Identifying optimal ALK inhibitors in first- and second-line treatment of patients with advanced ALK-positive non-small-cell lung cancer: a systematic review and network meta-analysis.

OBJECTIVES: To compare the efficacy, safety and effects on quality of life of different ALK-inhibitors for global and Asian patients with advanced ALK-positive non-small-cell lung cancer (NSCLC). METHODS: The included RCTs were identified through a systematic search of PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and major cancer conferences. The assessment of progression-free survival (PFS), intracranial PFS, overall survival (OS), and patient-reported outcomes (PROs) was carried out using restricted mean survival time (RMST) model, fractional polynomial model and Royston-Parmar model. Time-invariant hazard ratio (HR) models were also used to validate and supplement the primary analysis. Objective response rate (ORR) and adverse events with any grade, grade 3-5 were assessed through a Bayesian network meta-analysis. The primary measures for OS, PFS, and PROs were HR and RMST. The odds ratio was the metric for evaluating safety, ORR, 12-month PFS rate, 24-month OS rate, and the 12-month non-deterioration rate of PROs. Subgroup analyses based on patient characteristics were performed. RESULTS: A total of fourteen studies (ten for first-line, four for second-line) consisting of nine treatments (chemotherapy, crizotinib, alectinib [600mg BID], low-dose alectinib [300mg BID], brigatinib, ceritinib, ensartinib, envonalkib, and lorlatinib) were included. In the first-line setting, alectinib showed a significant advantage over crizotinib and had the longest OS among all ALK-inhibitors. Compared to crizotinib, lorlatinib had the best efficacy regarding PFS for global patients, followed closely by alectinib and brigatinib. For Asian patients, alectinib significantly improved PFS compared to other treatments. In second-line, alectinib had the highest PFS for patients pretreated with crizotinib, followed by brigatinib, ceritinib and chemotherapy. Alectinib, irrespective of the dose, was the safest first-line option, whereas lorlatinib, brigatinib, and ceritinib showed poorer safety profiles. Alectinib was also the safest ALK-inhibitor for crizotinib-resistant patients. Brigatinib had the best performance in terms of PROs. CONCLUSIONS: Considering both efficacy and safety, alectinib appears to be the preferable treatment in first-line and second-line, particularly for Asian patients.

A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer.

BACKGROUND: Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis. METHODS: RCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3-5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics. RESULTS: A total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings. CONCLUSIONS: CDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results' uncertainty, further trials comparing these novel treatments are warranted. TRIAL REGISTRATION: Registration number: PROSPERO (CRD42022377431).

Estimating the cost-effectiveness threshold of advanced non-small cell lung cancer in China using mean opportunity cost and contingent valuation method.

OBJECTIVES: Monetizing health has sparked controversy and has implications for pricing strategies of emerging health technologies. Medical insurance payers typically set up thresholds for quality-adjusted life years (QALY) gains based on health productivity and budget affordability, but they rarely consider patient willingness-to-pay (WTP). Our study aims to compare Chinese payer threshold and patient WTP toward QALY gain of advanced non-small cell lung cancer (NSCLC) and to inform a potential inclusion of patient WTP under more complex decision-making scenarios. METHODS: A regression model was constructed with cost as the independent variable and QALY as the dependent variable, where the regression coefficients reflect mean opportunity cost, and by transforming these coefficients, the payer threshold can be obtained. Patient WTP was elicited through a contingent valuation method survey. The robustness of the findings was examined through sensitivity analyses of model parameters and patient heterogeneity. RESULTS: The payer mean threshold in the base-case was estimated at 150,962 yuan (1.86 times per capita GDP, 95% CI 144,041-159,204). The two scenarios analysis generated by different utility inputs yielded thresholds of 112,324 yuan (1.39 times per capita GDP) and 111,824 yuan (1.38 times per capita GDP), respectively. The survey included 85 patients, with a mean WTP of 148,443 yuan (1.83 times per capita GDP, 95% CI 120,994-175,893) and median value was 106,667 yuan (1.32 times the GDP per capita). Due to the substantial degree of dispersion, the median was more representative. The payer threshold was found to have a high probability (98.5%) of falling within the range of 1-2 times per capita GDP, while the robustness of patient WTP was relatively weak. CONCLUSIONS: In China, a country with a copayment system, payer threshold was higher than patient WTP, indicating that medical insurance holds significant decision-making authority, thus temporarily negating the need to consider patient WTP.

