Evaluation of disease-free survival as a predictor of overall survival and assessment of real-world burden of disease recurrence in resected early-stage non-small cell lung cancer.

BACKGROUND: Intermediate endpoints, such as disease-free survival (DFS), have shown good correlation with overall survival (OS) in early-stage non-small cell lung cancer (NSCLC) clinical trials. However, real-world data are limited, and no previous real-world study has quantified the clinical and economic burden of disease recurrence. OBJECTIVE: To examine the association between real-world DFS (rwDFS) and OS and quantify the association between NSCLC recurrence and health care resource utilization (HCRU), health care costs, and OS in patients with resected early-stage NSCLC in the United States. METHODS: Data from the Surveillance, Epidemiology, and End Results-Medicare database (2007-2019) for patients with newly diagnosed stage IB (tumor size ≥ 4 cm) to IIIA (American Joint Committee on Cancer 7th edition) NSCLC who underwent surgery for primary NSCLC were analyzed in this retrospective observational study. Baseline patient demographic and clinical characteristics were described. rwDFS and OS were compared between patients with vs without recurrence using Kaplan-Meier curves and the log-rank test; their correlation was assessed using normal scores rank correlation. All-cause and NSCLC-related HCRU and health care costs were summarized, and mean monthly allcause and NSCLC-related health care costs were compared between cohorts using generalized linear models. RESULTS: Of the 1,761 patients who underwent surgery, 1,182 (67.1%) had disease recurrence; these patients had shorter OS from the index date and shorter subsequent OS at each postsurgery landmark (ie, 1, 3, and 5 years) than those without recurrence (all P < 0.001). OS and rwDFS were significantly correlated (0.57; P < 0.001). Patients with recurrence also had significantly higher all-cause and NSCLC-related HCRU and mean monthly all-cause and NSCLC-related health care costs during the study period. CONCLUSIONS: Postsurgery rwDFS was significantly correlated with OS in patients with early-stage NSCLC. Patients with postsurgery recurrence had a higher risk of death and incurred higher HCRU and health care costs than those without recurrence. These findings highlight the importance of preventing or delaying recurrence in patients with resected NSCLC. DISCLOSURES: Dr West is Senior Medical Director at AccessHope and an Associate Professor at City of Hope. He also serves on the advisory board for Amgen, AstraZeneca, Genentech/Roche, Gilead, Merck, Mirati Therapeutics, Regeneron, Summit Therapeutics, and Takeda and as a speaker for AstraZeneca and Merck. Drs Hu, Chirovsky, and Samkari are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and own stock/stock options in Merck & Co., Inc., Rahway, NJ, USA. Drs Zhang, Song, Gao, and Signorovitch, Mr Lerner, and Ms Jiang are employees of Analysis Group, Inc., a consulting company that has provided paid consulting services to Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, which funded the development and conduct of this study and article. This study used the linked SEER-Medicare database. The interpretation and reporting of these data are the sole responsibility of the authors. The collection of cancer incidence data used in this study was supported by the California Department of Public Health pursuant to California Health and Safety Code Section 103885; Centers for Disease Control and Prevention's National Program of Cancer Registries, under cooperative agreement 5NU58DP006344; the National Cancer Institute's SEER Program under contract HHSN261201800032I awarded to the University of California, San Francisco, contract HHSN261201800015I awarded to the University of Southern California, and contract HHSN261201800009I awarded to the Public Health Institute. The ideas and opinions expressed herein are those of the authors and do not necessarily reflect the opinions of the State of California, Department of Public Health, the National Cancer Institute, and the Centers for Disease Control and Prevention or their contractors and subcontractors.

Clinical and economic impact of recurrence in early-stage non-small-cell lung cancer following complete resection.

Aim: Real-world data on outcomes for early-stage non-small-cell lung cancer (NSCLC) are needed to better understand the benefits of new therapies. Methods: In this retrospective study using the ConcertAI Patient360™ database, overall survival and healthcare resource utilization were compared among patients with recurrent and non-recurrent completely resected stage IB-IIIA NSCLC. Results: Recurrence was associated with a shorter median overall survival compared with non-recurrence (31.5 months vs 75.6 months, respectively), lower survival probability 5-years post-resection, and higher healthcare resource utilization. Patients with late recurrence had a longer restricted mean survival time versus patients with early recurrence. Conclusion: Results from this real-world study highlight the potential value of preventing or delaying recurrence in patients with early-stage NSCLC.

