Considering Severity in Health Technology Assessment: Can We Do Better?

There is strong evidence that individuals and the public assign relatively greater value to health gains from relatively more severe health states. This preference is increasingly reflected in health technology assessment, with some consideration of severity incorporated by health technology assessment bodies in, among others, The Netherlands, England and Wales, Norway, Sweden, and the United States. If a societal "severity premium" is to be considered fairly and consistently, we argue that a more explicit and quantitative approach is needed. We highlight drawbacks of categorical approaches, especially discontinuities between severity categories that arguably violate concepts of vertical equity, and argue that a more continuous approach to understanding severity is needed. We also note challenges to more explicit approaches, including implications of a lower threshold for less severe conditions and the relative complexity of calculating a continuous severity adjustment.

On Effective Graphic Communication of Health Inequality: Considerations for Health Policy Researchers.

Policy Points: Effective graphs can be a powerful tool in communicating health inequality. The choice of graphs is often based on preferences and familiarity rather than science. According to the literature on graph perception, effective graphs allow human brains to decode visual cues easily. Dot charts are easier to decode than bar charts, and thus they are more effective. Dot charts are a flexible and versatile way to display information about health inequality. Consistent with the health risk communication literature, the captions accompanying health inequality graphs should provide a numerical, explicitly calculated description of health inequality, expressed in absolute and relative terms, from carefully thought-out perspectives. CONTEXT: Graphs are an essential tool for communicating health inequality, a key health policy concern. The choice of graphs is often driven by personal preferences and familiarity. Our article is aimed at health policy researchers developing health inequality graphs for policy and scientific audiences and seeks to (1) raise awareness of the effective use of graphs in communicating health inequality; (2) advocate for a particular type of graph (ie, dot charts) to depict health inequality; and (3) suggest key considerations for the captions accompanying health inequality graphs. METHODS: Using composite review methods, we selected the prevailing recommendations for improving graphs in scientific reporting. To find the origins of these recommendations, we reviewed the literature on graph perception and then applied what we learned to the context of health inequality. In addition, drawing from the numeracy literature in health risk communication, we examined numeric and verbal formats to explain health inequality graphs. FINDINGS: Many disciplines offer commonsense recommendations for visually presenting quantitative data. The literature on graph perception, which defines effective graphs as those allowing the easy decoding of visual cues in human brains, shows that with their more accurate and easier-to-decode visual cues, dot charts are more effective than bar charts. Dot charts can flexibly present a large amount of information in limited space. They also can easily accommodate typical health inequality information to describe a health variable (eg, life expectancy) by an inequality domain (eg, income) with domain groups (eg, poor and rich) in a population (eg, Canada) over time periods (eg, 2010 and 2017). The numeracy literature suggests that a health inequality graph's caption should provide a numerical, explicitly calculated description of health inequality expressed in absolute and relative terms, from carefully thought-out perspectives. CONCLUSIONS: Given the ubiquity of graphs, the health inequality field should learn from the vibrant multidisciplinary literature how to construct effective graphic communications, especially by considering to use dot charts.

Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

PURPOSE: Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. METHODS: We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. RESULTS: Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. CONCLUSIONS: Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

Choosing vs. allocating: discrete choice experiments and constant-sum paired comparisons for the elicitation of societal preferences.

BACKGROUND: There is growing evidence of a reluctance to allocate health care solely on the basis of maximizing quality-adjusted life years (QALYs). Stated preference methods can be used to elicit preferences for efficiency vs. equity in the allocation of health-care resources. OBJECTIVE: To compare discrete choice experiment (DCE) and constant-sum paired comparison (CSPC) methods for eliciting societal preferences. METHODS: Over a series of choice pairs, DCE respondents allocated a fixed budget to one preferred group and CSPC respondents allocated budget percentages between the groups. Questionnaires were compared in terms of completion rates, preference consistency, dominant preferences and derived attribute importance. RESULTS: There was no significant difference in the proportions that rated the questionnaires somewhat or extremely difficult, but a significantly greater proportion completed the DCE compared to the CSPC. Preference consistency was also higher in the DCE. The incidence of dominant preferences, including for aggregate QALYs, was low and not significantly different between questionnaires. Similarly, no CSCP respondents equalized budgets or outcomes in every task. Final health state was the most important attribute in both questionnaires, but the rankings diverged for the other attributes. Notably, the total patients' treated attribute was important in the CSPC but insignificant in the DCE, perhaps reflecting a 'prominence effect'. CONCLUSIONS: Despite lower completion rates and preference consistency, CSPC may offer advantages over DCE in eliciting preferences over the distribution of resources and/or outcomes as well as attribute levels, avoiding extreme 'all-or-nothing' distributions and possibly aligning respondent attention more closely with a societal perspective.

