We aimed to estimate the cost-effectiveness, burden of disease and budget impact of inclisiran added to standard-of-care lipid-lowering therapy in the real-world secondary cardiovascular prevention population in Switzerland.

Pharmacoeconomics 2022; 40:791-806.

Patients often rely on the advice of their general practitioner (GP) to decide which treatment best fits their needs. Hospitals, in turn, might influence GPs’ referral decision through kickbacks. We present a model with a monopolistic hospital and competitive GPs who vary in the degree of altruism towards their heterogeneous patients and show that an equilibrium without crowding out exists that separates GPs into referrers and care providers. Naïve patients visit purely selfish (referring) GPs, while rational patients sort themselves between the two groups of GPs. Finally, we investigate the scope for regulation, including an optimal coinsurance rate.

German Economic Review, DOI: 10.1515/ger-2020-0007

Background
Lack of nutrition, inadequate housing, low education and limited access to quality care can negatively affect children’s health over their lifetime. Implemented in 2003, the Bolsa Familia (“Family Stipend”) Program (PBF) is a conditional cash transfer program targeting poor households in Brazil. This study investigates the long-term benefits of cash transfers through intergenerational transmission of health and poverty by assessing the early life exposure of the mother to the PBF.

Methods
We used data from the 100M SINASC-SIM cohort compiled and managed by the Center for Data and Knowledge Integration for Health (CIDACS), containing information about participation in the PBF and socioeconomic and health indicators. We analyzed five measures of newborn health: low (less than 2,500 g) and very low (less than 1,500 g) birth weight, premature (less than 37 weeks of gestation) and very premature (less than 28 weeks of gestation) birth, and the presence of some type of malformation (according to ICD-10 codes). Furthermore, we measured the early life exposure to the PBF of the mother as PBF coverage in the previous decade in the city where the mother was born. We applied multilevel logistic regression models to assess the associations between birth outcomes and PBF exposures.

Results
Results showed that children born in a household where the mother received BF were less likely to have low birth weight (OR 0.93, CI; 0.92-0.94), very low birth weight (0.87, CI; 0.84-0.89), as well as to be born after 37 weeks of gestation (OR 0.98, CI; 0.97-0.99) or 28 weeks of gestation (OR 0.93, CI; 0.88-0.97). There were no significant associations between households where the mother received BF and congenital malformation.

On average, the higher the early life exposure to the PBF of the mother, the lower was the prevalence of low birth weight, very low birth weight and congenital malformation of the newborn. No trend was noted for preterm birth.

Conclusion
The PBF might have indirect intergenerational effects on children’s health. These results provide important implications for policymakers who have to decide how to effectively allocate resources to improve child health.

BMC Public Health. 2022 Jan 30;22(1):201.
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Objectives
Health interventions for patients can also affect the health of their informal carers and family members. These changes in carer or family member health could be reflected in cost-utility analyses (CUAs) through the inclusion of their quality-adjusted life-years (QALYs). We conducted a systematic review to identify and describe all CUAs that have included family member health-related QALYs.

Methods
A total of 4 bibliographic databases were searched from inception to July 2021. A 2-stage sifting process for inclusion of studies was undertaken. We performed data extraction using a standardized data extraction form and performed a narrative synthesis of the evidence.

Results
A total of 40 CUAs published between 1999 and 2021 were identified. CUAs were conducted in 15 different countries. CUAs examined 13 different conditions including 15 CUAs on vaccination, 5 on Alzheimer's disease, 2 on Parkinson's disease, 3 on dementia, and 2 on terminal illness. The EQ-5D was the most commonly used measure of family member health. Generally, including carer QALYs resulted in lower incremental cost-effectiveness ratios.

Conclusions
When considering the total number of economic evaluations published, few have included family member QALYs and the methods for doing so are often inconsistent and data sources often limited. Estimation of family member QALYs in patient CUAs was regularly uncertain and often substantial in magnitude. The findings highlight the variation among methods and call for greater consistency in methods for incorporating family member QALYs in patient CUAs.

