed on progression by irinotecan combination cost 13,174 pounds per life-year gained (LYG) and 10,338 pounds per quality-adjusted life-year (QALY) gained. Irinotecan combination followed on progression by additional second-line therapies was estimated to cost 12,418 pounds per LYG and 13,630 pounds per QALY gained. 5-FU followed on progression by oxaliplatin combination was estimated to cost 23,786 pounds per LYG and 31,556 pounds per QALY gained. Oxaliplatin combination followed on progression by additional second-line therapies was estimated to cost 43,531 pounds per LYG and 67,662 pounds per QALY gained. Evaluations presented in this paragraph should be interpreted with caution owing to missing information on the costs of salvage therapies in the trial from which data were drawn. Irinotecan combination followed on progression by oxaliplatin combination cost 12,761 pounds per LYG and 16,663 pounds per QALY gained. Oxaliplatin combination followed on progression by irinotecan combination cost 16,776 pounds per LYG and 21,845 pounds per QALY gained. The evaluation suggests that these two sequences have a cost-effectiveness profile that is favourable in comparison to other therapies currently funded by the NHS. However, the differences in OS observed between the two trials from which data were taken may be a result of heterogeneous patient populations, unbalanced protocol-driven intensity biases or other differences between underlying health service delivery systems. CONCLUSIONS: Treatment with three active therapies appears most clinically effective and cost-effective. NHS routine data could be used to validate downstaging findings and a meta-analysis using individual patient-level data is suggested to validate the optimal treatment sequence.

Modelling the cost-effectiveness and capacity impact of changes to colposcopy referral guidelines for women with mild dyskaryosis in the UK Cervical Screening Programme.

OBJECTIVE: To evaluate the capacity implications and health economic impact of new guidelines recommending referral to colposcopy after one mild result during cervical screening rather than after two consecutive mild results. DESIGN: A mathematical model of the country's colposcopy services and the clinical pathways from smear result through to treatment is constructed. The model incorporates national questionnaire data on referral numbers and management practices, routine data and published research results. SETTING: All English NHS colposcopy services. POPULATION: Women aged 25 to 64 years. METHODS: The national average workload impact of the change in referral guidelines is predicted, and the impact in differing local circumstances is evaluated within the model. A long-term health economic model examines the resulting costs and predicted change in quality-adjusted life years (QALYs). MAIN OUTCOME MEASURES: Colposcopy workload implications for single mild dyskaryosis referral and cost per QALY analysis. RESULTS: We found that single mild dyskaryosis referral implies, on average, a 21% increase in colposcopy workload for services not currently operating this policy. The health economic model predicted a cost per QALY gained as a result of the implementation of the new referral guidelines of around pound7,500. CONCLUSIONS: Referral after one mild result will increase workload at colposcopy; however, it may be possible to counterbalance the additional workload by altering other clinical practice. The change to referral guidelines would be considered cost-effective in comparison with many interventions routinely available on the NHS.

Cost-effectiveness of oxaliplatin and capecitabine in the adjuvant treatment of stage III colon cancer.

For many years, the standard treatment for stage III colon cancer has been surgical resection followed by 5-fluorouracil in combination with folinic acid (5-FU/LV). Ongoing clinical trial evidence suggests that capecitabine and oxaliplatin (in combination with 5-FU/LV) may improve disease-free survival and overall survival when compared against 5-FU/LV alone in the adjuvant setting. This study evaluates the cost-effectiveness profiles of these two regimens in comparison to standard chemotherapy, using evidence from two international randomised controlled trials. Survival modelling techniques were employed to extrapolate survival curves from the two trials in order to estimate the long-term benefits of alternative treatment options over the remaining lifetime of patients. The health economic analysis suggests that capecitabine is expected to produce greater health gains at a lower cost than 5-FU/LV. Oxaliplatin in combination with 5-FU/LV is estimated to cost pounds 2970 per additional QALY gained when compared to 5-FU/LV alone. Future research should attempt to elucidate uncertainties concerning the optimal roles of capecitabine and/or oxaliplatin in the adjuvant setting in order to achieve the maximum level of clinical benefit.

The clinical and cost-effectiveness of oxaliplatin and capecitabine for the adjuvant treatment of colon cancer: systematic review and economic evaluation.

