Hypothetical Cohort Research Articles

Cost-Effectiveness Comparison between Ticagrelor and Clopidogrel in Acute Coronary Syndrome in Iran.

The present study aimed to determine the cost-effectiveness of ticagrelor compared with clopidogrel in Iranian patients with acute coronary syndrome (ACS). A 1-year decision tree model combined with a 20-year Markov transition model was used to simulate the long-term cost and effectiveness of both ticagrelor and clopidogrel in Iran based on an Iranian payer's perspective. Clinical efficacy data were extracted from the PLATO trial and other published studies. Costs were estimated based on local prices in public sectors. Deterministic and probabilistic sensitivity analyses were used to test the robustness of base-case results over the uncertainties of model inputs. All calculations, analyses, and modeling were done in TreeAge 2011 and Microsoft Excel 2013. Compared with clopidogrel, the treatment of Iranian ACS patients with ticagrelor for 20 years resulted in an additional cost of US$ 2.39 in a hypothetical cohort of 1000 patients. However, ticagrelor led to 7.2 quality-adjusted life-years (QALYs) gained per 1000 hypothetical patients. Accordingly, the estimated incremental cost-effectiveness ratio for this analysis was US$ 332.032 per 1 QALY gained. Ticagrelor was a cost-effective antiplatelet medicine compared with clopidogrel in Iranian patients with ACS. This could help Iran's policymakers to allocate resources more efficiently to ACS.

Exchangeability of measures of association before and after exposure status is flipped: its relationship with confounding in the counterfactual model.

The counterfactual definition of confounding is often explained in the context of exchangeability between the exposed and unexposed groups. One recent approach is to examine whether the measures of association (e.g., associational risk difference) are exchangeable when exposure status is flipped in the population of interest. We discuss the meaning and utility of this approach, showing their relationships with the concept of confounding in the counterfactual framework. Three hypothetical cohort studies are used, in which the target population is the total population. After providing an overview of the notions of confounding in distribution and in measure, we discuss the approach from the perspective of exchangeability of measures of association (e.g., factual associational risk difference vs. counterfactual associational risk difference). In general, if the measures of association are non-exchangeable when exposure status is flipped, confounding in distribution is always present, although confounding in measure may or may not be present. Even if the measures of association are exchangeable when exposure status is flipped, there could be confounding both in distribution and in measure. When we use risk difference or risk ratio as a measure of interest and the exposure prevalence in the population is 0.5, testing the exchangeability of measures of association is equivalent to testing the absence of confounding in the corresponding measures. The approach based on exchangeability of measures of association essentially does not provide a definition of confounding in the counterfactual framework. Subtly differing notions of confounding should be distinguished carefully.

Cost-effectiveness of opportunistic QCT-based osteoporosis screening for the prediction of incident vertebral fractures.

Opportunistic quantitative computed tomography (oQCT) derived from non-dedicated routine CT has demonstrated high accuracy in diagnosing osteoporosis and predicting incident vertebral fractures (VFs). We aimed to investigate the cost-effectiveness of oQCT screening compared to dual-energy X-ray absorptiometry (DXA) as the standard of care for osteoporosis screening. Three screening strategies ("no osteoporosis screening", "oQCT screening", and "DXA screening") after routine CT were simulated in a state-transition model for hypothetical cohorts of 1,000 patients (women and men aged 65 years) over a follow-up period of 5 years (base case). The primary outcomes were the cumulative costs and the quality-adjusted life years (QALYs) estimated from a U.S. health care perspective for the year 2022. Cost-effectiveness was assessed based on a willingness-to-pay (WTP) threshold of $70,249 per QALY. The secondary outcome was the number of prevented VFs. Deterministic and probabilistic sensitivity analyses were conducted to test the models' robustness. Compared to DXA screening, oQCT screening increased QALYs in both sexes (additional 2.40 per 1,000 women and 1.44 per 1,000 men) and resulted in total costs of $3,199,016 and $950,359 vs. $3,262,934 and $933,077 for women and men, respectively. As a secondary outcome, oQCT screening prevented 2.6 and 2.0 additional VFs per 1,000 women and men, respectively. In the probabilistic sensitivity analysis, oQCT screening remained cost-effective in 88.3% (women) and 90.0% (men) of iterations. oQCT screening is a cost-effective ancillary approach for osteoporosis screening and has the potential to prevent a substantial number of VFs if considered in daily clinical practice.