A Longer Life or a Quality Death? A Discrete Choice Experiment to Estimate the Relative Importance of Different Aspects of End-of-Life Care in the United Kingdom.

Background. Advocates argue that end-of-life (EOL) care is systematically disadvantaged by the quality-adjusted life-year (QALY) framework. By definition, EOL care is short duration and not primarily intended to extend survival; therefore, it may be inappropriate to value a time element. The QALY also neglects nonhealth dimensions such as dignity, control, and family relations, which may be more important at EOL. Together, these suggest the QALY may be a flawed measure of the value of EOL care. To test these arguments, we administered a stated preference survey in a UK-representative public sample. Methods. We designed a discrete choice experiment (DCE) to understand public preferences over different EOL scenarios, focusing on the relative importance of survival, conventional health dimensions (especially physical symptoms and anxiety), and nonhealth dimensions such as family relations, dignity, and sense of control. We used latent class analysis to understand preference heterogeneity. Results. A 4-class latent class multinomial logit model had the best fit and illustrated important heterogeneity. A small class of respondents strongly prioritized survival, whereas most respondents gave relatively little weight to survival and, generally speaking, prioritized nonhealth aspects. Conclusions. This DCE illustrates important heterogeneity in preferences within UK respondents. Despite some preferences for core elements of the QALY, we suggest that most respondents favored what has been called "a good death" over maximizing survival and find that respondents tended to prioritize nonhealth over conventional health aspects of quality. Together, this appears to support arguments that the QALY is a poor measure of the value of EOL care. We recommend moving away from health-related quality of life and toward a more holistic perspective on well-being in assessing EOL and other interventions. Highlights: Advocates argue that some interventions, including but not limited to end-of-life (EOL) care, are valued by patients and the public but are systematically disadvantaged by the quality-adjusted life-year (QALY) framework, leading to an unfair and inefficient allocation of health care resources.Using a discrete choice experiment, we find some support for this argument. Only a small proportion of public respondents prioritized survival in EOL scenarios, and most prioritized nonhealth aspects such as dignity and family relations.Together, these results suggest that the QALY may be a poor measure of the value of EOL care, as it neglects nonhealth aspects of quality and well-being that appear to be important to people in hypothetical EOL scenarios.

Patient Preferences for Treatment in Relapsed/Refractory Acute Leukemia in the United Kingdom: A Discrete Choice Experiment.

Background: Acute leukemia is a cancer of the white blood cells which progresses rapidly and aggressively. There are two types: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The latter has a rare subtype: acute promyelocytic leukemia (APL). For some patients, following first-line treatment, remission is not achieved ("refractory disease"), and for others the leukemia returns after achieving remission ("relapse"). For these individuals, outcomes are typically poor. It is, therefore, important to understand patients' treatment priorities in this context. Methods: Building upon formative qualitative research, an online survey containing a discrete choice experiment (DCE) was designed to explore patients' treatment preferences in the relapsed/refractory setting. The DCE attributes were mode of administration; quality of life during treatment; chance of response; duration of response; and quality of life during response. Each respondent completed twelve scenarios containing two hypothetical treatments. Participants were eligible if they lived in the United Kingdom and had a diagnosis of acute leukemia. The data were analysed using a latent class model. Results: A total of 95 patients completed the survey. The latent class analysis identified two classes. For both, chance of response was the most important attribute. For class 1, every attribute was important, whereas for class 2, the only important attributes were quality of life (during treatment and response) and chance of response. A greater proportion of respondents would fall into class 1 overall, and those with ALL or APL and those more recently diagnosed were more likely to be in class 2. Conclusion: Our results indicate that patients are strongly concerned about the chance of response, as well as quality of life (to a lesser extent), when faced with different treatment options in the relapsed/refractory setting. However, there is significant preference heterogeneity within the patient population, and other treatment characteristics also matter to many.