Value Health, doi: 10.1016/j.jval.2022.02.008.

Background
A growing literature has documented the high global morbidity, mortality and mental health burden associated with the current Covid-19 pandemic. In this paper, we aimed to quantify the total utility and quality of life loss resulting from Covid-19-related government restrictions imposed at the national, regional and global levels.

Methods
We conducted quality of life online surveys in France, India, Italy, UK and the United States of America between June 21st and September 13th 2021, and used regression models to estimate the average quality of life loss due to light and severe restrictions in these countries. We then combined estimated disutility weights from the pooled sample with the latest data on Covid-19 restrictions exposure in each country to estimate the total disutility generated by restrictions at the national, regional and global level. We also embedded a discrete choice experiment (DCE) into the online survey to estimate average willingness to pay to avoid specific restrictions.

Findings
A total of 947 surveys were completed. Thirty-five percent of respondents were female, and 69.5% were between 18 and 39 years old. The weighted average utility weight was 0.71 (95% CIs 0.69–0.74) for light restrictions, and 0.65 (0.63–0.68) for severe restrictions. At the global scale, this implies a total loss of 3259 million QALYs (95% 3021, 3496) as of September 6th, 2021, with the highest burden in lower and upper middle-income countries. Utility losses appear to be particularly large for closures of schools and daycares as well as restaurants and bars, and seem relatively small for wearing masks and travel restrictions.

Interpretation
The results presented here suggest that the QALY losses due to restrictions are substantial. Future mitigation strategies should try to balance potential reductions in disease transmission achievable through specific measures against their respective impact on quality of life. Additional research is needed to determine differences in restriction-specific disutilities across countries, and to determine optimal policy responses to similar future disease threats.

Preventive medicine reports,
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Objective
We aimed to identify the most cost-effective of all prophylactic measures available in Switzerland for women not yet affected by breast and ovarian cancer who tested positive for a BRCA1/2 mutation.

Methods
Prophylactic bilateral mastectomy (PBM), salpingo-oophorectomy (PBSO), combined PBM&PBSO and chemoprevention (CP) initiated at age 40 years were compared with intensified surveillance (IS). A Markov model with a life-long time horizon was developed from the perspective of the Swiss healthcare system using mainly literature-derived data to evaluate costs, quality-adjusted life years (QALYs) and survival. Costs and QALYs were discounted by 3% per year. Robustness of the results was tested with deterministic and probabilistic sensitivity analyses.

Results
All prophylactic measures were found to be cost-saving with an increase in QALYs and life years (LYs) compared to IS. PBM&PBSO were found to be most cost-effective and dominated all other strategies in women with a BRCA1 or BRCA2 mutation. Lifetime costs averaged to 141,293 EUR and 14.5 QALYs per woman with a BRCA1 mutation under IS, versus 76,639 EUR and 19.2 QALYs for PBM&PBSO. Corresponding results for IS per woman with a BRCA2 mutation were 102,245 EUR and 15.5 QALYs, versus 60,770 EUR and 19.9 QALYs for PBM&PBSO. The results were found to be robust in sensitivity analysis; no change in the dominant strategy for either BRCA-mutation was observed.

Conclusion
All more invasive strategies were found to increase life expectancy and quality of life of women with a BRCA1 or BRCA2 mutation and were cost-saving for the Swiss healthcare system compared to IS.

European Journal of Health Economics,
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We consider medical decision-making under diagnostic and therapeutic uncertainty and analyze how ambiguity aversion affects the decisions to test and treat, thereby contributing to the understanding of the observed heterogeneity of such decisions. We show that under diagnostic ambiguity (i.e., the probability of disease is ambiguous), prior testing becomes more attractive if the default option is no treatment and less so if the default option is treatment. Conversely, with therapeutic ambiguity (i.e., the probability of a successful treatment is ambiguous), ambiguity aversion reduces the tolerance toward treatment failure so that the test option is chosen at a lower probability of failure. We differentiate between conditional and unconditional ambiguity aversion and show that this differentiation has implications for the propensity to test. We conclude by discussing the normative scope of ambiguity aversion for the recommendations and decisions of regulatory bodies.