Standard diagnostics with and without urine-based lipoarabinomannan testing for tuberculosis disease in HIV-infected patients in a high-burden setting-A cost-effectiveness analysis.

Recent clinical findings reported the reduced mortality associated with treatment guided by sputum-based molecular test with urine-based lipoarabinomannan (LAM) assay for tuberculosis (TB) disease in HIV-infected individuals. We aimed to evaluate the cost-effectiveness of sputum-based Xpert tests with and without urine-based LAM assays among HIV-infected individuals with signs and symptoms of TB disease (TBD) from the perspective of South African healthcare providers. A one-year decision-analytic model was constructed to simulate TB-related outcomes of 7 strategies: Sputum smear microscope (SSM), Xpert, Xpert Ultra, Xpert with AlereLAM, Xpert Ultra with AlereLAM, Xpert with FujiLAM, and Xpert Ultra with FujiLAM, in a hypothetical cohort of adult HIV-infected individuals with signs and symptoms of TB. The model outcomes were TB-related direct medical cost, mortality, early treatment, disability-adjusted life-years (DALYs) and incremental cost per DALY averted (ICER). The model inputs were retrieved from literature and public data. Base-case analysis and sensitivity analysis were conducted. In the base-case analysis, the Xpert Ultra with FujiLAM strategy showed the highest incidence of early treatment (267.7 per 1000 tested) and lowest mortality (29.0 per 1000 tested), with ICER = 676.9 USD/DALY averted. Probabilistic sensitivity analysis of 10,000 Monte Carlo simulations showed the cost-effective probability of Xpert Ultra with FujiLAM was the highest of all 7 strategies at the willingness-to-pay (WTP) threshold >202USD/DALY averted. Standard sputum-based TB diagnostic Xpert Ultra with urine-based FujiLAM for TBD testing in HIV-infected individuals appears to be the preferred cost-effective strategy from the perspective of the health service provider of South Africa.

Estimation of migraine prevalence considering active and inactive states across different age groups

BackgroundMigraine is a very common headache disorder on the population level, characterized by symptomatic attacks (activity). For many people with migraine, the migraine symptoms intermittently or permanently cease during their lifetime (inactive migraine). The current diagnostic classification of migraine considers two states: active migraine (having migraine symptoms within the last year) and not having active migraine (including both individuals with inactive migraine and those who never had migraine). Defining a state of inactive migraine that has gone into remission may better capture the trajectories of migraine across the lifespan and contribute to a better understanding of its biological processes. We aimed to quantify the prevalence of never, active, and inactive migraine separately, using modern prevalence and incidence estimation methodology to better describe the complexity of migraine trajectories at the population level.MethodsUsing a multistate modeling approach, data from the Global Burden of Disease (GBD) study, and results from a population-based study, we estimated the transition rates by which individuals moved between migraine disease states and estimated prevalences of never, active and inactive migraine. We used data from the GBD project and a hypothetical cohort of 100,000 people with a starting age of 30 and 30 years of follow-up, both in Germany and globally, stratified by sex.ResultsIn Germany, the estimated rate of transition from active to inactive migraine (remission rate) increased after the age of 22.5 in women and 27.5 in men. The pattern for men in Germany was similar to the one observed on the global level. The prevalence of inactive migraine among women reaches 25.7% in Germany and 16.5% globally at age 60. For men, the inactive migraine prevalence estimates at the same age were 10.4% in Germany and 7.1% globally.ConclusionsConsidering an inactive migraine state explicitly reflects a different epidemiological picture of migraine across the lifecourse. We have demonstrated that many women of older ages may be in an inactive migraine state. Many pressing research questions can only be answered if population-based cohort studies collect information not only on active migraine but also on inactive migraine states.

