QALYs, euthanasia and the puzzle of death

Cost-effectiveness analysis in cardiac surgery: A review of its concepts and methodologies

This study demonstrates an empirical example that uses quality-adjusted life year (QALY) as a common metric for occupational health assessment to measure the utility loss of potential lead-exposed children delivered by female lead-battery-exposed workers. A set of nationwide health examination data was used for 1726 lead workers. Among them, there were 649 female workers. The numbers of offspring from female lead workers were estimated by multiplying the age-specific fertility rate (ASFR) by the number of workers in each age stratum. The quality of life assessment for these offspring was assumed impaired by increased absorption of lead using a measure of utility for quality of life that was adapted from Rosser’s index of health-related quality of life. The total utility loss was calculated by summing up the loss of QALY for these expected offspring. Dose-response and exposure assessments were based on their mothers’ blood lead levels. It was estimated that more than 38 babies were delivered in 1 yr. There would be 19 babies born with blood lead levels over 30 µg/dl, and about 17 babies with blood lead between 10 and 29 µg/dl. The expected utility loss of the babies was estimated to be about 216 QALY, of which 51.6 QALY was attributed to the babies with moderate blood lead level, while that of high blood lead was 164.4 QALY. An effective industrial hygiene program to reduce blood lead to 5, 10, and 15 µg/dl in female lead-exposed workers would decrease the utility loss to 169.5, 126.8, and 92.3 QALY, respectively, in the offspring. An alternative policy of raising the age of female workers by 5 or 10 yr before employment would also reduce the loss to 174.6 or 107.4 QALY. Data suggest that an effective industrial hygiene program should be implemented, and the use of QALY as a common metric for comparative assessment of occupational health policy may be feasible.

Despite existing therapies, people with lupus nephritis progress to kidney failure and have reduced life expectancy. Belimumab and voclosporin are two new disease-modifying therapies recently approved for the treatment of lupus nephritis. A de novo economic model was developed to estimate the cost-effectiveness of these therapies, including the following health states: "complete response," "partial response," and "active disease" defined by eGFR and proteinuria changes, kidney failure, and death. Short-term data and mean cohort characteristics were sourced from pivotal clinical trials of belimumab (the Belimumab International Study in Lupus Nephritis) and voclosporin (the Aurinia Urinary Protection Reduction Active-Lupus with Voclosporin trial and Aurinia Renal Response in Active Lupus With Voclosporin). Risk of mortality and kidney failure were on the basis of survival modeling using published Kaplan-Meier data. Each drug was compared with the standard of care as represented by the comparator arm in its respective pivotal trial(s) using US health care sector perspective, with a societal perspective also explored. In the health care perspective probabilistic analysis, the incremental cost-effectiveness ratio for belimumab compared with its control arm was estimated to be approximately $95,000 per quality-adjusted life year. The corresponding incremental ratio for voclosporin compared with its control arm was approximately $150,000 per quality-adjusted life year. Compared with their respective standard care arms, the probabilities of belimumab and voclosporin being cost effective at a threshold of $150,000 per quality-adjusted life year were 69% and 49%, respectively. Cost-effectiveness was dependent on assumptions made regarding survival in response states, costs and utilities in active disease, and the utilities in response states. In the analysis from a societal perspective, the incremental ratio for belimumab was estimated to be approximately $66,000 per quality-adjusted life year, and the incremental ratio for voclosporin was estimated to be approximately $133,000 per quality-adjusted life year. Compared with their respective standard care arms, belimumab but not voclosporin met willingness-to-pay thresholds of $100,000 per quality-adjusted life year. Despite potential clinical superiority in the informing trials, there remains high uncertainty around the cost-effectiveness of voclosporin.