This study looked at how people with early-stage non-small-cell lung cancer did after surgery to completely remove the disease. It compared two groups of patients: those whose disease came back after surgery and those whose disease did not come back after surgery. The group of people whose disease came back after surgery did not live as long as those whose disease did not come back after surgery (31.5 months vs 75.6 months). Patients whose disease came back had a lower chance of living at least 5 years after surgery and they had more hospital visits and doctor's office visits. In addition, those whose disease came back within 1 year did not live as long as those whose disease came back between 1 and 5 years after surgery. Preventing or delaying the return of disease after surgery is important for improving the lives of patients with early-stage non-small-cell lung cancer.

Treatment Patterns and Outcomes in Resected Early-stage Non-small Cell Lung Cancer: An Analysis of the SEER-Medicare Data.

BACKGROUND: As the non-small cell lung cancer (NSCLC) adjuvant treatment landscape evolves, an evaluation of treatment patterns and outcomes of patients with early-stage, resected NSCLC eligible for adjuvant treatment in routine clinical practice is needed to better understand the unmet needs in this patient population. MATERIALS AND METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2019) were used to identify patients with newly diagnosed stage IB (tumor size ≥4cm)-IIIA (AJCC 7th edition) NSCLC who received primary surgery (index date). We assessed adjuvant treatment patterns, real-world disease-free survival (rwDFS; time from index date to first recurrence or death) and overall survival (OS; time from index date to death), and loco-regional recurrence pattern and treatment distribution. RESULTS: Among 1761 patients with primary surgery, mean age was 73.8 years; 47.9% were male; and 83.9% were white. Approximately 41% of patients received adjuvant chemotherapy; median time from surgery to adjuvant chemotherapy initiation was 48 days, and the most frequently observed adjuvant chemotherapy regimen was carboplatin+paclitaxel (24.5%). In the overall population, median rwDFS was 24.8 months and OS was 76.7 months; 5-year rwDFS and OS rates were 29.3% and 57.5%, respectively. Among 392 patients with loco-regional recurrence, the most frequently observed treatment was curative radiation monotherapy (28.2%). CONCLUSION: Despite clinical guideline recommendations, rate of adjuvant chemotherapy among patients with resected early-stage NSCLC was low in clinical practice. Overall, among patients with early-stage NSCLC treated with conventional primary surgery, poor survival outcomes were observed, highlighting the need for and importance of more effective adjuvant treatments.

Impact of the implementation of carbon emission trading on corporate financial performance: Evidence from listed companies in China.

With the development of ecological paradigm coupled with the relentless implementation of myriad environmental policies in China, the rapid development of carbon emission trading and carbon trading market has had a vital impact on the financial performance of enterprises at the microlevel. This study has sampled the A-share listed companies in China, from 2009 to 2018, and adopted the difference-in-difference (DID) method to investigate the effect of the carbon emission trading on corporate financial performance from the microlevel. Evidence showed that the implementation of carbon emission trading effectively improved the total asset-liability ratio of enterprises, though it reduced the value of the current capital market. Moreover, in the regions under strict legal environment, the enhancement effect of the total asset-liability ratio was more obvious, whereas in the regions under loose legal environment, the reduction effect of the value of the capital market was more obvious. Further analysis showed that the implementation of carbon emission trading could not promote Chinese enterprises to increase R&D investment. Hence the implementation of carbon emission trading has improved the level of non-business income of enterprises incorporated into the trading system, but its impact on the investment income of enterprises was not significant.

The effect of environmental regulations on innovation in heavy-polluting and resource-based enterprises: Quasi-natural experimental evidence from China.

Environmental protection regulations adopted by governments affect the microeconomic behavior of enterprises. The Chinese government began piloting the outgoing leading officials' accountability audit of natural resources assets (OANRA) in some regions in 2014. Based on this quasi-natural experimental setting, this paper chose heavy-polluting and resource-based enterprises in pilot regions of China from 2011 to 2016 as examples for studying the impact of the OANRA on enterprise innovation and further examines the role of government subsidies in this process. The study finds that the OANRA has no significant impact on enterprise innovation. However, with support from government subsidies, the OANRA dramatically accelerates enterprise innovation investment. The results are still seen after applying propensity matching analysis (PSM), balancing panel data and deleting special provinces. Further analysis shows that this effect is more obvious among small-scale, state-owned enterprises that are located in areas with high degrees of marketization and high bank credit constraints. This study advances the research of the OANRA's effects on the microeconomic behavior of enterprises. Moreover, the adjustment effect of government subsidies also provides great reference value to making rational use of policy to cooperate with the OANRA.

