Multiway Sensitivity Analysis Research Articles

Human papilloma virus vaccination programs reduce health inequity in most scenarios: a simulation study.

BackgroundThe global and within-country epidemiology of cervical cancer exemplifies health inequity. Public health programs may reduce absolute risk but increase inequity; inequity may be further compounded by screening programs. In this context, we aimed to explore what the impact of human papillomavirus (HPV) vaccine might have on health equity allowing for uncertainty surrounding the long-term effect of HPV vaccination programs.MethodsA simple static multi-way sensitivity analysis was carried out to compare the relative risk, comparing after to before implementation of a vaccination program, of infections which would cause invasive cervical cancer if neither prevented nor detected, using plausible ranges of vaccine effectiveness, vaccination coverage, screening sensitivity, screening uptake and changes in uptake.ResultsWe considered a total number of 3,793,902 scenarios. In 63.9% of scenarios considered, vaccination would lead to a better outcome for a population or subgroup with that combination of parameters. Regardless of vaccine effectiveness and coverage, most simulations led to lower rates of disease.ConclusionsIf vaccination coverage and screening uptake are high, then communities are always better off with a vaccination program. The findings highlight the importance of achieving and maintaining high immunization coverage and screening uptake in high risk groups in the interest of health equity.

Sensitivity analysis to explore responsiveness and dynamic range of multi-metric fish-based indices for assessing the ecological status of estuaries and lagoons

Fish-based multi-metric indices are an integral tool in implementing effective water policy initiatives for transitional waters. This study analysed the behaviour of three fish indices (TFCI in the UK, ELFI in France and EFAI in Portugal) developed for monitoring in line with the European Water Framework Directive, by applying a supervised multi-way sensitivity analysis with national monitoring data. The relative variation in the index outcome was analysed under different simulation scenarios by setting metric values at various levels and accounting for the co-variation between metrics. Subsets of key metrics were identified based on their higher influence in determining the index output. Index results under manipulations of metric scores clearly indicated that metric type, number of metrics used and correlations between metrics are important in determining their behaviour. This has implications for implementing management/conservation plans, for example, by prioritising restoration and/or conservation of metrics influencing more the ecological status. Indices including uncorrelated metrics (e.g. EFAI) or metrics with a skewed distribution (e.g. TFCI) are less affected by extreme metric changes, reducing the effectiveness of management actions aimed at improving the ecological status of a water body and thus adjustments may be needed to increase their sensitivity to changes in their metrics.

Treatment of Ulnar Neuropathy at the Elbow: Cost–Utility Analysis

The choice of surgical treatment for ulnar neuropathy at the elbow (UNE) remains controversial. A cost-utility analysis was performed for 4 surgical UNE treatment options. We hypothesized that simple decompression would emerge as the most cost-effective strategy. A cost-utility analysis was performed from the societal perspective. A decision analytic model was designed comparing 4 strategies: (1) simple decompression followed by a salvage surgery (anterior submuscular transposition) for a poor outcome, (2) anterior subcutaneous transposition followed by a salvage surgery for a poor outcome, (3) medial epicondylectomy followed by a salvage surgery for a poor outcome, and (4) anterior submuscular transposition. A poor outcome when anterior submuscular transposition was the initial surgery was considered an end point in the model. Preference values for temporary health states for UNE, the surgical procedures, and the complications were obtained through a time trade-off survey administered to family members and friends who accompanied patients to physician visits. Probabilities of clinical outcomes were derived from a Cochrane Collaboration meta-analysis and a systematic MEDLINE and EMBASE search of the literature. Medical care costs (in 2009 U.S. dollars) were derived from Medicare reimbursement rates. The model estimated quality-adjusted life-years and costs for a 3-year time horizon. A 3% annual discount rate was applied to costs and quality-adjusted life-years. Incremental cost-effectiveness ratios were calculated, and sensitivity analyses performed. Simple decompression as an initial procedure was the most cost-effective treatment strategy. A multi-way sensitivity analysis varying the preference values for the surgeries and a model structure sensitivity analysis varying the model assumptions did not change the conclusion. Under all evaluated scenarios, simple decompression yielded incremental cost-effectiveness ratios less than US$2,027 per quality-adjusted life-year. Simple decompression as an initial treatment option is cost-effective for UNE according to commonly used cost-effectiveness thresholds. Economic and Decision Analysis III.

