Lifetime Quality-adjusted Life Years Research Articles

Decision-analysis modeling of effectiveness and cost-effectiveness of pharmacologic thromboprophylaxis for surgical inpatients using variable risk assessment models or other strategies

BackgroundSurgical inpatients are at a risk of venous thromboembolism (VTE), which can be life-threatening or result in chronic complications. Thromboprophylaxis reduces the VTE risk but incurs costs and may increase bleeding risk. Risk assessment models (RAMs) are currently used to target thromboprophylaxis at high-risk patients. ObjectivesTo determine the balance of cost, risk, and benefit for different thromboprophylaxis strategies in adult surgical inpatients, excluding patients who underwent major orthopedic surgery or were under critical care and pregnant women. MethodsDecision analytic modeling was performed to estimate the following outcomes for alternative thromboprophylaxis strategies: thromboprophylaxis usage; VTE incidence and treatment; major bleeding; chronic thromboembolic complications; and overall survival. Strategies compared were as follows: no thromboprophylaxis; thromboprophylaxis for all; and thromboprophylaxis given according to RAMs (Caprini and Pannucci). Thromboprophylaxis is assumed to be given for the duration of hospitalization. The model evaluates lifetime costs and quality-adjusted life-years (QALYs) within England’s health and social care services. ResultsThromboprophylaxis for all surgical inpatients had a 70% probability of being the most cost-effective strategy (at a £20 000 per QALY threshold). RAM-based prophylaxis would be the most cost-effective strategy if a RAM with a higher sensitivity (99.9%) were available for surgical inpatients. QALY gains were mainly due to reduced postthrombotic complications. The optimal strategy was sensitive to several other factors such as the risk of VTE, bleeding and postthrombotic syndrome, duration of prophylaxis, and patient age. ConclusionThromboprophylaxis for all eligible surgical inpatients seemed to be the most cost-effective strategy. Default recommendations for pharmacologic thromboprophylaxis, with the potential to opt-out, may be superior to a complex risk-based opt-in approach.

Cost-effectiveness of Intensive vs Standard Blood Pressure Control Among Older Patients With Hypertension

Older patients with hypertension receiving intensive systolic blood pressure control (110-130 mm Hg) have lower incidences of cardiovascular events than those receiving standard control (130-150 mm Hg). Nevertheless, the mortality reduction is insignificant, and intensive blood pressure management results in more medical costs from treatments and subsequent adverse events. To examine the incremental lifetime outcomes, costs, and cost-effectiveness of intensive vs standard blood pressure control in older patients with hypertension from the health care payer's perspective. This economic analysis was conducted with a Markov model to examine the cost-effectiveness of intensive blood pressure management among patients aged 60 to 80 years with hypertension. Treatment outcome data from the Trial of Intensive Blood-Pressure Control in Older Patients With Hypertension (STEP trial) and different cardiovascular risk assessment models for a hypothetical cohort of STEP-eligible patients were used. Costs and utilities were obtained from published sources. The incremental cost-effectiveness ratio (ICER) against the willingness-to-pay threshold was used to evaluate whether the management was cost-effective. Extensive sensitivity, subgroup, and scenario analyses were performed to address uncertainty. The US and UK population using race-specific cardiovascular risk models were conducted in the generalizability analysis. Data for the STEP trial were collected from February 10 to March 10, 2022, and were analyzed for the present study from March 10 to May 15, 2022. Hypertension treatments with a systolic blood pressure target of 110 to 130 mm Hg or 130 to 150 mm Hg. Incremental lifetime quality-adjusted life-years (QALYs), costs, and ICER are discounted at the given rates annually. After simulating 10 000 STEP-eligible patients assumed to be 66 years of age (4650 men [46.5%] and 5350 women [53.5%]) in the model, the ICER values were ¥51 675 ($12 362) per QALY gained in China, $25 417 per QALY gained in the US, and £4679 ($7004) per QALY gained in the UK. Simulations projected that the intensive management in China being cost-effective were 94.3% and 100% below the willingness-to-pay thresholds of 1 time (¥89 300 [$21 364]/QALY) and 3 times (¥267 900 [$64 090]/QALY) the gross domestic product per capita, respectively. The US had 86.9% and 95.6% probabilities of cost-effectiveness at $50 000/QALY and $100 000/QALY, respectively, and the UK had 99.1% and 100% of probabilities of cost-effectiveness at £20 000 ($29 940)/QALY and £30 000 ($44 910)/QALY, respectively. In this economic evaluation, the intensive systolic blood pressure control in older patients produced fewer cardiovascular events and had acceptable costs per QALY gained, well below the typical willingness-to-pay thresholds. The cost-effective advantages of intensive blood pressure management in older patients were consistent over various clinical scenarios across different countries.