A privacy protection method for health care big data management based on risk access control.

With the rapid development of modern information technology, the health care industry is entering a critical stage of intelligence. Faced with the growing health care big data, information security issues are becoming more and more prominent in the management of smart health care, especially the problem of patient privacy leakage is the most serious. Therefore, strengthening the information management of intelligent health care in the era of big data is an important part of the long-term sustainable development of hospitals. This paper first identified the key indicators affecting the privacy disclosure of big data in health management, and then established the risk access control model based on the fuzzy theory, which was used for the management of big data in intelligent medical treatment, and solves the problem of inaccurate experimental results due to the lack of real data when dealing with actual problems. Finally, the model is compared with the results calculated by the fuzzy tool set in Matlab. The results verify that the model is effective in assessing the current safety risks and predicting the range of different risk factors, and the prediction accuracy can reach more than 90%.

Trends in the Price per Median and Mean Life-Year Gained Among Newly Approved Cancer Therapies 1995 to 2017.

BACKGROUND: The prices of newly approved cancer drugs have risen over the past decades. A key policy question is whether the clinical gains offered by these drugs in treating specific cancer indications justify the price increases. OBJECTIVES: To evaluate the price per median and mean life year gained among newly approved cancer therapies from 1995 to 2017. METHODS: We collected data on the price (in 2017 USD) per life-year gained among cancer drug-indication pairs approved by the US Food and Drug Administration (FDA) between 1995 and 2017. We modeled trends using fractional polynomial and linear spline regression models that controlled for route of administration and cancer type fixed effects. RESULTS: We found that between 1995 and 2012, price increases outstripped median survival gains, a finding consistent with previous literature. Nevertheless, price per mean life-year gained increased at a considerably slower rate, suggesting that new drugs have been more effective in achieving longer-term survival. Between 2013 and 2017, price increases reflected equally large gains in median and mean survival, resulting in a flat profile for benefit-adjusted launch prices in recent years. CONCLUSIONS: Although drug costs have been rising more rapidly than median survival gains, they have been rising at about the same rate as mean survival gains. This suggests that when accounting for longer-term survival gains, the benefits of new drugs are roughly keeping pace with their costs, despite rapid cost growth.

Non-professional caregiver burden is associated with the severity of patients' cognitive impairment.

BACKGROUND/OBJECTIVES: To analyse the relationship between caregiver burden and severity of patients' cognitive impairment. DESIGN: Data were drawn from the cross-sectional 2015/2016 Adelphi Real World Dementia Disease-Specific Programme. SETTING: This research was multi-national and studied physicians and their consulting patients with cognitive impairment. PARTICIPANTS: 1,201 caregivers completed self-assessment forms. MEASUREMENTS: Validated instruments of caregiver wellbeing and burden (EQ-5D-3L questionnaire, EQ-VAS, Zarit Burden Interview, and Work Productivity and Activity Impairment questionnaire) and number of caregiver hours were analysed by severity of patients' cognitive impairment, categorised according to the Mini-Mental State Examination. Data were analysed using Spearman's rank correlation coefficients and ordinary least squares regression models, to compare outcomes between caregivers of patients with prodromal, mild, moderate, and severe dementia. RESULTS: The majority of caregivers were female (69.1%), lived with the patient they cared for (75.8%), and only approximately one third (28.3%) were in part- or full-time employment. There were statistically significant (p<0.001) increases in caregiver time (36.9 versus 108.6 hours per week for prodromal versus severe dementia, respectively) and measures of caregiver burden and health status (EQ-5D-3L, EQ-VAS, and Zarit Burden Interview) and increases in measures of work productivity and activity impairment with increasing severity of patients' disease. CONCLUSION: This study of real-world data confirmed an association between increased caregiver burden and severity of patients' cognitive impairment by analysis of a wide range of validated measures of caregiver burden. These findings suggest that maintaining patients in the earliest stages of their disease for as long as possible may potentially help to protect caregiver wellbeing, although further research is required to confirm this hypothesis.

