Cost-effectiveness of precision screening for esophageal cancer based on individualized risk stratification in China: Real-world evidence from the ESECC trial.

Background: Conventional universal endoscopic screening with pathology-based endoscopic re-examination for esophageal squamous cell carcinoma is in need of reform in China. We established a "two-step" precision screening strategy using two risk prediction models and have evaluated the cost-effectiveness of this precision strategy compared with the traditional strategy based on a large population-level randomized controlled trial from a healthcare provider's perspective. Methods: Four precision screening strategies with different risk cutoffs at baseline screening and endoscopic surveillance were constructed, and then compared with traditional strategy through modeling using subjects from the screening cohort of the ESECC (Endoscopic Screening for Esophageal Cancer in China) trial. Total screening costs and the number of SDA (severe dysplasia and above in lesions of the esophagus) cases were obtained to calculate the average screening cost per SDA detected, the incremental cost-effectiveness ratio (ICER) and protection rates. Sensitivity analysis was conducted to evaluate uncertainties. Results: Compared to traditional strategy, all precision screening strategies have much lower average costs for detection of one SDA case ($7,148~$11,537 vs. $14,944). In addition, precision strategies 1&2 (strategies 1,2,3,4 described below) achieved higher effectiveness (143~150 vs. 136) and higher protection rates (87.7%~92.0% vs. 83.4%) at lower cost ($1,649,727~$1,672,221 vs. $2,032,386), generating negative ICERs (-$54,666/SDA~-$25,726/SDA) when compared to the traditional strategy. The optimal strategies within different willingness-to-pay (WTP) ranges were all precision screening strategies, and higher model sensitivities were adopted as WTP increased. Conclusions: Precision screening strategy for esophageal cancer based on risk stratification is more cost-effective than use of traditional screening strategy and has practical implications for esophageal cancer screening programs in China.

Economic Burden Conferred by Population-Level Cancer Screening on Resource-Limited Communities: Lessons From the ESECC Trial.

Objectives: Upper gastrointestinal (G.I.) cancer screening has been conducted in China for decades. However, the economic burden for treatment "intensively" occurred in advance due to screening in resource-limited communities remain unclear. Methods: We compared the treatment costs for upper G.I. cancers from the screening and control arms of a population-based randomized trial in a high-risk area for esophageal cancer (EC) in China based on claims data from the health insurance system in the local area which included whole population coverage. Results: The average out-of-pocket cost per treatment of EC in the screening arm was lower than that in the control arm ($5,972 vs. $7,557). This difference was a consequence of down-staging from screening which resulted in lower cost therapy for earlier stage cancers. Moreover, this result is similar for cardial and non-cardial gastric cancer in the two study arms ($7,933 vs. $10,605). However, three times as many (103 vs. 36) families in the screening arm suffered catastrophic health expenditure for all cancer types. The overall treatment cost for all EC patients in the screening arm ($1,045,119) was 2.44 times that in the control arm ($428,292), and the ratio for cardial and non-cardial gastric cancer was 1.12 ($393,261 vs. $351,557). Conclusion: Cancer treatment secondary to screening may triple the likelihood of catastrophic patient medical expenditure, and sharply increase the economic pressure on the local community, particularly for cancer types which are of high prevalence. Financial support for patients and the health insurance system should be taken into consideration when planning budgets for cancer screening programs in communities which are resource-limited.

An evaluation of EQ-5D-3L health utility scores using five country-specific tariffs in a rural population aged 45-69 years in Hua county, Henan province, China.

BACKGROUND: This study aims to compare the performance of the recently developed Chinese (city) tariff of the EQ-5D-3L against the UK, US, Japanese and Korean tariffs in a general rural population in China. METHODS: From November 2015 to September 2016, 12,085 permanent residents aged 45-69 from 257 villages randomly selected from Hua County, Henan Province, China, were interviewed using EQ-5D-3L, and a one-on-one questionnaire investigation was used to collect data on factors associated with HRQOL. The health utility scores were calculated using the UK, US, Japanese, Korean and Chinese (city) tariffs. The agreement, known-groups validity and sensitivity of these five tariffs were evaluated. Transition scores for pairs of observed EQ-5D-3L health states were calculated and compared. RESULTS: The Korean tariff yielded the highest mean health utility score (0.963), followed by the Chinese (city) (0.948), US (0.943), UK (0.930) and Japanese (0.921) tariffs, but the differences in the scores of any two tariffs did not exceed the MCID. The Chinese (city) tariff showed higher ICC values (ICCs> 0.89, 95% CI:0.755-0.964) and narrower limits of agreement (0.099-0.167) than the Korean tariff [(ICCs> 0.71, 95% CI:0.451-0.955); (0.146-0.253)]. The Chinese (city) tariff had a higher relative efficiency and effect size statistics in 10 out of 11 variables as compared to the UK, US and Japanese tariffs. The Chinese (city) tariff (0.215) was associated with moderate mean absolute transition scores compared with the UK (0.342), US (0.230), Japanese (0.149) and Korean (0.189) tariffs for 1485 observed pairs of the EQ-5D-3L health states. CONCLUSIONS: Health utility scores derived from the five tariffs differed. The Chinese (city) tariff was the most suitable of these tariffs and was without obvious weakness. We recommend adopting the Chinese (city) tariff when applying EQ-5D-3L to assess quality of life among the elderly in China's agricultural region with socio-economic status similar to Hua County. Results of this study had provided a crucial basis for health surveys, health promotion projects, health intervention trials, and health economic evaluation taking HRQOL as a target in rural areas of China.