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

BackgroundAcute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka.MethodsEconomic analysis was applied using public healthcare system payer perspective.Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008.ResultsAn affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.ConclusionsPost ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours.

Cost comparison of robotic, laparoscopic, and open partial nephrectomy.

394 Background: Laparoscopic and robotic partial nephrectomy (LPN and RPN) are increasingly common minimally invasive alternatives to open partial nephrectomy (OPN) for management of renal tumors. The cost discrepancies of these approaches warrants evaluation. We compared hospital costs associated with RPN, LPN, and OPN. Methods: Variable hospital costs including operating room (OR) time, supplies, anesthesia, inpatient care, radiology, pharmacy, and laboratory charges were captured for 25 patients who underwent OPN, LPN, and RPN at our institution between 11/2008 -9/2010. Fixed costs of acquisition of a laparoscopic suite and a robotic system (including maintenance) were amortized over 7 years. We considered alternative scenarios through one-way and multi-way sensitivity analysis. Results: We found similar overall variable costs for OPN, LPN, and RPN. Sensitivity analysis demonstrated that RPN and LPN are more cost effective than OPN (excluding fixed costs) if the average hospital stay is < 2 days, or OR time less is than 204 and 196 mins, respectively. By including fixed costs of equipment, RPN and LPN are always more costly than OPN. Conclusions: There was no difference among variable hospital costs of OPN, LPN, and RPN. Minimizing OR time and hospital stay reduces RPN and LPN costs to levels comparable to OPN. Inclusion of fixed costs makes LPN and RPN more expensive than OPN, but increased utilization and efficiency can decrease cost per case. [Table: see text]

Venous Thromboembolism: A United States Cost Model for a Preventable and Costly Adverse Event,

Abstract 4224 Introduction.Venous thromboembolism (VTE) is comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE). VTE is a common cause of serious morbidity and mortality associated predominantly with hospitalization. The concept of “preventable” DVT has recently emerged in the medical literature. VTE remains the number one cause of preventable death in hospitalized patients.To date, VTE costs at a United States (US) national level for total costs, hospital-acquired costs, and “preventable” hospital-acquired costs have not yet been well-defined. Recently, investigators have defined US annual total, hospital-acquired, and preventable DVT costs ranged from $7.5 to $39.5 billion, $5 to $26.5 billion, and $2.5 to $19.5 billion, respectively, in 2010 US dollars. When a multi-way sensitivity analysis was applied, taking into consideration higher incidence rates and costs, annual US total, hospital-acquired, and “preventable” DVT costs ranged from $9.8 to $52 billion, $6.8 to $36 billion, and $3.4 to $27 billion, respectively. In addition, it was estimated that the US annual prophylaxis cost of at-risk patients is less than $600 million per year.PE costs have not yet been defined within the US. Defining PE costs would allow for definition of total US VTE costs on an annual basis. Methods.The authors undertook a thorough research review to identify morbidities, incident rates of morbidities, costs of morbidities and incidences of death associated with PE. Identified references were then hand-searched to ensure no pertinent publications had been overlooked. A decision tree and cost model were developed to estimate the United States healthcare costs for PE, total hospital-acquired PE, and total “preventable” PE. The decision tree contains probability information on: PE's that are hospital-acquired or community-acquired; fatal vs. non-fatal; readmissions; VTE recurrence; minor bleed; major bleed; heparin induced thrombocytopenia; chronic thromboembolic pulmonary hypertension; and resolution of symptoms.Based on the decision tree, a cost model with calculations performed via Microsoft Office Excel was developed. The cost model contains all potential outcomes, representing all branches, to reflect all possible outcomes for a PE patient. The product of each outcome's probabilities and costs yields the average cost of a patient going down that respective path of the PE decision tree. Similarly, each branch contains a sum that reflects the average cost of a patient in that branch. Results.Preliminary estimates of US annual direct total, hospital-acquired, and preventable PE costs are likely to range (at a minimum) from $5 to $27 billion, $2.5 to $18 billion, and $2.1 to $15.4 billion, respectively, in 2010 US dollars. Indirect costs, primarily from death due to PE, are estimated to be a minimum of $19.5 billion per year with approximately $11 billion per year of this being “preventable.”A multi-way sensitivity analysis will be applied which will take into consideration higher incidence rates and costs. Final results of the cost analysis, with the multi-way sensitivity analysis will be presented. Preliminary estimates suggest minimum total annualized, direct, VTE costs of approximately $12.5 to $66 billion per year with a minimum of $4.6 to $34.9 billion per year being “preventable.” When factoring in the indirect costs of $11 billion per year, minimum, “preventable” VTE costs within the US appear to range from $15.6 to $45.9 billion per year. Final results of the cost analysis with the multi-way sensitivity analysis will be presented. Conclusions.Considerable savings and reduced morbidity and mortality could be realized if improved prevention rates were achieved and systems were implemented throughout the US. To date, US VTE costs have been underestimated. The DVT and PE cost models may be applied to estimate costs in the European Union and other countries. VTE prophylaxis is cost effective and may be a good target for healthcare savings with healthcare reform on the horizon. Mandating VTE quality measures, such as those from the Joint Commission and National Quality Forum, would expedite reducing health care costs and reduce unnecessary morbidity and mortality. Disclosures:No relevant conflicts of interest to declare.

Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis

Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown. Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses. In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests.

Economic impact of fatal and nonfatal road traffic injuries in Belize in 2007

To estimate the economic cost of road traffic injuries in Belize in 2007. A cross-sectional study was conducted using secondary cost data, assuming the health system and social perspectives. Epidemiologic information was obtained from the mortality database, the national hospital discharge database, and administrative records from police and the Ministry of Health. A health provider survey was carried out in order to estimate the postdischarge ambulatory utilization figures. Direct cost was estimated with the World Health Organization WHO-CHOICE (CHOosing Interventions that are Cost Effective) database. Prehospital costs were obtained from the Belize emergency response team. After estimating years of potential life lost using the Belize life expectancy for 2008 and methodology proposed by the Pan American Health Organization, the indirect cost associated with premature death was estimated with the human capital approach. Total estimation of road traffic injuries' economic costs used a decision tree model approach. Multiway sensitivity analysis was used to incorporate uncertainty in the estimations. Sixty-one people died due to road traffic injuries during 2007, 338 were hospitalized, and 565 people were estimated to be slightly injured. A total of 2,501 years of potential life were lost in Belize due to premature death, with a total economic cost of US$11,062,544. This figure represents 0.9% of the Belize gross domestic product. Direct cost was estimated at US$163,503, of which 2.4% was spent on fatalities, 46.7% on the severely injured, and 50.9% on the slightly injured. The economic cost estimations make clear the need to prevent road traffic injuries with a strategic and multisectoral approach that focuses on addressing the main problems identified.

Cryptogenic Stroke in a Patient With a PFO: A Decision Analysis

Octogenarian Israeli prime-minister Ariel Sharon recently sustained a mild, reversible stroke. A patent foramen ovale (PFO) was detected and anticoagulants were given pending PFO closure. A few days later, he sustained major intracerebral hemorrhage and has since remained in vegetative state. The events triggered serious criticism in the mass media, experts promoting one management option over others. Because knowledge of outcome and hindsight bias evaluation of appropriateness of care, we sought to systematically review the clinical case. We performed a formal decision analysis to identify the preferred management between anticoagulation, antiplatelets, PFO closure, or no treatment. Using the best evidence available, we built a decision tree. recurrent stroke and treatment complications within 1 year. Optimal decision was found to be critically sensitive to assumptions about etiology, efficacy and safety of treatments, recurrence risk, and to small changes in utilities. In multiway sensitivity analysis, when the risk of recurrent stroke was <0.12 per year, no treatment was the best management. PFO closure is dominant only when the risk of recurrent stroke is >0.12 per year closure effectiveness is assumed to be <0.28. When closure effectiveness is >0.6, it is inferior to anticoagulation and antiplatelet management. Uncertainties precluded a clear-cut answer and choice was found to be a "toss-up," often associated with much controversy. Use of novel therapies, such as PFO closure, outside clinical trials will not reduce uncertainty about efficacy.