OBJECTIVES: To assess the clinical and cost-effectiveness of oxaliplatin in combination with 5-fluorouracil/leucovorin (5-FU/LV), and capecitabine monotherapy (within their licensed indications), as adjuvant therapies in the treatment of patients with Stage III (Dukes' C) colon cancer after complete surgical resection of the primary tumour, as compared with adjuvant chemotherapy with an established fluorouracil-containing regimen. DATA SOURCES: Ten electronic bibliographic databases were searched from inception to January 2005. Searches were supplemented by hand searching relevant articles, sponsor and other submissions of evidence to the National Institute of Health and Clinical Excellence and conference proceedings. REVIEW METHODS: A systematic review and meta-analysis (where appropriate) of clinical efficacy evidence and a cost-effectiveness review and economic modelling were carried out. Marginal costs, life years gained and cost-effectiveness acceptability curves were estimated. Probabilistic sensitivity analysis was used to generate information on the likelihood that each of the interventions was optimal. RESULTS: Three randomised active-controlled trials, of varying methodological quality, were included in the review. The MOSAIC trial and NSABP C-07 study considered the addition of oxaliplatin to adjuvant treatment (albeit administered in different 5-FU/LV regimens) and the X-ACT study compared oral capecitabine with bolus 5-FU/LV alone. A review of the available evidence indicated that in patients with Stage III colon cancer, oxaliplatin in combination with an infusional de Gramont schedule of 5-FU/LV (FOLFOX4) was more effective in preventing and delaying disease recurrence than infusional 5-FU/LV alone (de Gramont regimen). Serious adverse events and treatment discontinuations due to toxicity were more evident with oxaliplatin-based regimens (FOLFOX4 and FLOX regimen) than infusional or bolus 5-FU/LV alone (de Gramont and Roswell Park regimen). Oral capecitabine was at least equivalent in disease-free survival to the bolus Mayo Clinic 5-FU/LV regimen for patients with resected Stage III colon cancer. Although, the safety and tolerability profile of capecitabine was superior to that of the Mayo Clinic 5-FU/LV regimen, it has not been evaluated in comparison with other less toxic 5-FU/LV regimens currently in common use in the UK. Based on the assumptions and survival analysis methods used, the cost-effectiveness analysis using economic modelling estimated that capecitabine was a dominating strategy and resulted in a cost-saving of approximately pound 3320 per patient in comparison with the Mayo Clinic 5-FU/LV regimen, while also providing an additional 0.98 quality-adjusted life-years (QALYs) over a 50-year model time horizon. Oxaliplatin in combination with 5-FU/LV (FOLFOX4 regimen) is estimated to cost an additional pound 2970 per QALY gained when compared with the de Gramont 5-FU/LV regimen and demonstrated superior survival outcomes with marginal costs. The uncertainty analysis suggests that both interventions have a high probability of being cost-effective at a threshold of both pound 20,000 and pound 30,000. An indirect comparison of the FOLFOX4 and Mayo Clinic 5-FU/LV regimens suggests that the use of FOLFOX4 in place of the Mayo Clinic 5-FU/LV regimen would cost an additional pound 5777 per QALY gained. An incremental cost-effectiveness ratio (ICER) is estimated to be approximately pound 13,000 per QALY gained from treatment with FOLFOX4 compared with capecitabine. However, if the Mayo Clinic and the de Gramont 5-FU/LV regimens are assumed to be equivalent in terms of effectiveness, the ICER of FOLFOX4 in comparison with capecitabine may be greater than pound 30,000 per QALY. CONCLUSIONS: The evidence suggests that both capecitabine and FOLFOX4 are clinically effective and cost-effective in comparison with 5-FU/LV regimens (Mayo Clinic and de Gramont schedules). Further research is suggested into the effectiveness, tolerability, patient acceptability and costs of different oxaliplatin/fluoropyrimidine schedules in the adjuvant setting; the effects of treatment duration on efficacy; adverse events; resource data collection strategies and reporting of summary statistics; subgroups benefiting most from adjuvant chemotherapy; and methods for estimating mean survival.

Methods for expected value of information analysis in complex health economic models: developments on the health economics of interferon-beta and glatiramer acetate for multiple sclerosis.

OBJECTIVES: To develop methods for performing expected value of perfect information (EVPI) analysis in computationally expensive models and to report on the developments on the health economics of interferon-beta and glatiramer acetate in the management of multiple sclerosis (MS) using this methodological framework. DATA SOURCES: Electronic databases and Internet resources, reference lists of relevant articles. REVIEW METHODS: A methodological framework was developed for undertaking EVPI analysis for complex models. The framework identifies conditions whereby EVPI may be calculated numerically, where the one-level algorithm sufficiently approximates the two-level algorithm, and whereby metamodelling techniques may accurately approximate the original simulation model. Metamodelling techniques, including linear regression, neural networks and Gaussian processes (GP), were systematically reviewed and critically appraised. Linear regression metamodelling, GP metamodelling and the one-level EVPI approximation were used to estimate partial EVPIs using the ScHARR MS cost-effectiveness model. RESULTS: The review of metamodelling approaches suggested that in general the simpler techniques such as linear regression may be easier to implement, as they require little specialist expertise although may provide only limited predictive accuracy. More complex methods such as Gaussian process metamodelling and neural networks tend to use less-restrictive assumptions concerning the relationship between the model inputs and net benefits, and therefore may permit greater accuracy in estimating EVPIs. Assuming independent treatment efficacy, the 'per patient' EVPI for all uncertainty parameters within the ScHARR MS model is 8855 British pounds. This leads to a population EVPI of 86,208,936 British pounds, which represents the upper estimate for the overall EVPI over 10 years. Assuming all treatment efficacies are perfectly correlated, the overall per patient EVPI is 4271 British pounds. This leads to a population EVPI of 41,581,273 British pounds, which represents the lower estimate for the overall EVPI over 10 years. The partial EVPI analysis, undertaken using both the linear regression metamodel and Gaussian process metamodel clearly, suggests that further research is indicated on the long-term impact of these therapies on disease progression, the proportion of patients dropping off therapy and the relationship between the EDSS, quality of life and costs of care. CONCLUSIONS: The applied methodology points towards using more sophisticated metamodelling approaches in order to obtain greater accuracy in EVPI estimation. Programming requirements, software availability and statistical accuracy should be considered when choosing between metamodelling techniques. Simpler, more accessible techniques are open to greater predictive error, whilst sophisticated methodologies may enhance accuracy within non-linear models, but are considerably more difficult to implement and may require specialist expertise. These techniques have been applied in only a limited number of cases hence their suitability for use in EVPI analysis has not yet been demonstrated. A number of areas requiring further research have been highlighted. Further clinical research is required concerning the relationship between the EDSS, costs of care and health outcomes, the rates at which patients drop off therapy and in particular the impact of disease-modifying therapies on the progression of MS. Further methodological research is indicated concerning the inclusion of epidemiological population parameters within the sensitivity analysis; the development of criteria for selecting a metamodelling approach; the application of metamodelling techniques within health economic models and in the specific application to EVI analyses; and the use of metamodelling for EVSI and ENBS analysis.