Estimation of disability free life expectancy in non small cell lung cancer based on real world data.

To quantify the societal impact of disability in patients with non-small cell lung cancer (NSCLC), this study estimated the disability-free life expectancy (DFLE), loss-of-DFLE and explored their associations with quality-adjusted life expectancy (QALE) and loss-of-QALE. We interlinked national databases and applied a rolling-over algorithm to estimate the lifetime survival function for patients with NSCLC. Using the EuroQOL-5 Dimension (EQ-5D) and Barthel index (BI), we repeatedly measured the quality-of-life and disability functions of NSCLC patients who visited our hospital from 2011 to 2020. Age-, sex-matched referents were simulated from lifetables of the same calendar year of diagnosis. We categorized BI scores ≤ 70 as in need of long-term care and constructed linear mixed models to estimate the utility values and disability scores. We collected 960 cases and 3088 measurements. The proportions of measurements without disability at age 50-64 and in stage I-IIIa, 50-64 and stage IIIb-IV, 65-89 and stage I-IIIa and 65-89 and stage IIIb-IV were 97.3%, 89.3%, 94.8%,78.3%, corresponding to DFLEs of 15.3, 2.4, 6.8, 1.2 years and losses-of-DFLE of 8.1, 20.7, 4.0, 8.6 years, respectively, indicating that advanced stage had a stronger effect than old age. Survivors in advanced stages showed increased demands for assistance in almost all subitems. The DFLEs seemed to be approximate to the QALEs and the latter were shorter than the former due to discomfort and depression. From a societal perspective, future health technology assessment should consider the impact of lifetime duration of functional disability. Early diagnosis of NSCLC may decrease the burden of long-term care.

Estimating time and transportation costs associated with lung cancer screening and diagnostic lung procedures in Taiwan: a cross-sectional survey in a medical centre.

OBJECTIVES: Earlier research has evaluated the non-medical costs after lung cancer diagnosis. This study estimated the time costs and transportation costs associated with low-dose CT (LDCT) screening and diagnostic lung procedures in Taiwan. DESIGN: Cross-sectional study. SETTING: A tertiary referral medical centre. PARTICIPANTS AND INTERVENTIONS: The study participants were individuals aged 50-80 years who underwent LDCT screening or diagnostic lung procedures between 2021 and 2022. Participants completed a questionnaire including items on time spent on receiving care, time spent on travel and its cost and time taken off from work by the participant and any accompanying caregiver. OUTCOME MEASURES: Time costs were valued using the age- and sex-specific average daily wage for employed participants/caregivers. Costs of informal healthcare sector consisted of time cost of the participant, transportation cost and time cost of the caregiver. RESULTS: A total of 209 participants who underwent LDCT screening (n=84) or non-surgical (n=12) or surgical (n=113) diagnostic lung procedures for the first time were enrolled. Considering the purchasing power parity, the average costs of informal healthcare sector were US$126.4 (95% CI 101.6 to 151.2), US$290.7 (95% CI 106.9 to 474.5) and US$749.8 (95% CI 567.3 to 932.4), respectively, for LDCT screening, non-surgical procedures and surgical procedures. CONCLUSIONS: This study estimated time and transportation costs associated with LDCT screening and diagnostic lung procedures, which could be used for future analysis of cost-effectiveness of lung cancer screening in Taiwan.

Cost-effectiveness of first-line immunotherapies for advanced non-small cell lung cancer.