Frontiers in Health Services, Cost and Resource Allocation, doi:10.3389/frhs.2022.825315.

Objective
We examined real-world effects of cantonal legislations to direct surgery patients from the inpatient to the outpatient setting in Switzerland.

Methods
Analyses were based on claims data of the Helsana Group, a leading Swiss health insurance. The study population consisted of 13'145 (in 2014), 12'455 (in 2016), and 12'875 (in 2018) insured persons aged >18 years who had haemorrhoidectomy, inguinal hernia repair, varicose vein surgery, knee arthroscopy/meniscectomy or surgery of the cervix/uterus. We assessed the proportion of inpatient procedures, index costs, length of hospital stays, outpatient costs and hospitalizations during follow-up, stratified by procedure, in-/outpatient setting, and the presence (enacted/effective in 2018) of a cantonal legislation. We used difference-in-differences methods to study the impact of cantonal legislations.

Results
Overall, the proportion of procedures performed in the inpatient setting decreased between 2014 and 2018 (p < 0.001). The decrease between 2016 and 2018 was significantly steeper in cantons with a legislation (p < 0.001; effect size: 0.57; 95% CI: 0.51, 0.64), leading to steeper decreases in healthcare costs of index procedures in cantons with a legislation, with no impact on length of hospital stays. The legislation also had no impact on outpatient costs or hospitalizations during follow-up.

Conclusions
The cantonal legislations achieved the intended effects of inpatient surgery substitution by outpatient surgery, with no evidence suggesting negative effects on costs or hospitalizations during follow-up.

Health Policy,
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A genetic test is a test for the presence or absence of a genetic mutation. A positive test outcome that reveals a mutation associated with increased risk for a disease may lead a patient to seek preventive treatment provided that the penetrance (probability of developing the disease given the mutation) is sufficiently high. We derive the test threshold and the test-treatment threshold, which confine the mutation probability interval for the use of the genetic test. Test and treatment costs as well as a low penetrance rate of the mutation narrow this interval. We illustrate the model with parameters of the test for BRCA1 and BRCA2 genes as well as of preventive treatment options for breast cancer.

The European Journal of Health Economics, doi: 10.1007/s10198-021-01410-0

Introduction
Pembrolizumab monotherapy or in combination with chemotherapy are two new treatment options for patients with metastatic non-squamous non-small cell lung cancer (NSCLC) and high (≥ 50%) programmed death ligand 1 (PD-L1) expression. We conducted a cost-effectiveness analysis for Switzerland comparing these two options but also pembrolizumab to chemotherapy.

Methods
We constructed a 3-state Markov model with a time horizon of 10 years. Parametric functions were fitted to Kaplan–Meier overall survival (OS) and progression-free survival (PFS) using 2-year follow-up data from the KN-024 and KN-189 registration trials. We included estimated costs for further treatment lines and costs for best supportive care. Costs were assessed from the Swiss healthcare payer perspective. We used published utility values.

Results
Combination therapy resulted in an expected gain of 0.17 quality-adjusted life years (QALYs) per patient and incremental costs of Swiss Francs (CHF) 81,085 as compared to pembrolizumab. These estimates led to an incremental cost-effectiveness ratio (ICER) of CHF 475,299/QALY. Pembrolizumab in comparison to chemotherapy was estimated to generate mean incremental QALYs of 0.83 and incremental costs of CHF 56,585, resulting in an ICER of CHF 68,580/QALY. Results were most sensitive to changes in costs of 1L pembrolizumab and combination therapy, together with changes in PFS. In the probabilistic sensitivity analysis, we estimated combination therapy was cost-effective in 4.9% of the simulations and pembrolizumab monotherapy in 82.9%, assuming a willingness-to-pay threshold of CHF 100,000 per QALY gained.

Conclusions
Pembrolizumab is likely to be cost-effective from the Swiss healthcare payer perspective, whereas pembrolizumab plus chemotherapy is not.