Value of an Integrated Home Dialysis Model in the United Kingdom: A Cost-Effectiveness Analysis

ObjectivesThis study aimed to determine the lifetime cost-effectiveness of increasing home hemodialysis as a treatment option for patients experiencing peritoneal dialysis technique failure compared with the current standard of care. MethodsA Markov model was developed to assess the lifetime costs, quality-adjusted life-years, and cost-effectiveness of increasing the usage an integrated home dialysis model compared with the current patient pathways in the United Kingdom. A secondary analysis was conducted including only the cost difference in treatments, minimizing the impact of the high cost of dialysis during life-years gained. Sensitivity and scenario analyses were performed, including analyses from a societal rather than a National Health Service perspective. ResultsThe base-case probabilistic analysis was associated with incremental costs of £3413 and a quality-adjusted life-year of 0.09, resulting in an incremental cost-effectiveness ratio of £36 341. The secondary analysis found the integrated home dialysis model to be dominant. Conclusions on cost-effectiveness did not change under the societal perspective in either analysis. ConclusionsThe base-case analysis found that an integrated home dialysis model compared with current patient pathways is likely not cost-effective. These results were primarily driven by the high baseline costs of dialysis during life-years gained by patients receiving home hemodialysis. When excluding baseline dialysis-related treatment costs, the integrated home dialysis model was dominant. New strategies in kidney care patient pathway management should be explored because, under the assumption that dialysis should be funded, the results provide cost-effectiveness evidence for an integrated home dialysis model.

Cost-effectiveness analysis of recombinant factor IX Fc fusion protein compared with recombinant factor IX for the treatment of moderate-severe to severe hemophilia B in China.

To evaluate the lifetime cost-effectiveness of recombinant factor IX Fc fusion protein (rFIXFc) and recombinant factor IX (rFIX) for the treatment of hemophilia B (HB) in China. We developed a decision-analytic Markov model including three health states: alive, requiring surgery, and dead. This model estimated the lifetime cost and quality-adjusted life-years (QALYs) of prophylaxis in childhood, followed by on-demand treatment in adulthood for moderate-severe to severe HB patients from China's healthcare system perspective. Efficacy data derived from pivotal clinical trials, clinical guideline recommendations, and expert consultation were applied to two scenarios (full dose and low dose). One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of the model. Lifetime cost, QALYs, and the incremental cost-effectiveness ratio were calculated, and the results were compared with willingness-to-pay (WTP) thresholds of one to three times the gross domestic product per capita of China in 2021 ($12,551-$37,653). RFIXFc was associated with lower cost and more QALYs than rFIX in both scenarios, which suggested that it is a dominant strategy (more effective and cheaper) for moderate-severe to severe HB in China. In the full-dose scenario, rFIXFc saved more money and yielded more QALYs than in the low-dose scenario (low doses are the typical clinical reality in China). PSA demonstrated that rFIXFc had an over 90% probability of being cost-effective with full-dose and low-dose treatment at WTP thresholds of $12,551-$37,653. Compared with rFIX, rFIXFc appears to be a cost-effective option for the lifetime management of moderate-severe to severe HB patients in China.

The Estimated Lifetime Quality-Adjusted Life-Years Lost Due to Chlamydia, Gonorrhea, and Trichomoniasis in the United States in 2018.

Comprehensive evaluation of the quality-adjusted life-years (QALYs) lost attributable to chlamydia, gonorrhea, andtrichomoniasis in the United States is lacking. We adapted a previous probability-tree model to estimate the average number of lifetime QALYs lost due to genital chlamydia, gonorrhea, and trichomoniasis, per incident infection and at the population level, by sex and age group. We conducted multivariate sensitivity analyses to address uncertainty around key parameter values. The estimated total discounted lifetime QALYs lost for men and women, respectively, due to infections acquired in 2018, were 1541 (95% uncertainty interval [UI], 186-6358) and 111 872 (95% UI, 29 777-267 404) for chlamydia, 989 (95% UI, 127-3720) and 12 112 (95% UI, 2 410-33 895) for gonorrhea, and 386 (95% UI, 30-1851) and 4576 (95% UI, 13-30 355) for trichomoniasis. Total QALYs lost were highest among women aged 15-24 years with chlamydia. QALYs lost estimates were highly sensitive to disutilities (health losses) of infections and sequelae, and to duration of infections and chronic sequelae for chlamydia and gonorrhea in women. The 3 sexually transmitted infections cause substantial health losses in the United States, particularly gonorrhea and chlamydia among women. The estimates of lifetime QALYs lost per infection help to prioritize prevention policies and inform cost-effectiveness analyses of sexually transmitted infection interventions.

