Uncertainty In Cost-effectiveness Research Articles

Cost-effectiveness uncertainty may bias the decision of coal power transitions in China

A transition away from coal power always maintains a high level of complexity as there are several overlapping considerations such as technical feasibility, economic costs, and environmental and health impacts. Here, we explore the cost-effectiveness uncertainty brought by policy implementation disturbances of different coal power phaseout and new-built strategies (i.e., the disruption of phaseout priority) in China based on a developed unit-level uncertainty assessment framework. We reveal the opportunity and risk of coal transition decisions by employing preference analysis. We find that, the uncertainty of a policy implementation might lead to potential delays in yielding the initial positive annual net benefits. For example, a delay of six years might occur when implementing the prior phaseout practice. A certain level of risk remains in the implementation of the phaseout policy, as not all strategies can guarantee the cumulative positive net benefits from 2018–2060. Since the unit-level heterogeneities shape diverse orientation of the phaseout, the decision-making preferences would remarkably alter the selection of a coal power transition strategy. More strikingly, the cost-effectiveness uncertainty might lead to missed opportunities in identifying an optimal strategy. Our results highlight the importance of minimizing the policy implementation disturbance, which helps mitigate the risk of negative benefits and strengthen the practicality of phaseout decisions.

SA45 Dealing with Uncertainty in Cost-Effectiveness and Affordability to Inform Risk-Averse Healthcare Decision Makers

Decision makers are increasingly concerned about both cost-effectiveness and affordability, resulting in the use of willingness-to-pay (WTP) and budget impact thresholds. The cost-effectiveness acceptability curve (CEAC) is widely used to summarize uncertainty in cost-effectiveness analysis (CEA) results. As CEAC ignores the resources necessary to fund the intervention and assumes a risk neutral attitude for decision makers, cost-effectiveness affordability curves (CEAFC), and since 2021, cost-effectiveness risk-aversion curves (CERAC) have been proposed to complement CEACs. We aim to assess whether the use of CEAFC has increased and where CERAC has been applied in economic evaluations of healthcare technologies.

Methods for Communicating the Impact of Parameter Uncertainty in a Multiple-Strategies Cost-Effectiveness Comparison.

PurposeAnalyzing and communicating uncertainty is essential in medical decision making. To judge whether risks are acceptable, policy makers require information on the expected outcomes but also on the uncertainty and potential losses related to the chosen strategy. We aimed to compare methods used to represent the impact of uncertainty in decision problems involving many strategies, enhance existing methods, and provide an open-source and easy-to-use tool.MethodsWe conducted a systematic literature search to identify methods used to represent the impact of uncertainty in cost-effectiveness analyses comparing multiple strategies. We applied the identified methods to probabilistic sensitivity analysis outputs of 3 published decision-analytic models comparing multiple strategies. Subsequently, we compared the following characteristics: type of information conveyed, use of a fixed or flexible willingness-to-pay threshold, output interpretability, and the graphical discriminatory ability. We further proposed adjustments and integration of methods to overcome identified limitations of existing methods.ResultsThe literature search resulted in the selection of 9 methods. The 3 methods with the most favorable characteristics to compare many strategies were 1) the cost-effectiveness acceptability curve (CEAC) and cost-effectiveness acceptability frontier (CEAF), 2) the expected loss curve (ELC), and 3) the incremental benefit curve (IBC). The information required to assess confidence in a decision often includes the average loss and the probability of cost-effectiveness associated with each strategy. Therefore, we proposed the integration of information presented in an ELC and CEAC into a single heat map.ConclusionsThis article presents an overview of methods presenting uncertainty in multiple-strategy cost-effectiveness analyses, with their strengths and shortcomings. We proposed a heat map as an alternative method that integrates all relevant information required for health policy and medical decision making.HighlightsTo assess confidence in a chosen course of action, decision makers require information on both the probability and the consequences of making a wrong decision.This article contains an overview of methods for presenting uncertainty in multiple-strategy cost-effectiveness analyses.We propose a heat map that combines the probability of cost-effectiveness from the cost-effectiveness acceptability curve (CEAC) with the consequences of a wrong decision from the expected loss curve.Collapsing of the CEAC can be reduced by relaxing the CEAC, as proposed in this article.Code in Microsoft Excel and R is provided to easily analyze data using the methods discussed in this article.