Cost-effectiveness and potential budget impact of non-pharmacological interventions for early management in prehypertensive people: an economic evaluation for China.

BACKGROUND: Non-pharmacological interventions (NPIs) could be considered in the early management of prehypertensive population. This study aimed to evaluate the potential cost-effectiveness of NPIs and the budget impact of implementing NPIs on prehypertensive population in China and provide evidence of chronic disease management innovation for decision-makers. METHODS: Five NPIs including usual care, lifestyle, strengthen exercise, relaxation, and diet therapy were selected based on the practice of hypertension management in China. A nine-state Markov model was constructed to evaluate the lifetime costs and health outcomes of five NPIs and a non-intervention group from the perspective of Chinese healthcare system. The effectiveness of NPIs was obtained from a published study. Parameters including transition probabilities, costs and utilities were extracted or calculated from published literature and open-access databases. Sensitivity analyses were conducted to test the uncertainty of all parameters. The impact of duration of intervention was considered in scenario analyses. A budget impact analysis (BIA) was conducted to evaluate the total cost and the medical cost saving of a hypothetical nationwide implementation of potential cost-effective NPI in prehypertensive people. Management strategies including focusing on patients with specific ages or different CVE risk levels, and different duration of implementation were taken into consideration. RESULTS: Strengthen exercise was the most cost-effective intervention with a probability of 78.1% under the given WTP threshold. Our results were sensitive to the cost of interventions, and the utility of prehypertension and hypertension. The duration of implementation had limited impact on the results. BIA results showed that the program cost was hefty and far more than the medical cost saving with the course of simulation time. Applying management strategies which focused on individual characteristics could largely reduce the program cost despite it remained higher than medical cost saving. CONCLUSIONS: Strengthen exercise was a potential NPI that can be considered in priority for early management in prehypertensive population. Although early management can acquire medical cost saving, the related program cost can be quite hefty. Precise strategies which may help reduce the cost of early management should be taken into consideration in program design.

Safety and immunogenicity of heterologous ChAdOx1-nCoV19 and BNT162b2 vaccination: A meta-analysis of the heterologous COVID-19 vaccination outcomes.

INTRODUCTION: Here, we systematically assessed the safety and immunogenicity of the heterologous ChAd/BNT vaccination regimens. MATERIALS AND METHODS: We evaluated the immunogenicity by the geometric mean titers ratio (GMTR) of the neutralizing antibody and anti-spike IgG. The safety of heterologous ChAd/BNT vaccination was evaluated using the pooled risk ratios (RRs) calculated by the random-effects model about the adverse events. Our study was registered with PROSPERO, CRD42021265165. RESULTS: Eleven studies were included in the analyses. Compared to the homologous ChAd/ChAd vaccination, the heterologous ChAd/BNT vaccination showed significantly higher immunogenicity in terms of the neutralizing antibody and GMTR of anti-spike IgG, but at the same time displayed higher incidence of total adverse reactions, especially for the local adverse reactions. Moreover, heterologous ChAd/BNT vaccination showed similar immunogenicity to the homologous BNT/BNT vaccination (GMTR of neutralizing antibody and anti-spike IgG) and similar safety. DISCUSSION: Heterologous ChAd/BNT vaccination showed robust immunogenicity and tolerable safety.

Effectiveness and cost-effectiveness analysis of 11 treatment paths, seven first-line and three second-line treatments for Chinese patients with advanced wild-type squamous non-small cell lung cancer: A sequential model.