A cost-effectiveness analysis of reduced viral transmission with baloxavir marboxil versus oseltamivir or no treatment for seasonal and pandemic influenza management in the United Kingdom.

BACKGROUND: Baloxavir marboxil is an oral, single-dose, cap-dependent endonuclease inhibitor that reduces the duration of influenza symptoms and rapidly stops viral shedding. We developed a susceptible, exposed, infected, recovered (SEIR) model to inform a cost-effectiveness model (CEM) of baloxavir versus oseltamivir or no antiviral treatment in the UK. RESEARCH DESIGN AND METHODS: The SEIR model estimated the attack rates among otherwise healthy and high-risk individuals in seasonal and pandemic settings. The CEM assumed that a proportion of infected patients would receive antiviral treatment. Results were reported at the population level (per 10,000 at risk of infection). RESULTS: The SEIR model estimated greater reductions in infections with baloxavir. In a seasonal setting, baloxavir provided incremental cost-effectiveness ratios (ICERs) of £1884 per quality-adjusted life-year (QALY) gained versus oseltamivir and a dominant cost-effectiveness position versus no antiviral treatment in the total population; ICERs of £2574/QALY versus oseltamivir and £128/QALY versus no antiviral treatment were seen in the high-risk population. Baloxavir was also cost-effective versus oseltamivir or no antiviral treatment and reduced population-level health system occupancy concerns during a pandemic. CONCLUSION: Baloxavir treatment resulted in the fewest influenza cases and was cost-effective versus oseltamivir or no antiviral treatment from a UK National Health Service perspective.

Baloxavir marboxil ('baloxavir') is a prescription medicine for people who become ill with influenza (or 'the flu') that can reduce how long flu symptoms last and the likelihood of complications from the flu that may require going to the hospital. Baloxavir can also reduce the amount and duration of virus shed by infected individuals thus potentially slow or stop the flu from spreading to healthy people. We studied differences in reducing predicted flu infections between baloxavir and another flu treatment, known as oseltamivir, or no flu treatment at all. Treatment with baloxavir resulted in fewer flu infections in the UK population than oseltamivir or no treatment. We then studied how these differences might affect costs between baloxavir and oseltamivir or no treatment at a population level in the UK. Overall, in the majority of scenarios explored in the model, baloxavir was cost-effective as an antiviral treatment for people with the flu in the UK.

Modelling Spillover Effects on Informal Carers: The Carer QALY Trap.

The provision of informal (unpaid) care can impose significant 'spillover effects' on carers, and accounting for these effects is consistent with the efficiency and equity objectives of health technology assessment (HTA). Inclusion of these effects in health economic models, particularly carer health-related quality of life (QOL), can have a substantial impact on net quality-adjusted life year (QALY) gains and the relative cost effectiveness of new technologies. Typically, consideration of spillover effects improves the value of a technology, but in some circumstances, consideration of spillover effects can lead to situations whereby life-extending treatments for patients may be considered cost ineffective due to their impact on carer QOL. In this piece we revisit the classic 'QALY trap' and introduce an analogous 'carer QALY trap' which may have practical implications for economic evaluations where the inclusion of carer QOL reduces incremental QALY gains. Such results may align with a strict QALY-maximisation rule, however we consider the extent to which this principle may be at odds with the preferences of carers themselves (and possibly society more broadly), potentially leading decision makers into the carer QALY trap as a result. We subsequently reflect on potential solutions, highlighting the important (albeit limited) role that deliberation has to play in HTA.

Unmet Parenthood Goals, Health-Related Quality of Life and Apparent Irrationality: Understanding the Value of Treatments for Infertility.

An increasing number of prospective parents are experiencing infertility along with associated negative impacts on mental health and life satisfaction that can extend across a network of individuals and family members. Assistive reproductive technologies (ART) can help prospective parents achieve their parenthood goals but, like any health technology, they must demonstrate acceptable 'value for money' to qualify for public funding. We argue that current approaches to understanding the value of ART, including quality-adjusted life-year (QALY) gains based on changes in health-related quality of life (HRQOL) and, more often, cost per live birth, are too narrow to capture the full impact of unmet parenthood goals and ART. We see a fundamental disconnect between measures of HRQOL and broader measures of wellbeing associated with met and unmet parenthood goals. We also suggest that simple concepts such as 'patient' and 'carer' are of limited applicability in the context of ART, where 'spillovers' extend across a wide network of individuals, and the person receiving treatment is often not the infertile individual. Consideration of individual and societal wellbeing beyond HRQOL is necessary to understand the full range of negative impacts associated with unmet parenthood goals and the corresponding positive impacts of successful ART. We suggest moving towards a wellbeing perspective on value to achieve a fuller understanding of value and promote cross-sector allocative efficiency.