We aimed to assess utility weight of health states associated with colorectal cancer (CRC) that reflect the societal preference of the Korean population and to estimate the quality-adjusted life year (QALY) loss with CRC. We recruited 607 individuals from the Korean population; they were surveyed via face-to-face computer-assisted interviews. The participants evaluated each CRC-associated health state using standard gamble. Utility weight for each health state was calculated as the possibility of full health restoration. Moreover, we estimated total QALY loss due to CRC in Korean individuals aged ≥30 years in 2013. To calculate QALY due to morbidity, we yielded utility weights and used epidemiologic data of CRC on severity from the National Cancer Control Institute. QALY loss due to mortality was calculated using mortality of CRC and life expectancy data from the Korean Statistical Information Service. The highest and lowest utility weights were assigned to “adenomatous polyps” and “metastatic colon cancer”, respectively. Total QALY loss due to CRC in Korea was 173,662; these patients were more likely to be men or be included in the 70–74-year age group. These utility weights may be useful for conducting cost-utility studies of cancer screening for CRC and for measuring disease burden with QALY.

Timely identification of occult atrial fibrillation following cryptogenic stroke facilitates consideration of oral anticoagulation therapy. Extended electrocardiography monitoring beyond 24 to 48 h Holter monitoring improves atrial fibrillation detection rates, yet uncertainty remains due to upfront costs and the projected long-term benefit. We sought to determine the cost-effectiveness of three electrocardiography monitoring strategies in detecting atrial fibrillation after cryptogenic stroke. A decision-analytic Markov model was used to project the costs and outcomes of three different electrocardiography monitoring strategies (i.e. 30-day electrocardiography monitoring, three-year implantable loop recorder monitoring, and conventional Holter monitoring) in acute stroke survivors without previously documented atrial fibrillation. The lifetime discounted costs and quality-adjusted life years were $206,385 and 7.77 quality-adjusted life years for conventional monitoring, $207,080 and 7.79 quality-adjusted life years for 30-day extended electrocardiography monitoring, and $210,728 and 7.88 quality-adjusted life years for the implantable loop recorder strategy. Additional quality-adjusted life years could be attained at a more favorable incremental cost per quality-adjusted life year with the implantable loop recorder strategy, compared with the 30-day electrocardiography monitoring strategy, thereby eliminating the 30-day strategy by extended dominance. The implantable loop recorder strategy was associated with an incremental cost per quality-adjusted life year gained of $40,796 compared with conventional monitoring. One-way sensitivity analyses indicated that the model was most sensitive to the rate of recurrent ischemic stroke. An implantable loop recorder strategy for detection of occult atrial fibrillation in patients with cryptogenic stroke is more economically attractive than 30-day electrocardiography monitoring compared to conventional monitoring and is associated with a cost per quality-adjusted life year gained in the range of other publicly funded therapies. The value proposition is improved when considering patients at the highest risk of recurrent ischemic stroke. However, the implantable loop recorder strategy is associated with increased health care costs, and the opportunity cost of wide scale implementation must be considered.

The quality-adjusted life year (QALY) approach as a paradigmatic measure of health outcomes is widely used in the economic evaluation of health policies and is even trying to be emulated in other public policy areas. The objective of this paper is to structure the arguments underlying the use of QALYs in cost-effectiveness analyses, which condition its applicability. To this effect, the paper intervenes in the unreasonable use of the approach in terms of its limitations when prioritizing health services. In short, the authors are generally in favor of the instrument but do not have blanket enthusiasm in support of it.

Cost-Effectiveness of Epcoritamab in Relapsed or Refractory Diffuse Large B-Cell Lymphoma after at Least Two Lines of Therapy in the United States