Lifetime quality-adjusted life years lost due to genital herpes acquired in the United States in 2018: a mathematical modeling study

Genital herpes (GH), caused by herpes simplex virus type 1 and type 2 (HSV-1, HSV-2), is a common sexually transmitted disease associated with adverse health outcomes. Symptoms associated with GH outbreaks can be reduced by antiviral medications, but the infection is incurable and lifelong. In this study, we estimate the long-term health impacts of GH in the United States using quality-adjusted life years (QALYs) lost. We used probability trees to model the natural history of GH secondary to infection with HSV-1 and HSV-2 among people aged 18-49 years. We modelled the following outcomes to quantify the major causes of health losses following infection: symptomatic herpes outbreaks, psychosocial impacts associated with diagnosis and recurrences, urinary retention caused by sacral radiculitis, aseptic meningitis, Mollaret's meningitis, and neonatal herpes. The model was parameterized based on published literature on the natural history of GH. We summarized losses of health by computing the lifetime number of QALYs lost per genital HSV-1 and HSV-2 infection, and we combined this information with incidence estimates to compute the total lifetime number of QALYs lost due to infections acquired in 2018 in the United States. We estimated 0.05 (95% uncertainty interval (UI) 0.02-0.08) lifetime QALYs lost per incident GH infection acquired in 2018, equivalent to losing 0.05 years or about 18 days of life for one person with perfect health. The average number of QALYs lost per GH infection due to genital HSV-1 and HSV-2 was 0.01 (95% UI 0.01-0.02) and 0.05 (95% UI 0.02-0.09), respectively. The burden of genital HSV-1 is higher among women, while the burden of HSV-2 is higher among men. QALYs lost per neonatal herpes infection was estimated to be 7.93 (95% UI 6.63-9.19). At the population level, the total estimated lifetime QALYs lost as a result of GH infections acquired in 2018 was 33,100 (95% UI 12,600-67,900) due to GH in adults and 3,140 (95% UI 2,260-4,140) due to neonatal herpes. Results were most sensitive to assumptions on the magnitude of the disutility associated with post-diagnosis psychosocial distress and symptomatic recurrences. GH is associated with substantial health losses in the United States. Results from this study can be used to compare the burden of GH to other diseases, and it provides inputs that may be used in studies on the health impact and cost-effectiveness of interventions that aim to reduce the burden of GH. The Center for Disease Control and Prevention.

Cost-effectiveness of immediate initiation of dapagliflozin in patients with a history of heart failure.

To compare the cost-effectiveness of immediate and 12-month delayed initiation of dapagliflozin treatment in patients with a history of hospitalization for heart failure (HHF) from the UK, Canadian, German, and Spanish healthcare perspectives. A cost-utility analysis was conducted using a decision-analytic Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire scores, type 2 diabetes mellitus status and incidence of heart failure (HF) events. Patient-level data for patients with prior HHF from the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial were used to inform the model inputs on clinical events and utility values. Healthcare costs were sourced from the relevant national reference databases and the published literature. Compared to standard therapy, immediate initiation of dapagliflozin decreased HHF (187 events), urgent HF visits (32 events) and cardiovascular mortality (18 events). Standard therapy was associated with lifetime costs of £13 224 and 4.02 quality-adjusted life years (QALYs). Twelve-month delayed initiation of dapagliflozin was associated with total discounted lifetime costs and QALYs of £16 660 and 4.61, respectively, compared to £16 912 and 4.66, respectively, for immediate initiation. Compared to standard therapy, immediate and 12-month delayed initiation of dapagliflozin yielded an incremental cost-effectiveness ratio (ICER) of £5779 and £5821, respectively. Compared to 12-month delayed initiation, immediate initiation of dapagliflozin had an ICER of £5263. Results were similar from the Canadian, German, and Spanish healthcare perspectives. Both immediate and 12-month delayed initiation of dapagliflozin are cost-effective. However, immediate initiation provides greater clinical benefits, with almost 10% additional QALYs gain, compared to 12-month delayed initiation of dapagliflozin and should be considered standard of care.

Cost-effectiveness of immune checkpoint inhibition and targeted treatment in combination as adjuvant treatment of patient with BRAF-mutant advanced melanoma

BackgroundImmune checkpoint inhibitors (ICIs) and targeted treatments have improved the health outcomes of patients with advanced melanoma. However, due to the high cost of novel therapies, it is crucial to evaluate their value by considering both effectiveness and cost. To compare the cost-effectiveness of these novel agents (atezolizumab-vemurafenib-cobimetinib, vemurafenib-plus-cobimetinib, dabrafenib-plus-trametinib, and encorafenib-plus-binimetinib) for first-line treatment of metastatic melanoma with the BRAFV600 mutation.MethodsA patient-level model was developed to project the health outcomes of 4 strategies for patients with advanced melanoma. We estimated transition probabilities from the IMspire150 (ClinicalTrials.gov, NCT02908672), COMBI-AD (NCT01682083), and COLUMBUS (NCT01909453) trials using a parametric survival model. All health outcomes, including direct cost, quality-adjusted life-years (QALYs) and the incremental cost-effectiveness ratio (ICER), were estimated from the US payer perspective. Lifetime cost, QALYs, life-years (LYs), and ICERs were calculated. Univariable and probabilistic sensitivity analyses were performed to test model robustness, along with multiple scenario analyses.ResultsOf the 4 competing strategies, atezolizumab-vemurafenib-cobimetinib produced the best health outcomes, and the vemurafenib-cobimetinib strategy was the least expensive option. Atezolizumab-vemurafenib-cobimetinib, dabrafenib-plus-trametinib, and vemurafenib-cobimetinib formed the cost-effective frontier, indicating that the ordered ICERs were $325,113/QALYs for dabrafenib-plus-trametinib vs. vemurafenib-cobimetinib strategies and $2,247,500/QALYs for atezolizumab-vemurafenib-cobimetinib vs. dabrafenib-plus-trametinib strategies. Encorafenib-plus-binimetinib was dominated by the other 3 competing strategies. The drug price and first-line utility significantly influenced the model utcomes.ConclusionsFor BRAF-mutant advanced melanoma, the vemurafenib-cobimetinib strategy could be considered the most cost-effective treatment at the willingness-to-pay threshold of $150,000.