Background: A total of 11 treatment sequences for advanced wild-type squamous non-small cell lung cancer are recommended by Chinese Society of Clinical Oncology Guidelines, consisting of seven first-line and three second-line treatments. Five of these treatments were newly approved in China between 2021 and 2022. We evaluated the effectiveness and cost-effectiveness of these strategies from the Chinese healthcare system perspective. Methods: Network meta-analysis with non-proportional hazards was used to calculate the relative efficacy between interventions. A sequential model was developed to estimate costs and quality-adjusted life years (QALY) for treatment sequences with first-line platinum- and paclitaxel-based chemotherapy (SC) with or without nedaplatin, tislelizumab, camrelizumab, sintilimab, sugemalimab or pembrolizumab, followed by second-line docetaxel, tislelizumab or nivolumab. SC and docetaxel were used as comparators for first-line and second-line treatments, respectively. QALY and incremental cost-effectiveness ratio (ICER) were used to evaluate effectiveness and cost-effectiveness, respectively. Cost-effective threshold was set as USD 19,091. Subgroup analysis was conducted to determine the best first-line and second-line therapy. Results: Pembrolizumab + SC, followed by docetaxel (PED) was the most effective treatment sequence. QALYs for patients received SC, nedaplatin + SC, tislelizumab + SC, sintilimab + SC, camrelizumab + SC, sugemalimab + SC, pembrolizumab + SC followed by docetaxel were 0.866, 0.906, 1.179, 1.266, 1.179, 1.266, 1.603, 1.721, 1.807; QALYs for SC, nedaplatin + SC followed by tislelizumab were 1.283, 1.301; QALYs for SC, nedaplatin + SC followed by nivolumab were 1.353, 1.389. Camrelizumab + SC, followed by docetaxel (CAD) was the most cost-effective. Compared to SC with or without nedaplatin, tislelizumab, or sintilimab followed by docetaxel, ICERs of CAD were USD 12,276, 13,210, 6,974, 9,421/QALY, respectively. Compared with nedaplatin or SC followed by tislelizumab, the ICERs of CAD were USD 4,183, 2,804/QALY; CAD was dominant compared with nedaplatin or SC followed by nivolumab; The ICER of sugemalimab + SC followed by docetaxel and PED were USD 522,023, 481,639/QALY compared with CAD. Pembrolizumab + SC and camrelizumab + SC were the most effective and cost-effective first-line options, respectively; tislelizumab was the most effective and cost-effective second-line therapy. Tislelizumab used in second-line was more effective than first-line, no significant differences between their cost-effectiveness. Sensitivity and scenario analysis confirmed robustness of the results. Conclusions: PED and CAD are the most effective and cost-effective treatment sequence, respectively; pembrolizumab + SC and camrelizumab + SC are the most effective and cost-effective first-line choice, respectively; tislelizumab is the most effective and cost-effective second-line choice.

Impact of Extrapolation Model Choices on the Structural Uncertainty in Economic Evaluations for Cancer Immunotherapy: A Case Study of Checkmate 067.

OBJECTIVES: The aim of this study was to compare the performance of different extrapolation modeling techniques and analyze their impact on structural uncertainties in the economic evaluations of cancer immunotherapy. METHODS: The individual patient data was reconstructed through published Checkmate 067 Kaplan Meier curves. Standard parametric models and six flexible techniques were tested, including fractional polynomial, restricted cubic splines, Royston-Parmar models, generalized additive models, parametric mixture models, and mixture cure models. Mean square errors (MSE) and bias from raw survival plots were used to test the model fitness and extrapolation performance. Variability of estimated incremental cost-effectiveness ratios (ICERs) from different models was used to inform the structural uncertainty in economic evaluations. All indicators were analyzed and compared under cut-offs of 3 years and 6.5 years, respectively, to further discuss model impact under different data maturity. R Codes for reproducing this study can be found on GitHub. RESULTS: The flexible techniques in general performed better than standard parametric models with smaller MSE irrespective of the data maturity. Survival outcomes projected by long-term extrapolation using immature data differed from those with mature data. Although a best-performing model was not found because several models had very similar MSE in this case, the variability of modeled ICERs significantly increased when prolonging simulation cycles. CONCLUSIONS: Flexible techniques show better performance in the case of Checkmate 067, regardless of data maturity. Model choices affect ICERs of cancer immunotherapy, especially when dealing with immature survival data. When researchers lack evidence to identify the 'right' model, we recommend identifying and revealing the model impacts on structural uncertainty.

Serplulimab Plus Chemotherapy vs Chemotherapy for Treatment of US and Chinese Patients with Extensive-Stage Small-Cell Lung Cancer: A Cost-Effectiveness Analysis to Inform Drug Pricing.