Evaluación costo-efectividad de las prótesis con superficie cerámica-polietileno vs. metal-polietileno para reemplazo articular primario de cadera en Colombia

BackgroundThere is a statistically significant difference of 1.2% in the revision rate in a 15 year follow in favour of the use of ceramic on highly cross-linked polyethylene (CP) recently described in the Australian National Joint Registry. The purpose of this study is to compare the cost-effectiveness of CP implants and metal-on-highly cross-linked polyethylene (MP) implants in patients undergoing total hip replacement (THR). Materials and methodsA TreeAge Pro® decision tree was constructed in order to determine cost-effectiveness between two bearing surfaces: CP or MP from the perspective of the Colombian Health Care System (CHCS). The model parameters where taken from the best available evidence. For the effectiveness, a systematic review of the literature was performed, and costs were taken from local market rates. The incremental cost-effectiveness ratio was determined assuming a time horizon of 15 years, and a discount rate of 5% was used for costs and effectiveness. Cost-effectiveness uncertainty was controlled with deterministic and probabilistic sensitivity analysis. ResultsFor the CHCS, with a 1PIB per capita threshold adjusted per QALY in adults undergoing (THR), the use of a CP implant is not cost-effective, given that the effectiveness is similar (11.32 QALY for MP vs 11.36 QALY for CP), and the cost is three times higher (MP $ 861.826 COP vs CP $ 2.298.090 COP). The deterministic sensitivity analysis showed that the most important variable in the results is the ceramic cost. Discussionfor the CHCS the routine use of ceramic-highly cross-linked polyethylene bearing surface in a THR is not a cost-effective strategy.Evidence Level: I

Cost-Effectiveness of the Manchester Approach to Identifying Lynch Syndrome in Women with Endometrial Cancer.

Lynch syndrome (LS) is a hereditary cancer syndrome responsible for 3% of all endometrial cancer and 5% in those aged under 70 years. It is unclear whether universal testing for LS in endometrial cancer patients would be cost-effective. The Manchester approach to identifying LS in endometrial cancer patients uses immunohistochemistry (IHC) to detect mismatch repair (MMR) deficiency, incorporates testing for MLH1 promoter hypermethylation, and incorporates genetic testing for pathogenic MMR variants. We aimed to assess the cost-effectiveness of the Manchester approach on the basis of primary research data from clinical practice in Manchester. The Proportion of Endometrial Tumours Associated with Lynch Syndrome (PETALS) study informed estimates of diagnostic performances for a number of different strategies. A recent microcosting study was adapted and was used to estimate diagnostic costs. A Markov model was used to predict long-term costs and health outcomes (measured in quality-adjusted life years, QALYs) for individuals and their relatives. Bootstrapping and probabilistic sensitivity analysis were used to estimate the uncertainty in cost-effectiveness. The Manchester approach dominated other reflex testing strategies when considering diagnostic costs and Lynch syndrome cases identified. When considering long-term costs and QALYs the Manchester approach was the optimal strategy, costing £5459 per QALY gained (compared to thresholds of £20,000 to £30,000 per QALY commonly used in the National Health Service (NHS)). Cost-effectiveness is not an argument for restricting testing to younger patients or those with a strong family history. Universal testing for Lynch syndrome in endometrial cancer patients is expected to be cost-effective in the U.K. (NHS), and the Manchester approach is expected to be the optimal testing strategy.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

PCN411 HOW ARE SINGLE-ARM TRIALS PERCEIVED IN HEATH TECHNOLOGY ASSESSMENTS FOR CHRONIC LEUKAEMIA ACROSS THE EU5, AUSTRALIA AND CANADA?