‘Universal ultrasound scanning for macrosomia… is not cost-effective… is not warranted.’ Wastlund et al. offer this conclusion from a cost-effectiveness analysis (CEA) of universal versus selective screening for macrosomia with ultrasound BJOG, 2019;126:1243–5). This decisive statement reveals interesting observations about CEA in obstetrics. The authors conclude that universal screening for macrosomia is not cost-effective based on a widely accepted threshold in the UK: €20,000–30,000 per quality-adjusted life year (QALY). As the incremental cost-effectiveness ratio (ICER) of universal screening with induction of labour for macrosomia was €52,719 per QALY when compared with selective ultrasound plus labour induction, it is not considered to be cost-effective. Intriguingly, this is cost-effective by a US standard of <USD 100,000 per QALY. Also, cost-effectiveness thresholds – such as P-values or blood pressure cutoffs – are fairly arbitrary and are highly contested. The binary summary based on a yes or no conclusion about cost-effectiveness fails to capture this nuance. In the typical CEA, all costs are converted to a standard cost and all outcomes are converted to a single effectiveness outcome – the QALY. Using QALYs is useful so that unrelated outcomes, or outcomes of disparate clinical significance, can be compared across CEAs. This is right-minded. Without a single health outcome measure, it is nearly impossible for a health system to decide whether, for instance, they should invest in an intervention to reduce caesarean sections or one to prevent neonatal morbidity. Although there are well-reasoned arguments for its use in CEA, QALYs in obstetrics are often misinterpreted and sometimes misused. Important questions about CEA in obstetrics are unresolved and may be unresolvable. Are maternal and neonatal QALYs equal? Should maternal and neonatal QALYs be combined? When a pregnancy results in the death of the mother or newborn, can QALYs account fully for this effect on the family or community? The complexity and conflicting nature of the maternal-fetal dyad is often lost due to the pedantic simplicity and opaqueness of the QALY. In the study by Westland et al., universal ultrasound reduced the number of deaths by 23 in 100 000 deliveries, at a cost of about €500,000 per death. Whether that cost is ‘worth it’ may be more consequential than whether to spend €50,000 for an additional QALY. Surprisingly few studies attempt to estimate the health utility state of families dealing an adverse obstetric outcome. Because of this, the experience of the patient may be lost. In converting all obstetric outcomes to QALY for simplicity and standardisation, there is a risk of ascribing too much validity and weight to this outcome measure. Although QALYs are useful, they are clearly not the whole story. The reader of a CEA (or policy maker) should look beyond the dichotomous conclusion of cost-effectiveness by a given threshold. Cost-effectiveness is less ‘true’ or ‘false,’ and more ‘if’ and ‘when’. An understanding of the unique outcome trade-offs is needed. New data describing the short- and long-term health states of families affected by adverse obstetric events are also needed. Perhaps something to replace or supplement QALY is needed. Looking beyond QALY, providers and patients may find that the answer to the question ‘is it worth it?’ differs from the answer given by a cost-effectiveness threshold. None declared. Completed disclosure of interests form available to view online as supporting information. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

ObjectiveTo assess the cost-effectiveness of the elbasvir/grazoprevir (EBR/GZR) regimen in patients with genotype 1 chronic hepatitis C virus (HCV) infection with severe and end-stage renal disease compared to no treatment.DesignThis study uses a health economic model to estimate the cost-effectiveness of treating previously untreated and treatment experienced chronic hepatitis C patients who have severe and end stage renal disease with the elbasvir-grazoprevir regimen versus no treatment in the French context. The lifetime homogeneous markovian model comprises of forty combined health states including hepatitis C virus and chronic kidney disease. The model parameters were from a multicentre randomized controlled trial, ANRS CO22 HEPATHER French cohort and literature. 1000 Monte Carlo simulations of patient health states for each treatment strategy are used for probabilistic sensitivity analysis and 95% confidence intervals calculations. The results were expressed in cost per quality-adjusted life year (QALY) gained.PatientsThe mean age of patients in the HEPATHER French cohort was 59.6 years and 56% of them were men. 22.3% of patients had a F0 fibrosis stage (no fibrosis), 24.1% a F1 stage (portal fibrosis without septa), 7.1% a F2 stage (portal fibrosis with few septa), 21.4% a F3 stage (numerous septa without fibrosis) and 25% a F4 fibrosis stage (compensated cirrhosis). Among these HCV genotype 1 patients, 30% had severe renal impairment stage 4, 33% had a severe renal insufficiency stage 5 and 37% had terminal severe renal impairment stage 5 treated by dialysis.InterventionFixed-dose combination of direct-acting antiviral agents elbasvir and grazoprevir compared to no-treatment.ResultsEBR/GZR increased the number of life years (6.3 years) compared to no treatment (5.1 years) on a lifetime horizon. The total number of QALYs was higher for the new treatment because of better utility on health conditions (6.2 versus 3.7 QALYs). The incremental cost-utility ratio (ICUR) was of €15,212 per QALY gained for the base case analysis.ConclusionsThis cost-utility model is an innovative approach that simultaneously looks at the disease evolution of chronic hepatitis C and chronic kidney disease. EBR/GZR without interferon and ribavirin, produced the greatest benefit in terms of life expectancy and quality-adjusted life years (QALY) in treatment-naïve or experienced patients with chronic hepatitis C genotype 1 and stage 4–5 chronic kidney disease including dialysis patients. Based on shape of the acceptability curve, EBR/GZR can be considered cost-effective at a willingness to pay of €20,000 /QALY for patients with renal insufficiency with severe and end-stage renal disease compared to no treatment.