Cost-effectiveness of office-based buprenorphine treatment for opioid use disorder

AimTo assess the effectiveness and cost-effectiveness of office-based buprenorphine treatment (OBBT) in the U.S. Design setting and participantsWe performed a model-based analysis of buprenorphine treatment provided in a primary care setting for the U.S. population with OUD. InterventionBuprenorphine treatment provided in a primary care setting. MeasurementsFatal and nonfatal overdoses and deaths over five years, discounted lifetime quality-adjusted life years (QALYs), costs. FindingsFor a cohort of 100,000 untreated individuals who enter OBBT, approximately 9350 overdoses would be averted over five years; of these, approximately 900 would have been fatal. OBBT compared to no treatment would yield 1.07 incremental lifetime QALYs per person at an incremental cost of $17,000 per QALY gained when using a healthcare perspective. If OBBT is half as effective and twice as expensive as assumed in the base case, the incremental cost when using a healthcare perspective is $25,500 per QALY gained. Using a limited societal perspective that additionally includes patient costs and criminal justice costs, OBBT is cost-saving compared to no treatment even under pessimistic assumptions about efficacy and cost. ConclusionsExpansion of OBBT would be highly cost-effective compared to no treatment when considered from a healthcare perspective, and cost-saving when reduced criminal justice costs are included. Given the continuing opioid crisis in the U.S., expansion of this care option should be a high priority.

Cost-utility of minimally invasive therapies vs. pharmacotherapy as initial therapy for benign prostatic hyperplasia A Canadian healthcare payer perspective.

Recently, minimally invasive surgical therapies (MIST s) have become an alternative to surgery or pharmacotherapy to manage benign prostatic hyperplasia (BPH ). This study evaluated the cost-utility of water vapor thermal therapy (WVTT ) and prostatic urethral lift (PUL) compared to pharmacotherapy as initial treatment for patients with moderate-to-severe BPH. In this model-based economic evaluation, we simulated BPH progression in men (mean age 65 years, average International Prostate Symptom Score 16.6) over their lifetime and estimated healthcare costs (from the Canadian healthcare payer perspective) per quality-adjusted life year (QALY), discounted at 1.5% annually. In the model, men could receive up to three lines of therapy: 1) initial pharmacotherapy with MIST as second-line, and TURP or pharmacotherapy as third-line; 2) initial MIST (WVTT or PUL) with MIST again, TURP, or pharmacotherapy as second-line, and TURP as third-line. The model was populated using data from the published literature. The expected lifetime QALYs and costs were 15.50 QALYs and $14 626 for initial treatment with WVTT, 15.35 QALYs and $11 795 for pharmacotherapy followed by WVTT, 15.29 QALYs and $13 582 for pharmacotherapy followed by PUL, and 15.29 QALYs and $19 151 for initial treatment with PUL. Strategies involving PUL procedures were dominated by strategies involving WVTT. The incremental cost per QALY gained was $18 873 for initial WVTT compared to initial pharmacotherapy followed by WVTT. WVTT appears to be a cost-effective procedure and may be an appropriate first-line alternative to pharmacotherapy for patients with BPH and prostate volume less than 80 cm3 who seek faster improvement and no lifelong commitment to daily medications.

Impact of collateral flow on cost-effectiveness of endovascular thrombectomy.

Acute ischemic stroke patients with large-vessel occlusion and good collateral blood flow have significantly better outcomes than patients with poor collateral circulation. The purpose of this study was to evaluate the cost-effectiveness of endovascular thrombectomy (EVT) based on collateral status and, in particular, to analyze its effectiveness in ischemic stroke patients with poor collaterals. A decision analysis study was performed with Markov modeling to estimate the lifetime quality-adjusted life-years (QALYs) and associated costs of EVT based on collateral status. The study was performed over a lifetime horizon with a societal perspective in the US setting. Base-case analysis was done for good, intermediate, and poor collateral status. One-way, two-way, and probabilistic sensitivity analyses were performed. EVT resulted in greater effectiveness of treatment compared to no EVT/medical therapy (2.56 QALYs in patients with good collaterals, 1.88 QALYs in those with intermediate collaterals, and 1.79 QALYs in patients with poor collaterals), which was equivalent to 1050, 771, and 734 days, respectively, in a health state characterized by a modified Rankin Scale (mRS) score of 0-2. EVT also resulted in lower costs in patients with good and intermediate collaterals. For patients with poor collateral status, the EVT strategy had higher effectiveness and higher costs, with an incremental cost-effectiveness ratio (ICER) of $44,326/QALY. EVT was more cost-effective as long as it had better outcomes in absolute numbers in at least 4%-8% more patients than medical management. EVT treatment in the early time window for good outcome after ischemic stroke is cost-effective irrespective of the quality of collateral circulation, and patients should not be excluded from thrombectomy solely on the basis of collateral status. Despite relatively lower benefits of EVT in patients with poor collaterals, even smaller differences in better outcomes have significant long-term financial implications that make EVT cost-effective.