BACKGROUND: Serplulimab is a potential valuable therapy, while patients, physicians, and decision-makers are uncertain about the cost-effectiveness of this novel drug and its corresponding reasonable price. This study aimed to simulate the price at which serplulimab was cost-effective as first-line therapy for United States (US) and Chinese extensive-stage small-cell lung cancer (ES-SCLC) patients. METHODS: In this economic evaluation, a partitioned survival model was constructed from the perspective of US and Chinese payers. Baseline characteristics of patients and critical clinical data were obtained from ASTRUM-005. Costs and utilities were collected from open-access databases and published literature. Cumulative costs (in US dollars), life years, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were measured and compared. Price simulation was conducted to inform the pricing strategy at the given willingness-to-pay (WTP) threshold. The robustness of the model was assessed via sensitivity analyses and scenario analyses; subgroup analyses were also included. RESULTS: Base-case analysis indicated that serplulimab ($818.16/100 mg) would be cost-effective in the US at the WTP threshold of $150,000, with improved effectiveness of 0.61 QALYs and an additional cost of $64,918 (ICER $106,757). Serplulimab ($818.16/100 mg, patient assistance program considered) was cost-effective in China, with improved effectiveness of 0.58 QALYs and an increased overall cost of $19,369 (ICER $33,392). The price simulation results indicated that serplulimab was favored in the US when the price was less than $762.11/100 mg and $1261.57/100 mg at the WTP threshold of $100,000 and $150,000, respectively; it was cost-effective at the WTP threshold of $38,184 when the price was less than $373.37/100 mg in China. Sensitivity analyses revealed that the above results were stable. Subgroup analysis results indicated an overall trend for subgroups with better survival advantages to have a higher probability of cost-effectiveness, despite serplulimab not being cost-effective in some subgroups. CONCLUSIONS: Serplulimab might be a valuable and cost-effective therapy in both the US and China. The evidence-based pricing strategy provided by this study could benefit decision-makers in making optimal decisions and clinicians in general clinical practice. More evidence about the budget impact and affordability for patients is needed.

Cost-effectiveness analysis of sintilimab vs. placebo in combination with chemotherapy as first-line therapy for local advanced or metastatic oesophageal squamous cell carcinoma.

Objective: Results of Orient 15 indicated the health benefits to patients with local advanced or metastatic oesophageal squamous cell carcinoma (OSCC). This study aimed to evaluate the cost-effectiveness of sintilimab plus chemotherapy in treating OSCC from the perspective of Chinese healthcare system. Methods: A partitioned survival model was constructed to evaluate the cost-effectiveness of sintilimab plus chemotherapy vs. chemotherapy in treating OSCC. Baseline characteristics of patients and key clinical data were extracted from Orient 15. Costs and utilities were collected from published studies and open-access databases. Costs, quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICER) were chosen as economic outcome indicators. We also performed sensitivity analyses and subgroup analyses to verify the stability of results. Results: Combination therapy provided additional 0.84 QALYs and 1.46 life-years with an incremental cost of $25,565.48 than chemotherapy, which had an ICER of $30,409.44 per QALY. The probabilistic sensitivity analysis indicated that combination therapy had a 98.8% probability of cost-effectiveness at the willingness-to-pay threshold (WTP) of $38,184 per QALY. Deterministic sensitivity analysis showed that model outcomes were sensitive to the utilities of progression-free survival and progression disease. The subgroup analysis revealed that combination therapy was cost-effective in patients with high expression of PD-L1 and several specific subgroups. Conclusion: In this economic evaluation, sintilimab plus chemotherapy was likely to be cost-effective compared with chemotherapy in the first-line therapy of advanced OSCC from the perspective of Chinese healthcare system. Our findings may provide evidence for clinicians to make optimal decisions in clinical practice and for decision-makers to evaluate the cost-effectiveness of sintilimab.

A systematic review and network meta-analysis of first-line immune checkpoint inhibitor combination therapies in patients with advanced non-squamous non-small cell lung cancer.

