Cost-effectiveness of TB diagnostic technologies in Ethiopia: a modelling study.

BACKGROUND: Tuberculosis (TB) is a major threat to public health, particularly in countries where the disease is highly prevalent, such as Ethiopia. Early diagnosis and treatment are the main components of TB prevention and control. Although the national TB guideline recommends the primary use of rapid TB diagnostics whenever feasible, there is limited evidence available that assess the efficiency of deploying various diagnostic tools in the country. Hence, this study aims to evaluate the cost-effectiveness of rapid TB/MDR-TB diagnostic tools in Ethiopia. METHODS: A hybrid Markov model for a hypothetical adult cohort of presumptive TB cases was constructed. The following TB diagnostic tools were evaluated: X-pert MTB/RIF, Truenat, chest X-ray screening followed by an X-pert MTB/RIF, TB-LAMP, and smear microscopy. Cost-effectiveness was determined based on incremental costs ($) per Disability-adjusted Life Years (DALY) averted, using a threshold of one times Gross Domestic Product (GDP) per capita ($856). Data on starting and transition probabilities, costs, and health state utilities were derived from secondary sources. The analysis is conducted from the health system perspective, and a probabilistic sensitivity analysis is performed. RESULT: The incremental cost-effectiveness ratio for X-pert MTB/RIF, compared to the next best alternative, is $276 per DALY averted, making it a highly cost-effective diagnostic tool. Additionally, chest X-ray screening followed an X-pert MTB/RIF test is less cost-effective, with an ICER of $1666 per DALY averted. Introducing X-pert MTB/RIF testing would enhance TB detection and prevent 9600 DALYs in a cohort of 10,000 TB patients, with a total cost of $3,816,000. CONCLUSION: The X-pert MTB/RIF test is the most cost-effective diagnostic tool compared to other alternatives. The use of this diagnostic tool improves the early detection and treatment of TB cases. Increased funding for this diagnostic tool will enhance access, reduce the TB detection gaps, and improve treatment outcomes.

Estimating the Allocation of the Economic Value Generated by Utilization of All-Oral Direct-Acting Antivirals for Hepatitis C in the United States, 2015-2019.

OBJECTIVES: Between 2013-2019, several all-oral direct-acting antivirals (DAAs) were launched with the potential to cure patients with hepatitis C virus (HCV). They generated economic value in terms of the health gains for patients and cost-savings for the US healthcare system. We estimated the share of this value allocated to four manufacturers vs society. METHODS: For 2015-2019, we estimated the incremental impact of DAAs on HCV health outcomes and costs. We used the CDAF Polaris Observatory database to estimate utilization. Per-patient projections of lifetime quality-adjusted life-years (QALYs) gained and medical costs avoided were based on a standard 9-state HCV disease-progression model for DAA treatment vs alternatives. Annual QALY gains were valued at $114,000 per QALY. Outcomes and costs were discounted at 3%. Estimated revenues were based on reported sales. RESULTS: An estimated 1,080,000 patients received DAAs: 81.5% would not have received the pre-DAA standard of care. On average, these patients were projected to gain 4.4 QALYs and save $104,400 in lifetime healthcare costs, generating $531.8 billion in value. Those who would have received treatment gained 1.7 QALYs and saved $41,500 in lifetime costs, generating $47.4 billion in economic value. As treatment costs fell nearly 75%, the four manufacturers reported $37.4 billion from DAA sales-an allocation of 6.5% of the total value. CONCLUSIONS: The great majority (∼90%) of the economic value of curing HCV with DAAs were health benefits to patients and net cost-savings to society. DAA manufacturers received a minority share (6.5%) of the aggregate economic value generated.

Evaluating Policies of Expanding Versus Restricting First-Line Treatment Choices: A Cost-Effectiveness Analysis Framework.