Cost-utility of the 21-gene recurrence score assay in node-negative and node-positive breast cancer.

The 21-gene recurrence score (Oncotype DX: RS) appears to augment clinico-pathologic prognostication and is predictive of adjuvant chemotherapy benefit in node-negative (N-) and node-positive (N+), endocrine-sensitive breast cancer. RS is a costly assay that is associated with good 'value for money' in N- disease, while economic evaluations in N+ disease based on most recent data have not been conducted. We examined the cost-utility (CU) of a RS-guided adjuvant strategy, compared to current practice without RS in N- and N+, endocrine-sensitive, breast cancer from a Canadian health care system perspective. A generic state-transition model was developed to compute cumulative costs and quality-adjusted life years (QALYs) over a 25-year horizon. Patient outcomes with and without chemotherapy in RS-untested cohorts and in those with low, intermediate and high RS were examined based on the reported prognostic and predictive impact of RS in N- and N+ disease. Chemotherapy utilization (current vs. RS-guided), unit costs and utilities were derived from a Nova Scotia Canadian population-based cohort, local unit costs and the literature. Costs and outcomes were discounted at 3% annually, and costs were reported in 2011 Canadian dollars ($). Probabilistic and one-way sensitivity analyses were conducted for key model parameters. Compared to a non-RS-guided strategy, RS-guided adjuvant therapy was associated with $2,585 and $864 incremental costs, 0.27 and 0.06 QALY gains, and resultant CUs of $9,591 and $14,844 per QALY gained for N- and N+ disease, respectively. CU estimates were robust to key model parameters, and were most sensitive to chemo utilization proportions. RS-guided adjuvant therapy appears to be a cost-effective strategy in both N- and N+, endocrine-sensitive breast cancer with resultant CU ratios well below commonly quoted thresholds.

How Do People with Experience of Infertility Value Different Aspects of Assistive Reproductive Therapy? Results from a Multi-Country Discrete Choice Experiment.

OBJECTIVES: Assistive reproductive therapies can help those who have difficulty conceiving but different forms of assistive reproductive therapies are associated with different treatment characteristics. We undertook a large, multinational discrete choice experiment to understand patient preferences for assistive reproductive therapies. METHODS: We administered an online discrete choice experiment with persons who had experience with subfertility or assistive reproductive therapies in the USA, UK, the Nordic region (Denmark, Norway, Sweden, Finland), Spain, and China. Attributes encouraged trade-offs between effectiveness, risk of adverse effects, treatment (dis)comfort, (in)convenience, cost per cycle and shared decision making. We used multinomial logit and mixed-logit models to estimate preferences and attribute importance by country/region, and estimated willingness to pay for changes in attribute levels. RESULTS: A total of 7565 respondents participated. Mixed logit had a better fit than multinomial logit across all samples. Preferences moved in expected directions across all samples, but the relative importance of attributes differed between countries. Willingness to pay was greatest for improvements in effectiveness and a greater degree of shared decision making, and we observe a substantial 'option value' independent of treatment characteristics. Unexpectedly, preferences over cost were insignificant in the Chinese sample, limiting the use of willingness to pay in this sample. CONCLUSIONS: Respondents balanced concerns for effectiveness with other considerations, including the cost and (dis)comfort of treatment, and the degree of shared decision making, but there is also substantial option value independent of treatment characteristics, demonstrating value of assistive reproductive therapies to individuals with experience of subfertility. We hypothesise that price insensitivity in the Chinese sample may reflect a degree of social desirability bias.

An incremental economic evaluation of targeted and universal influenza vaccination in pregnant women.