Cost-Effectiveness of Glucose-Lowering Therapies as Add-on to Standard Care for People With Type 2 Diabetes in Malaysia

ObjectivesThis study aims to evaluate the cost-effectiveness of various glucose-lowering therapies as add-on to standard care for people with type 2 diabetes (T2D) in Malaysia. MethodsA state-transition microsimulation model was developed to compare the clinical and economic outcomes of 4 treatments: standard care, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists. Cost-effectiveness was assessed from a healthcare provider’s perspective over a lifetime horizon with 3% discount rate in a hypothetical cohort of people with T2D. Data input were informed from literature and local data when available. Outcome measures include costs, quality-adjusted life-years, incremental cost-effectiveness ratios, and net monetary benefits. Univariate and probabilistic sensitivity analyses were performed to assess uncertainties. ResultsOver a lifetime horizon, the costs to treat a person with T2D ranged from RM 12 494 to RM 41 250, whereas the QALYs gains ranged from 6.155 to 6.731, depending on the treatment. Based upon a willingness-to-pay threshold of RM 29 080 per QALY, we identified SGLT2i as the most cost-effective glucose-lowering treatment, as add-on to standard care over patient’s lifetime, with the net monetary benefit of RM 176 173 and incremental cost-effectiveness ratios of RM 12 279 per QALY gained. The intervention also added 0.577 QALYs and 0.809 LYs compared with standard care. Cost-effectiveness acceptability curve showed that SGLT2i had the highest probability of being cost-effective in Malaysia across varying willingness-to-pay threshold. The results were robust to various sensitivity analyses. ConclusionsSGLT2i was found to be the most cost-effective intervention to mitigate diabetes-related complications.

Ultrasound Surveillance of Small, Incidentally Detected Gallbladder Polyps: Projected Benefits by Sex, Age, and Comorbidity Level

ObjectiveIncidentally detected gallbladder polyps are commonly encountered when performing upper abdominal ultrasound. Our purpose was to estimate the life expectancy (LE) benefit of ultrasound-based gallbladder surveillance in patients with small (6-7 to <10 mm), incidentally detected gallbladder polyps, accounting for patient sex, age, and comorbidity level. MethodsWe developed a decision-analytic Markov model to evaluate hypothetical cohorts of women and men with small gallbladder polyps, with varying age (66-80 years) and comorbidity level (none, mild, moderate, severe). Drawing from current evidence, in the base case, we assumed no increased risk of gallbladder cancer in patients with small gallbladder polyps. To estimate maximal possible LE gains from surveillance, we assumed perfect cancer control consequent to 5 years of surveillance. We varied key assumptions including cancer risk and test performance characteristics in sensitivity analysis. ResultsProjected LE gains from surveillance were <3 days across most cohorts and scenarios evaluated. For 66- and 80-year-olds with no comorbidities, LE gains were 1.46 and 1.45 days, respectively, for women, and 0.67 and 0.75 days for men. With 10 years of surveillance, LE gains increased to 2.94 days for 66-year-old women with no comorbidities (men: 1.35 days). If we assumed a 10% increase in gallbladder cancer risk among individuals with polyps, LE gains increased slightly to 1.60 days for 66-year-old women with no comorbidities (men: 0.74 days). Results were sensitive to test performance and surgical mortality. DiscussionEven under unrealistic, optimistic assumptions of cancer control, ultrasound surveillance of incidentally detected small gallbladder polyps provided limited benefit.

Coste-efectividad de la polipíldora CNIC frente a los monocomponentes separados en prevención secundaria cardiovascular en España

Introduction and objectivesDespite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100mg, atorvastatin 20/40mg, ramipril 2.5/5/10mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain. Materials and methodsA Markov cost-utility model was adapted considering four health states (stable, subsequent major adverse cardiovascular event, subsequent ischemic stroke and death) and the SMART risk equation over a lifetime horizon from the perspective of the Spanish National Healthcare System. The CNIC-Polypill strategy was compared with monocomponents in a hypothetical cohort of 1000 secondary prevention patients. Effectiveness, epidemiological, cost and utilities data were obtained from the NEPTUNO study, official databases and literature. Outcomes were costs (in 2021euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 3% discount rate was applied. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of the model. ResultsThe CNIC-Polypill strategy in secondary prevention results in more LY (13.22) and QALY (11.64) gains at a lower cost than monocomponents. The CNIC-Polypill is dominant and saves €280.68 per patient compared with monocomponents. The probabilistic sensitivity analysis shows that 82.4% of the simulations are below the threshold of €25,000 per QALY gained. ConclusionsThe CNIC-Polypill strategy in secondary cardiovascular prevention is cost-effective compared with the same separate monocomponents, resulting in a cost-saving strategy to the Spanish National Healthcare System.