Single-arm trials are common in chronic leukaemia due to the rare nature of the disease and the urgent need to increase patient access to treatments where there are currently only limited options. The objective was to assess how single-arm trials are perceived in heath technology assessments (HTAs) for chronic leukaemia across the EU5, Australia and Canada. All interventions submitted to NICE in the last 4 years (January 2015 - December 2018) for chronic leukaemia and presenting only single-arm evidence were selected. Appraisals for these interventions were then searched in the rest of the EU5, Australia and Canada. Bosutinib, ponatinib and venetoclax as monotherapy met the search criteria. Amongst HTA bodies searched, 69.7% (23/33) of appraisal documents were publicly available and extracted. Mean time between regulatory approval and final HTA guidance was 20.4 months across all countries. Shortest and longest HTA processes were in Germany (mean 6.0 months) and Spain (mean 34.0 months), respectively. Most countries commented on the lack of comparative data, with G-BA mentioning a high risk of bias, awarding venetoclax the lowest added benefit rating for orphan drugs. The Spanish HTA bodies appreciated how clinical-effectiveness was shown in ponatinib and venetoclax where no other treatment was available, yet commented it was not possible to reliably estimate cost-effectiveness with single-arm trial data. Ponatinib and venetoclax were recommended in the UK and Spain, with caveats including indication restrictions, data collection requirements and price discounts. Multiple submissions were required in Australia, with criticisms surrounding the inability to reliably assess comparative efficacy indirectly, creating uncertainty in cost-effectiveness. All interventions received access in most markets, albeit with certain restrictions and conditions. However, significant challenges were raised in demonstrating cost-effectiveness, leading to price reductions, market access arrangements and longer durations of appraisal.

Cost-Effectiveness of One-Time Birth Cohort Screening for Hepatitis C as Part of the National Health Service Health Check Program in England

Background and ObjectivesBirth cohort screening for the hepatitis C virus (HCV) has been implemented in the US, but there is little evidence of its cost-effectiveness in England. We aim to evaluate the cost-effectiveness of one-time HCV screening for individuals born between 1950 and 1979 as part of the National Health Service health check in England, a health check for adults aged 40 to 74 years in primary care. MethodsA Markov model was developed to analyze add-on HCV testing to the National Health Service health check for individuals in birth cohorts between 1950 and 1979, versus current background HCV testing only, over a lifetime horizon. The model used data from a back-calculation model of the burden of HCV in England, sentinel surveillance of HCV testing, and published literature. Results are presented from a health service perspective in pounds in 2017, as incremental cost-effectiveness ratios per quality-adjusted life years gained. ResultsThe base-case incremental cost-effectiveness ratios ranged from £7648 to £24 434, and £18 681 to £46 024, across birth cohorts when considering 2 sources of HCV transition probabilities. The intervention is most likely to be cost-effective for those born in the 1970s, and potentially cost-effective for those born from 1955 to 1969. The model results were most sensitive to the source of HCV transition probabilities, the probability of referral and receiving treatment, and the HCV prevalence among testers. The maximum value of future research across all birth cohorts was £11.3 million at £20 000 per quality-adjusted life years gained. ConclusionBirth cohort screening is likely to be cost-effective for younger birth cohorts, although considerable uncertainty exists for other birth cohorts. Further studies are warranted to reduce uncertainty in cost-effectiveness and consider the acceptability of the intervention.

Improving Patient Access to New Drugs in South Korea: Evaluation of the National Drug Formulary System.

This study reviews and evaluates the national drug formulary system used to improve patient access to new drugs by making reimbursement decisions for new drugs as part of the South Korean national health insurance system. The national health insurance utilizes three methods for improving patient access to costly drugs: risk-sharing agreements, designation of essential drugs, and a waiver of cost-effectiveness analysis. Patients want reimbursement for new drugs to be processed quickly to improve their access to these drugs, whereas payers are careful about listing them given the associated financial burden and the uncertainty in cost-effectiveness. However, pharmaceutical companies are advocating for drug prices above certain thresholds to maintain global pricing strategies, cover the costs of drug development, and fund future investments into research and development. The South Korean government is expected to develop policies that will improve patient access to drugs with unmet needs for broadening health insurance coverage. Simultaneously, the designing of post-listing management methods is warranted for effectively managing the financial resources of the national health insurance system.