BACKGROUND: Researchers have not simultaneously compared the cost-effectiveness of six immunotherapies with chemotherapy for advanced non-small cell lung cancer. This study evaluated the cost-effectiveness across different programmed death-ligand 1 (PD-L1) levels. METHODS: A Markov model with lifetime horizon was created for seven regimens: pembrolizumab plus chemotherapy (pembro-chemo), nivolumab plus ipilimumab (nivo-ipi), nivolumab, ipilimumab plus chemotherapy (nivo-ipi-chemo), atezolizumab plus chemotherapy (atezo-chemo), atezolizumab, bevacizumab plus chemotherapy (atezo-beva-chemo), single-agent pembrolizumab, and chemotherapy alone. Input parameters were derived from trial data, a network meta-analysis, and other literature. We conducted the analysis from the perspective of US health care sector. RESULTS: For all patients without considering PD-L1 expression, the incremental cost-effectiveness ratio (ICER) of pembro-chemo versus chemotherapy was $183,299 per quality-adjusted life year (QALY). The preferred regimens based on ICERs differed by PD-L1 levels. For patients with PD-L1 ≥50%, pembrolizumab versus chemotherapy and pembro-chemo versus pembrolizumab resulted in ICERs of $96,189 and $198,913 per QALY, respectively. The other strategies were dominated. For patients with PD-L1 of 1%-49%, the ICER of pembro-chemo comparing to chemotherapy was $218,159 per QALY. The other regimens were dominated by pembro-chemo. For patients with PD-L1 <1%, nivo-ipi versus chemotherapy and nivo-ipi-chemo versus nivo-ipi resulted in ICERs of $161,277 and $881,975 per QALY, and the other regimens were dominated strategies. At the willingness-to-pay threshold of $150,000 per QALY, pembrolizumab had 87% and pembro-chemo had 1% probabilities being cost-effective in patients with PD-L1 ≥50% and 1%-49%, respectively. Nivo-ipi had a 34% probability being cost-effective in patients with PD-L1 <1%. CONCLUSIONS: The PD-L1 level should be incorporated into treatment decision-making. Our findings suggest that first-line pembrolizumab, pembro-chemo, and nivo-ipi are the preferred strategies for patients with PD-L1 ≥50%, 1%-49%, and <1%, respectively.

Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma.

Background: To compare the testing costs and testing turnaround times of tissue-first, plasma-first, and complementary next-generation sequencing (NGS) approaches in patients with treatment-naïve metastatic lung adenocarcinoma. Materials and Methods: We developed a decision tree model to compare three different approaches. Patients were entered into the model upon cancer diagnosis and those with both insufficient tissue specimens and negative liquid-based NGS were subjected to tissue re-biopsy. Actionable gene alterations with the U.S. Food and Drug Administration (FDA)-approved therapies included epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) gene rearrangement, ROS proto-oncogene 1 (ROS1) rearrangement, B-Raf proto-oncogene (BRAF) V600E mutation, rearranged during transfection (RET) gene rearrangement, mesenchymal-epithelial transition factor (MET) mutation, neurotrophic tyrosine receptor kinase (NTRK) gene rearrangement, K-Ras proto-oncogene (KRAS) G12C mutation, and human epidermal growth factor receptor 2 (HER2) mutation. Model outcomes were testing costs, testing turnaround times, and monetary losses taking both cost and time into consideration. We presented base-case results using probabilistic analysis. Stacked one-way and three-way sensitivity analyses were also performed. Results: In terms of testing costs, tissue-first approach incurred US$2,354($1,963-$2,779) and was the most cost-efficient strategy. Complementary approach testing turnaround time (days) of 12.7 (10.8 to 14.9) was found as the least time-consuming strategy. Tissue-first, complementary, and plasma-first approaches resulted in monetary losses in USD of $4,745 ($4,010-$5,480), $6,778 ($5,923-$7,600), and $7,006 ($6,047-$7,964) respectively, and identified the same percentage of patients with appropriate FDA-approved therapies. Costs for liquid-based NGS, EGFR mutation rates, and quantity of tissue specimens were the major determinants in minimizing monetary loss. Plasma-first approach would be the preferable strategy if its testing price was reduced in USD to $818, $1,343, and $1,869 for populations with EGFR mutation rates of 30%, 45%, and 60% respectively. Conclusion: The tissue-first approach is currently the best strategy in minimizing monetary loss. The complementary approach is an alternative for populations with a low EGFR mutation rate. The plasma-first approach becomes increasingly preferable as EGFR mutation rates gradually increase.