OBJECTIVE: Pregnancy is associated with increased influenza hospitalizations and physician visits (events) in healthy women and those with co-morbidities. Annual influenza immunization is recommended for all pregnant women. Although vaccination is expected to reduce influenza-related events, the economic implications are unclear. We developed an economic model to estimate the cost-effectiveness (CE) of different vaccination strategies in Nova Scotia. METHODS: A decision tree characterized the one-year costs and consequences of targeted (pregnant women with co-morbidities only) and universal (all pregnant women) vaccination strategies relative to a no-vaccination strategy. Baseline event probabilities, vaccine effectiveness, costs and quality-of-life weights were derived from individual-level Nova Scotia administrative databases, health system sources and published reports. Sensitivity analyses tested the impact of varying key parameters, including vaccine effectiveness and mode of delivery. RESULTS: Targeted vaccination was cost-saving relative to no vaccination when delivered by public health clinics (PHC) or routine family practitioner (FP) visit. Cost per quality-adjusted life year gained by universal vaccination relative to targeted strategy was < $40,000 when delivered by PHC or routine FP visit. Net cost of universal vaccination by PHC or a routine FP visit was < $10 per pregnant woman. CONCLUSION: Universal vaccination of pregnant women appears cost-effective when delivered by PHC or as part of a routine FP prenatal visit. Targeted vaccination of pregnant women with co-morbidities can be cost-saving, but the possibility of higher vaccine uptake with a universal compared to a targeted strategy must be considered in addition to costs in program planning.

Is the public supportive and willing to pay for a national assistive reproductive therapies programme? Results from a multicountry survey.

OBJECTIVES: To understand attitudes towards infertility and willingness to pay (WTP) towards a publicly funded national assistive reproductive therapies (ART) programme. DESIGN: Attitudes survey with dichotomous and open-ended WTP questions. SETTING: Online survey administered in the USA, UK, Norway, Sweden, Finland, Denmark and China. PARTICIPANTS: 7945 respondents, analysed by country. Nordic respondents were pooled into a regionally representative sample. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were proportion of sample agreeing with different infertility-related and ART-related value statements and supporting a monthly contribution to fund a national ART programme, expressed in local currency. Secondary outcome measure was maximum WTP. RESULTS: Across the nationally representative samples, 75.5% of all respondents agreed with infertility as a medical condition and 82.3% and 83.7% with ART eligibility for anyone who has difficulty having a baby or a medical problem preventing them from having a baby, respectively. 56.4% of respondents supported a defined monthly contribution and 73.9% supported at least some additional contribution to fund a national ART programme. Overall, converting to euros, median maximum WTP was €3.00 and mean was €15.47 (95% CI 14.23 to 16.72) per month. Maximum WTP was highest in China and the USA and lowest in the European samples. CONCLUSIONS: This large, multicountry survey extends our understanding of public attitudes towards infertility and fertility treatment beyond Europe. It finds evidence that a majority of the public in all sampled countries/regions views infertility as a treatable medical condition and supports the idea that all infertile individuals should have access to treatments that improve the chance of conception. There was also strong agreement with the idea that the desire for children is a basic human need. WTP questions showed that a majority of respondents supported a monthly contribution to fund a national ART programme, although there is some evidence of an acquiescence bias that may overstate support among specific samples.

The cost-utility of sequential adjuvant trastuzumab in women with Her2/Neu-positive breast cancer: an analysis based on updated results from the HERA Trial.

BACKGROUND: The efficacy of sequential adjuvant trastuzumab (aTZ) after chemotherapy in women with early-stage human epidermal growth factor-2 (HER2/neu)-positive breast cancer reported by the updated Herceptin Adjuvant (HERA) trial appears less favorable than originally reported. Based on these updated results, we estimated the cost-utility (CU) of sequential aTZ relative to chemotherapy alone in terms of incremental cost per quality-adjusted life-year (QALY) gained. METHODS: A Markov model estimated incremental costs and outcomes of 12 months of aTZ after adjuvant chemotherapy in women with HER2/neu-positive breast cancer over a 25-year horizon. The model incorporated four broad health states (disease-free, local recurrence [LCR], distant recurrence [DCR], death), stratified with or without symptomatic cardiotoxicity. Baseline event rates and 3-year relative risk (RR = 0.75) were derived from the HERA trial. As the duration of the benefit remains uncertain, the analysis considered 5-year and 3-year duration of benefit in two scenarios. Costs and utility weights were from the literature. The analysis took a direct payer perspective, with costs reported in 2007 Canadian dollars. Costs and QALYs were discounted by 3% annually. RESULTS: The mean CU of sequential aTZ at a 25-year horizon was $72,292 per QALY gained in the 5-year scenario and $127,862 per QALY gained in the 3-year scenario. Results were particularly sensitive to the magnitude and duration of carryover benefit. CONCLUSIONS: The CU of sequential aTZ is primarily dependent on the magnitude and duration of benefit. Further clinical research is required to establish the optimum sequence and duration of aTZ therapy and clarify the magnitude and duration of treatment benefit.