Indefinite Anticoagulant Therapy for First Unprovoked Venous Thromboembolism : A Cost-Effectiveness Study.

Clinical practice guidelines recommend indefinite anticoagulation for a first unprovoked venous thromboembolism (VTE). To estimate the benefit-harm tradeoffs of indefinite anticoagulation in patients with a first unprovoked VTE. Markov modeling study. Systematic reviews and meta-analyses for the long-term risks and case-fatality rates of recurrent VTE and major bleeding. Published literature for costs, quality of life, and other clinical events. Patients with a first unprovoked VTE who have completed 3 to 6 months of initial anticoagulant treatment. Lifetime. Canadian health care public payer. Indefinite anticoagulation with direct oral anticoagulants. Recurrent VTE events, major bleeding events, costs in 2022 Canadian dollars (CAD), and quality-adjusted life-years (QALYs). When compared with discontinuing anticoagulation after initial treatment in a hypothetical cohort of 1000 patients aged 55 years, indefinite anticoagulation prevented 368 recurrent VTE events, which included 14 fatal pulmonary emboli, but induced an additional 114 major bleeding events, which included 30 intracranial hemorrhages and 11 deaths from bleeding. Indefinite anticoagulation cost CAD $16 014 more per person and did not increase QALYs (-0.075 per person). Model results were most sensitive to the case-fatality rate of major bleeding and the annual risk for major bleeding during extended anticoagulation. The model assumed that risks for recurrent VTE and major bleeding measured in clinical trials at 1 year remained constant during extended anticoagulation. Clinicians should use shared decision making to incorporate individual patient preferences and values when considering treatment duration for unprovoked VTE. Canadian Institutes of Health Research.

Cost-effectiveness of the CNIC-Polypill versus separate monocomponents in cardiovascular secondary prevention in Spain

Introduction and objectivesDespite advances in treatment, cardiovascular disease is the second leading cause of death in Spain. The objective of this study was to determine the cost-effectiveness of the CNIC-Polypill strategy (acetylsalicylic acid 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) compared with the same separate monocomponents for the secondary prevention of recurrent cardiovascular events in adults in Spain. Materials and methodsA Markov cost-utility model was adapted considering 4 health states (stable, subsequent major adverse cardiovascular event, subsequent ischemic stroke and death) and the SMART risk equation over a lifetime horizon from the perspective of the Spanish National Healthcare System. The CNIC-Polypill strategy was compared with monocomponents in a hypothetical cohort of 1000 secondary prevention patients. Effectiveness, epidemiological, cost and utilities data were obtained from the NEPTUNO study, official databases and literature. Outcomes were costs (in 2021 euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 3% discount rate was applied. Deterministic one-way and probabilistic sensitivity analyses evaluated the robustness of the model. ResultsThe CNIC-Polypill strategy in secondary prevention results in more LY (13.22) and QALY (11.64) gains at a lower cost than monocomponents. The CNIC-Polypill is dominant and saves є280.68 per patient compared with monocomponents. The probabilistic sensitivity analysis shows that 82.4% of the simulations are below the threshold of є25,000 per QALY gained. ConclusionsThe CNIC-Polypill strategy in secondary cardiovascular prevention is cost-effective compared with the same separate monocomponents, resulting in a cost-saving strategy to the Spanish National Healthcare System.