Economic Analysis of Exclusionary EGFR Test Versus Up-Front NGS for Lung Adenocarcinoma in High EGFR Mutation Prevalence Areas.

BACKGROUND: This study sought to determine whether exclusionary EGFR mutation testing followed by next-generation sequencing (NGS) is a cost-efficient and timely strategy in areas with high prevalence rates of EGFR mutation. METHODS: We developed a decision tree model to compare exclusionary EGFR testing followed by NGS and up-front NGS. Patients entered the model upon diagnosis of metastatic lung adenocarcinoma. Gene alterations with FDA-approved targeted therapies included EGFR, ALK, ROS1, BRAF, RET, MET, NTRK, and KRAS. Model outcomes were testing-related costs; time-to-test results; monetary loss, taking both costs and time into consideration; and percentage of patients who could be treated by FDA-approved therapies. Stacked 1-way and 3-way sensitivity analyses were performed. RESULTS: Exclusionary EGFR testing incurred testing-related costs of US $1,387 per patient, a savings of US $1,091 compared with the costs of up-front NGS. The time-to-test results for exclusionary EGFR testing and up-front NGS were 13.0 and 13.6 days, respectively. Exclusionary EGFR testing resulted in a savings of US $1,116 in terms of net monetary loss, without a reduction of patients identified with FDA-approved therapies. The EGFR mutation rate and NGS cost had the greatest impact on minimizing monetary loss. Given that the tissue-based NGS turnaround time was shortened to 7 days, up-front NGS testing would become the best strategy if its price could be reduced to US $568 in Taiwan. CONCLUSIONS: In areas with high prevalence rates of EGFR mutation, exclusionary EGFR testing followed by NGS, rather than up-front NGS, is currently a cost-efficient strategy for metastatic lung adenocarcinoma.

Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer.

BACKGROUND: First-line treatment with nivolumab plus ipilimumab (N+I) or nivolumab plus ipilimumab with two cycles of chemotherapy (N+I+chemotherapy) improve overall survival and progression-free survival for patients with metastatic non-small cell lung cancer (NSCLC), yet researchers have not concomitantly compared the cost-effectiveness of N+I and N+I+chemotherapy with chemotherapy alone. MATERIALS AND METHODS: Using outcomes data from the CheckMate 227 and CheckMate 9LA phase 3 randomized trials, we developed a Markov model with lifetime horizon to compare the costs and effectiveness of N+I and N+I+chemotherapy versus chemotherapy from the U.S. health care sector perspective. Subgroup analysis by programmed death-ligand 1 (PD-L1) expression levels (≥1% and <1%) and probabilistic analysis were performed. RESULTS: The incremental cost-effectiveness ratio (ICER) of N+I versus chemotherapy was $239,072 per QALY, and $838,198 per QALY for N+I+chemotherapy versus N+I. The ICER of N+I versus chemotherapy was $246,584 per QALY for patients with PD-L1 ≥ 1% and $185,620 per QALY for those with PD-L1 < 1%. In probabilistic analysis, N+I had a 2.6% probability of being cost-effective at a willingness-to-pay threshold of $150,000 per QALY. The probability was 0.4% for patients with PD-L1 ≥ 1% and 10.6% for patients with PD-L1 < 1%. CONCLUSION: First-line N+I or N+I+chemotherapy for metastatic NSCLC was not cost-effective regardless of PD-L1 expression levels from the U.S. health care sector perspective.

QALYs and medical costs saved from prevention of a cancer: Analysis of nation-wide real-world data of Taiwan with lifetime horizon.