OBJECTIVES: Healthcare payers often implement coverage policies that restrict the utilization of costly new first-line treatments. Cost-effectiveness analysis can be conducted to inform these decisions by comparing the new treatment with an existing one. However, this approach may overlook important factors such as treatment effect heterogeneity and endogenous treatment selection, policy implementation costs, and diverse patient preferences across multiple treatment options. We aimed to develop a cost-effectiveness analysis framework that considers these real-world factors, facilitating the evaluation of alternative policies related to expanding or restricting first-line treatment choices. METHODS: We introduced a metric of incremental cost-effectiveness ratio (ICER) that compares an expanded choice set (CS) including the new first-line treatment with a restricted CS excluding the new treatment. ICER(CS) accounts for treatment selection influenced by heterogeneous treatment effects and policy implementation costs. We examined a basic scenario with 2 standard first-line treatment choices and a more realistic scenario involving diverse preferences toward multiple choices. To illustrate the framework, we conducted a retrospective evaluation of including versus excluding abiraterone acetate plus prednisone (AAP) (androgen deprivation therapy [ADT] + AAP) as a first-line treatment for metastatic hormone-sensitive prostate cancer. RESULTS: The traditional ICERs for ADT + AAP versus ADT alone and ADT+ docetaxel were $104 269 and $206 324/quality-adjusted life-year, respectively. The ICER(CS) for comparing an expanded CS with ADT + AAP with a restricted CS without ADT + AAP was $123 179/quality-adjusted life-year. CONCLUSIONS: The proposed framework provides decision makers with policy-relevant tools, enabling them to assess the cost-effectiveness of alternative policies of expanding versus restricting patients' and physicians' first-line treatment choices.

Health Interventions May Have Divergent Impacts on Health and Economic Equity: A Case Study of the Community-Based Hypertension Improvement Project in Ghana.

BACKGROUND AND OBJECTIVE: Improving health and economic equity are key objectives in priority setting, particularly in low-income and middle-income countries. This study aims to assess the distributional impacts of the Community-based Hypertension Improvement Project (ComHIP) on health and economic outcomes across wealth quintiles in Ghana. METHODS: We developed a decision analytical model to simulate a 30 million cohort of Ghanaians aged 15-49 years. The study specified health outcomes as the prevention of stroke cases and averting deaths among those with hypertension. Furthermore, we explored economic impacts, including savings in out-of-pocket costs for stroke patients and government spending. Financial risk protection against catastrophic and impoverishing health expenditures was also examined. We assessed these outcomes across wealth quintiles, and the corresponding concentration indexes (CIXs) were determined. RESULTS: It was estimated that ComHIP could prevent 1450 stroke cases and 564 related deaths annually. Health benefits were observed to be more significant among the wealthier quintiles (CIX 0.217), mainly attributed to a higher occurrence of hypertension within these groups. ComHIP was also projected to result in an annual saving of USD 49,885 in individuals' out-of-pocket costs (CIX 0.262) and USD 37,578 in government spending (CIX 0.146). These savings correspond to the prevention of 335 catastrophic health expenditure cases (CIX - 0.239) and 11 impoverishing health expenditure cases (CIX - 0.600). CONCLUSIONS: While ComHIP provides greater health benefits to wealthier groups, it offers substantial financial risk protection for the less wealthy. This study highlights the importance of considering equity in both health and financial risk when making priority-setting decisions.

Gene Therapy Versus Common Care for Eligible Individuals With Sickle Cell Disease in the United States : A Cost-Effectiveness Analysis.

BACKGROUND: Sickle cell disease (SCD) and its complications contribute to high rates of morbidity and early mortality and high cost in the United States and African heritage community. OBJECTIVE: To evaluate the cost-effectiveness of gene therapy for SCD and its value-based prices (VBPs). DESIGN: Comparative modeling analysis across 2 independently developed simulation models (University of Washington Model for Economic Analysis of Sickle Cell Cure [UW-MEASURE] and Fred Hutchinson Institute Sickle Cell Disease Outcomes Research and Economics Model [FH-HISCORE]) using the same databases. DATA SOURCES: Centers for Medicare & Medicaid Services claims data, 2008 to 2016; published literature. TARGET POPULATION: Persons eligible for gene therapy. TIME HORIZON: Lifetime. PERSPECTIVE: U.S. health care sector and societal. INTERVENTION: Gene therapy versus common care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs), equity-informed VBPs, and price acceptability curves. RESULTS OF BASE-CASE ANALYSIS: At an assumed $2 million price for gene therapy, UW-MEASURE and FH-HISCORE estimated ICERs of $193 000 per QALY and $427 000 per QALY, respectively, under the health care sector perspective. Corresponding estimates from the societal perspective were $126 000 per QALY and $281 000 per QALY. The difference in results between models stemmed primarily from considering a slightly different target population and incorporating the quality-of-life (QOL) effects of splenic sequestration, priapism, and acute chest syndrome in the UW model. From a societal perspective, acceptable (>90% confidence) VBPs ranged from $1 million to $2.5 million depending on the use of alternative effective metrics or equity-informed threshold values. RESULTS OF SENSITIVITY ANALYSIS: Results were sensitive to the costs of myeloablative conditioning before gene therapy, effect on caregiver QOL, and effect of gene therapy on long-term survival. LIMITATION: The short-term effects of gene therapy on vaso-occlusive events were extrapolated from 1 study. CONCLUSION: Gene therapy for SCD below a $2 million price tag is likely to be cost-effective when applying a societal perspective at an equity-informed threshold for cost-effectiveness analysis. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.