Costs of needlestick injuries and subsequent hepatitis and HIV infection

ABSTRACTBackground: Physicians, nurses and other healthcare workers (HCWs) are at risk of bloodborne pathogens infection from needlestick injuries, but costs of needlesticks are little studied.Methods: We used the cost-of-illness and incidence approaches. We used the perspective of the medical provider (medical costs) and the individual (lost product­ivity). Data on needlesticks, infections from hepatitis B and C (HBV, HCV) and human immune-deficiency (HIV) among HCWs, as well as data on per-unit costs were culled from research literature, Centers for Disease Control and Prevention reports, and Bureau of Labor Statistics reports. We also generated estimates based upon industry employment and scenarios for source-patients. These data and estimates were combined with assumptions to produce a model that generated base-case estimates as well as one-way and multi-way probabilistic sensitivity analyses. Future costs were discounted by 3%.Results: We estimated 644 963 needlesticks in the healthcare industry for 2004 of which 49% generated costs. Medical costs were $107.3 million of which 96% resulted from testing and prophylaxis and 4% from treating long-term infections (34 persons with chronic HBV, 143 with chronic HCV, and 1 with HIV). Lost-work productivity generated $81.2 million, for which 59% involved testing and prophylaxis and 41% involved long-term infections. Combined medical and work productivity costs summed to $188.5 million. Multi-way sensitivity analysis suggested a range on combined costs from $100.7 million to $405.9 million.Conclusion: Detailed methodology was developed to estimate costs of needlesticks and subsequent infections for hospital-based and non-hospital-based health care workers. The combined medical and lost productivity costs comprised roughly 0.1% of all occupational injury and illness costs for all jobs in the economy. We did not account for lost home production or pain and suffering costs, however, nor did we estimate benefit/cost ratios of specific interventions to reduce needlesticks.

Cost‐effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2‐positive breast cancer

Adding trastuzumab to adjuvant chemotherapy provides significant clinical benefit in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. A cost-effectiveness analysis was performed to assess clinical and economic implications of adding trastuzumab to adjuvant chemotherapy, based upon joint analysis of NSABP B-31 and NCCTG N9831 trials. A Markov model with 4 health states was used to estimate the cost utility for a 50-year-old woman on the basis of trial results through 4 years and estimates of long-term recurrence and death based on a meta-analysis of trials. From 6 years onward, rates of recurrence and death were assumed to be the same in both trastuzumab and chemotherapy-only arms. Incremental costs were estimated for diagnostic and treatment-related costs. Analyses were from payer and societal perspectives, and these analyses were projected to lifetime and 20-year horizons. Over a lifetime, the projected cost of trastuzumab per quality-adjusted life year (QALY; discount rate 3%) gained was 26,417 dollars (range 9,104 dollars-69,340 dollars under multiway sensitivity analysis). Discounted incremental lifetime cost was 44,923 dollars, and projected life expectancy was 3 years longer for patients who received trastuzumab (19.4 years vs 16.4 years). During a 20-year horizon, the projected cost of adding trastuzumab to chemotherapy was 34,201 dollars per QALY gained. Key cost-effectiveness drivers were discount rate, trastuzumab price, and probability of metastasis. The cost-effectiveness result was robust to sensitivity analysis. Trastuzumab for adjuvant treatment of early stage breast cancer was projected to be cost effective over a lifetime horizon, achieving a cost-effectiveness ratio below that of many widely accepted oncology treatments.

Cost Effectiveness of Adjuvant Trastuzumab in Human Epidermal Growth Factor Receptor 2–Positive Breast Cancer

To evaluate the cost-effectiveness of 12-month adjuvant trastuzumab therapy in women with high-risk human epidermal growth factor receptor 2 (HER2) -positive early breast cancer. A Markov model tracked quarterly patients' transitions between five health states: disease free, local relapse, disease free after local relapse, metastatic disease, and death. Patients were allowed to incur symptomatic or asymptomatic transient cardiac dysfunction during trastuzumab administration. Probabilities were derived mainly from the combined report of the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 trials (95% node positive) and a meta-analysis by the Early Breast Cancer Trialists' Collaborative Group. Costs were estimated from the perspective of the Italian and US health care systems. The analysis was run during a 15-year time horizon. A 3% yearly discount rate was applied to both costs and life-years. Second-order Monte-Carlo and probabilistic sensitivity analyses were performed. Adjuvant trastuzumab increases life expectancy by 1.54 (1.18 discounted) quality-adjusted life-years (QALYs). At a cost of 675 euros and 767 dollars per weekly dose in the Italian and US setting, respectively, trastuzumab achieves its clinical benefit at a cost of 14,861 euros (95% CI, 3,917 euros to 44,028 euros) and 18,970 dollars (95% CI, 6,014 dollars to 45,621 dollars) per QALY saved. The incremental cost effectiveness was higher than 50,000 euros/QALY (or 60,000 dollars/QALY) at time horizons shorter than 7.8 years and for patients older than 76 years or with a 10-year risk of relapse lower than 15%. The results confirmed the cost effectiveness when simulating a Herceptin Adjuvant Trial (HERA) -like scenario at multiway sensitivity analysis. In a long-term horizon, adjuvant trastuzumab is a cost-effective therapy for patients with HER2-positive, high-risk, early breast cancer.