A cluster-randomized trial to reduce caesarean delivery rates in Quebec: cost-effectiveness analysis

BackgroundWidespread increases in caesarean section (CS) rates have sparked concerns about risks to mothers and infants and rising healthcare costs. A multicentre, two-arm, cluster-randomized trial in Quebec, Canada assessed whether an audit and feedback intervention targeting health professionals would reduce CS rates for pregnant women compared to usual care, and concluded that it reduced CS rates without adverse effects on maternal or neonatal health. The effect was statistically significant but clinically small. We assessed cost-effectiveness to inform scale-up decisions.MethodsA prospective economic evaluation was undertaken using individual patient data from the Quality of Care, Obstetrics Risk Management, and Mode of Delivery (QUARISMA) trial (April 2008 to October 2011). Analyses took a healthcare payer perspective. The time horizon captured hospital-based costs and clinical events for mothers and neonates from labour onset to 3 months postpartum. Resource use was identified and measured from patient charts and valued using standardized government sources. We estimated the changes in CS rates and costs for the intervention group (versus controls) between the baseline and post-intervention periods. We examined heterogeneity between clinical subgroups of high-risk versus low-risk pregnancies and estimated the joint uncertainty in cost-effectiveness over 20,000 trial simulations. We decomposed costs to identify drivers of change.ResultsThe intervention group experienced per-patient reductions of 0.005 CS (95% confidence interval (CI): −0.015 to 0.004, P = 0.09) and $180 (95% CI: −$277 to − $83, P < 0.001). Women with low-risk pregnancies experienced statistically significant reductions in CS rates and costs; changes for the high-risk subgroup were not significant. The intervention was “dominant” (effective in reducing CS and less costly than usual care) in 86.08% of simulations. It reduced costs in 99.99% of simulations. Cost reductions were driven by lower rates of neonatal complications in the intervention group (−$190, 95% CI: −$255 to − $125, P < 0.001). Given 88,000 annual provincial births, a similar intervention could save $15.8 million (range: $7.3 to $24.4 million) in Quebec annually.ConclusionsFrom a healthcare payer perspective, a multifaceted intervention involving audits and feedback resulted in a small reduction in caesarean deliveries and important cost savings. Cost reductions are consistent with improved quality of care in intervention group hospitals.Trial registrationInternational Clinical Trials Registry Platform, ISRCTN95086407. Registered on 23 October 2007

Impact of small study bias on cost-effectiveness acceptability curves and value of information analyses.

It is well known that small, randomized, controlled trials (RCTs) have limited validity. When comparing the results of meta-analyses with those of later large trials or with those of large trials removed from the meta-analyses, discrepancies were reported. This paper addresses two issues: (1) how measures of the uncertainty in cost-effectiveness, i.e., cost-effectiveness acceptability curves (CEACs), and the expected value of perfect information (EVPI) are affected by the limited validity of small trials and (2) how to deal with this bias. To this end, the paper adopts a Bayesian approach. Using empirical estimates for the validity of small RCTs compared to larger RCTs, the probability of cost-effectiveness drops by almost 10 %, while the EVPI is three times higher. In conclusion, traditional CEACs and EVPI analyses based on (small) RCTs may need careful appraisal. Ignoring prior evidence on the validity of small-size trials leads to an underestimation of uncertainty in cost-effectiveness. For future economic analyses, it is important to incorporate aspects of uncertainty which are caused by flawed data on effectiveness .