Introduction: Clinical evidence suggests that first-line immune checkpoint inhibitor (ICI) combination therapies can improve survival in patients with advanced non-squamous non-small cell lung cancer (nsq-NSCLC). However, the optimal strategy remains unknown without a systematic comparison of their long-term effects. Methods: We performed a systematic review and network meta-analysis by retrieving up-to-date literature from PubMed® (National Library of Medicine, Bethesda, MD, USA), Embase® (Elsevier, Amsterdam, Netherlands), MEDLINE® (National Library of Medicine), ClinicalTrials.gov (National Library of Medicine), and major international conference publications. Published studies and abstracts comparing first-line ICI combination therapies with other treatments for patients with advanced nsq-NSCLC were included. Restricted mean survival time (RMST) was measured over 12 months for progression-free survival (PFS) and 18 months for overall survival (OS), and the Royston-Parmar model was used to extrapolate and compare data for the long-term outcomes. Results: We included a total of 11 trials involving 12 therapies and 6,130 patients. Pembrolizumab plus chemotherapy exhibited the best overall survival (OS) benefit at both 18 and 60 months [RMST = 2.95, 95% confidence interval (CI) 1.96 to 3.97; life-years gained over a 5-year period = 2.18 years]. Nivolumab plus bevacizumab plus chemotherapy was found to present the best progression-free survival (PFS) benefit at 12 months (RMST 3.02, 95% CI 2.11 to 3.91), whereas atezolizumab plus bevacizumab plus chemotherapy showed the best PFS benefit at 36 months (life-years gained over 3 years = 1.22 years). Subgroup analyses showed that among patients with programmed death-ligand 1 (PD-L1) expression ≥ 50%, atezolizumab plus chemotherapy and nivolumab plus ipilimumab resulted in superior OS benefits at 18 and 60 months, respectively. Among patients with PD-L1 expression< 1%, pembrolizumab plus chemotherapy was associated with OS benefits at both 18 and 60 months. Sintilimab plus chemotherapy was associated with relatively fewer grade ≥ 3 adverse events than other ICI combination therapies. Conclusion: Our results show that ICI combination therapies showed better survival benefits than chemotherapy. Pembrolizumab plus chemotherapy could provide the best OS benefits to patients with advanced nsq-NSCLC, whereas atezolizumab plus bevacizumab plus chemotherapy could bring the best PFS benefits. The optimal ICI combination therapy varies depending on PD-L1 expression level. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=325005, identifier CRD42022325005.

Identifying optimal PD-1/PD-L1 inhibitors in first-line treatment of patients with advanced squamous non-small cell lung cancer in China: Updated systematic review and network meta-analysis.

Objective: After Gemstone-302 was published in Lancet in January 2022, seven PD-(L)1 inhibitors launched or about to be launched in China, but there are no head-to-head RCTs reporting the comparative efficacy for squamous non-small cell lung cancer (sq-NSCLC). Therefore, we aimed to indirectly compare the efficacy of these treatments to provide evidence for clinical decision and Chinese national reimbursement drug listing. Methods: We collected phase III clinical trials targeted on stage IIIB-IV patients for first-line immunotherapy of sq-NSCLC by systematically searching databases. Relative effects of competing treatments were assessed by Bayesian network meta-analysis and non-parametric restricted mean survival time (RMST) model. Hazard ratio (HR), severe adverse events (SAEs, grade 3-5), progression-free survival (PFS) and overall survival (OS) years were the outcomes. Subgroup analysis was done according to PD-(L)1 expression, smoking, gender, Eastern Cooperative Oncology Group performance status, age and disease stage. Sensitivity analysis using the range of parameters distribution as well as different comparison methods was performed to test the robustness of the results. Results: A total of 7 clinical trials with 2,640 patients were included. For OS, the efficiency (HR, 95%CI) ranks from high to low were sugemalimab (0.48, 0.32-0.73), camrelizumab (0.55, 0.40-0.76), sintilimab (0.56, 0.35-0.90), pembrolizumab (0.71, 0.58-0.87) and atezolizumab (0.88, 0.73-1.05). For PFS, the efficiency ranks from high to low were sugemalimab (0.33, 0.24-0.45), camrelizumab (0.37, 0.30-0.46), tislelizumab (0.53, 0.36-0.79), sintilimab (0.54, 0.42-0.69), toripalimab (0.56, 0.38-0.83), pembrolizumab (0.57, 0.47-0.70) and atezolizumab (0.71, 0.59-0.85). Proportional hazard models and non-proportional hazard models showed consistent efficiency ranks. When extrapolated to long-term survival benefit, under non-proportional hazard ratio, sugemalimab achieved the highest PFS benefit (lifeyears, LYs) in 2 years (1.323), with camrelizumab (1.320), sintilimab (1.243), tislelizumab (1.189), pembrolizumab (0.990) and atezolizumab (0.947) ranking in order; Camrelizumab achieved the highest OS benefit (LYs) in 10 years (2.723), with atezolizumab (2.445) and pembrolizumab (2.397) ranking in order. RMST model showed similar results. In terms of safety, PD-(L)1 inhibitors increased the incidence of SAEs when combined with chemotherapy, sugemalimab and camrelizumab was the safest drugs. Conclusion: Sugemalimab is superior both in HR and long-term survival benefit for Chinese patients with advanced sq-NSCLC.