Cost Effectiveness of Lopinavir/Ritonavir Compared with Atazanavir??plus Ritonavir in Antiretroviral-Experienced Patients in??the US

To estimate the cost effectiveness and long-term combined effects of HIV disease and antiretroviral (ARV) therapy-related risk for coronary heart disease (CHD) on quality-adjusted survival and healthcare costs for ARV-experienced patients. A previously validated Markov model was updated and supplemented with the Framingham CHD risk equation. The representative patient in the model was male, aged 37 years and had a baseline 10-year CHD risk of 4.6%. Patients started with either lopinavir/ritonavir (LPV/r) or ritonavir-boosted atazanavir (ATV+RTV) as the protease inhibitor (PI). The proportions of patients with viral suppression below 400 and 50 copies/mL, respectively, at week 48 reported in clinical trials were used to estimate the differences between these two therapies. The daily ARV costs were $US 24.60 for LPV/r capsules (2005 costs) and $US 26.54 for LPV/r tablets (2006 costs), $US 29.76 for ATV and $US 8.57 for ritonavir (2005 costs). Costs of other ARV drugs were taken from average wholesale drug reports for 2005. The cost of AIDS events was estimated from Medicaid billing databases and reflected a medical care system perspective and 2005 treatment costs. Cost-effectiveness calculations assumed a lifetime time horizon. The effects of different model assumptions were tested in a multiway sensitivity analysis by combining extreme values of parameters. The model estimated a clinical and economic advantage to using LPV/r over ATV+RTV, which varied depending upon the use of LPV/r capsules or tablets. Using LPV/r capsules was comparatively beneficial for ARV-experienced patients in quality-adjusted life-months (QALMs) of 4.6 (corrected for differences in CHD risk) compared with ATV+RTV. In addition, there were 5- and 10-year overall per-patient cost savings of $US 17,995 and $US 21,298, respectively. Estimates for the LPV/r tablet formulation approved in 2005 (assuming similar efficacy) improved cost savings over 5- and 10-year periods to $US 19,598 and $US 23,126 per patient, respectively, because of a drug price differential. Sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. Model limitations were the uncertainty associated with the model parameters used. LPV/r appears to be a highly cost-effective regimen relative to ATV+RTV for the treatment of HIV. The long-term CHD risk associated with LPV/r was minimal compared with the increased risk of AIDS/death and costs projected for a less efficacious PI-based regimen.

Optimizing Choledocholithiasis Management

Endoscopic retrograde cholangiopancreatography (ERCP) is more cost-effective for managing incidental choledocholithiasis (CDL) after laparoscopic cholecystectomy and intraoperative cholangiogram (LC/IOC) than laparoscopic common bile duct exploration (LCBDE). A cost-effectiveness analysis was performed to compare ERCP with LCBDE. Sensitivity analyses were performed to determine the key contributors to cost-effectiveness between the 2 treatment options. Costs were approached from the institutional perspective considering a typical patient undergoing LC/IOC at a large referral center. The base case patient evaluated was a woman 18 years of age or older with symptomatic cholelithiasis and incidental CDL discovered at the time of LC/IOC. Endoscopic retrograde cholangiopancreatography with drainage procedure performed after LC/IOC or LCBDE during LC/IOC. Costs, quality-adjusted life years gained, mean cost-effectiveness ratios, and incremental cost-effectiveness ratios. In the base case analysis, ERCP was the optimal treatment choice with a cost of $24 300 for 0.9 quality-adjusted life years gained compared with $28 400 and 0.88 quality-adjusted life years for LCBDE. Endoscopic retrograde cholangiopancreatography remained the optimal strategy for CDL in multiway probabilistic sensitivity analysis. If LCBDE were performed and the cost of a potential operative case lost was $3100 or less and the cost of ERCP hospitalization was $18 000 or more, then LCBDE became the preferred treatment for CDL. Endoscopic retrograde cholangiopancreatography was both less costly and more effective than LCBDE. Factors important to choosing the best strategy for CDL management included the cost of a potential case lost due to LCBDE performance and the cost of ERCP hospitalization.