Buy now, saved later? The critical impact of time-to-pandemic uncertainty on pandemic cost-effectiveness analyses

Background Investment in pandemic preparedness is a long-term gamble, with the return on investment coming at an unknown point in the future. Many countries have chosen to stockpile key resources, and the number of pandemic economic evaluations has risen sharply since 2009. We assess the importance of uncertainty in time-to-pandemic (and associated discounting) in pandemic economic evaluation, a factor frequently neglected in the literature to-date. Methods We use a probability tree model and Monte Carlo parameter sampling to consider the cost effectiveness of antiviral stockpiling in Cambodia under parameter uncertainty. Mean elasticity and mutual information (MI) are used to assess the importance of time-to-pandemic compared with other parameters. We also consider the sensitivity to choice of sampling distribution used to model time-to-pandemic uncertainty. Results Time-to-pandemic and discount rate are the primary drivers of sensitivity and uncertainty in pandemic cost effectiveness models. Base case cost effectiveness of antiviral stockpiling ranged between is US$112 and US$3599 per DALY averted using historical pandemic intervals for time-to-pandemic. The mean elasticities for time-to-pandemic and discount rate were greater than all other parameters. Similarly, the MI scores for time to pandemic and discount rate were greater than other parameters. Time-to-pandemic and discount rate were key drivers of uncertainty in cost-effectiveness results regardless of time-to-pandemic sampling distribution choice. Conclusions Time-to-pandemic assumptions can “substantially” affect cost-effectiveness results and, in our model, is a greater contributor to uncertainty in cost-effectiveness results than any other parameter. We strongly recommend that cost-effectiveness models include probabilistic analysis of time-to-pandemic uncertainty.

Clinical Haematology Services In The Community. A Case Study

Background Clinical Haematology is a specialised service largely delivered in District General &amp; Tertiary Hospitals. Most haematological malignancies are chronic disorders often in the elderly with a simple clinical management plan, requiring periodic clinical monitoring. Many cases are non progressive. In English NHS, provision of specialised care in community is proposed as a cost efficiency measure &amp; also sits well with ‘Localism where possible, centralisation where necessary' principle. There is little published evidence in context of clinical haematology services in the community. Research Methodology This research is confined to clinical haematology services in West Kent, England evaluating attitudes and behaviours of health professionals, analysing desirable features in a community model of care and finally comparing costs in hospital and community settings. This is a descriptive non experimental cross sectional qualitative comparative group study with a two stage strategy. In the first stage, an anonymised web based survey consisting of open and closed items was conducted in a convenience sample of key stakeholders. To secure completeness and gain broader and holistic understanding of the rationale behind the survey findings, individual face to face semi structured interviews were conducted. Pilot survey (7 respondents) ; Main survey : convenience sample of 228 stakeholders; 49 responded (21.5%) with 35 complete datasets and 14 datasets missing some information. Respondent characteristics (n=49): age (&lt; 39 years, n = 5), (40 – 54, 19), (&gt; 55, 11) ; males 20 ; females 15; job type: Commissioners n = 3, Hospital managers 7 , Haematologists 7 &amp; Primary care practitioners 19. Survey &amp; Interview Content analysis There is an increasing demand for clinical haematology services with a rising elderly population. At least 25 percent clinical haematology outpatient and day case services may be safely shifted to a community setting. There were wide variations in views with regards to policy priorities. There are professional divisions with hospitals less likely to drive the change. Respondents identified the following barriers in providing community care: technological; regulatory and governance; skill set (lack of specialist skills); patient safety (resuscitation facilities; specialist supervision) &amp; uncertainty of cost effectiveness. Qualitative analyses of interviews suggest professional barriers are probably surmountable by the positive contribution of system leadership, collaborative working, introduction of appropriate technological tools and robust communication. Clinical commissioners will have to provide systemic leadership. There is a desire to ‘integrate' services though there was lack of clarity about what ‘integration' meant. Attitudinal differences Haematologists appeared to be more sceptical of policies. Hospital managers, haematologists and those above 40 years were more supportive of hospital based outpatient clinics. Those above 55 years and hospital managers were less likely to support ‘localism' while it resonated strongly with commissioners. There were wide variations in views with regards to policy priorities and ‘statistically significant' differences (p value .003 at 95 percent CI) between those in favour of hospital care (haematologists &amp; hospital managers) and primary care (primary care practitioners &amp; commissioners) (Figure 1). Conclusion Specialist haemato-oncology services are clearly necessary and this research project does not seek to challenge that. In face of the policy of ‘centralising' specialist services, these findings suggest an ‘anomaly' that barriers can be overcome and specialist services to some extent can be provided in the community (Figure 2). Innovative ways of delivering specialised care is fundamental to meet this challenge. Recommendations An inductive – deductive cycle of discovery will further improve our understanding of why ‘closer to home' services may or may not work for some specialities such as clinical haematology and define the ‘boundary' conditions better. The project will aid commissioners &amp; decision makers involved in reconfiguration of clinical haematology services in English NHS. Disclosures: No relevant conflicts of interest to declare.