Cost-effectiveness analysis of camrelizumab plus chemotherapy as first-line treatment for advanced squamous NSCLC in China.

Objective: Results of CameL-sq has revealed the clinical benefits to patients with advanced squamous non-small-cell lung cancer (sq-NSCLC). This study aims to evaluate the cost-effectiveness of camrelizumab plus chemotherapy to treat sq-NSCLC from the perspective of the Chinese healthcare system. Methods: We used a partitioned survival model with a lifetime horizon to evaluate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in treating sq-NSCLC. Baseline characteristics of patients and key clinical data were extracted from CameL-sq. Costs and utilities were collected from the open-access database and published literature. Costs, quality-adjusted life-years (QALYs), life-years gained, and incremental cost-effectiveness ratios (ICERs) were chosen as economic outcome indicators. We also performed a sensitivity analysis, subgroup analysis, and scenario analysis to verify the stability of the basic analysis results and explore the results under different scenarios. Results: Combination therapy added 0.47 QALYS and 0.91 life-years with an incremental cost of $6,347.81 compared with chemotherapy, which had an ICER of $13,572 per QALY. The probabilistic sensitivity analysis indicated that camrelizumab plus chemotherapy had a 37.8% probability of cost-effectiveness at a willingness-to-pay threshold (WTP) of 1 time GDP per capital. When WTP was set as 3 times GDP per capital, combination therapy had significant cost-effectiveness. Deterministic sensitivity analysis showed that cost of the best supportive care was the factor with the greatest influence. The subgroup analysis found that combination therapy was associated with cost-effectiveness in several subgroups, namely, patients with disease stage IIIB/IIIC and with PD-L1 tumor proportion score ≤ 1%. Scenario analysis showed that ICER was positively correlated with the price of camrelizumab. Conclusion: In this economic evaluation, camrelizumab plus chemotherapy was unlikely to be cost-effective compared with chemotherapy in the first line therapy of sq-NSCLC from a perspective of the Chinese healthcare system. Reducing the price of camrelizumab and tailoring treatments based on individual patient factors might improve the cost-effectiveness. Our findings may provide evidence for clinicians in making optimal decisions in general clinical practice.

Short-term efficacy of non-pharmacological interventions for global population with elevated blood pressure: A network meta-analysis.

Background: This study aims to compare the potential short-term effects of non-pharmacological interventions (NPIs) on prehypertensive people, and provide evidence for intervention models with potential in future community-based management. Methods: In this Bayesian network meta-analysis, Pubmed, Embase, and Web of science were screened up to 16 October 2021. Prehypertensive patients (systolic blood pressure, SBP 120-139 mmHg/diastolic blood pressure, DBP 80-89 mmHg) with a follow-up period longer than 4 weeks were targeted. Sixteen NPIs were identified during the scope review and categorized into five groups. Reduction in SBP and DBP was selected as outcome variables and the effect sizes were compared using consistency models among interventions and intervention groups. Grade approach was used to assess the certainty of evidence. Results: Thirty-nine studies with 8,279 participants were included. For SBP, strengthen exercises were the most advantageous intervention group when compared with usual care (mean difference = -6.02 mmHg, 95% CI -8.16 to -3.87), and combination exercise, isometric exercise, and aerobic exercise were the three most effective specific interventions. For DBP, relaxation was the most advantageous intervention group when compared with usual care (mean difference = -4.99 mmHg, 95% CI -7.03 to -2.96), and acupuncture, meditation, and combination exercise were the three most effective specific interventions. No inconsistency was found between indirect and direct evidence. However, heterogeneity was detected in some studies. Conclusion: NPIs can bring short-term BP reduction benefits for prehypertensive patients, especially exercise and relaxation. NPIs could potentially be included in community-based disease management for prehypertensive population once long-term real-world effectiveness and cost-effectiveness are proven. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=151518, identifier: CRD42020151518.