The Relative Importance of Clinical, Economic, Patient Values and Feasibility Criteria in Cancer Drug Reimbursement in Canada: A Revealed Preferences Analysis of Recommendations of the Pan-Canadian Oncology Drug Review 2011-2017.

BACKGROUND: Most Canadian provinces and territories rely on the pan-Canadian Oncology Drug Review (pCODR) to provide recommendations regarding public reimbursement of cancer drugs. The pCODR review process considers four dimensions of value-clinical benefit, economic evaluation, patient-based values and adoption feasibility-but they do not define weights for individual decision criteria or an acceptable threshold for any of the criteria. Given this implicit review process, it is of interest to understand which factors appear to carry the most weight in pCODR recommendations using a revealed preferences approach. METHODS: Using publicly available decision summaries (n = 91) describing submissions and resulting recommendations 2011-2017, we extracted ten attributes that characterized each submission. Using logistic regression, we identified statistically significant attributes and estimated their relative impact in final recommendations. RESULTS: Clinical aspects appear to carry the greatest weight in the decision to reject or not reject, along with aspects of patient value (treatments with no alternatives were less likely to be rejected). Cost effectiveness does not appear to play a role in the initial decision to reject or not reject but is critical in full versus conditional approvals. There is evidence of a maximum acceptable threshold of around $Can140,000 per quality-adjusted life-year (QALY) gained. CONCLUSION: A set of factors driving pCODR recommendations is identifiable, supporting the consistency of the review process. However, the implicit nature of the review process and the difficulty of extracting and interpreting some of the attribute levels used in the analysis suggests that the process may still lack full transparency.

Adjuvant Statin Therapy for Esophageal Adenocarcinoma: A Cost-Utility Analysis.

BACKGROUND: Emerging preclinical evidence indicates statins, medications commonly used in the prevention of cardiovascular disease (CVD), inhibit proliferation, promote apoptosis and limit invasiveness of esophageal adenocarcinoma (EAC). Population-based observational data demonstrate statin treatment after diagnosis of EAC is associated with significant reductions in all-cause and cancer-specific mortality. A feasibility study of adjuvant statin therapy following potentially curative resection for EAC has been completed, with planned progression to a full phase III, randomized controlled trial. OBJECTIVE: The aim was to estimate the cost-utility of statin therapy following surgical resection for EAC from a UK National Health Service (NHS) perspective. METHODS: A Markov model was developed to estimate the costs and outcomes [quality-adjusted life years (QALYs)] for hypothetical cohorts of patients with EAC exposed or not exposed to statins following potentially curative surgical resection. Model parameters were based on estimates from published observational and trial data. Costs, utilities and transition probabilities were modeled to reflect clinical practice from a payer's perspective. Probabilistic and one-way sensitivity analyses were performed to account for uncertainty in key parameters. RESULTS: Overall, a cost saving of £6781 per patient was realized with statin treatment compared to no statins. In probabilistic sensitivity analysis, 99% of all iterations were cost saving and 99% of all iterations were less than £20,000 per QALY gained. These results were robust to changes in the price and effectiveness of statins. CONCLUSIONS: The cohort exposed to statins had lower costs and better QALY outcomes than the no statin cohort. Assuming a causal improvement in disease outcomes following resection for EAC, statin therapy is very likely to be a cost-saving treatment.

The cost-effectiveness of extended-duration antithrombotic prophylaxis after total hip arthroplasty.