Targeted screening for Coeliac Disease among irritable bowel syndrome patients: analysis of cost-effectiveness and value of information

A high prevalence of Coeliac Disease (CD) is found among patients with a clinical diagnosis of irritable bowel syndrome (IBS) compared to the general population. Symptoms of CD are quite similar to IBS, but its treatment is different. The aim of this study was to evaluate the cost-effectiveness of screening for CD in patients with diarrhoea/mixed type IBS (IBS-D/mix) in terms of cost per quality adjusted life year (QALY) in the Netherlands. A decision model was constructed to evaluate the costs and health benefits of serological testing followed by confirmatory endoscopy with biopsy. Probabilistic sensitivity analysis (PSA) was performed to examine the effect of parameter uncertainty. Finally, the budget impact of implementing the screening process was also computed for implementation over a 10-year time horizon. Screening resulted in an increase of about 0.07 quality life years (QALYs) per patient over a lifetime horizon. The incremental cost effectiveness ratio was about 6,200 euro/QALY compared to no screening. The PSA showed that the uncertainty in cost effectiveness results is not considerable. The value of information analysis confirmed the robustness of the results. Screening all current patients with diarrhea/mixed type IBS would require a total budget of about 25 million Euros over a 10 year time period. Screening patients with IBS-D or IBS-mix for CD is almost certainly cost-effective. The screening program would improve the quality of life of those patients with IBS symptoms who actually have CD at a relatively low cost.

PCV59 Where Did the Time Go?: Temporal Uncertainty in Cost-Effectiveness Decision Models

WHERE DID THE TIME GO?: TEMPORAL UNCERTAINTY IN COSTEFFECTIVENESS DECISION MODELS Mahon R1, Manca A2, Palmer S1 1University of York, York, North Yorkshire, UK, 2University of York, Heslington, York, UK OBJECTIVES: Since the required time horizon in a cost effectiveness decision model often exceeds the evidence time horizon, numerous temporal uncertainties arise regarding model parameters and structures. The objective of this study is to demonstrate, through a motivating example: (i) why temporal uncertainty ought to be addressed more thoroughly than it has been to date; (ii) how this uncertainty might be expressed in decision models; and (iii) the consequences for the costeffectiveness results when temporal uncertainty is incorporated into the analysis. METHODS: Taking the example of a decision model seeking to estimate the costeffectiveness of an early interventional strategy for patients with non-ST-elevation acute coronary syndrome, we firstly highlight the model components that are exposed to temporal uncertainty. Focusing on two key model parameters, we explore the extent to which the existing short-term evidence could reasonably be extrapolated over time. We then suggest a means to quantitatively convey the temporal uncertainty pertaining to these parameters within the model. RESULTS: Temporal uncertainty is shown to have a significant impact on the cost-effectiveness results. Value-of-Information analysis (specifically population EVPPI) suggests that for this example, it may have been more cost-effective to delay adoption recommendation until further evidence on the temporal behaviour of parameters was collected. CONCLUSIONS: Temporal uncertainty, though rarely formally modelled, is a significant characteristic of cost-effectiveness decision models. It is possible and desirable to express temporal uncertainty within a decision model, as the complete model may show that it is more cost-effective to collect further information on the temporal behaviour of model parameters before issuing an adoption recommendation.