European Journal of Health Economics,
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Growing evidence from evolutionary biology demonstrates how early life shocks trigger physiological changes designed to be adaptive in challenging environments. We examine the implications of one type of physiological adaptation - immunity formation - for human capital accumulation. Using variation in early life malaria risk generated by an interrupted disease control program in Zambia, we show that exposure to infectious diseases during the first two years of life can reduce the harmful effects of malaria exposure on cognitive development during the preschool years. These findings suggest a non-linear and trajectory-dependent relationship between early life adversity and human capital formation.

Journal of Health Economics, doi: 10.1016/j.jhealeco.2021.102532.

Background
Consolidation immunotherapy with the programmed death ligand 1 (PD-L1) inhibitor durvalumab improves survival in patients with stage III non-small-cell lung cancer responding to radiochemotherapy. The aim of this study was to assess the cost-effectiveness of durvalumab in Switzerland based on the most recent PACIFIC survival follow-up.

Materials and methods
We constructed a Markov model based on the 3-year follow-up data of the PACIFIC trial and compared consolidation durvalumab with observation. We used published utility values and assessed costs for treatment strategies from the perspective of the Swiss health care payers. Cost-effectiveness was tested both in the intention-to-treat population of the PACIFIC trial unselected for PD-L1 tumor expression and in patients with PD-L1-expressing tumors (≥1%).

Results
In the unselected/PD-L1-positive patients, durvalumab showed an incremental effectiveness of 0.76/1.18 quality-adjusted life year (QALY) and incremental costs of Swiss Francs (CHF) 67 239/78 177, resulting in incremental cost-effectiveness ratios of CHF 88 703/66 131 per QALY gained, respectively. The most influential factors for the incremental cost-effectiveness ratio were the utility before first progression, costs for durvalumab, and the hazard ratio for overall survival under durvalumab versus observation. The cost-effectiveness of durvalumab was better than CHF 100 000 per QALY gained in 75% of the simulations in probabilistic sensitivity analysis.

Conclusion
Assuming a willingness-to-pay threshold of CHF 100 000 per QALY gained, consolidation durvalumab is likely to be cost-effective both in patients with inoperable stage III non-small-cell lung cancer (NSCLC) unselected for PD-L1 status and in patients with PD-L1-expressing tumors in Switzerland.

Ann Oncol,
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We use unique data on direct observations of patient-provider interactions linked to detailed patient exit interviews and household surveys to study the relationship between patients’ socioeconomic status and the quality of antenatal care in the Democratic Republic of Congo. We find a significant wealth-quality gradient: a 1 standard deviation in household wealth is associated with a 1.6–3.2 percentage point increase in protocol compliance, depending on the data source and the definition of the compliance index. A large part of the overall wealth-quality gradient is driven by generally lower facility quality in poorer areas. However, we also find a statistically significant within-village wealth-quality relationship that is primarily driven by wealthier women seeking care at higher-quality facilities even if they are more distant. Finally, we find some evidence that even within the same facilities, poorer women tend to receive worse care but, on average, also pay less for care of a given quality.

Economic Development and Cultural Change, Please click here for the full article.

Abstract
Literature on consumer choice has demonstrated that the inclusion of an inferior alternative choice (decoy) can increase interest in a target product or action. In two online studies, we tested the impact of decoys on the probability of previous non-intenders to have a screening test which could significantly lower their chances of dying of colorectal cancer. We find that the presence of a decoy increased the probability to choose screening at the target hospital (over no screening) from 39% to 54% and 37% to 59% depending on how many hospital attributes were communicated and how strongly the decoy was dominated by the target. We also show that the presence of the decoy was associated with lower levels of reported decisional complexity while not undermining information seeking and knowledge acquisition. These findings offer a ‘proof of principle’ that decoys have the potential to increase screening uptake without negatively influencing informed choice.

Background
The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy.

Methods
Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person’s EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living.

Results
224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon’s evenness index score of 0.86) than the EQ-5D-3L (Shannon’s evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index.