Assessment of Water and Nitrogen Use Efficiencies Through UAV-Based Multispectral Phenotyping in Winter Wheat.

Unmanned aerial vehicle (UAV) based remote sensing is a promising approach for non-destructive and high-throughput assessment of crop water and nitrogen (N) efficiencies. In this study, UAV was used to evaluate two field trials using four water (T0 = 0 mm, T1 = 80 mm, T2 = 120 mm, and T3 = 160 mm), and four N (T0 = 0, T1 = 120 kg ha-1, T2 = 180 kg ha-1, and T3 = 240 kg ha-1) treatments, respectively, conducted on three wheat genotypes at two locations. Ground-based destructive data of water and N indictors such as biomass and N contents were also measured to validate the aerial surveillance results. Multispectral traits including red normalized difference vegetation index (RNDVI), green normalized difference vegetation index (GNDVI), normalized difference red-edge index (NDRE), red-edge chlorophyll index (RECI) and normalized green red difference index (NGRDI) were recorded using UAV as reliable replacement of destructive measurements by showing high r values up to 0.90. NGRDI was identified as the most efficient non-destructive indicator through strong prediction values ranged from R 2 = 0.69 to 0.89 for water use efficiencies (WUE) calculated from biomass (WUE.BM), and R 2 = 0.80 to 0.86 from grain yield (WUE.GY). RNDVI was better in predicting the phenotypic variations for N use efficiency calculated from nitrogen contents of plant samples (NUE.NC) with high R 2 values ranging from 0.72 to 0.94, while NDRE was consistent in predicting both NUE.NC and NUE.GY by 0.73 to 0.84 with low root mean square errors. UAV-based remote sensing demonstrates that treatment T2 in both water 120 mm and N 180 kg ha-1 supply trials was most appropriate dosages for optimum uptake of water and N with high GY. Among three cultivars, Zhongmai 895 was highly efficient in WUE and NUE across the water and N treatments. Conclusively, UAV can be used to predict time-series WUE and NUE across the season for selection of elite genotypes, and to monitor crop efficiency under varying N and water dosages.

Development and validation of high-throughput and low-cost STARP assays for genes underpinning economically important traits in wheat.

KEY MESSAGE: We developed and validated 56 gene-specific semi-thermal asymmetric reverse PCR (STARP) markers for 46 genes of important wheat quality, biotic and abiotic stress resistance, grain yield, and adaptation-related traits for marker-assisted selection in wheat breeding. Development of high-throughput, low-cost, gene-specific molecular markers is important for marker-assisted selection in wheat breeding. In this study, we developed 56 gene-specific semi-thermal asymmetric reverse PCR (STARP) markers for wheat quality, tolerance to biotic and abiotic stresses, grain yield, and adaptation-related traits. The STARP assays were validated by (1) comparison of the assays with corresponding diagnostic STS/CAPS markers on 40 diverse wheat cultivars and (2) characterization of allelic effects based on the phenotypic and genotypic data of three segregating populations and 305 diverse wheat accessions from China and 13 other countries. The STARP assays showed the advantages of high-throughput, accuracy, flexibility, simple assay design, low operational costs, and platform compatibility. The state-of-the-art assays of this study provide a robust and reliable molecular marker toolkit for wheat breeding programs.

Precision screening for esophageal squamous cell carcinoma in China.

Esophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal cancer in China, and this neoplasm is associated with high morbidity and mortality as well as clear geographical heterogeneity. Since primary prevention for ESCC lacks a clear intervention target, secondary prevention, also known as screening and early diagnosis and early treatment, has become the mainstay of ESCC prevention and control in China. ESCC screening in China has been subject to decades of evaluation and practice. However, the ESCC screening strategy currently adopted in China has encountered a developmental bottleneck. In this review, we have summarized studies and significant findings for ESCC screening and proposed advancement of screening strategies as follows: 1) evidence from randomized controlled trials is needed to support the effectiveness and health economic value of endoscopic screening for ESCC; 2) the current traditional screening and surveillance strategies warrant reform, and a risk-prediction-based precision strategy should be established; and 3) a deeper understanding of the value of opportunistic screening in the prevention and control of ESCC in China is called for. Due to the low absolute prevalence of precancerous lesions, substantial investment of resources and nonnegligible risks of invasive screening techniques, precision and individualization should be the main direction of cancer screening programs for the future. We advocate cooperation on the part of Chinese scientists to solve this major China-specific health problem in the next decades.

Using health insurance reimbursement data to identify incident cancer cases.

OBJECTIVES: The objective of this study was to establish an optimal population-level follow-up strategy for identifying incident cancers using health insurance reimbursement data in rural China. STUDY DESIGN AND SETTING: We compared active follow-up and passive linkage with claims data for identification of incident cancer cases. Claims data were derived from the New Rural Cooperative Medical Scheme (NCMS). Follow-up data from subject enrollment to December 31, 2016, regarding 33,948 subjects in a large-scale randomized controlled trial were used in this study. RESULTS: The overall sensitivity of passive linkage with NCMS claims data was significantly higher than that of active follow-up (95.6% vs. 54.9%, P < 0.001). Of 12 cases missed by the NCMS data set, seven were treated on an outpatient basis and there were therefore no records in the NCMS system, and five were diagnosed at primary (township-level) health facilities and excluded from the quality control process. Of the 123 cases missed by active follow-up, 54 were reported as negative, 69 were reported as positive but had inaccurate information regarding the site of cancer, or exceeded the 6-month limitation from the date of diagnosis. CONCLUSION: Passive linkage with NCMS claims data is an efficient approach for identifying incident cancers in areas without cancer registries in rural China.

Accuracy assessment of plant height using an unmanned aerial vehicle for quantitative genomic analysis in bread wheat.

BACKGROUND: Plant height is an important selection target since it is associated with yield potential, stability and particularly with lodging resistance in various environments. Rapid and cost-effective estimation of plant height from airborne devices using a digital surface model can be integrated with academic research and practical wheat breeding programs. A bi-parental wheat population consisting of 198 doubled haploid lines was used for time-series assessments of progress in reaching final plant height and its accuracy was assessed by quantitative genomic analysis. UAV-based data were collected at the booting and mid-grain fill stages from two experimental sites and compared with conventional measurements to identify quantitative trait loci (QTL) underlying plant height. RESULTS: A significantly high correlation of R 2 = 0.96 with a 5.75 cm root mean square error was obtained between UAV-based plant height estimates and ground truth observations at mid-grain fill across both sites. Correlations for UAV and ground-based plant height data were also very high (R 2 = 0.84-0.85, and 0.80-0.83) between plant height at the booting and mid-grain fill stages, respectively. Broad sense heritabilities were 0.92 at booting and 0.90-0.91 at mid-grain fill across sites for both data sets. Two major QTL corresponding to Rht-B1 on chromosome 4B and Rht-D1 on chromosome 4D explained 61.3% and 64.5% of the total phenotypic variations for UAV and ground truth data, respectively. Two new and stable QTL on chromosome 6D seemingly associated with accelerated plant growth was identified at the booting stage using UAV-based data. Genomic prediction accuracy for UAV and ground-based data sets was significantly high, ranging from r = 0.47-0.55 using genome-wide and QTL markers for plant height. However, prediction accuracy declined to r = 0.20-0.31 after excluding markers linked to plant height QTL. CONCLUSION: This study provides a fast way to obtain time-series estimates of plant height in understanding growth dynamics in bread wheat. UAV-enabled phenotyping is an effective, high-throughput and cost-effective approach to understand the genetic basis of plant height in genetic studies and practical breeding.