A systematic review and economic evaluation of the clinical effectiveness and cost-effectiveness of aldosterone antagonists for postmyocardial infarction heart failure

Two aldosterone inhibitors are currently licensed for heart failure (HF) in the UK: spironolactone and eplerenone. Recent clinical guidelines recommend eplerenone after an acute myocardial infarction (MI) for patients with symptoms and/or signs of HF and left ventricular dysfunction. The primary objective was to evaluate relative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone in patients with postMI HF and explore the possibility of conducting an indirect comparison of spironolactone and eplerenone. A second objective was to undertake value-of-information (VOI) analyses to determine the need for further research to identify research questions critical to decision-making and to help inform the design of future studies. Relevant databases including MEDLINE, EMBASE and CENTRAL were searched between September and December 2008. Randomised controlled trials (RCTs) of spironolactone, eplerenone, canrenone or potassium canrenoate were included if conducted in a postMI HF population. Trials of general HF patients with a subgroup of postMI HF patients were considered if they had at least 100 ischaemic participants per arm and the authors provided subgroup data when contacted. Adverse events summary data were sought from recognised reference sources and RCTs or observational studies in any population that recruited more than 100 participants. The comparative clinical effectiveness and cost-effectiveness of spironolactone and eplerenone was derived using Bayesian meta-regression drawing on a wider 'network' of aldosterone trials to those considered in the main clinical effectiveness review. An alternative scenario was also considered assuming a 'class effect' for the aldosterone antagonists in terms of major clinical events, but allowing for potential differences in side effect profiles. Cost-effectiveness was assessed using incremental cost-effectiveness ratios (ICERs) where appropriate. Uncertainty in cost-effectiveness results was also presented and used to inform future research priorities using VOI analyses based on expected value of perfect information (EVPI). A probabilistic decision analytic model was developed to estimate cost-effectiveness of spironolactone, eplerenone and standard care for management of postMI HF, provide estimates relevant to the NHS and explore alternative approaches to an indirect comparison between spironolactone and eplerenone. The model incorporated a lifetime horizon to estimate outcomes in terms of quality-adjusted life-years (QALYs) and costs from the NHS persepctive. In the base-case analysis, 2-year treatment duration was assumed, consistent with the follow-up in the main RCTs. Other scenarios were explored to examine the robustness of alternative assumptions including impact of different treatment durations. Searches yielded five RCTs: two spironolactone trials of poor methodological quality and three trials of which only one (of eplerenone) specifically examined postMI HF (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study, EPHESUS). One trial of spironolactone (Randomised Aldactone Evaluation Study, RALES) and one of canrenone (Antiremodelling Effect of Aldosterone receptors blockade with canrenone In mild Chronic Heart Failure, AREA IN-CHF) comprised general HF, but data were available for an ischaemic subgroup. Structural similarity of spironolactone and eplerenone suggests that they may be interchangeable, but formal indirect comparison between the three trials was severely limited by trial differences. Relative safety data were limited from RCTs and observational sources. Hyperkalaemia rates varied, but were generally higher than for placebo; data were insufficient to assess discontinuation because of hyperkalaemia.Gynaecomastia rates were higher with spironolactone. Adverse event data were sparse. Systematic review of economic evidence identified three main published studies but none used a UK perspective or attempted to compare cost-effectiveness in postMI HF. The new decision model indicated that eplerenone was the most cost-effective strategy for postMI HF (ICER of eplerenone compared with standard care was 4457 pounds per QALY, increasing to 7893 pounds per QALY if treatment continued over the patient's lifetime); in neither scenario did spironolactone appear cost-effective. The ICER of eplerenone was consistently under the 20,000-30,000 pounds per QALY threshold used to establish value for money in the NHS. Uncertainty resulted in EVPI estimates between 820M pounds (base-case) and 1265M pounds (lifetime treatment duration scenario). When class effect for mortality and hospitalisations was assumed spironolactone emerged as the most cost-effective treatment and EVPI estimates were negligible. If class effect is considered more plausible than the results of the evidence synthesis model then there would be limited value in additional research. Exchangeability between trials was poor and there was a lack of robust data in RCTs. Only two good-quality trials of aldosterone inhibitors in the postMI HF population were found, but lack of exchangeability with respect to study populations, meant that a comparison between these drugs could not be done. It consistently emerged that, compared with usual care, use of an aldosterone antagonist appears to be a highly cost-effective strategy for the management of postMI HF patients in the NHS. An adequately powered, well-conducted RCT that directly compares spironolactone and eplerenone is required to provide more robust evidence on the optimal management of postMI HF patients.