Cost-effectiveness analysis of imatinib versus dasatinib in the treatment of pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia when combined with conventional chemotherapy in China

BackgroundTyrosine kinase inhibitors combined with conventional chemotherapy (CC) in treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) has achieved promising efficacy and safety outcomes. The study was conducted to compare the cost-effectiveness between imatinib (HANSOH Pharma, Jiangsu, China) and dasatinib (CHIATAI TIANQING Pharma, Jiangsu, China) in treating pediatric Ph-positive ALL when combined with CC from the perspective of the health system in China.MethodsA Markov model was established to simulate a hypothetical cohort of pediatric Ph-positive ALL patients receiving imatinib or dasatinib, combined with CC. The model was designed using a 10-year horizon, a 3- month cycle, and a 5% discount rate. Three health states were included: alive with progression-free survival, progressed disease, and death. Patient characteristics and transition probabilities were estimated based on clinical trials. Other relevant data, such as direct treatment costs and health utility data were extracted from published literature and Sichuan Province’s centralized procurement and supervision platform. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to assess the robustness of the results. The willingness-to-pay (WTP) was set as three times China’s GDP per capita in 2021.ResultsIn the base-case analysis, the total medical costs were $89,701 and $101,182, and the quality-adjusted life years (QALYs) gained were 1.99 and 2.70, for imatinib and dasatinib regimens, respectively. The incremental cost-effectiveness ratio for dasatinib versus imatinib was $16,170/QALY. The probabilistic sensitivity analysis indicated that treatment with dasatinib combined with CC achieved a 96.4% probability of cost-effectiveness at a WTP threshold of $37,765/QALY.ConclusionsDasatinib combined with CC is likely to be a cost-effective strategy compared to imatinib combination therapy for pediatric Ph-positive ALL in China at a WTP threshold of $37,765/QALY.

Preimplantation genetic testing for sickle cell disease: a cost-effectiveness analysis

To evaluate the cost-effectiveness of invitro fertilization with preimplantation genetic testing for monogenic disease (IVF + PGT-M) in the conception of a nonsickle cell disease (non-SCD) individual compared with standard of care treatment for a naturally conceived, sickle cell disease (SCD)-affected individual. A Markov simulation model was constructed to evaluate a one-time IVF + PGT-M treatment compared with the lifetime standard of care costs of treatment for an individual potentially born with SCD. Using an annual discount rate of 3% for cost and outcome measures, quality-adjusted life years were constructed from utility weights and life expectancy values and then used as the effectiveness measurement. An incremental cost-effectiveness ratio was calculated for both treatment arms, and a willingness-to-pay threshold of $50,000 per quality-adjusted life year was assumed. Tertiary care or university medical center. A hypothetical cohort of 10,000 patients was analzyed over a lifetime horizon using yearly cycles. Invitro fertilization with preimplantation genetic testing for monogenic disease use in conception of a non-SCD individual. The primary outcomes of interest were the incremental cost and effectiveness of an IVF+PGT-M conception compared with the SOC treatment of an SCD-affected individual. Invitro fertilization with preimplantation genetic testing for monogenic disease was the optimal strategy in 93.17% of the iterations. An incremental savings of $137,594 was demonstrated with a gain of 1.96 QALYs and 3.69 life years over a lifetime. Sensitivity analysis demonstrated that SOC treatment never met equivalent cost-effectiveness. Our model demonstrates that IVF + PGT-M for selection against SCD, compared with lifetime SOC treatment for those affected, is the most cost-effective strategy within the United States healthcare sector.

Cost-effectiveness analysis of dyevert™ Power XT in patients with chronic kidney disease undergoing percutaneous coronary intervention procedures in Spain.

To assess the efficiency of Dyevert™ Power XT compared to the standard clinical practice when used for percutaneous coronary interventions (PCI). A Markov model was developed to estimate, over 3-month cycles and a lifetime time horizon, the cumulative costs and health outcomes (life years gained [LYG] and quality-adjusted life years [QALY]) in a hypothetical cohort of 1,000 patients with chronic kidney disease (CKD) 3b-4 and an average age of 72 years.The incidence of contrast-induced acute kidney injury for these patients is 18.89% in routine practice and 7.78% with Dyevert. QALYs were estimated by applying utilities by health state. Transitions between states and utilities were obtained from the literature. Overall all-cause and state-specific mortality were considered. The total cost (€2,022) estimated with the National Health System perspective included cost of the procedure and of CKD management. The parameters were validated by a panel of experts. A discount rate (3% per year) was applied to costs and outcomes. The use of Dyevert yielded more health benefits (34.60 LYG and 5.69 QALYs) compared to the current standard practice (33.11 LYG and 5.38 QALYs). Lifetime cost accumulated at the end of the simulation resulted €30,211/patient with Dyevert and €33,895/patient with current standard clinical practice. The use of Dyevert™ Power XT resulted dominant option, due to its higher effectiveness and lower cost as compared to standard clinical practice and, therefore, a preferred option in patients with CKD stages 3b-4 undergoing PCI in Spain.