First-line pembrolizumab in PD-L1 positive non-small-cell lung cancer: A cost-effectiveness analysis from the UK health care perspective.

BACKGROUND: Pembrolizumab has shown significant survival benefits in treating chemotherapy-naïve non-small-cell lung cancer patients (NSCLC) with increased level of PD-L1 expression. This analysis aimed to evaluate the cost-effectiveness of pembrolizumab as a first-line treatment for patients with PD-L1 positive NSCLC from the UK health care perspective. METHODS: A Markov model with progression-free, progressive disease and death states was developed. Clinical parameters were informed by the KEYNOTE-024 trial. Utility values were sourced from published literature. Cost data including drug acquisition costs, disease management costs, and adverse event costs were derived from British National Formulary and published literature. The model was run until 99% patients died. Both health outcomes and costs were discounted at an annual rate of 3.5%. Deterministic and probabilistic sensitivity analyses were performed to address the uncertainties around model parameters. RESULTS: In the base case, pembrolizumab is projected to increase patient's life expectancy by 1.32 life-years over chemotherapy (2.45 vs. 1.13) and 0.83 QALYs (1.55 vs. 0.71) at an additional cost of £72,465, yielding an incremental cost-effectiveness ratio of £86,913/QALY. When parameters were varied in the deterministic sensitivity analyses, results are most sensitive to duration of median overall survival in both groups. Probability sensitivity analyses showed that using a willingness-to-pay threshold of £50,000 per QALY, the probability of pembrolizumab being cost-effective is 29.4%. CONCLUSION: Using a willingness-to-pay threshold of £50,000, pembrolizumab is not cost-effective at its current list price and a discount of 50% or more is required for it to be cost-effective comparing to commonly prescribed chemotherapy. Risk-sharing contracts may be helpful in resolving some of the underlying uncertainty associated with the long-term survival and varying extent of patient response.

Economic Burden, Mortality, and Institutionalization in Patients Newly Diagnosed with Alzheimer's Disease.

BACKGROUND: Current information is scarce regarding comorbid conditions, treatment, survival, institutionalization, and health care utilization for Alzheimer's disease (AD) patients. OBJECTIVES: Compare all-cause mortality, rate of institutionalization, and economic burden between treated and untreated newly-diagnosed AD patients. METHODS: Patients aged 65-100 years with ≥1 primary or ≥2 secondary AD diagnoses (ICD-9-CM:331.0] with continuous medical and pharmacy benefits for ≥12 months pre-index and ≥6 months post-index date (first AD diagnosis date) were identified from Medicare fee-for-service claims 01JAN2011-30JUN2014. Patients with AD treatment claims or AD/AD-related dementia diagnosis during the pre-index period were excluded. Patients were assigned to treated and untreated cohorts based on AD treatment received post-index date. Total 8,995 newly-diagnosed AD patients were identified; 4,037 (44.8%) were assigned to the treated cohort. Time-to-death and institutionalization were assessed using Cox regression. To compare health care costs and utilizations, 1 : 1 propensity score matching (PSM) was used. RESULTS: Untreated patients were older (83.85 versus 81.44 years; p < 0.0001), with more severe comorbidities (mean Charlson comorbidity index: 3.54 versus 3.22; p < 0.0001). After covariate adjustment, treated patients were less likely to die (hazard ratio[HR] = 0.69; p < 0.0001) and were associated with 20% lower risk of institutionalization (HR = 0.801; p = 0.0003). After PSM, treated AD patients were less likely to have hospice visits (3.25% versus 9.45%; p < 0.0001), and incurred lower annual all-cause costs ($25,828 versus $30,110; p = 0.0162). CONCLUSION: After controlling for comorbidities, treated AD patients have better survival, lower institutionalization, and sometimes fewer resource utilizations, suggesting that treatment and improved care management could be beneficial for newly-diagnosed AD patients from economic and clinical perspectives.

Systematic review of clinical, humanistic, and economic outcome comparisons between radiographic and non-radiographic axial spondyloarthritis.