Cost-utility analysis of transcatheter aortic valve implantation versus surgery in severe aortic stenosis patients with intermediate surgical risk in Thailand.

Transcatheter Aortic Valve Implantation (TAVI) has been shown to provide comparable survival benefit and improvement in quality of life to surgical aortic valve replacement (SAVR) for treating patients with severe aortic stenosis (AS) at intermediate surgical risk. This study aimed to evaluate the cost-utility of TAVI compared with SAVR for severe aortic stenosis with intermediate surgical risk in Thailand. A two-part constructed model was used to analyze lifetime costs and quality-adjusted life-years (QALYs) from societal and healthcare perspectives. The study cohort comprised severe AS patients at intermediate surgical risk with an average age of 80 years. The landmark trials were used to populate the model in terms of mortality and adverse event rates. All cost-related data and quality of life were based on Thai population. Costs and QALYs were discounted at 3% annually and presented as 2021 values. Incremental cost-effectiveness ratios (ICERs) were calculated. Deterministic and probabilistic sensitivity analyses were conducted. In comparison to SAVR, TAVI resulted in higher total cost (THB 1,717,132 [USD 52,415.51] vs. THB 893,524 [USD 27,274.84]) and higher QALYs (4.88 vs. 3.98) in a societal perspective. The estimated ICER was THB 906,937/QALY (USD 27,684.27/QALY). From a healthcare system perspective, TAVI also had higher total cost than SAVR (THB 1,573,751 [USD 48,038.79] vs. THB 726,342 [USD 22,171.63]) with similar QALYs gained to the societal perspective. The estimated ICER was THB 933,145/QALY (USD 933,145/QALY). TAVI was not cost-effective at the Thai willingness to pay (WTP) threshold of THB 160,000/QALY (USD 4,884/QALY). The results were sensitive to utility of either SAVR or TAVI treatment and cost of TAVI valve. In patients with severe AS at intermediate surgical risk, TAVI is not a cost-effective strategy compared with SAVR at the WTP of THB 160,000/QALY (USD 4,884/QALY) from the perspectives of society and healthcare system.

Cost-effectiveness of 5 fraction and partial breast radiotherapy for early breast cancer in the UK: model-based multi-trial analysis

PurposeWe estimated the cost-effectiveness of 4 radiotherapy modalities to treat early breast cancer in the UK. In a subgroup of patients eligible for all modalities, we compared whole-breast (WB) and partial breast (PB) radiotherapy delivered in either 15 (WB15F, PB15F) or 5 fractions (WB5F, PB5F). In a subgroup ineligible for PB radiotherapy, we compared WB15F to WB5F.MethodsWe developed a Markov cohort model to simulate lifetime healthcare costs and quality-adjusted life years (QALYs) for each modality. This was informed by the clinical analysis of two non-inferiority trials (FAST Forward and IMPORT LOW) and supplemented with external literature. The primary analysis assumed that radiotherapy modality influences health only through its impact on locoregional recurrence and radiotherapy-related adverse events.ResultsIn the primary analysis, PB5F had the least cost and greatest expected QALYs. WB5F had the least cost and the greatest expected QALYs in those only eligible for WB radiotherapy. Applying a cost-effectiveness threshold of £15,000/QALY, there was a 62% chance that PB5F was the cost-effective alternative in the PB eligible group, and there was a 100% chance that WB5F was cost-effective in the subgroup ineligible for PB radiotherapy.ConclusionsHypofractionation to 5 fractions and partial breast radiotherapy modalities offer potentially important benefits to the UK health system.

Economic evaluation of tislelizumab versus chemotherapy as second-line treatment for advanced or metastatic esophageal squamous cell carcinoma in China.

Background and purpose: The latest RATIONALE-302 trial (NCT03430843) showed that tislelizumab therapy significantly improved overall survival benefits for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) compared with traditional chemotherapy. This study aimed to compare the cost-effectiveness of tislelizumab versus chemotherapy as a second-line treatment for advanced or metastatic ESCC in China. Methods: A partitioned survival model was developed to predict patients' lifetime quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) from the Chinese healthcare payers' perspective. We extracted efficacy and safety data from the RATIONALE-302 trial and the local cost and resource use data from online databases and published studies. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analysis (PSA) were performed to explore model uncertainty. Results: Compared with chemotherapy, tislelizumab generated a higher cost (US$ 10211.78 vs. US$ 7294.72) but yielded more QALY (0.78 vs. 0.51 QALYs). The ICER for tislelizumab was US$11073.85 per QALY gained. The PSA results indicated that the probability of tislelizumab being economical was 76% under a willingness-to-pay (WTP) threshold of 1.5 times per capita GDP ($17915) in China. Conclusion: Tislelizumab could be a promising cost-effective strategy as the second-line treatment for patients with ESCC compared with chemotherapy in the Chinese setting.