QTPI: A quasi-toxicity probability interval design for phase I trials with multiple-grade toxicities.

The common terminology criteria for adverse events by the National Cancer Institute has greatly facilitated the revolution of drug development and an increasing number of Phase I trials have started to collect multiple-grade toxicity endpoints. Appropriate and yet transparent Phase I statistical designs for multiple-grade toxicities are therefore in great needs. In this article, we propose a quasi-toxicity probability interval (qTPI) design that incorporates a quasi-continuous measure of the toxicity probability () into the Bayesian theoretic framework of the interval based designs. Multiple-grade toxicity outcomes of each patient are mapped to according to a severity weight matrix. Dose-toxicity curve underlying the dosing decisions in the qTPI design is continuously updated using accumulating trial data. Numerical simulations investigating the operating characteristics of qTPI show that qTPI achieved better safety, accuracy and reliability compared to designs that rely on binary toxicity data. Furthermore, parameter elicitation in qTPI is simple and does not involve multiple hypothetical cohorts specification. Finally, a hypothetical soft tissue sarcoma trial with six toxicity types and grade 0 to grade 4 severity grades is illustrated with patient-by-patient dose allocation under the qTPI design.

Cost-effectiveness of Myomectomy versus Hysterectomy in Women with Uterine Fibroids

Increasing evidence suggests that hysterectomy to treat uterine fibroids (UFs), even with ovarian conservation (OC), is associated with a 33% increased risk of coronary artery disease (CAD). We sought to compare the cost-effectiveness of various treatment approaches for UFs to understand the trade-offs among development of CAD vs new fibroids. We developed a Markov model to include women with UFs who no longer desired pregnancy. The outcomes of interest were quality-adjusted life-years (QALYs) and total treatment costs. We conducted sensitivity analyses to test the effect of uncertain model inputs. Health system perspective. A hypothetical cohort of 10000 40-year-old women. Myomectomy, hysterectomy with OC, and hysterectomy without OC. Myomectomy was the best-value strategy, costing US$528217 and providing 19.38 QALYs. Neither hysterectomy with OC nor hysterectomy without OC was found to be cost-effective, assuming a willingness-to-pay threshold of $100000 per QALY gain as hysterectomy with OC provided more benefit than myomectomy at an average cost of $613144 to gain one additional QALY. The sensitivity analyses showed that if the risk of new symptomatic UFs that required treatment after myomectomy was more than 13%, annually (base case, 3.6%), or the quality of life after myomectomy was less than 0.815 (base case, 0.834), then myomectomy would no longer be cost-effective, under a willingness-to-pay amount of US$100000. Myomectomy is an optimal treatment of UFs compared with hysterectomy among women aged 40 years. The increased risk of CAD after hysterectomy and its associated costs and the effects on morbidity and quality of life made hysterectomy a costlier and less effective long-term strategy.

Cost-effectiveness analysis of different combination therapies for the treatment of chronic lymphocytic leukaemia in India.

Over the years, there has been introduction of newer drugs, like bendamustine and ibrutinib, for the management of chronic lymphocytic leukaemia (CLL). Though these drugs lead to better survival, they are also associated with higher cost. The existing evidence on cost effectiveness of these drugs is from high-income countries, which has limited generalisability for low-income and middle-income counties. Therefore, the present study was undertaken to assess the cost-effectiveness of three therapeutic regimens, chlorambucil plus prednisolone (CP), bendamustine plus rituximab (BR) and ibrutinib for CLL treatment in India. A Markov model was developed for estimating lifetime costs and consequences in a hypothetical cohort of 1000 CLL patients following treatment with different therapeutic regimens. The analysis was performed based on a limited societal perspective, 3% discount rate and lifetime horizon. The clinical effectiveness of each regime in the form of progression-free survival and occurrence of adverse events were assessed from various randomised controlled trials. A structured comprehensive review of literature was undertaken for the identification of relevant trials. The data on utility values and out of pocket expenditure was obtained from primary data collected from 242 CLL patients across six large cancer hospitals in India. As compared to the most affordable regimen comprising of CP as first-line followed by BR as second-line therapy, none of the other therapeutic regimens were cost-effective at one time per capita gross-domestic product of India. However, if the current price of either combination of BR and ibrutinib or even ibrutinib alone could be reduced by more than 80%, regimen comprising of BR as first-line therapy followed by second-line ibrutinib would become cost-effective. At the current market prices, regimen comprising of CP as first-line followed by BR as second-line therapy is the most cost-effective strategy for CLL treatment in India. Department of Health Research, Government of India.