Estimation of Cost for Endoscopic Screening for Esophageal Cancer in a High-Risk Population in Rural China: Results from a Population-Level Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Population-level endoscopic screening for esophageal cancer has been conducted in China for years. In this study, we aim to provide an updated and precise cost estimation for esophageal cancer screening based on a randomized controlled trial in a high-risk area in China. METHODS: We estimated the cost of esophageal cancer screening with chromoendoscopy using a micro-costing approach based on primary data of the ESECC (Endoscopic Screening for Esophageal Cancer in China) randomized controlled trial (NCT01688908) from a health sector perspective. Unit costs and quantities of resources were collected to obtain annual screening costs. The screening project was then theoretically expanded to a 10-year period to explore long-term trends of costs. Costs were adjusted to US dollars for the year 2018. RESULTS: In the ESECC trial, screening cost per endoscopy with a valid pathologic diagnosis was $196, accounting for 3.82% of the gross domestic product per capita in Hua County, and the costs for detecting one esophageal cancer and one early-stage esophageal cancer were $26,347 and $37,687, respectively. In conventional screening in which protocol-driven costs were excluded, costs as above were $134, $18,074, and $25,853. The cost for detecting one gastric cardia cancer or stomach cancer was nine times higher than detecting one esophageal cancer owing to low prevalences of the two cancers. In a simulated 10-year screening project, annual cost decreased notably over time. CONCLUSIONS: Despite the relatively low absolute cost, population-level endoscopic screening will still be a heavy burden on local government considering the socioeconomic conditions. Long-lasting programs would be less costly and population-level screening would make little sense in non-high-risk regions.

Development and validation of KASP assays for genes underpinning key economic traits in bread wheat.

KEY MESSAGE: We developed and validated a robust marker toolkit for high-throughput and cost-effective screening of a large number of functional genes in wheat. Functional markers (FMs) are the most valuable markers for crop breeding programs, and high-throughput genotyping for FMs could provide an excellent opportunity to effectively practice marker-assisted selection while breeding cultivars. Here we developed and validated kompetitive allele-specific PCR (KASP) assays for genes that underpin economically important traits in bread wheat including adaptability, grain yield, quality, and biotic and abiotic stress resistances. In total, 70 KASP assays either developed in this study or obtained from public databases were validated for reliability in application. The validation of KASP assays were conducted by (a) comparing the assays with available gel-based PCR markers on 23 diverse wheat accessions, (b) validation of the derived allelic information using phenotypes of a panel comprised of 300 diverse cultivars from China and 13 other countries, and (c) additional testing, where possible, of the assays in four segregating populations. All KASP assays being reported were significantly associated with the relevant phenotypes in the cultivars panel and bi-parental populations, thus revealing potential application in wheat breeding programs. The results revealed 45 times superiority of the KASP assays in speed than gel-based PCR markers. KASP has recently emerged as single-plex high-throughput genotyping technology; this is the first report on high-throughput screening of a large number of functional genes in a major crop. Such assays could greatly accelerate the characterization of crossing parents and advanced lines for marker-assisted selection and can complement the inflexible, high-density SNP arrays. Our results offer a robust and reliable molecular marker toolkit that can contribute towards maximizing genetic gains in wheat breeding programs.

Economic burden of gastrointestinal cancer under the protection of the New Rural Cooperative Medical Scheme in a region of rural China with high incidence of oesophageal cancer: cross-sectional survey.

OBJECTIVE: To evaluate the financial burden of oesophageal cancer under the protection of the new Rural Cooperative Medical Scheme (NCMS) and to provide evidence and suggestions to policymakers in a high-incidence region in China. METHODS: We analysed inpatient claim data for oesophageal cancer, gastric cancer and colorectal cancer from 1 January to 31 December 2013. The data were extracted from the NCMS management system of Hua County, Henan Province, a typical high-risk region for oesophageal cancer in China. Cancer-specific health economic indicators were calculated to evaluate the financial burden under the protection of the local NCMS. RESULTS: The total cost of oesophageal cancer was 2.7-3.6 times higher than that of gastric cancer and colorectal cancer, respectively, due to high incidence of oesophageal cancer. For each hospitalisation to treat oesophageal cancer, the average total cost and out-of-pocket expenses after reimbursement equalled an entire year's gross domestic product per capita and per capita disposable income, respectively, for the local area. The average total cost per hospitalisation for oesophageal cancer increased monotonically with hospital level for surgical hospitalisations, and it increased more rapidly for non-surgical hospitalisations (from $301 to $2589, 860%) than for gastric cancer (from $289 to $1453, 503%) and colorectal cancer (from $359 to $1610, 448%). Vulnerable groups with less access to high-level hospitals were found in different gender and age groups. CONCLUSIONS: Oesophageal cancer imposes serious financial burdens on communities and patients' households in this high-incidence region, and no preferential policy from the local NCMS has been designed to address this issue. A special supportive policy should be developed on the basis of local disease profiles and population characteristics to alleviate the financial burden of populations at high risk for certain high-cost diseases.