Estimating the Potential Benefits of Confirmatory Trials for Drugs with Accelerated Approval: A Comprehensive Value of Information Framework.

BACKGROUND: The US Food and Drug Administration's Accelerated Approval (AA) policy provides a pathway for patients to access potentially life-saving drugs rapidly. However, the use of surrogate endpoints, single-arm designs, and small sample sizes in preliminary trials that support AAs can lead to uncertainty regarding the clinical benefits of such drugs. This study aims to develop a comprehensive value of information (VOI) framework for assessing the potential benefits of future confirmatory trials, accounting for the various uncertainties inherent in preliminary trials. METHODS: I formulated an expected value of information from confirmatory trial (EVICT) metric, which evaluates the potential benefits of a confirmatory trial that would reduce those uncertainties by using a clinically meaningful endpoint, a randomized control, and increased sample size. The EVICT metric can quantify the expected benefits of a well-designed confirmatory trial or an inadequately designed one that continues to use surrogate endpoints or single-arm design. The framework was illustrated using a hypothetical AA drug for metastatic breast cancer. RESULTS: The case study demonstrates that a highly uncertain preliminary trial of an AA drug was associated with a substantial EVICT. A confirmatory trial with an increased sample size for this AA drug, utilizing a clinically meaningful endpoint and randomized control, yielded a population-level EVICT of $12.6 million. Persistently using a surrogate endpoint and single-arm trial design would reduce the EVICT by 60%. CONCLUSIONS: This framework can provide accurate VOI estimates to guide coverage policies, value-based pricing, and the design of confirmatory trials for AA drugs.

Gender Disparities in Blood Pressure and the Role of Body Mass Index: A Birth Cohort Analysis in China.

BACKGROUND: The slow decline in cardiovascular disease (CVD) mortality and the stagnant or increasing hypertension prevalence in low- and middle-income countries necessitate investigation. Evolving gender disparities suggested that male cardiovascular health disadvantage may be preventable, offering potential for enhancing population cardiovascular health. Despite global body mass index (BMI) increases, its role in shaping the gender disparities remains underexplored. OBJECTIVE: This study investigated the birth cohort dynamics of gender disparities in systolic/diastolic blood pressure (SBP/DBP) in China, one of the world's largest low- and middle-income countries, and explored the potential role of BMI in explaining the changing gender disparities. METHODS: Data from the China Health and Nutrition Survey (1991-2015) were analyzed using multilevel growth-curve models to estimate gender- and cohort-specific SBP/DBP trajectories among individuals born between 1950 and 1975. RESULTS: Men had higher SBP and DBP than women at the sample's mean age of 41.7 years. The gender disparities in SBP and DBP increased with each successive one-year cohort from 1950 to 1975 by 0.14 mm Hg and 0.09 mm Hg, respectively. Adjusting for BMI reduced the increasing gender disparities in SBP and DBP by 31.9% and 34.4%, respectively. CONCLUSION: Chinese men experienced a greater increase in SBP/DBP across successive cohorts compared to women. The increasing gender disparities in SBP/DBP were partially attributable to a greater BMI increase across cohorts among men. Given these findings, prioritizing interventions that aim to reduce BMI, particularly among men, could potentially alleviate the burden of CVD in China through lowering SBP/DBP.

Associating Health-Related Quality-of-Life Score with Time Uses to Inform Productivity Measures in Cost-Effectiveness Analysis.