Cost-effectiveness of trastuzumab deruxtecan in HER2 low metastatic breast cancer.

1593 Background: In recent years, metastatic breast cancer treatment has been revolutionized by new therapies that improve overall survival in phase three randomized clinical trials. These drugs are often more expensive than traditional cytotoxics. In 2022, the Destiny-Breast04 trial results showed that trastuzumab deruxtecan (T-DXd) improved survival in HER2 low metastatic breast cancer patients; FDA approval shortly thereafter greatly expanded the potential market capitalization of T-DXd. While the trial demonstrated T-DXd’s clinical efficacy, its cost-effectiveness remains unknown. Methods: We developed a decision-analytic state transition Markov model to simulate a hypothetical cohort of HER2 low metastatic breast cancer patients to assess the cost-effectiveness of T-DXd compared to a physician's choice chemotherapy from a US healthcare payer perspective over a lifetime horizon. Each month, simulated patients could remain progression-free, progress, have a non-interstitial lung disease (ILD) treatment-related adverse event leading to drug discontinuation (TRAE), have ILD leading to drug discontinuation, progress after either a TRAE or ILD, or die. Patients with either a TRAE or ILD were presumed to be progression free directly after discontinuation of the offending agent, and hence eligible for a different therapy. We calibrated the model to outcome data from the Destiny-Breast04 trial, supplemented with data from other relevant metastatic breast cancer clinical trials. Health-related quality-of-life weights were derived from studies of metastatic breast cancer patients. Drug prices (2020 USD) were extracted from the Federal Supply Schedule. Outcomes included discounted (3% annual) quality-adjusted life years (QALYs), life years, lifetime costs, and incremental cost-effectiveness ratios (ICER). We varied T-DXd price and efficacy in a two-way sensitivity analysis to assess our findings’ robustness. Results: Modeled life expectancies with T-DXd and chemotherapy were 26.5 and 21.5 months, respectively (T-DXd: 1.19 QALYs; chemotherapy: 0.93 QALYs). Discounted lifetime costs were 315,000 for T-DXd and 203,000 for chemotherapy; T-DXd cost 431,000 per QALY gained, surpassing a cost effectiveness threshold of 150,000 per QALY gained. The two-way sensitivity analysis showed that, across a range of plausible efficacies, T-DXd would need a price reduction of approximately 50% to be cost-effective at the $150,000 threshold. Conclusions: While providing clinical benefits, our model-based analysis finds that at current prices, T-DXd for HER2 low metastatic breast cancer is not cost-effective at traditional thresholds. Substantial price reduction for T-DXd to a level much closer to prices of comparator cytotoxics could greatly increase the value for money T-DXd provides patients.

Comparison of characteristics of patients with lung cancer in U.K. primary care databases: Clinical Practice Research Datalink Aurum and GOLD.

In recent years, the number of general practices contributing to the Clinical Practice Research Datalink (CPRD) database GOLD is decreasing. Therefore, for research questions addressing for instance novel treatments requiring up-to-date data, sample size will become an important consideration in study feasibility. In recent years, CPRD Aurum, containing information of practices that use EMIS software, has become an additional data source that is being used for CPRD studies. In order to establish whether Aurum is suited to act as data source for future studies in the field of lung cancer research, we aimed to compare characteristics between patients with lung cancer in Aurum and GOLD. A retrospective study was performed comparing characteristics and overall survival (OS) of patients with lung cancer in Aurum and GOLD. To further evaluate similarity, hypothetical eligibility of these patients in Aurum and GOLD was compared for 11 randomized clinical trials (RCTs). Baseline characteristics registered in Aurum and GOLD were largely similar, with some clinically irrelevant differences for previous malignancies, deviant laboratory values and drug use. Median OS was 9.8 and 9.0 months for patients in Aurum and GOLD, respectively. Potential RCT eligibility varied between 49.4% and 79.5% and 49.1% and 78.1% for patients in Aurum and GOLD, respectively. Mortality rates and the comparison of the obtained HRs per hypothetical eligibility cohort per RCT were similar in Aurum and GOLD. This study showed that data of patients with lung cancer in Aurum and GOLD are largely comparable, suggesting that Aurum is suitable for future epidemiological lung cancer research.