BACKGROUND: Although the risk of thromboembolism after total hip arthroplasty continues beyond hospital discharge, the cost-effectiveness of extending prophylaxis beyond hospitalization is unclear. We compared the cost-effectiveness of an extended duration of antithrombotic prophylaxis following total hip arthroplasty, with use of low-molecular-weight heparin or warfarin administered for twenty-eight days beyond hospital discharge, in terms of incremental cost per quality-adjusted life year gained. METHODS: The economic analysis was structured around a decision tree characterizing the consequences of extended prophylaxis choices following total hip arthroplasty. The health benefits of extended antithrombotic prophylaxis, measured as the reduction in symptomatic venous thromboembolic events and deaths for each treatment alternative, were determined through a systematic review of the literature. Gains in quality-adjusted life years were based on the distribution of life years remaining for all patients undergoing total hip arthroplasty in Canada in 2003, weighted by utilities derived from the literature. The cost analysis, in 2006 Canadian dollars, took a direct payer perspective with a ninety-day time horizon. RESULTS: There was a net gain in quality-adjusted life years in both cohorts that received extended prophylaxis relative to the cohort that received no extended prophylaxis (7.5 quality-adjusted life years per 1000 patients treated with low-molecular-weight heparin and 5.5 quality-adjusted life years per 1000 patients treated with warfarin), although these gains were not significant. The net treatment costs per 1000 patients treated were $799,104 with low-molecular-weight heparin and $72,236 with warfarin. In comparison with the cohort that received no extended prophylaxis, the cost-effectiveness of low-molecular-weight heparin was $106,454 per quality-adjusted life year gained and the cost-effectiveness of warfarin was $13,115 per quality-adjusted life year gained. CONCLUSIONS: There is insufficient economic evidence to support extended thromboprophylaxis with low-molecular-weight heparin following total hip arthroplasty. Although the cost-effectiveness of warfarin was potentially quite favorable, this finding was based on limited clinical evidence. Further research is required to clarify the benefits of extended prophylaxis, particularly with warfarin. LEVEL OF EVIDENCE: Economic and decision analysis, Level I. See Instructions to Authors for a complete description of levels of evidence.

Computed tomographic pulmonary angiography vs ventilation-perfusion lung scanning in patients with suspected pulmonary embolism: a randomized controlled trial.

CONTEXT: Ventilation-perfusion (V(dot)Q(dot) lung scanning and computed tomographic pulmonary angiography (CTPA) are widely used imaging procedures for the evaluation of patients with suspected pulmonary embolism. Ventilation-perfusion scanning has been largely replaced by CTPA in many centers despite limited comparative formal evaluations and concerns about CTPA's low sensitivity (ie, chance of missing clinically important pulmonary embuli). OBJECTIVES: To determine whether CTPA may be relied upon as a safe alternative to V(dot)Q(dot scanning as the initial pulmonary imaging procedure for excluding the diagnosis of pulmonary embolism in acutely symptomatic patients. DESIGN, SETTING, AND PARTICIPANTS: Randomized, single-blinded noninferiority clinical trial performed at 4 Canadian and 1 US tertiary care centers between May 2001 and April 2005 and involving 1417 patients considered likely to have acute pulmonary embolism based on a Wells clinical model score of 4.5 or greater or a positive D-dimer assay result. INTERVENTION: Patients were randomized to undergo either V(dot)Q(dot scanning or CTPA. Patients in whom pulmonary embolism was considered excluded did not receive antithrombotic therapy and were followed up for a 3-month period. MAIN OUTCOME MEASURE: The primary outcome was the subsequent development of symptomatic pulmonary embolism or proximal deep vein thrombosis in patients in whom pulmonary embolism had initially been excluded. RESULTS: Seven hundred one patients were randomized to CTPA and 716 to V(dot)Q(dot scanning. Of these, 133 patients (19.2%) in the CTPA group vs 101 (14.2%) in the V(dot)Q(dot scan group were diagnosed as having pulmonary embolism in the initial evaluation period (difference, 5.0%; 95% confidence interval [CI], 1.1% to 8.9%) and were treated with anticoagulant therapy. Of those in whom pulmonary embolism was considered excluded, 2 of 561 patients (0.4%) randomized to CTPA vs 6 of 611 patients (1.0%) undergoing V(dot)Q(dot scanning developed venous thromboembolism in follow-up (difference, -0.6%; 95% CI, -1.6% to 0.3%) including one patient with fatal pulmonary embolism in the V(dot)Q(dot group. CONCLUSIONS: In this study, CTPA was not inferior to V(dot)Q(dot scanning in ruling out pulmonary embolism. However, significantly more patients were diagnosed with pulmonary embolism using the CTPA approach. Further research is required to determine whether all pulmonary emboli detected by CTPA should be managed with anticoagulant therapy. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN65486961.