BACKGROUND: The Second Panel on Cost Effectiveness in Health and Medicine recommended that cost-effectiveness analyses (CEA) explicitly incorporate the valuation of productive time from a societal perspective. We developed a new approach to capture productivity impacts in CEA without direct evidence on these impacts by associating varying levels of health-related quality-of-life (HrQoL) score with different time uses in the United States. METHODS: We conceptualized a framework that estimates the association between HrQoL score with productivity through time uses. We used the American Time-Use Survey (ATUS) from year 2012-2013, when data on a Well-Being Module (WBM) was additionally collected alongside ATUS. The WBM measured the quality of life (QoL) score using a visual analog scale. To operationalize our conceptual framework, we employed an econometric approach that addressed three technical issues in the observed data: (i) distinction between overall QoL and HrQoL, (ii) correlation across different categories of time use and the share structure of time-use data, and (iii) reverse causality between time uses and HrQoL score in a cross-sectional setting. Furthermore, we developed a metamodel-based algorithm to summarize the numerous estimates from the primary econometric model efficiently. Finally, we illustrated the use of our algorithm to calculate productivity and time spent seeking care costs in an empirical CEA of a prostate cancer treatment. RESULTS: We provide the estimates of the metamodel algorithm. Incorporating these estimates into the empirical CEA reduced the incremental cost-effectiveness ratio by 27%. CONCLUSION: Our estimates can facilitate the inclusion of productivity and time spent seeking care in CEA as recommended by the Second Panel.

Long-term survival with sickle cell disease: a nationwide cohort study of Medicare and Medicaid beneficiaries.

To our knowledge, we report the first population-based period life table, the expected lifetime survival for Medicare and Medicaid beneficiaries with sickle cell disease (SCD), and the disparities in survival by insurance types in the United States. We constructed a retrospective cohort of individuals with diagnosed SCD receiving common care (any real-world patterns of care except transplant) based on nationwide Medicare and Medicaid claim data (2008-2016), covering beneficiaries in all 50 states. We analyzed lifetime survival probabilities using Kaplan-Meier curves and projected life expectancies at various ages for all, stratified by sex and insurance types. Our analysis included 94 616 individuals with SCD that have not undergone any transplant. Life expectancy at birth was 52.6 years (95% confidence interval: 51.9-53.4). Compared with the adults covered by Medicaid only, those covered by Medicare for disabilities or end-stage renal disease and those dually insured by Medicare and Medicaid had significantly worse life expectancy. Similarly, for beneficiaries aged ≥65 years, these 2 insurance types were associated with significantly shorter life expectancy than those enrolled in Medicare old age and survivor's insurance. Our study underscores the persistent life expectancy shortfall for patients with SCD, the burden of premature mortality during adulthood, and survival disparities by insurance status.

Economic Evaluation of a Point-of-Care Test for Bacterial Vaginosis Among Women With Vaginal Symptoms.

BACKGROUND: There is an unmet need for a clinical diagnostic technology to detect bacterial vaginosis (BV) rapidly and accurately. Novel point-of-care (POC) tests have the potential to fulfill this gap. Our objective was to determine the cost-effectiveness of a hypothetical clinician-administered POC test for diagnosing BV in the United States. METHODS: We developed a state-transition microsimulation model to evaluate the cost-effectiveness of using the POC test versus usual care among women of reproductive age with vaginal symptoms. We adopted a healthcare sector perspective that included relevant healthcare costs and a societal perspective that further incorporated productivity costs. Model parameters were empirically estimated based on commercial insurance claims data or derived from published literature. The primary model outcome was incremental cost-effectiveness ratio. We started with analyzing a hypothetical POC test with a sensitivity and specificity of 0.9 and a cost of $40, followed by extensive sensitivity analyses. RESULTS: Using the hypothetical POC test to diagnose BV increased costs by $16 and quality-adjusted life-years by 0.0005 per person compared with the usual care, leading to an incremental cost-effectiveness ratio of $31,108 per quality-adjusted life-year gained. When also capturing the productivity costs, the POC test resulted in an average cost savings of $57. The sensitivity analyses showed that the POC test's sensitivity was more influential on its cost-effectiveness than specificity. CONCLUSIONS: Using the POC test to diagnose BV is likely to be cost-effective relative to usual care, especially with a high sensitivity or a substantial positive effect on productivity.

Value-Based Pricing for Patent-Protected Medicines Over the Product Life Cycle: Pricing Anomalies in the "Age of Cures" and Their Implications for Dynamic Efficiency.