Cost-effectiveness of Human Papillomavirus Self-collection Intervention on Cervical Cancer Screening Uptake among Underscreened U.S. Persons with a Cervix.

We evaluate the cost-effectiveness of human papillomavirus (HPV) self-collection (followed by scheduling assistance for those who were HPV+ or inconclusive) compared with scheduling assistance only and usual care among underscreened persons with a cervix (PWAC). A decision tree analysis was used to estimate the incremental cost-effectiveness ratios (ICER), or the cost per additional PWAC screened, from the Medicaid/state and clinic perspectives. A hypothetical cohort represented 90,807 low-income, underscreened individuals. Costs and health outcomes were derived from the MyBodyMyTest-3 randomized trial except the usual care health outcomes were derived from literature. We performed probabilistic sensitivity analyses (PSA) to evaluate model uncertainty. Screening uptake was highest in the self-collection alternative (n = 65,721), followed by the scheduling assistance alternative (n = 34,003) and usual care (n = 18,161). The self-collection alternative costs less and was more effective than the scheduling assistance alternative from the Medicaid/state perspective. Comparing the self-collection alternative with usual care, the ICERs were $284 per additional PWAC screened from the Medicaid/state perspective and $298 per additional PWAC screened from the clinic perspective. PSAs demonstrated that the self-collection alternative was cost-effective compared with usual care at a willingness-to-pay threshold of $300 per additional PWAC screened in 66% of simulations from the Medicaid/state perspective and 58% of simulations from the clinic perspective. Compared with usual care and scheduling assistance, mailing HPV self-collection kits to underscreened individuals appears to be cost-effective in increasing screening uptake. This is the first analysis to demonstrate the cost-effectiveness of mailed self-collection in the United States.

Cost-effectiveness of targeted treatment vs chemoimmunotherapy in treatment-naive unfit CLL without TP53 aberrations

AbstractSeveral targeted treatments, such as venetoclax + obinutuzumab (VenO) and ibrutinib, have been developed to treat patients with treatment-naive chronic lymphocytic leukemia (CLL) and have been shown to improve progression-free survival compared with chlorambucil + obinutuzumab (ClbO). However, novel targeted agents are associated with a significant cost investment. The objective of this study was to investigate the cost-effectiveness of VenO compared with ClbO and ibrutinib in treatment-naive CLL without del17p/TP53 mutation in Denmark. We used a decision-analytic modeling approach to simulate hypothetical cohorts of patients with CLL from the initiation of first-line treatment to death, including the full treatment pathway and second-line therapy. VenO, ClbO, or ibrutinib was included as first-line therapy followed by either Ven + rituximab or ibrutinib. Model outcomes were expected quality-adjusted life years (QALYs), life years (LYs), and cost per patient, which were used to calculate incremental cost-effectiveness ratios (ICERs) with a willingness to pay from €23 600 to €35 600 per QALY. Compared with ClbO, VenO was associated with a QALY gain of 1.30 (1.42 LYs) over a lifetime. The incremental cost was €12 360, resulting in an ICER of €9491 per QALY gained, indicating that VenO is cost-effective. Compared with VenO, ibrutinib was associated with a QALY gain of 0.82 (1.74 LYs) but at a substantially increased incremental cost of €247 488 over a lifetime horizon. The ICER was €302 156 per QALY, indicating that ibrutinib in first-line treatment would not be considered cost-effective in Danish health care, compared with VenO. Future analyses in fit patients with CLL are needed to determine the cost-effectiveness of VenO.