BACKGROUND/PURPOSE: To quantify savings of loss-of-QALE (quality-adjusted life expectancy) and lifetime medical costs from prevention of different cancers. METHODS: We collected nation-wide data on 808,700 new cancer cases of 14 different organ systems and followed them from 1998 to 2014 in Taiwan. We also collected 13,005 cancer patients from a medical center and 47,320 repeated measurements of quality of life (QoL) of EQ-5D to obtain utility values and multiplied them with the corresponding survival rates to calculate QALE. With Kaplan-Meier estimation to survival function to the end of follow-up, we extrapolated to lifetime through a rolling over algorithm on the logit transform of the survival ratio between the index cohort and age-, sex, and calendar year matched referents simulated from vital statistics. Lifetime costs for each cancer were estimated by multiplying survival with average monthly costs after adjustment with annual discount rate. The loss-of-QALE was estimated by the difference in QALE between the index cancer cohort and corresponding referents. RESULTS: The dynamic changes and weighted averages of the QoL utility values of 14 different cancers ranged from 0.82 to 0.95. Successful prevention of liver, lung, esophagus, or nasopharynx cancer would save more than 10 quality-adjusted life years and more than 21,000 USD per case for both genders. Since the saving of loss-of-QALE was adjusted for different age, sex, and calendar-year distributions, it could be used in cost effectiveness evaluation. CONCLUSION: Savings of loss-of-QALE and lifetime costs could be used for comparison of prevention, diagnosis, treatment and rehabilitation from a lifetime horizon.

Downstream Complications and Healthcare Expenditure after Invasive Procedures for Lung Lesions in Taiwan.

This study aimed to estimate the downstream complications and healthcare expenditure after invasive procedures for lung lesions, which in turn could be used for future cost-effectiveness analyses of lung cancer screening in Taiwan. We interlinked the Taiwan National Beneficiary Registry with the National Health Insurance Reimbursement databases to identify non-lung cancer individuals aged 50-80 years who underwent invasive lung procedures within one month after non-contrast chest computed tomography between 2014 and 2016. We directly matched one individual with 10 controls by age, gender, calendar year, residence area, comorbidities, and the past one-year healthcare expenditure to calculate incremental one-month complication rates and attributable costs. A total of 5805 individuals who underwent invasive lung procedures were identified and matched with 58,050 controls. The incremental one-month complication rates were 13.4% (95% CI: 10.9% to 15.8%), 10.7% (95% CI: 9.2% to 12.1%), and 4.4% (95% CI: 2.0% to 6.7%) for thoracic surgery, bronchoscopy, and needle biopsy, respectively. The incremental one-month healthcare expenditure for minor, intermediate, and major complications were NT$1493 (95% CI: NT$-3107 to NT$6092), NT$18,422 (95% CI: NT$13,755 to NT$23,089), and NT$58,021 (95% CI: NT$46,114 to NT$69,929), respectively. Individuals aged 60-64 years incurred the highest incremental costs. Downstream complications and the healthcare expenditure after invasive procedures for lung lesions would be substantial for non-lung cancer individuals 50-80 years of age. These estimates could be used in modeling the cost-effectiveness of the national lung screening program in Taiwan.

Comparative effectiveness and cost-effectiveness of three first-line EGFR-tyrosine kinase inhibitors: Analysis of real-world data in a tertiary hospital in Taiwan.

INTRODUCTION: Comparison of the effectiveness and cost-effectiveness of three first-line EGFR-tyrosine kinase inhibitors (TKIs) would improve patients' clinical benefits and save costs. Using real-world data, this study attempted to directly compare the effectiveness and cost-effectiveness of first-line afatinib, erlotinib, and gefitinib. METHODS: During May 2011-December 2017, all patients with non-small cell lung cancer (NSCLC) visiting a tertiary center were invited to fill out the EuroQol five-dimension (EQ-5D) questionnaires and World Health Organization Quality of Life, brief version (WHOQOL-BREF), and received follow-ups for survival and direct medical costs. A total of 379 patients with EGFR mutation-positive advanced NSCLC under first-line TKIs were enrolled for analysis. After propensity score matching for the patients receiving afatinib (n = 48), erlotinib (n = 48), and gefitinib (n = 96), we conducted the study from the payers' perspective with a lifelong time horizon. RESULTS: Patients receiving afatinib had the worst lifetime psychometric scores, whereas the differences in quality-adjusted life expectancy (QALE) were modest. Considering 3 treatments together, afatinib was dominated by erlotinib. Erlotinib had an incremental cost-effectiveness of US$17,960/life year and US$12,782/QALY compared with gefitinib. Acceptability curves showed that erlotinib had 58.6% and 78.9% probabilities of being cost-effective given a threshold of 1 Taiwanese per capita GDP per life year and QALY, respectively. CONCLUSION: Erlotinib appeared to be cost-effective. Lifetime psychometric scores may provide additional information for effectiveness evaluation.