OBJECTIVES: Conventional cost-effectiveness analysis (CEA) for the value-based pricing of new medicines largely ignores the implications of limited market exclusivity (ie, patent-protection periods plus any exclusivity granted by regulators). This paper explores the implications of this methodological shortcoming, which produces several pricing anomalies with potentially unintended effects on research and development (R&D) incentives. METHODS: We illustrate these implications by comparing 4 stylized examples of increasing complexity, from short-term cures for acute conditions to long-term cures for rare, health-catastrophic conditions. RESULTS: (1) Conventional-CEA will project a different result than an adjusted CEA that considers generic or biosimilar entry; (2) free and flexible pricing of long-term treatments (eg, statins for hypercholesterolemia) or repeated-dose cures (eg, insulin for type 1 diabetes) for chronic conditions will likely result in predictable price increases at the end of the exclusivity period that may be perceived as unjustified or unsupported; and (3) one-time administration "cures" (eg, gene therapy for spinal muscular atrophy) have the potential to allocate a large share of the social surplus to the manufacturer over the product lifetime, which may or may not be dynamically efficient per se, but may also inadvertently disadvantage the development of valuable long-term treatments or repeated-dose cures for chronic conditions. CONCLUSIONS: We highlight the need for additional research on long-term solutions to these issues that would aim to promote dynamically efficient global R&D. More work is needed on the following: (1) relationships between social surplus allocation and the amount and composition of global R&D, as we may be as likely to be encouraging excessive R&D in some areas as to be undersupplying it in others; and (2) relating the size of the surplus reward to R&D cost and, thus, the return on investment.

Lifetime medical costs attributable to sickle cell disease among nonelderly individuals with commercial insurance.

Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity, mortality, and a disproportionate burden on Black and Hispanic communities. Our objective was to estimate the total healthcare costs and out-of-pocket (OOP) costs attributable to SCD among commercially insured individuals over their nonelderly lifetimes (0 to 64 years of age). We constructed a retrospective cohort of individuals with diagnosed SCD using Truven Health Marketscan commercial claims data from 2007 through 2018, compared with matched control subjects from the Medical Expenditure Panel Survey. We estimated Kaplan-Meier sample average costs using previously reported survival curves for SCD and control subjects. Individuals with SCD (20 891) and control subjects (33 588) were included in our analysis. The SCD sample had a mean age of 25.7 (standard deviation, 17.4) years; 58.0% were female. Survival-adjusted costs of SCD peaked at age 13 to 24 years and declined at older ages. There was no significant difference in total medical costs or OOP costs between the sexes. SCD-attributable costs over 0 to 64 years of age were estimated to be $1.6 million (95% confidence interval [CI], $1.3M-$1.9M) and $1.7 million (95% CI, $1.4M-$2.1M) for females and males with SCD, respectively. The corresponding OOP estimates were $42 395 (95% CI, $34 756-$50 033) for females and $45 091 (95% CI, $36 491-$53 691) for males. These represent a 907% and 285% increase in total medical and OOP costs over control subjects, respectively. Although limited to the commercially insured population, these results indicate that the direct economic burden of SCD is substantial and peaks at younger ages, suggesting the need for curative and new medical therapies.

Prevalence of comorbidities associated with sickle cell disease among non-elderly individuals with commercial insurance-A retrospective cohort study.

Sickle cell disease (SCD) is a severe monogenic disease associated with high morbidity and mortality and a disproportionate burden on Black communities. Few population-based studies have examined the prevalence of comorbidities among persons with SCD. We estimated the prevalence of comorbidities experienced by individuals with SCD enrolled in employer-based health insurance plans in the US over their non-elderly lifetimes (0-64 years of age) with a retrospective cohort design using Truven Health MarketScan commercial claims data from 2007-2018. ICD-9/10 codes were used to identify individuals with SCD using a previously published algorithm. For this cohort, comorbidities associated with SCD were identified across 3 age categories (<18, 18-45, 46-64 years-old), based on the CMS Chronic Comorbidities Warehouse or SCD-specific diagnosis codes, when applicable. The total number of SCD patients available for analysis in each age category was 7,502 (<18 years), 10,183 (18-45 years) and 4,459 (46-64 years). Across all ages, vaso-occlusive pain, infections (non-specific), and fever were the most common comorbidities. Vaso-occlusive pain and infection were the most prevalent conditions for persons age <18- and 18-45-year-olds, while in the 46-54-year-old age group, infection and cardiovascular including pulmonary hypertension were most prevalent. Compared to persons <18 years old, the prevalence of vaso-occlusive pain, fever, and acute chest syndrome claims declined in older populations. The comorbidity burden of SCD is significant across all age groups. SCD patients experience comorbidities of age such as chronic pain, cardio-vascular conditions including pulmonary hypertension and renal disease at far higher rates than the general population. Novel disease modifying therapies in development have the potential to significantly reduce the comorbidity burden of SCD.