Safflower yellow pigment and Sanqi Panax notoginseng in the treatment of acute cerebral infarction: a systematic review, meta-analysis, and cost-effectiveness analysis.

BACKGROUND: Sanqi Panax notoginseng injection and safflower yellow injection were Chinese traditional medicine injections for the treatment of cardiovascular diseases and were used to treat acute cerebral infarction patients in public hospital widely. The aim of this study was to compare and analyze the published reports of efficacy and safety of Sanqi Panax notoginseng injection and safflower yellow injection for the treatment of acute cerebral infarction. The cost-effectiveness of these drug formulations was also evaluated. METHODS: China National Knowledge Infrastructure (CNKI), Wanfang, SinoMed, VIP, PubMed, Embase, and the Chinese Biomedical Literature (CBM) were searched with the restrictions keywords in Chinese and English between 2006 and 2019 to obtain RCTs. A meta-analysis and a meta-regression analysis were undertaken in Reviewer Manager 5.3 software to compare the efficacy and safety of Sanqi Panax notoginseng and safflower yellow injection. This study used a decision tree model to analyze the cost-effectiveness of the two treatments. The TreeAge Pro software was used to comprehensively evaluate the economics of these medications. RESULTS: Twelve papers were all randomized controlled trials (RCTs) in which Sanqi Panax notoginseng injection was applied in the control group, while safflower yellow injection was applied in the experimental group and the quality of them were good. The results of the 12 papers were compared, and the total effective rate of the treatment group (91.18%) was significant and showed no significant difference with the control group (74.83%) (RR =1.24, 95% CI: 1.19, 1.30, P<0.00001). From the perspective of pharmacoeconomics, compared with Sanqi Panax notoginseng group, the ICER of safflower yellow injection is 3,885.75 RMB. The sensitivity analysis results were consistent with the basic analysis results, indicating that the basic analysis results were relatively stable. CONCLUSIONS: Comparing with Sanqi Panax notoginseng injection, safflower yellow injection and related combination therapy can improve the total effective rate and are safer with fewer adverse reactions. It is also more cost-effective than the use of Sanqi Panax notoginseng injection.

Effectiveness and Efficiency of Non-drug Therapy Among Community-Dwelling Adults With Hypertension in China: A Protocol for Network Meta-Analysis and Cost-Effectiveness Analysis.

Introduction: The Chinese government has established a nationwide community-based chronic disease management program since 2009 with hypertension a vital part of it. Though drugs have been proven effective with hypertensive patients, they bring economic burden as well, especially for those who with elevated blood pressure and are potentially eligible for national programs. When the effectiveness of pharmacotherapy-only interventions remains uncertain on these patients, non-pharmacological interventions have demonstrated non-inferior effectiveness and may have economic advantages. To date, there rarely are evidences on the effectiveness and cost-effectiveness of non-pharmacological treatment in comparison with pharmacological interventions for patients with varying severity of blood pressure. This study aims to propose a study for a network meta-analysis and cost-effectiveness analysis to explore what kind of intervention is potentially effective and cost-effective to four specific patient groups, stage I-III hypertensive patients and patients with elevated blood pressure, and to provide recommendations for hypertensive management to Chinese decision makers. Methods: We will systematically search databases (MEDLINE, PubMed, Cochrane Library, etc.,) for randomized controlled trials and observational studies with qualified study design in recent decade that assess the effectiveness of non-pharmacological, pharmacological, or combined intervention aimed at adult populations who are diagnosed with the above four types of hypertension in China. The effectiveness outcomes will include changes in SBP/DBP, rate of comorbidities, mortality, and health related quality of life. We will use network meta-analysis to compare and rank effectiveness of different interventions. Subgroup analyses and meta-regression analyses will be performed to analyze and explain heterogeneity. The economic outcome will include cost-effectiveness based on simulation results from Markov models. Under study perspective of Chinese health system, life-time direct cost will be included. Discussion: This study aims to compare and rank the effectiveness and cost-effectiveness of pharmacological, non-pharmacological and combined interventions for stage I-III hypertensive patients and those who with elevated blood pressure. Compared to existing studies, this comprehensive synthesis of relevant evidences will influence future practice with better efficiency and generalizability for community-based hypertensive management programs in China. The study might also be valuable for other low- and middle-income countries to find their own solutions. PROSPERO registration number: CRD42020151518.