Conclusion
Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

Health Qual Life Outcomes
doi: 10.1186/s12955-020-01564-0.

Social accountability programs are increasingly used to improve the performance of public service providers in low-income settings. Despite their growing popularity, evidence on the effectiveness of social accountability programs remains mixed. In this manuscript, we assess the impact of a social accountability intervention on health facility management exploring quasiexperimental variation in program exposure in Tanzania. We find that the social accountability intervention resulted in a 1.8 SD reduction in drug stockouts relative to the control group, but did not improve facility infrastructure maintenance. The results of this study suggest that social accountability programs may be effective in areas of health service provision that are responsive to changes in provider behavior but may not work in settings where improvements in outcomes are conditional on larger health systems features.

Health Economics, DOI:10.1002/hec.4219

Background
The EQ-5D-3L and EQ-5D-5L are two generic health-related quality of life measures, which may be used in clinical and health economic research. They measure impairment in 5 aspects of health: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The aim of this study was to assess the performance of the EQ-5D-3L and EQ-5D-5L in measuring the self-reported health status of older patients with substantial multimorbidity and associated polypharmacy.

Methods
Between 2017 and 2019, we administered EQ-5D-3L and EQ-5D-5L to a subset of patients participating in the OPERAM trial at 6 months and 12 months after enrolment. The OPERAM trial is a two-arm multinational cluster randomised controlled trial of structured medication review assisted by a software-based decision support system versus usual pharmaceutical care, for older people (aged ≥ 70 years) with multimorbidity and polypharmacy. In the psychometric analyses, we only included participants who completed the measures in full at 6 and 12 months. We assessed whether responses to the measures were consistent by assessing the proportion of EQ-5D-5L responses, which were 2 or more levels away from that person’s EQ-5D-3L response. We also compared the measures in terms of informativity, and discriminant validity and responsiveness relative to the Barthel Index, which measures independence in activities of daily living.

Results
224 patients (mean age of 77 years; 56% male) were included in the psychometric analyses. Ceiling effects reported with the EQ-5D-5L (22%) were lower than with the EQ-5D-3L (29%). For the mobility item, the EQ-5D-5L demonstrated better informativity (Shannon’s evenness index score of 0.86) than the EQ-5D-3L (Shannon’s evenness index score of 0.69). Both the 3L and 5L versions of EQ-5D demonstrated good performance in terms of discriminant validity, i.e. (out of all items of the EQ-5D-3L and EQ-5D-5L, the pain/discomfort and anxiety/depression items had the weakest correlation with the Barthel Index. Both the 3L and 5L versions of EQ-5D demonstrated good responsiveness to changes in the Barthel Index.

Conclusion
Both EQ-5D-3L and EQ-5D-5L demonstrated validity and responsiveness when administered to older adults with substantial multimorbidity and polypharmacy who were able to complete the measures.

BMC Health Serv Res,
doi: 10.1186/s12913-020-05930-y

Despite public health efforts, uptake of preventive health technologies remains low in many settings. In this paper, we develop a formal model of prevention and test it through a laboratory experiment. In the model, rational agents decide whether to take up health technologies that reduce, but do not eliminate the risk of adverse health events. As long as agents are sufficiently risk averse and priors are diffuse, we show that initial uptake of effective technologies will be limited. Over time, the model predicts that take-up will decline as users with negative experiences revise their effectiveness priors towards zero. In our laboratory experiments, we find initial uptake rates between 65 and 80% for effective technologies with substantial declines over time, consistent with the model’s predictions. We also find evidence of decision-making not consistent with our model: subjects respond most strongly to the most recent health outcomes, and react to negative health outcomes by increasing their willingness to invest in prevention, even when health risks without prevention are known by all subjects. Our findings suggest that high uptake of preventive technologies should only be expected if the risk of adverse health outcomes without prevention is high, or if preventive technologies are so effective that the risk of adverse outcomes is negligible with prevention.

Health Economics, doi: 10.1007/s10683-020-09668-6