Cost-effectiveness analysis of telemedical devices for pre-clinical traffic accident emergency rescue in Germany

The purpose of this study is to assess the cost-effectiveness (net costs per life year gained) of telemedical devices for pre-clinical traffic accident emergency rescue in Germany. Two equipment versions of a telemedical device are compared from a societal perspective with the baseline in Germany, i.e. the non-application of telemedicine in emergency rescues. The analysis is based on retrospective statistical data covering a period of 10 years with discounted costs not adjusted for inflation. Due to the uncertainty of data, certain assumptions and estimates were necessary. The outcome is measured in terms of "life years gained" by reducing therapy-free intervals and improvements in first-aid provided by laypersons. The introduction of the basic equipment version, "Automatic Accident Alert", is associated with net costs per life year gained of euro 247,977 (at baseline assumptions). The full equipment version of the telemedical device would lead to estimated net costs of euro 239,524 per life year gained. Multi-way sensitivity-analysis with best and worst case scenarios suggests that decreasing system costs would disproportionately reduce total costs, and that rapid market penetration would largely increase the system's benefit, while simultaneously reducing costs. The net costs per life year gained in the application of the two versions of the telemedical device for pre-clinical emergency rescue of traffic accidents are estimated as quite high. However, the implementation of the device as part of a larger European co-ordinated initiative is more realistic.

Cost-effectiveness analysis of trastuzumab in the adjuvant setting for treatment of HER2+ breast cancer

6023 Background: The addition of trastuzumab (H) to a standard adjuvant therapy regimen (doxorubicin, cyclophosphamide, and paclitaxel; AC→T) is associated with a 52% reduction in risk (p &lt; 0.0001) of disease recurrence in patients with HER2 positive operable breast cancer (Romond et al, NEJM 2005). A cost-effectiveness analysis was performed to assess the lifetime clinical and economic implications of this important clinical finding. Methods: A Markov model with three health states (disease-free survival [DFS], recurrence, and death) was used to estimate the likely cost-effectiveness (CE) for a 50 yr old woman. Efficacy results from both trials (NCCTG N9831/NSABP B-31) were used through 4 years, and projections of time to recurrence and death were based on the literature (EBCTCG, Lancet 2005). After 4 years, annual transition probabilities to recurrence and death are assumed to be the same in both arms. Cardiotoxicity was higher with H (Perez EA, ASCO 2005). Actual total dose of H was used which was lower than scheduled dose. Incremental costs associated with addition of H to adjuvant therapy were estimated using average wholesale prices, Medicare reimbursement rates and other published data. These costs included testing for HER2 status, drug and administration costs for H, cardiac monitoring, treatment of cardiotoxicity, treatment following recurrence, and end-of-life costs for dying patients. Utility estimates were derived from the literature. Results: Over a lifetime, the cost per quality-adjusted life year gained (QALY; discount rate 3%) is $27,800, with a range of $17,900 to $39,100 under multi-way sensitivity analysis. Projected life expectancy from the Markov model is 3 years longer for H patients (19.4 v 16.4 yrs). Over a 20-year horizon, addition of H to AC→T is estimated to cost an additional $46,300 on average, with an expected gain of 1.28 QALYs-a cost/QALY of $36,100. The key drivers of CE are the cost of treatment and the improvement in DFS. Conclusion: The model projects a cost-utility ratio that is below that of many treatments used for oncology patients. The use of trastuzumab in the adjuvant setting for HER2+ breast cancer is projected to be cost-effective. [Table: see text]

The clinical and cost-effectiveness of left ventricular assist devices for end-stage heart failure: a systematic review and economic evaluation