Does Clinical Evidence of Heterogeneity Impact Treatment Selection? A Case Study of Abiraterone for Metastatic Prostate Cancer.

BACKGROUND: Two pivotal randomized controlled trials (RCTs) demonstrate that abiraterone acetate + prednisone (AAP) combined with androgen deprivation therapy (ADT) significantly extends the survival of men with metastatic hormone-sensitive prostate cancer (mHSPC) compared with ADT alone. Their subgroup analyses indicate that the survival benefit is significant for younger men but not older men. We aimed to assess whether publication of the RCTs was associated with differential real-world AAP utilization by age groups. METHODS: Using TriNetX electronic medical records data collected from 43 healthcare organizations across the United States, we performed a difference-in-differences event study among men with newly diagnosed mHSPC observed from June 2014 to June 2019. Eligible subjects were identified based on a comprehensive published algorithm. We analyzed the change in utilization rate of AAP before versus after publication of the RCTs among men aged <70 years versus ≥70 years, adjusting for demographic factors and clinical conditions. RESULTS: Our study included 6,888 men with newly diagnosed mHSPC with 12,738 observations, of whom 46% were aged <70 years. The prepublication trends of AAP utilization were similar between the age groups, whereas publication of the RCTs was associated with a 3.5% higher adjusted uptake rate of AAP among younger men (95% CI, 1.2%-5.8%) relative to older men. This estimate reflects an uptake rate nearly 3 times higher than would have been expected had younger men followed the same utilization trends as older men. The estimates remained consistent throughout the postpublication period. CONCLUSIONS: Our study suggests that publication of the RCTs was associated with faster uptake of AAP among younger versus older men with newly diagnosed mHSPC, despite the absence of clinical guidance for differential treatment selection. This finding highlights the importance of confirmatory studies among older men, considering the uncertainties of subgroup analyses in RCTs.

Application of validated mapping algorithms between generic PedsQL scores and utility values to individuals with sickle cell disease.

PURPOSE: There is a paucity of empirically estimated health state utility (HSU) values to estimate health-related quality of life among individuals with sickle cell disease (SCD). This study aims to map the Pediatric Quality of Life Inventory generic core scales (PedsQL GCS) to HSUs for children and adolescents with SCD in the United States, using published algorithms, and to assess the construct validity of these HSUs against SCD-specific PedsQL scores. METHODS: We used the published mapping algorithms identified in four published articles, in which the PedsQL GCS was mapped to either the EuroQol-5 Dimension 3-Level, Youth Version or the Child Health Utility 9-Dimension to obtain HSUs. We employed the algorithms to calculate HSUs for a sample of children and adolescents from the Sickle Cell Clinical Research and Intervention Program. To assess the construct validity of the mapped HSUs in SCD patients, we computed Spearman's correlation coefficient comparing the HSUs with the PedsQL SCD total score and separately with each PedsQL SCD dimension-specific score. RESULTS: The mean mapped HSU across published algorithms was 0.792 (95% CI: 0.782-0.801). It was significantly higher among children aged 5-12 years than children aged 13-17 years. The Spearman's correlation coefficient for HSUs versus PedsQL SCD total scores was 0.64 (95% CI: 0.57-0.71). Correlations ranged from 0.40 (95% CI: 0.32-0.48) to 0.60 (95% CI: 0.54-0.66) for HSUs versus PedsQL SCD dimension-specific scores. CONCLUSIONS: The existing mapping algorithms show acceptable construct validity in children and adolescents with SCD. Additional algorithms are needed for adults and for specific SCD comorbidities.

Medical and Non-medical Costs of Sickle Cell Disease and Treatments from a US Perspective: A Systematic Review and Landscape Analysis.

