Health Economic Evaluation For The Early Detection And Early Treatment Of The Esophageal Cancer In High Risk Areas Of China

BackgroundEsophageal cancer is one of the most common cancer worldwide and China is the high risk region for esophageal squamous cell carcinoma(ESCC).Endoscopic screening is widely accepted as an appropriate strategy for secondary prevention of ESCC in China.However,the efficacy and cost-effectiveness of endoscopic screening for ESCC has not been evaluated by high-quality evidence from randomized controlled trials.Firstly,there are limited studies evaluating the screening cost and treatment cost in screening programs,and most previous evidence were based on data from questionnaires or financial system of health facilities with unsatisfying accuracy.Besides,the traditional screening strategy in China is "once for all" with or without "endoscopic surveillance based on pathologic diagnosis",leading to considerable over diagnosis and missed diagnosis.Efforts have been made regarding this challenge to develop "precision screening strategies"based on the prevalence risk prediction model and the progression risk prediction model for esophageal cancer built in high risk areas of China.And health economic evaluations are needed to compare the "precision screening strategies" with traditional screening strategies,providing scientific evidence for rational policy making.In this study,based on our population-level randomized controlled endoscopic screening trial in a high-risk area of ESCC in China,we made use of first-hand project financial records and medical reimbursement cost data of local communities to accurately estimate the screening cost and treatment cost in a screening program,and a decision tree model was built to evaluate the cost-effectiveness of screening strategies under the "traditional screening modality" and the "precision screening modality".MethodThe Endoscopic Screening for Esophageal Cancer in China(ESECC;NCT01688908)is a cluster randomized controlled trial aiming at investigating the efficacy and cost-effectiveness of endoscopic screening on esophageal cancer in a high prevalent population in China.There were three parts of researches were conducted based on the ESECC trial.Firstly,detailed first-hand financial records of the program were collected using the"micro-costing approach" to estimate the screening cost both in the "ESECC trial scenario"and the "conventional screening scenario".Secondly,individual reimbursement data in the local medical insurance system were used to accurately calculate the cancer-related treatment cost for upper gastrointestinal cancer cases from both arms of the ESECC trial.Comparisons were conducted between the screening arm and the control arm to investigate the impact of increased treatment cost burden on patients' households and local medical insurance department caused by cancer screening.Thirdly,three kinds of "precision screening modalities" were designed in this study according to the "precision screening" conception by making different adoptions of the prevalence risk prediction model and the progression risk prediction model."Precision screening modality 1" conducted risk stratification with the prevalence risk prediction model at the baseline enrollment."Precision screening modality 2 " conducted risk stratification with the progression risk prediction model at the endoscopic surveillance."Precision screening modality 3" conducted risk stratification at both steps.A total of 12 screening strategies from the three "precision screening modalities" and the "traditional screening modality" were included in the cost-effectiveness analysis.Total screening cost and total number of SDA cases detected for each strategy were calculated using decision tree simulations.Probabilistic sensitivity analysis and scenario analysis were made to evaluate the uncertainty of model results and to discover the optimal screening strategy under varied willingness to pay(WTP).ResultsIn 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 prevalence of the two cancers.In a simulated 10-year screening project,annual cost decreased notably over time.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)due to down-staging by screening and less-costly therapy for earlier stages,and the result is similar forcardial and non-cardial gastric cancer in the two arms($7,933 vs.$10,605).However,three fold(103 vs.36)families in the screening arm suffered from 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).The average cost for detecting one severe dysplasia and above(SDA)case was the highest in traditional "once for all" screening strategy($17,370)with a protection rate of only 76.4%.All "precision screening strategies" showed great advantage over the "traditional screening strategies"."Precision modality 1" conducted risk stratification at baseline enrollment and notably cut down total amount of endoscopies as well as average cost for one SDA case($7,649 to $14,024),with similar protection rate to traditional screening strategies.'"Precision modality 2" conducted risk stratification at endoscopic surveillance and significantly increased protection rate by discovering more progression cases,and the average cost for one SDA case was also less than traditional strategies($13,571 to $14,159)."Precision modality 3"conducted risk stratification at both steps and achieved cost control and effectiveness increase simultaneously,generating the lowest average cost for one SDA case($7,148 to $11,537)at high protection rates over 90%.And "Precision screening strategies" showed great probabilities of dominance in sensitivity analysis.ConclusionsFirstly,an accurate estimation of endoscopic screening cost was reported based on the newest first-hand program data.It is discovered that,even though the absolute unit cost of endoscopic screening in China was much lower than that in foreign countries,it is still a relatively heavier burden considering the undeveloped socio-economic status of local communities.Screening cost showed a decreasing time trend in the 10 years' simulation and long-lasting programs were likely to be less costly.Average cost for detecting one case were less for cancer with higher incidence and population-level EC screening would make little sense in regions with a low incidence of disease.Secondly,for the first time,the treatment costs of cancer patients in a screening program were reported using the precise cost records of local medical reimbursement system,and the impact of economic burden on patients and insurance department of targeted communities caused by cancer treatment were thoroughly investigated.Average economic burden for cancer treatment was lower in the screening arm since most patients were detected at early stages and received early treatment at lower cost.However,cancer treatment may triple the occurrence of catastrophic medical expenditure among patients since more cancer cases were detected in advance by screening,and sharply increase the total economic pressure from all treated patients on the local insurance department,particularly for the high prevalent cancer types.Financial support for patients and the health insurance system should be considered when planning budgets for cancer screening programs in resource-limited communities.Thirdly,this is the first research comparing the cost-effectiveness of "traditional modality"and "precision modality" of endoscopic screening for ESCC in China.It is found that,compared to traditional practice,"precision screening modalities" based on the prevalence risk prediction model and the progression risk prediction model for esophageal cancer in high risk populations of China were proved to have better performance of cost-effectiveness and worth of recommendation,with lower average cost for detecting one SDA case and higher protection rate.To conclude,based on all research work in this thesis and precious experience from decades of cancer control,it is suggested that,systematic health economical evaluations for esophageal cancer screening in the future should be conducted under the framework of"Health Technology Assessment",which also pays attention to issues like adaptations,ethics and equity other than cost and effectiveness.