To assess the clinical and cost-effectiveness of left ventricular assist devices (LVADs) as a bridge to heart transplantation (BTT), as a bridge to myocardial recovery (BTR) or as a long-term chronic support (LTCS) for people with end-stage heart failure (ESHF). For the systematic review, electronic databases and bibliographies of related publications plus experts and manufacturers. For the economic evaluations, data originated from the systematic review of clinical and cost-effectiveness, UK hospitals, device manufacturers and expert opinion. For the systematic review, studies were selected and assessed against a set of rigorous criteria; data were then synthesised using a narrative approach through subgroup analysis based on the indication for treatment, type of LVAD and quality of studies. The economic evaluation developed two models to evaluate the use of LVADs, first as a BTT and second as LTCS for patients suffering from ESHF. Sixteen studies assessed the clinical effectiveness of LVADs as a BTT. Despite the poor methodological quality of the evidence, LVADs appeared beneficial compared to other treatment options (i.e. inotropic agents or usual care) or to no care (i.e. the natural history of ESHF) improving the survival of people with ESHF during the period of support and following heart transplantation. Patients supported by an LVAD appeared to have an improved functional status compared with those on usual care and experienced an improvement in their quality of life from before device implantation to the period during support. Serious adverse events are a risk for patients with an LVAD. With a scarcity of evidence directly comparing different devices, it is difficult to identify specific devices as the most clinically effective. The HeartMate LVAD is the only device that has evidence comparing it with the different alternatives, appearing to be more clinically effective than inotropic agents and usual care and as clinically effective as the Novacor device. Second generation devices, such as Jarvik 2000 and MicroMed Debakey LVADs, are early in their development but show considerable promise that should be assessed through long-term studies. Evidence of the clinical effectiveness of LVADs as a BTR was limited to seven non-comparative observational studies that appeared to show that the LVADs were beneficial in providing support until myocardial recovery. It was not possible to assess whether the LVADs are more effective than other alternatives or specific devices. No evidence was found on the quality of life or functional status of patients and limited information on adverse events was reported. Six studies assessed the clinical effectiveness of LVADs as an LTCS and from these it was evident that LVADs provided benefits in terms of improved survival, functional status and quality of life. Nineteen studies assessed the costs and cost-effectiveness of LVADS for people with ESHF, with the majority being simple costing studies and very few studies of the cost-effectiveness of LVADs. With no relevant cost-effectiveness studies available, an economic evaluation for BTT and LTCS was developed. The economic evaluation has shown that neither LVAD indication considered, that is, BTT and LTCS, is a cost-effective use. For the HeartMate LVAD used as a BTT the cost per QALY was pound 65,242. In the less restrictive indication, LTCS, where LVADs are not just given to patients awaiting transplantation, the analysis has shown that LTCS is not cost-effective. The baseline cost per QALY of the first-generation HeartMate LVAD was pound 170,616. One- and multi-way sensitivity analysis had limited effect on the cost per QALY. A hypothetical scenario based on the cost of a second-generation MicroMed DeBakey device illustrated that a 60% improvement in survival over first-generation devices was necessary before the incremental cost-effectiveness approached pound 40,000 per QALY. Although the review showed that LVADs are clinically effective as a BTT with ESHF, the economic evaluation indicated that they are not cost-effective. With the limited and declining availability of donor hearts for transplantation, it appears that the future of the technology is in its use as an LTCS. Further research is needed to examine the clinical effectiveness of LVADs for people with ESHF, assessing patient survival, functional ability, quality of life and adverse events. Evaluations of the clinical effectiveness of LVADs should include economic evaluations, as well as data on quality of life, utilities, resources and costs. A systematic review of the epidemiology of ESHF should be undertaken to assess its potential impact.

Orlistat for the treatment of obesity: cost utility model

This study aimed to assess the cost utility of orlistat treatment based on (i) criteria from recent guidance from the National Institute for Clinical Excellence (NICE) for England and Wales (treatment discontinued if weight loss < 5% at 3 months; and < 10% at 6 months); and (ii) alternative criteria from the European Agency for the Evaluation of Medicinal Products (EMEA) licence for orlistat prescription in the European Community (treatment discontinued if weight loss < 5% at 3 months). Subjects were 1398 obese individuals who participated in three large European Phase III trials of orlistat treatment for adults (BMI: 28-47 kg m(-2)). Measures were: response to treatment in orlistat and placebo treatment groups; health benefit expressed as quality adjusted life years (QALYs) gained associated with weight loss; costs associated with orlistat treatment. In the cost utility model with multiway sensitivity analysis, the cost/QALY gained using the NICE criteria was estimated to be 24,431 pounds (sensitivity analysis range: 10,856 to 77,197 pounds). The cost/QALY gained using the alternative EMEA criteria was estimated to be 19,005 pounds (range: 8,840 to 57,798 pounds). In conclusion, NICE guidance for the continued use of orlistat was supported in this updated cost utility model, comparing favourably with a previously published estimate of 45,881 pounds per QALY gained. Moreover, the value for money of orlistat treatment is improved further if EMEA treatment criteria for continued orlistat treatment are applied. The EMEA criteria should be considered in any future changes to the NICE guidance or in guidance issued by similar agencies.