BACKGROUND: Sickle cell disease (SCD) is a complex genetic disorder that manifests in infancy and progresses throughout life in the form of acute and chronic complications. As the upfront costs of potentially curative, genetic therapies will likely be high, an assessment and comprehensive characterization of the medical and non-medical cost burden will inform future decision making. OBJECTIVE: We sought to systematically summarize the existing literature surrounding SCD medical and non-medical costs. METHODS: We searched MEDLINE and EMBASE (2008-2020) and identified US-based studies that detailed medical or non-medical costs. Eligible studies provided empirical estimates about any aspect of cost or SCD individuals of all ages and their caregivers. Study quality was assessed using the Newcastle-Ottawa Scale, and costs were adjusted to 2019 US$. RESULTS: Search queries returned 479 studies, with 342 from medical burden searches and 137 from non-medical burden searches, respectively. Herein, we report the results of the 40 studies that contained relevant cost information: 39 detailed medical costs and 1 detailed non-medical costs. Costs were higher for SCD patients when compared with non-SCD individuals (cost difference range: $6636-$63,436 annually). The highest medical cost component for SCD patients was inpatient ($11,978-$59,851 annually), followed by outpatient and then pharmacy. No studies characterized the cost burden throughout the lifetime disease trajectory of an SCD individual, and no studies captured caregiver or productivity costs. CONCLUSION: Our results reveal an incomplete characterization of medical and non-medical costs within SCD. A deeper understanding of the medical and non-medical cost burden requires completion of additional studies that capture the burden across the patient's lifetime, in addition to expression of the impact of existing and emergent health technologies on disease trajectory.

A landscape analysis and discussion of value of gene therapies for sickle cell disease.

INTRODUCTION: Sickle cell disease (SCD) is a rare genetic disease with limited therapeutic options. Gene-based therapies are being investigated in clinical trials to evaluate their curative potential. The expected life-long benefits of one-time administration of genetically corrected stem cells present uncharted challenges in estimating value of these treatments. Our objective is to conduct a landscape analysis of clinical trials and prompt a discussion estimating the value of gene therapy as a therapeutic option for SCD. AREAS COVERED: We searched Clinicaltrials.gov to identify and characterize clinical trials in gene therapies for SCD. We report available results and discuss current concerns and elements of value necessary to consider as these products come to market. EXPERT OPINION: Gene therapies could represent a major advance in SCD treatment. Although clinical trials are ongoing, reports of serious adverse events have led to pause of these trials, emphasizing the need to prove long-term tolerability. Measured using the methods of health economic evaluation, we anticipate high up-front costs may be offset by potential life-long benefits of these treatments. During development and after treatment approval, attention should be focused on ensuring adequate availability and equitable access to emerging therapies in underserved areas and low-middle-income countries (LMIC).

Development of a conceptual model for evaluating new non-curative and curative therapies for sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a clinically heterogeneous disease with many acute and chronic complications driven by ongoing vaso-occlusion and hemolysis. It causes a disproportionate burden on Black and Hispanic communities. Our objective was to follow the SMDM/ISPOR Task Force recommendations for good practices and create a conceptual model of the progression of SCD under current clinical practice to inform cost-effectiveness analyses (CEA) of promising curative therapies in the pipeline over a lifetime horizon. METHODS: We used consultations with experts, providers, and patients to identify acute events and chronic conditions in the conceptual model. We compared our model structure to previous CEA models of interventions for SCD, assessed the prevalence of the identified disease attributes in Medicaid and Medicare claims databases, and identified relevant outcomes following the 2nd Panel in CEA. We determined an appropriate modeling technique and relevant data sources for parameterizing the model. RESULTS: The conceptual model structure included four dimensions of disease: chronic pain, acute events, chronic conditions, and treatment complications, spanning 26 disease attributes with significant impacts on health-related quality of life and resource. We modeled chronic pain separately to reflect its importance to patients and interaction with all other disease attributes. We identified additional data sources for health state utilities and non-medical costs and benefits of SCD. We will use a microsimulation model with age- and sex-specific transitions between health states predicted by patient demographic characteristics and disease history. CONCLUSION: Developing the model structure through an explicit process of model conceptualization can increase the transparency and accuracy of results. We will populate the conceptual model with the data sources described and evaluate the cost-effectiveness of curative therapies.

Urbanization and systolic/diastolic blood pressure from a gender perspective: Separating longitudinal from cross-sectional association.

