DataSheet_1_Economic Analysis of Tissue-First, Plasma-First, and Complementary NGS Approaches for Treatment-Naïve Metastatic Lung Adenocarcinoma.docx

BackgroundTo 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 MethodsWe 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.ResultsIn 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.ConclusionThe 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.</p

Cost-effectiveness scatter plots using (A) life expectancy and (B) QALE.

Individual dots represent results after 1,000 iterations. QALE: quality-adjusted life expectancy; QALY: quality-adjusted life year.</p

Clinical characteristics of the 192 propensity score-matched patients and those excluded after matching.

Clinical characteristics of the 192 propensity score-matched patients and those excluded after matching.</p

Additional file 1 of Typical antipsychotics is associated with increased risk of severe exacerbation in asthma patients: a nationwide population-based cohort study

Additional file 1. Table S1. Elimination half-life of each antipsychotic. Table S2. Ninth and 10th revision international classification of diseases codes of comorbidity. Table S3. List of comedications in the presented study. Table S4. Receptor-binding profile of antipsychotics with bronchial relaxation effect. Table S5. The adjusted odds ratio of all covariates in multivariable conditional logistic regression. Table S6. Risk of severe asthma exacerbation by different classes of antipsychotics and doses in patients with schizophrenia. Table S7. Risk of severe asthma exacerbation by different classes of antipsychotics and doses in patients with depression. Table S8. Risk of severe asthma exacerbation by different classes of antipsychotics and doses in patients with bipolar disorder. Table S9. Risk of severe asthma exacerbation by different classes of antipsychotics and doses after excluding patients had psychiatric disorder related admission or ED visiting. Table S10. Risk of severe asthma exacerbation by different classes of antidepressants and doses

Acceptability curves of cost-effectiveness thresholds using (A) US/lifeyear,and(B)US/life year, and (B) US/QALY.

The dash line represents a threshold of US$24,408 (1 GDP per capita of Taiwan in 2017) / life year or QALY. GDP: gross domestic product; QALY: quality-adjusted life year.</p

Lifetime costs and QALE of patients receiving different first-line treatments.

The survival curves (dashed lines), costs and QoL functions (dotted lines); cost- and quality-adjusted survival curves (solid lines) are shown, with the shaded areas representing the lifetime costs and QALE, respectively. 1 US dollar = 29.848 Taiwanese dollars. QALE: quality-adjusted life expectancy; QoL: quality of life.</p

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

IntroductionComparison 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.MethodsDuring 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.ResultsPatients 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.ConclusionErlotinib appeared to be cost-effective. Lifetime psychometric scores may provide additional information for effectiveness evaluation.</div

Costs, effectiveness, and ICER of the 192 propensity score-matched patients.

Costs, effectiveness, and ICER of the 192 propensity score-matched patients.</p

Costs, effectiveness, and ICER of the 379 patients before propensity score matching.

Costs, effectiveness, and ICER of the 379 patients before propensity score matching.</p

DataSheet_1_Cost-Effectiveness of Nivolumab Plus Ipilimumab With and Without Chemotherapy for Advanced Non-Small Cell Lung Cancer.doc

BackgroundFirst-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 methodsUsing 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 ResultsThe 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$185,620 per QALY for those with PD-L1 ConclusionFirst-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.</p