The role of modelling in prioritising and planning clinical trials.

To identify the role of modelling in planning and prioritising trials. The review focuses on modelling methods used in the construction of disease models and on methods for their analysis and interpretation. Searches were initially developed in MEDLINE and then translated into other databases. Systematic reviews of the methodological and case study literature were undertaken. Search strategies focused on the intersection between three domains: modelling, health technology assessment and prioritisation. The review found that modelling can extend the validity of trials by: generalising from trial populations to specific target groups; generalising to other settings and countries; extrapolating trial outcomes to the longer term; linking intermediate outcome measures to final outcomes; extending analysis to the relevant comparators; adjusting for prognostic factors in trials; and synthesising research results. The review suggested that modelling may offer greatest benefits where the impact of a technology occurs over a long duration, where disease/technology characteristics are not observable, where there are long lead times in research, or for rapidly changing technologies. It was also found that modelling can inform the key parameters for research: sample size, trial duration and population characteristics. One-way, multi-way and threshold sensitivity analysis have been used in informing these aspects but are flawed. The payback approach has been piloted and while there have been weaknesses in its implementation, the approach does have potential. Expected value of information analysis is the only existing methodology that has been applied in practice and can address all these issues. The potential benefit of this methodology is that the value of research is directly related to its impact on technology commissioning decisions, and is demonstrated in real and absolute rather than relative terms; it assesses the technical efficiency of different types of research. Modelling is not a substitute for data collection. However, modelling can identify trial designs of low priority in informing health technology commissioning decisions. Good practice in undertaking and reporting economic modelling studies requires further dissemination and support, specifically in sensitivity analyses, model validation and the reporting of assumptions. Case studies of the payback approach using stochastic sensitivity analyses should be developed. Use of overall expected value of perfect information should be encouraged in modelling studies seeking to inform prioritisation and planning of health technology assessments. Research is required to assess if the potential benefits of value of information analysis can be realised in practice; on the definition of an adequate objective function; on methods for analysing computationally expensive models; and on methods for updating prior probability distributions.

Cost-minimization analysis: radiation treatment with and without a multi-leaf collimator

Purpose: To compare the costs of radiation treatment on a linear accelerator with a multileaf collimator (MLC) versus treatment on a linear accelerator without an MLC. The study was designed to determine whether the increased throughput of fields and decreased block cutting made the MLC cost effective from an institutional perspective. Methods and Materials: The number of fields, basic treatment equivalent, equivalent simple treatment visits, and blocks were prospectively collected for the four linear accelerators. Building, equipment, staffing, and service costs were all obtained in 1999 Australian dollars from the manufacturers and hospital department heads. The Joint Radiation Oncology Centre at Westmead and Nepean Hospitals, which are Australian public hospitals, runs as one unit, with the same staff, and currently operates five linear accelerators. Currently, four of the linear accelerators are used for general radiotherapy, operating for exactly the same hours; the final machine operates more limited hours and is used for specialized radiotherapy techniques and emergency cases. Results: The two machines with MLCs, on average, treated 5,169 fields each, while the two machines without MLCs treated 4,543 fields in a 3-month period, a 12% increase in throughput. The two non-MLC machines required 155 premounted trays (PMTs) in total, while the MLC machines required 17 PMTs. Linear accelerators with MLCs were demonstrably more efficient, and while their capital costs were higher, the reduction in labor costs associated with block cutting and, particularly the increased throughput, more than offset these initial costs. The total cost of a radiation field with an MLC was found to be $A101.69 compared to $A106.98 without an MLC. A multiway sensitivity analysis showed the results to be robust. The worst-case scenario was a departmental savings of $A168,000 per year; the best-case scenario was a savings of $A680,000 per year. Conclusion: Under the conditions pertaining to the radiation oncology department in this group of hospitals, and in similar departments, the use of an MLC can be justified.