Dynamic Changes of Health Utility in Lung Cancer Patients Receiving Different Treatments: A 7-Year Follow-up.

INTRODUCTION: This study aimed to estimate the utility values of all subtypes of lung cancer. The trajectories after different kinds of treatments and their major determinants were explored on the basis of real-world data and repeated measurements. METHODS: From 2011 to 2017, all patients with lung cancer who visited a medical center were invited to fill out the EuroQol Five-Dimension and WHO Quality of Life-Brief questionnaires at each visit. Utility values of quality of life (QoL) after diagnosis and treatments were depicted using a kernel smoothing method. We constructed linear mixed models to predict health utility in each time period and cross-validated them with domain scores of the WHO Quality of Life-Brief. RESULTS: A total of 1715 patients were enrolled, with 6762 QoL measurements. Utility values were lower in patients with advanced-stage disease and older patients. Patients receiving second-line targeted therapy showed higher utility values at 0 to 3 months, 3 to 6 months, and 6 months and beyond (0.89, 0.90, and 0.88, respectively) than did those undergoing chemotherapy (0.81, 0.85, and 0.80, respectively). After using mixed models to control confounders, including poor performance status and disease progression, patients receiving second-line chemotherapy showed health utility similar to that at quasi-baseline, whereas utility values related to second-line targeted therapy were higher at 3 to 6 months and 6 months and beyond (ß = 0.07, p = 0.010 and ß = 0.07, p < 0.001, respectively). There was convergent validity between the utility values and scores of the physical and psychological domains. CONCLUSION: Targeted therapy provided treated patients with a higher health utility value than was provided to those treated with chemotherapy. Development of the longitudinal trajectory may help predict changes in QoL and improve the care of lung cancer survivors.

Effects of removing reimbursement restrictions on targeted therapy accessibility for non-small cell lung cancer treatment in Taiwan: an interrupted time series study.

INTERVENTIONS: Targeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008. OBJECTIVES: This study is aimed towards an exploration of the impacts of the Taiwan NHI reimbursement policies (removing reimbursement restrictions) related to accessibility of targeted therapies. SETTING: We retrieved 2004-2013 claims data for all patients with lung cancer diagnoses from the NHI Research Database. DESIGN AND OUTCOME MEASURES: Using an interrupted time series design and segmented regression, we estimated changes in the monthly prescribing rate by patient number and market shares by cost following each modification of the reimbursement policy for gefitinib and erlotinib for NSCLC treatment. RESULTS: Totally 92 220 patients with NSCLC were identified. The prescribing rate of the targeted therapies increased by 15.58%, decreased by 10.98% and increased by 6.31% following the introduction of gefitinib as a second-line treatment in 2007, erlotinib as a second-line treatment in 2008 and gefitinib as as first line treatment in 2011, respectively. The average time to prescription reduced by 65.84% and 41.59% following coverage of erlotinib by insurance and gefitinib/erlotinib as second-line treatments in 2007-2008 and following gefitinib as the first-line treatment in 2011. CONCLUSIONS: The changes in reimbursement policies had a significant impact on the accessibility of targeted therapies for NSCLC treatment. Removing reimbursement restrictions can significantly increase the level and the speed of drug accessibility.

Cost-effectiveness of implementing computed tomography screening for lung cancer in Taiwan.