Intervention study shows outpatient cardiac rehabilitation to be economically at least as attractive as inpatient rehabilitation

Since the late 1990 s, cost pressure has led to a growing interest in outpatient rehabilitation in Germany where predominantly inpatient rehabilitation has been provided. Taking into account the feasibility of a randomized design, the aim of this study was to compare outpatient and inpatient cardiac rehabilitation from a societal perspective. A comprehensive cohort design was applied. Costs during rehabilitation were measured using individual documentation of the rehabilitation centers. Economic end points were quality of life (EQ-5D), and total direct and indirect costs. A propensity score approach, integrated into a simultaneous regression framework for cost and effects, was used to control for selection bias. Bootstrap analysis was applied for assessing uncertainty in cost-effectiveness. A total of 163 patients were included in the study (112 inpatients, 51 outpatients). As randomization was chosen by only 2.5% of participants, the study had to be analyzed as an observational study. Direct costs during inpatient rehabilitation were significantly higher by 600 euro (+/-318; p < 0.001) compared to outpatient rehabilitation (2,016 euro +/- 354 euro vs. 1,416 euro +/- 315), while there was no significant difference in health-related quality of life. Over the 12-month follow-up period, adjusted costs difference in total cost was estimated at -2,895 euro (p = 0.102) and adjusted difference in effects at 0.018 quality-adjusted life years (QALYs) (n.s.) in favor of outpatient treatment. The ratio of mean cost over mean effect difference (incremental cost-effectiveness ratio) indicates dominance of outpatient rehabilitation, but at a considerable statistical uncertainty. However, outpatient rehabilitation cannot be rejected from an economic perspective.

Cost Effectiveness of Increasing the Dose Intensity of Chemotherapy with Granulocyte Colony-Stimulating Factor in Small-Cell Lung Cancer

The use of granulocyte colony-stimulating factor (G-CSF) can enable dose intensification of chemotherapy in small-cell lung cancer (SCLC). However, given its acquisition cost, it is important to assess its cost effectiveness within a resource-constrained health service. To assess the cost effectiveness, from the UK NHS perspective, of G-CSF given in addition to doxorubicin, cyclophosphamide and etoposide (ACE) versus ACE alone in the management of SCLC. Using data from a UK Medical Research Council trial (LU19) to assess chemotherapy dose intensification in patients with previously untreated SCLC of any disease extent, a retrospective cost-effectiveness analysis was undertaken. Resource use data, including hospitalisations and non-protocol cancer treatments, were collected during the first 6-month treatment phase of the trial. Mean costs ( pound, 2003 values) of managing patients in the two arms of the trial were calculated. Mean survival duration was calculated for the two groups using patient-specific follow-up data collected in the trial. Incremental cost-effectiveness analysis was undertaken, and uncertainty in cost effectiveness was expressed using cost-effectiveness acceptability curves. The use of G-CSF in addition to ACE chemotherapy is more costly ( 4647 pounds) but results in longer mean survival duration (0.20 years; 0.18 years when discounted). This generates an incremental cost per additional life-year of 25,816 pounds for ACE + G-CSF therapy. The probability of the addition of G-CSF being cost effective, if decision makers are willing to pay 30,000 pounds for an additional life-year, is 0.57. Secondary analysis suggests that cost effectiveness is likely to be sensitive to assumptions about the health-related quality of life (HR-QOL) experienced by patients. Based on data collected in the LU19 trial, chemotherapy dose intensification using G-CSF in SCLC adds to health service costs but increases survival duration. Its overall cost effectiveness is likely to be finely balanced.