OBJECTIVE: To evaluate similarities and differences between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) with regard to treatment effects and clinical, humanistic, and economic burdens. METHODS: In this systematic literature review, ACR 2015, EULAR 2015, EMBASE, and PubMed were searched for studies published between January 2010 and September 2015 that compared predefined clinical, humanistic, and economic aspects in nr-axSpA and AS. Publications were processed according to PRISMA guidelines, analyzed according to four research questions, and assessed for the GRADE level of evidence. RESULTS: Of 220 titles screened, 50 studies were evaluable. Treatment effects were reported by 22; clinical, humanistic, and economic burdens were specified by 38, 4, and 0, respectively. Fewer patients with increased C-reactive protein levels, less extensive structural damage, slower radiographic progression, and significantly lower Bath AS Metrology and Bath AS Functional Indices were reported for nr-axSpA than for AS. In contrast, the Bath AS Disease Activity Index, AS Disease Activity Score, and health-related quality of life were similar, indicating comparable clinical and humanistic burdens. Response to conventional therapies and TNFα inhibitors was similar between nr-axSpA and AS patients, although TNFα inhibitors were prescribed less frequently to nr-axSpA patients. CONCLUSIONS: Whether nr-axSpA is regarded as an early form of AS or as a distinct disease entity, it represents an important subgroup of axSpA. Ongoing clinical trials may provide the required evidence for a specified indication for TNFα inhibitors, important to prevent off-label use. Further research is crucial to better understand the disease spectrum and predictors of progression.

Burden of illness associated with non-radiographic axial spondyloarthritis: a multiperspective European cross-sectional observational study.

OBJECTIVES: To assess the impact of non-radiographic axial spondyloarthritis (nr-axSpA) on patients and society based on real-world evidence from the Adelphi nr-axSpA Disease Specific Programme, a cross-sectional survey of rheumatologists and their patients in Germany, France, Spain, Italy and the UK. METHODS: Physicians completed patient record forms for the next two patients consulting with nr-axSpA (diagnosis at the physician's judgement); patients were invited to complete a patient self-completion form. Outcomes were assessed in responders and non-responders and those treated with and without biological agents. RESULTS: In total, 631 patients were included. Fulfilment of classification criteria varied across countries. Assessment of SpondyloArthritis international Society classification criteria were most commonly met; other criteria, including Amor and European Spondyloarthropathy Study Group criteria, were applied less frequently. Most German and UK patients had their condition classified without formal criteria. Despite being diagnosed with nr-axSpA, 13% of patients met the criteria for ankylosing spondylitis. EuroQol 5-Dimensions (3L) utility scores were lower in patients with nr-axSpA versus general population matched controls (0.776 vs. 0.884; p<0.001); non-responders to treatment had impaired activity (as measured by the Work Productivity and Activity Impairment questionnaire) of 47.4% versus 33.3% in responders (p<0.001). Clinical outcomes were consistently better in biological-treated versus -naïve patients. Average pretreatment pain levels were 6.6 and 6.2, respectively (p=0.072) but reduced to 2.5 and 4.0, respectively (p<0.001) at the time of the survey. CONCLUSIONS: nr-axSpA was associated with a significant QoL and societal burden in this study of German, French, Spanish, Italian and UK patients. Treatment with biological agents was associated with improved QoL. Considerable variability in patients' clinical characteristics were observed across the countries studied and further education, aimed at improving awareness of the condition, may be needed.

Cost utility analysis of urethral bulking agents versus midurethral sling in stress urinary incontinence.

OBJECTIVE: The aim of this study was to determine the cost utility of urethral bulking agents (BA) compared with midurethral slings (MUS) in the treatment of stress urinary incontinence (SUI) in patients without urethral hypermobility. METHODS: A decision tree was constructed to compare the cost utility of urethral BA versus MUS in the setting of SUI without urethral hypermobility. Probability estimates for success, failure, and complications were obtained from the published literature. Immediate-term, short-term, and longer-term complications were accounted for over a 1-year time horizon in the model. One-way and 2-way sensitivity analyses and Monte Carlo simulations were performed to assess the robustness of our results. RESULTS: Our model demonstrated that MUS cost $436,465 more than BA for every 100 women treated in 1 year. Using MUS compared with BA leads to an incremental cost-effectiveness ratio of $70,400 per utility gained. Assuming a willingness to pay of $50,000, this makes MUS not cost-effective as a first-line treatment in many situations. When MUS costs less than $5132, it becomes a cost-effective first-line treatment, and when it costs less than $2035, it is cost saving. CONCLUSIONS: Bulking agents are more cost-effective than MUS over a 1-year time horizon in the treatment of SUI in patients without urethral hypermobility. In women who lack urethral hypermobility, BA remain a cost-effective option in this patient population.