BACKGROUND: A screening program for lung cancer requires more empirical evidence. Based on the experience of the National Lung Screening Trial (NLST), we developed a method to adjust lead-time bias and quality-of-life changes for estimating the cost-effectiveness of implementing computed tomography (CT) screening in Taiwan. METHODS: The target population was high-risk (≥30 pack-years) smokers between 55 and 75 years of age. From a nation-wide, 13-year follow-up cohort, we estimated quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures per case of lung cancer stratified by pathology and stage. Cumulative stage distributions for CT-screening and no-screening were assumed equal to those for CT-screening and radiography-screening in the NLST to estimate the savings of loss-of-QALE and additional costs of lifetime healthcare expenditures after CT screening. Costs attributable to screen-negative subjects, false-positive cases and radiation-induced lung cancer were included to obtain the incremental cost-effectiveness ratio from the public payer's perspective. RESULTS: The incremental costs were US$22,755 per person. After dividing this by savings of loss-of-QALE (1.16 quality-adjusted life year (QALY)), the incremental cost-effectiveness ratio was US$19,683 per QALY. This ratio would fall to US$10,947 per QALY if the stage distribution for CT-screening was the same as that of screen-detected cancers in the NELSON trial. CONCLUSIONS: Low-dose CT screening for lung cancer among high-risk smokers would be cost-effective in Taiwan. As only about 5% of our women are smokers, future research is necessary to identify the high-risk groups among non-smokers and increase the coverage.

Rasch models suggested the satisfactory psychometric properties of the World Health Organization Quality of Life-Brief among lung cancer patients.

The study examined whether the items of the World Health Organization Quality of Life-Brief questionnaire can assess its four underlying domains (Physical, Psychological, Social, and Environment) in a sample of lung cancer patients. All patients ( n = 1150) were recruited from a medical center in Tainan, and each participant completed the World Health Organization Quality of Life-Brief. Several Rasch rating scale models were used to examine the data-model fit, and Rasch analyses corroborated that each domain of the World Health Organization Quality of Life-Brief could be unidimensional. Although three items were found to have a poor fit, all the other items fit the unidimensionality with ordered thresholds.

Estimating the lifelong health impact and financial burdens of different types of lung cancer.

BACKGROUND: Owing to the high mortality and rapidly growing costs related to lung cancer, it is worth examining the health benefits of prevention for major types of lung cancer. This study attempts to quantify the quality-adjusted life expectancy (QALE), loss-of-QALE, and lifetime healthcare expenditures of patients with different pathological types of lung cancer. METHODS: A national cohort consisting of 66,535 patients with pathologically verified lung cancer was followed for 13 years (1998-2010) to obtain the survival function, which was further extrapolated to lifetime. Between 2011 and 2012, EuroQol 5-dimension questionnaires were used to measure the quality of life (QoL) for 1,314 consecutive, cross-sectional samples. After multiplying the lifetime survival function by the utility values of QoL, we estimated the QALE and loss-of-QALE. We also collected the monthly healthcare expenditures, which included National Health Insurance-reimbursed and out-of-pocket direct medical costs, for 2,456 patients from 2005 to 2012. These values were multiplied by the corresponding survival probabilities to calculate lifetime healthcare expenditures after adjustments with medical care inflation rates and annual discount rates. RESULTS: The QALE for patients with small cell lung cancer, squamous cell carcinoma, and adenocarcinoma were 1.21, 2.37, and 3.03 quality-adjusted life year (QALY), with the corresponding loss-of-QALE of 13.69, 12.22, and 15.03 QALY, respectively. The lifetime healthcare expenditures were US$ 18,455 ± 1,137, 20,599 ± 1,787, and 36,771 ± 1,998, respectively. CONCLUSIONS: The lifelong health impact and financial burdens in Taiwan are heavier for adenocarcinoma than for squamous cell carcinoma. The cost-effectiveness of prevention programs could be directly compared with that of treatment strategies to improve patient value. And the methodology could be applied to other chronic diseases for resources planning of healthcare services.