Two articles published in this issue, ‘‘A Comparison of EQ-5D Index Scores Derived from the US and UK Population-Based Scoring Functions’’ by Nan Luo and colleagues and ‘‘The Implications of Using US-Specific EQ-5D Preference Weights for Cost-Effectiveness Evaluation’’ by Katia Noyes and colleagues, substantially advance our understanding of the relative performance of USand UK-based EQ-5D preference scores. The study by Luo and others extends the previous work of its authors, who conducted the 2002 US valuation survey for the EQ-5D, using methods largely consistent with those of the 1993 UK valuation survey. Their new study compares the full complement of 243 EQ-5D health state scores predicted by the statistical models developed from the US and UK valuation surveys (both of which directly valued the same 42 common EQ-5D health states). Not surprisingly, like the authors’ earlier comparison of the directly valued health states, the US statistical model consistently predicted health state scores that were higher than those predicted by the UK model. Over the full set of EQ-5D health states, the difference in mean scores was 0.23, as compared with the 0.11 difference found for the smaller number of directly valued states in the earlier comparison. More notably, the new study found a mean difference in transitions between all pairs of health states of 0.25 for the US valuation model and 0.35 for the UK model: The range of all EQ-5D health state valuations in the US model was more compressed than in the UK model. The authors reasonably surmise that although incremental cost-effectiveness ratios (ICERs) calculated using the US model values would likely be less favorable than those using the UK model values, this result would depend on the nature of the condition under study, the severity of the health states, and the size of the health effect. Noyes and colleagues take another step and examine the differences in results between the USand UK-valued EQ-5D statistical models in a costeffectiveness analysis. Using the US values, they reanalyze data from a clinical trial comparing 2 alternative drug therapies (initial pramipexole v. levodopa) in patients with Parkinson disease, which originally used health state values from the UK EQ5D model (see references 15-17 in the article by Noyes and others). The comparative performance of the USand UK-valued EQ-5D models was consistent with the simulated results that Luo and others obtained: Measured over time, the USand UKspecific EQ-5D scores for patients with Parkinson disease followed similar trajectories, except that the US scores were higher on average. As in the simulation exercise, the range of scores using the US values was more compressed than that with the UK values. In particular, Noyes and others found greater differences between the US and UK estimates among subjects who reported problems with usual activities, pain/discomfort, or anxiety/depression than between the estimates for subjects not reporting these problems. As the authors conclude, the implications of the more compressed range of scores using the US valuation model are that the estimated 4-year gains in quality-adjusted life years (QALYs) of the experimental over the control therapy are less than half as large as those using the UK model, a much less favorable ICER ($108,000/QALY v. $43,000/QALY) and a lower probability that the experimental therapy is cost-effective at any dollar-per-QALY threshold. Taken together, these 2 studies offer insight into how valuations of health states based on the USand UK-valued EQ-5D statistical models compare From the Department of Health Policy, George Washington University School of Public Health and Health Services, Washington, DC.