Cost-Effectiveness Analysis of Frontline Treatment with Polatuzumab Vedotin in Diffuse Large B-Cell Lymphoma

Introduction: The POLARIX trial (NCT03274492) recently demonstrated that substituting polatuzumab vedotin (pola), a CD79b-targeted antibody-drug conjugate, for vincristine in standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemoimmunotherapy for first-line therapy can prolong progression-free survival in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). However, the medication cost of pola-R-CHP (pola, rituximab, cyclophosphamide, doxorubicin, and prednisolone) regimen is substantially higher than that of R-CHOP treatment. It remains unknown whether the lower rate of treatment failure with pola-R-CHP can be translated into reduced subsequent healthcare costs, increased life years (LYs), and improved quality of life, which may offset the higher medication cost. This study aimed to investigate the cost-effectiveness of substituting pola for vincristine in first-line therapy for patients with newly diagnosed DLBCL from a US payer perspective. Methods: We developed a decision analytic model to project lifetime quality-adjusted life years (QALYs) gained, LYs gained, and direct healthcare costs in newly diagnosed DLBCL patients. The model utilized a hypothetical cohort of patients at 65 years (the median age of disease onset). Direct healthcare costs were adjusted to 2021 US dollars, and an annual rate of 3% was used to discount future costs and benefits. Incremental cost-effectiveness ratios (ICERs) were calculated, and a willingness-to-pay (WTP) threshold of USD 150,000 per QALY gained was used as the acceptable level for determining cost-effectiveness. Sensitivity analyses and scenario analyses were conducted to assess the uncertainty of the base-case scenario and input parameters. Results: Pola-R-CHP, compared to standard R-CHOP, was associated with an incremental cost of USD 90,439, an improvement of 0.89 QALYs and 1.14 LYs, leading to an ICER of USD 101,510/QALY. The model was most sensitive to the survival benefit provided by pola-R-CHP, the age of the patients at initial treatment, and the price of pola. The ICER would increase significantly if pola-R-CHP is ineffective in providing long-term remissions. Furthermore, the ICER value increased as patients were older at the beginning of the treatment. When patients were older than 76.5 years at initial treatment, the ICER would exceed the WTP threshold of USD 150,000/QALY. To make the pola-R-CHP regimen cost-effective in all age groups (up to 80 years old), the current price of pola, which was estimated to be USD 19,307 for 170 mg per treatment cycle, needed to be reduced by 20%. In the probabilistic sensitivity analysis, 48% and 73% of the iterations produced ICERs below WTP thresholds of USD 100,000/ QALY and USD 150,000/ QALY, respectively. Conclusion: Our study findings suggest that pola-R-CHP, compared to the standard R-CHOP regimen, could be a cost-effective strategy in treatment-naïve DLBCL patients aged 65 years from a US payer perspective. However, several noticeable factors that could affect the cost-effectiveness profile of pola-R-CHP therapy should be considered in decision-making. The follow-up period of the POLARIX trial was relatively short, and mature survival data would be required to fully evaluate the value of pola in the treatment of newly diagnosed DLBCL.

Estimating the Lifetime Medical Cost Burden of an Allogeneic Hematopoietic Cell Transplantation Patient and the Value of Addressing the Unmet Need