There has been a generally negative view of the impact of urbanization on a rising burden of non-communicable diseases including cardiovascular disease. However, the evidence on the relationship between urbanization and cardiovascular health has remained inconclusive. A comprehensive picture of the relationship is lacking, given an implicit assumption that the longitudinal association between changes in cardiovascular health and an increasingly urbanized environment is similar between less and more urbanized communities, men and women. We used the longitudinal data on adults (18-64 years) from the China Health and Nutrition Survey (1991-2015) and employed within-between random-effects models to disaggregates the longitudinal and cross-sectional associations between urbanization and systolic/diastolic blood pressure (SBP/DBP) and examined heterogeneities in the longitudinal association by average urbanization level and gender. We found that the positive longitudinal association of urbanization with SBP/DBP was stronger in less urbanized than more urbanized communities. The cross-sectional association between urbanization and SBP was negative and significant, although the cross-sectional association between urbanization and DBP was of no statistical significance. Moreover, the positive longitudinal association between urbanization and DBP was stronger among men than women, although the gender heterogeneity in the longitudinal association of urbanization with SBP was not significant.

Is the Direct Anterior Approach to THA Cost-effective? A Markov Analysis.

BACKGROUND: The use of the direct anterior approach, a muscle-sparing technique for THA, has increased over the years; however, this approach is associated with longer procedure times and a more expensive direct cost. Furthermore, studies have shown a higher revision rate in the early stages of the learning curve. Whether the clinical advantages of the direct anterior compared with the posterior approach-such as less soft tissue damage, decreased short-term postoperative pain, a lower dislocation rate, decreased length of stay in the hospital, and higher likelihood of being discharged home-outweigh the higher cost is still debatable. Determining the cost-effectiveness of the approach may inform its utility and justify its use at various stages of the learning curve. QUESTIONS/PURPOSES: We used a Markov modeling approach to ask: (1) Is the direct anterior approach more likely to be a cost-effective approach than the posterior approach over the long-term for more experienced or higher volume hip surgeons? (2) How many procedures does a surgeon need to perform for the direct anterior approach to be a cost-effective choice? METHODS: A Markov model was created with three health states (well-functioning THA, revision THA, and death) to compare the cost-effectiveness of the direct anterior approach with that of the posterior approach in five scenarios: surgeons who performed one to 15, 16 to 30, 31 to 50, 51 to 100, and more than 100 direct anterior THAs during a 6-year span. Procedure costs (not charges), dislocation costs, and fracture costs were derived from published reports, and model was run using two different cost differentials between the direct anterior and posterior approaches (USD 219 and USD 1800, respectively). The lower cost was calculated as the total cost differential minus pharmaceutical and implant costs to account for differences in implant use and physician preference regarding postoperative pain management. The USD 1800 cost differential incorporated pharmaceutical and implant costs. Probabilities were derived from systematic review of the evidence as well as from the Australian Orthopaedic Association National Joint Replacement Registry. Utilities were estimated from best available literature and disutilities associated with dislocation and fracture were incorporated into the model. Quality of life was expressed in quality-adjusted life years (QALYs), which are calculated by multiplying the utility of a health state (ranging from 0 to 1) by the duration of time in that health state. The primary outcome measure was the incremental cost-effectiveness ratio, or the change in costs divided by the change in QALYs when the direct anterior approach was used for THA. USD 100,000 per quality-adjusted life years was used as a threshold for willingness to pay. One-way and probabilistic sensitivity analyses were performed for the scenario in which the direct anterior approach is cost-effective to further account for uncertainty in model inputs. RESULTS: At a cost differential of USD 219 (95% CI 175 to 263), the direct anterior approach was associated with lower cost and higher effectiveness compared with the posterior approach for surgeons with an experience level of more than 100 operations during a 6-year span. At a cost differential of USD 1800 (95% CI 1440 to 2160), the direct anterior approach remained a cost-effective strategy for surgeons who performed more than 100 operations. At both cost differentials, the direct anterior approach was not cost-effective for surgeons who performed fewer than 100 operations. One-way sensitivity analyses revealed the model to be the most sensitive to fluctuations in the utility of revision THA, probability of revision after the posterior approach THA, probability of dislocation after the posterior approach THA, fluctuations in the probability of dislocation after direct anterior THA, cost of direct anterior THA, and probability of intraoperative fracture with the direct anterior approach. At the cost differential of USD 219 and for surgeons with a surgical experience level of more than 100 direct anterior operations, the direct anterior approach was still the cost-effective strategy for the entire range of values. CONCLUSION: For high-volume hip surgeons, defined here as surgeons who perform more than 100 procedures during a 6-year span, the direct anterior approach may be a cost-effective strategy within the limitations imposed by our analysis. For lower volume hip surgeons, performing a more familiar approach appears to be more cost-effective.