BackgroundThe current standard of care (SOC) for whole breast radiotherapy (WBRT) in the US is conventional tangential photon fields. Advanced WBRT techniques may provide similar tumor control and better normal tissue sparing, but it is controversial whether the medical benefits of an advanced technology are significant enough to justify its higher cost.ObjectiveTo analyze the cost-effectiveness of six advanced WBRT techniques compared with SOC.MethodsWe developed a Markov model to simulate health states for one cohort of women (65-year-old) with early-stage breast cancer over 15 years after WBRT. The cost effectiveness analyses of field-in-field (FIF), hybrid intensity modulated radiotherapy (IMRT), full IMRT, standard volumetric modulated arc therapy (STD-VMAT), multiple arc VMAT (MA-VMAT), non-coplanar VMAT (NC-VMAT) compared with SOC were performed with both tumor control and radiogenic side effects considered. Transition probabilities and utilities for each health state were obtained from literature. Costs incurred by payers were adopted from literature and Medicare data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to evaluate the impact of uncertainties on the final results.ResultsFIF has the lowest ICER value of 1,511 $/QALY. The one-way analyses show that the cost-effectiveness of advanced WBRT techniques is most sensitive to the probability of developing contralateral breast cancer. PSAs show that SOC is more cost effective than almost all advanced WBRT techniques at a willingness-to-pay (WTP) threshold of 50,000 $/QALY, while FIF, hybrid IMRT and MA-VMAT are more cost-effective than SOC with a probability of 59.2%, 72.3% and 72.6% at a WTP threshold of 100,000 $/QALY, respectively.ConclusionsFIF might be the most cost-effective option for WBRT patients at a WTP threshold of 50,000 $/QALY, while hybrid IMRT and MA-VMAT might be the most cost-effective options at a WTP threshold of 100,000 $/QALY.

137 Background: Recent clinical trial data have demonstrated that 3 years (yr) of adjuvant imatinib therapy for patients with surgically resected GIST leads to a significant improvement in recurrence free survival and overall survival vs. 1 yr of therapy. The objective of this study is to assess cost-effectiveness of treating with 3 yrs vs. 1 yr of adjuvant imatinib in the US from a payer’s perspective. Methods: A Markov model was developed to predict GIST recurrence, treatment (txt) costs, and quality-adjusted survival over a lifetime horizon. Patients transitioned between 3 health states: recurrence free GIST, GIST recurrence, and death. Monthly recurrence and mortality rates for 3 yr and 1 yr imatinib were derived from SSGXVIII/AIO clinical trial. The 5-yr recurrence rate observed in the trial was extrapolated for the remaining duration of the model horizon. First recurrence after active txt was treated with imatinib 400mg daily (800mg daily if recurrence during active txt). For subsequent disease progression, patients were treated with imatinib 800mg, sunitinib or best supportive care. After 5 years, txt specific mortality rate was applied for patients with recurrence. Costs and utilities were derived from published literature. Expected costs and quality-adjusted life years (QALYs) were estimated for each txt strategy. Costs and QALYs were discounted at 3% per yr. Extensive sensitivity analyses were conducted. Results: Total lifetime cost per patient was $302,100 with 3 yrs vs. $217,800 for 1 yr of imatinib therapy. Patients on 3 yrs of imatinib had higher QALYs (8.53 vs 7.18) vs. 1yr of imatinib. Incremental cost effectiveness ratio of 3 yrs of imatinib vs 1 yr of imatinib was $62,600/QALY. Model results were sensitive to rate of GIST recurrence beyond 5 yrs and monthly cost of adjuvant imatinib. At a threshold of $100,000/QALY, 3 yr imatinib therapy was cost-effective in 100% of simulations vs. 1 yr of imatinib. Conclusions: Model results suggest that treating patients with 3 yrs of imatinib is cost-effective vs. 1 yr of imatinib below the widely used $100,000/QALY threshold. Both clinical and economic results suggest treating surgically resected GIST patients with 3 yrs of imatinib would result in improved quality-adjusted and overall survival.

How are clinical and costs data brought together?Clinical inputs and cost data are brought together using two main methods.The first is randomized controlled trials (RCTs), which collect both clinical and cost data simultaneously, often referred to as 'piggy-back' trials,

Annual cost of illness and quality-adjusted life year losses in the United States due to 14 foodborne pathogens.

PCN82 Cost-Effectiveness of Once Weekly Selinexor-Bortezomib-Dexamethasone (XVD) in Previously Treated Multiple Myeloma (MM)