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) management has evolved, with the emergence of molecular detection assays and therapies to treat post-HCT complications such as graft-versus-host disease (GVHD). However, this approach could increase the economic burden on healthcare systems by only managing complications that occur after the initial transplant. Instead, alternative therapies involving novel engineered donor allografts to replace standard allo-HCT to prevent late complications may potentially improve outcomes and address a greater unmet need. Objective: To estimate (1) the average total lifetime medical costs of an allo-HCT and (2) to estimate the net monetary savings and value associated with reducing late complications. Methods: A short-term decision tree (100-day) and a long-term semi-Markov partitioned survival model were developed that estimated the average per-patient lifetime cost and expected quality-adjusted life years (QALYs) for an allo-HCT patient from a United States healthcare system perspective. The allo-HCT patient population represented an average 53-year-old patient who was undergoing an allo-HCT to treat the three most common indications for allo-HCT: acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS), distributed as 51%, 21%, and 28%, respectively. Key model clinical inputs included: overall survival, GVHD-free relapse-free survival (GRFS), incidence of both acute and chronic GVHD, relapse of the primary disease, and infections. Following the first 100 days, the patient cohort was assigned to 3 mutually exclusive health states in a semi-Markov partitioned survival model for the remainder of their lifetime: (1) GRFS, (2) progressed and/or GVHD, and (3) death. The projected time spent in each health state was derived from data provided by CIBMTR. Costs pertaining to allo-HCT and associated complications were obtained from the published literature based on medical claims analyses of payments (paid amounts) and were converted into costs using the American Hospital Association (AHA) commercial payment-to-cost ratio. Maintenance therapy costs for FLT3-ITD positive AML and Ph+ ALL cases were also included and were based on published literature, expert opinion, and prescribing information. The key outcomes were direct medical costs and expected QALYs. Cost results were reported as a range based on varying the percent of chronic GVHD patients that remained on treatment after two years (15% or 39%) as derived from the published literature. Scenario analyses were conducted to estimate the potential clinical and economic value that may be realized by improving GRFS outcomes. The scenario analyses to address some of the unmet need were modeled as a doubled improvement in GRFS (69% GRFS in year 1 as opposed to 34%) to estimate changes in allo-HCT-associated costs and survival. A willingness-to-pay threshold of $150,000 was used to monetize the QALYs gained as a result of improving GRFS outcomes. Results: Over a lifetime, the average per-patient medical cost of allo-HCT was estimated to range from $942,373 to $1,247,917. Of those total costs, 23% to 30% were incurred within the 1st 100 days and 42% to 56% within the 1st year. Of the medical costs estimated, the majority of the costs were for chronic GVHD treatment (37% to 53%) followed by the allo-HCT procedure (15% to 19%). Expected lifetime QALYs of an allo-HCT patient were estimated to be 4.7. In the scenario analyses, the unmet need that could be addressed by improving GRFS outcomes (via the medical cost offsets and QALYs gained) was associated with a net monetary value that ranged from $695,709 to $911,062. Of the estimated net monetary value, 85% to 88% was driven by direct medical cost savings while the remaining 12% to 15% was due to value of the gain in expected QALYs. Conclusions: The current per-patient cost of allo-HCT carries a substantial medical cost burden often exceeding $1M over the lifetime of the patient. Innovative research efforts focused on disease control and reduction or elimination of late complications altogether, particularly cGVHD, may provide the greatest value in improved patient outcomes and reduced healthcare spending. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Gene Therapy Equity in Sickle Cell Disease: Distributional Cost-Effectiveness Analysis (DCEA) of Gene Therapy Vs. Standard-of-Care in Patients with Sickle Cell Disease in the United States

Introduction: Patients with sickle cell disease (SCD) face substantial mortality risks and decreased quality-of-life for every year lived with disease. Once approved in the United States (US), gene therapy treatment for patients with SCD would allow the possibility of lifelong disease remission and, unlike allotransplantation, do so without the concomitant risks of allotransplantation. While gene therapy has previously been projected to be cost-ineffective using traditional cost-effectiveness criteria in the US, this does not include a quantification of the health disparities present in the clinical care of patients with SCD. We sought to address this knowledge gap by conducting the first distributional cost-effectiveness analysis, a method that quantifies the tradeoffs between traditional cost-effectiveness outcomes and health equity, for gene therapy use in SCD. Methods: We built and validated a Markov simulation model of patients with a diagnosis of mild, moderate, or severe SCD to examine the cost-effectiveness of gene therapy versus patients treated with standard-of-care (SOC). Gender-, age-, and disease-severity-specific annual costs and transition probabilities between disease severities were informed by ten years of real-world data from commercially insured patients in the United States with SCD (2007-2017; Optum claims data). Disease severity was defined based on annual number of hospitalizations and SOC was inclusive of hydroxyurea, opioid therapy, antibiotics, vaccinations, blood transfusions, and stem cell transplantation. Quality-adjusted life-years (QALYs) were informed by published lifetime simulation of patients living with SCD and matched controls. These were originally derived from a polynomial fit linking Euroqual-5 Dimensions to the visual analog scale for pain in patients with SCD in several studies. Age-, gender- and disease-specific background mortality probabilities were employed. Traditional cost-effectiveness was quantified using an incremental cost-effectiveness ratio (ICER) and a cost-effectiveness threshold of $100,000/QALY. Base-case gene therapy was assumed to cost $2.1 million based on other recently approved indications, be 100% effective in achieving disease remission, and applied to a minimum eligibility age of 12, as studied in randomized, controlled trials. To account for health inequities in SCD we then conducted a distributional cost-effectiveness analysis (DCEA), which applies an inequality aversion parameter (i.e., equity weight) to the distribution of outcomes across relevant sub-groups. Specifically, we derived the threshold inequality aversion parameters needed for gene therapy to be favored over SOC and justify funding per DCEA standards. These were compared to prior estimates for commonly used equity weights in the US (range 0.5-3.0) and the United Kingdom (UK) (11.0-28.9). Results: Base-case gene therapy versus SOC treatment starting at age 12 yields 25.5 versus 16.0 discounted lifetime QALYs at costs of $2.4 and $1.1 million, respectively. The ICER of $144,000/QALY is not good value for money using traditional cost-effectiveness methods and a cost-effectiveness threshold of $100,000/QALY. When using DCEA that account for health disparities in SCD, the inequality aversion parameter threshold is 1.7. This implies a preference for reducing disparities in SCD care that is in line with prior estimates in the US and well below those of the UK, per DCEA standards to favor gene therapy over SOC. A corresponding price range for gene therapy for SCD across the range of commonly used equity weights in the US is $1.4-$3.0 million (Figure 1). Conclusion: Gene therapy can be an equitable therapeutic strategy for patients with SCD in the United States despite a projected minimum cost of $2.1 million once approved, based on commonly-used equity weight values used in DCEA. Equitable gene therapy use would include expanding eligibility to include patients with mild and moderate disease severity, in addition to those with severe SCD, assuming similar therapeutic efficacy of gene therapy across disease severity. Rather than relying on ranges of commonly-used equity weights, nationally representative surveys should be fielded to empirically deriving an inequality aversion parameter value for addressing this SCD-specific health disparity to further help inform an equitable price benchmark for gene therapy in the US. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Cost-effectiveness of recombinant tissue-type plasminogen activator for acute ischaemic stroke with unknown time of onset: a Markov modelling analysis from the Chinese and US perspectives

ObjectiveThe effectiveness of MRI-guided intravenous recombinant tissue-type plasminogen activator (r-tPA) for acute ischaemic stroke (AIS) with an unknown time of onset has been demonstrated by the WAKE-UP Trial. We aim...

Universal Screening for Malnutrition Prior to Total Knee Arthroplasty Is Cost-Effective: A Markov Analysis

BackgroundPatients undergoing total knee arthroplasty (TKA) who have malnutrition possess an increased risk of periprosthetic joint infection (PJI). Although malnutrition screening and intervention may decrease the risk of PJI, it utilizes healthcare resources. To date, no cost-effectiveness analyses have been performed on the screening and treatment of malnutrition prior to TKA. MethodsA Markov model projecting lifetime costs and quality-adjusted life years (QALYs) was built to determine the cost-effectiveness of malnutrition screening and intervention for TKA patients from a societal perspective. Costs, health state utilities, and state transition probabilities were obtained from previously published literature, hospital costs at our institution, and expert opinions. Two important assumptions included that 30% of patients would be malnourished and that a malnutrition intervention would be 50% effective. The primary outcome of this study was the incremental cost-effectiveness ratio, with a willingness-to-pay threshold of $100,000 per QALY. One-way and two-way sensitivity analyses were performed to evaluate model parameter assumptions. ResultsWhen using the base case values, universal malnutrition screening and intervention was cost-effective compared to no malnutrition screening or intervention, with an incremental cost-effectiveness ratio of $6,454 per QALY. Universal screening and intervention remained cost-effective, provided the cost of screening remained less than $3,373, the cost of nutritional intervention remained less than $12,042, the prevalence of malnutrition among surgical candidates was higher than 2%, and the risk of PJI among patients with malnutrition was greater than 1%. ConclusionUniversal preoperative malnutrition screening and intervention among TKA candidates is cost-effective at parameters encountered in clinical practice. Nutritional optimization programs should be considered to facilitate malnutrition screening and intervention and future studies should evaluate their efficacy at lowering PJI risk.

Economic evaluation of new blood pressure target for hypertensive patients in Taiwan according to the 2022 hypertension clinical practice guidelines of the Taiwan society of cardiology: a simulation modeling study.

With the promising cardiovascular benefits in the STEP and SPRINT trials, the2022 Taiwan's hypertension guidelines redefined the hypertension threshold as 130/80 mmHg and a universal blood-pressure target of <130/80 mmHg. This study's objective was to examine the cost-effectiveness of the intensive blood-pressure target for hypertensive patients using estimated lifetime medical costs and quality-adjusted life years (QALY) from the Taiwan national payer's perspective. We developed a lifetime Markov model comparing the intensive and conservative blood-pressure targets. Incremental cost-effectiveness ratio (ICER) against the willing-to-pay thresholds at the one-time [US$34,000(NT$1,020,000)] and three-time [US$100,000(NT$3,000,000)] gross domestic product per capita were defined as very cost-effect and only cost-effective. The cost-effectiveness in different age stratifications and cardiovascular risks treated with a more intensive target (120 mmHg) were examined in the subgroup analyses. The new blood-pressure treatment target produced more lifetime medical costs [US$31,589(NT$947,670) versus US$26,788(NT$803,640)] and QALYs (12.54 versus 12.25), and the ICER was US$16,589(NT$497,670), which was 99.1% and 100% probability of a very cost-effective and cost-effective strategy. The ICERs in all age stratifications had more than a 90% probability of being very cost-effective, and ICERs decreased with age. More intensive control in patients with high cardiovascular risks produced a lower ICER [US$14,547(NT$436,410)]. In conclusion, Taiwan's new blood-pressure treatment target can prevent more cardiovascular events with acceptable costs per QALY below the willing-to-pay thresholds. The cost-effectiveness of intensive control is consistent across different ages and more pronounced with the increase in age and cardiovascular risk.