Cost-effectiveness Of Preventive Treatment In Close Contacts Of Pulmonary Tuberculosis(PTB)Cases

ObjectivesTo obtain the costs,the TB cases prevented,the deaths related TB averted,the QALY obscured and cost-effectiveness of untreated,Self-Administered Treatment With Three Months Of Weekly Rifapentine Plus Isoniazid(3HP-SAT),Directly Observed Treatment With Three Months Of Weekly Rifapentine Plus Isoniazid(3HP-DOT),Self-Administered Treatment With Six Months Of Daily Isoniazid(6H-SAT)and Directly Observed Treatment With Six Months Of Daily Isoniazid(6H-DOT)and then decide a dominant strategy performed among latent tuberculosis infected close contacts of PTB cases,which can provide reference for the promotion of preventive treatment for latent tuberculosis infection(LTBI)in China.MethodsAccording to the severity and natural history of tuberculosis,the occurrence and development of LTBI was divided into different markov states and decision-markov models were also constructed to evaluate the cost-effectiveness of five preventive strategies.Parameters related to probability,costs and effectiveness for the models were collected through field surveys,literature analysis,and consultation with experts.Probability parameters of the decision models were mainly obtained through field surveys.To obtain the completion rate of preventive treatment for LTBI,the follow-up data of 898 close contacts who should have ended treatment in "the 13th Five-Year Plan" project were selected for statistical analysis,including 463 close contacts treated by 3H-SAT and 435 close contacts treated by 6H-SAT.To obtain the incidence of adverse reactions,a questionnaire survey through face-to-face or telephone interviews were conducted in 224 close contacts who had ended preventive treatment for LTBI,including 111 close contacts treated by 3HP and 113 close contacts treated by 6H.Other transfer probability parameters were collected through literature analysis,concluding the probability of developing from LTBI to active TB,of curing active TB,of relapsing in cured active TB,of self-healing from chronic TB,of developing to active TB from self-cured chronic TB and the mortality of all states.To obtain the direct medical expenses excluding DOT in the costs of preventive treatment for LTBI,an analysis on the costs of testing collected from 34 county-level tuberculosis designated medical institutions was conducted,which are responsible for the management of preventive treatment for LTBI in "the 13th Five-Year Plan" project.The costs of DOT were obtained through consultation with public health and clinical experts majoring in TB control and prevention.To obtain the indirect medical expenses and indirect expenses in the costs of preventive treatment for LTBI,an analysis on fee of food,transportation and loss of working time collected from 224 treated close contacts was conducted.To obtain the costs of TB treatment,a literature performed by China CDC focusing on the cost of 1163 PTB cases was analyzed.To obtain annual QALYs of different markov states,an EQ-5D questionnaire survey was performed for statistical analysis and transformation by face to face or telephone interview in 392 close contacts with LTBI,40 rifampin-sensitive PTB cases and 92 cured rifampin-sensitive PTB cases,in the spot of "the 13th Five-Year Plan" project.Other effectiveness parameters were collected through literature analysis,concluding the annual QALYs of rifampin-resistant PTB cases,cured active TB,chronic TB cases,and self-cured chronic TB.Using TreeAge Pro 2011,a markov cohort simulation running for 20 stages at the start age of 38 years old was conducted in 10000 latent tuberculosis infected close contacts to compare TB case,deaths prevented and QALYs obscured by four preventive strategies comparing with untreated.And cost-effectiveness analysis operated by decision-markov models was conducted to compare the cost-effectiveness of five strategies and determine the most cost-effective strategy.One way sensitivity analysis and probabilistic sensitivity analysis were also conducted to test the influence of assumptions and parameters on cost-effectiveness analysis.Results1.The costs of untreated,3HP-SAT,3HP-DOT,6H-SAT and 6H-DOT were 825.14,1142.44,1252.62,1693.60,and 2563.67 yuan,respectively,increasing in turn.2.Compared with untreated,3HP-SAT,3HP-DOT,6H-SAT and 6H-DOT can reduce the incidences of TB by 75.07%,82.31%,47.18%and 55.50%,while can reduce the incidences of TB death by 2.78%、2.96%、1.85%and 2.16%,respectively.Among the four preventive strategies,the QALYs of each treated close contact can be increased are 0.0836,0.0862,0.0733 and 0.0762 QALYs.The 3HP-DOT strategy has the best effect,followed by 3HP-SAT,6H-DOT and 6H-SAT.3.While comparing untreated,3HP-SAT,3HP-DOT,6H-SAT and 6H-DOT,6H-SAT and 6H-DOT were eliminated as absolute dominated strategy.3HP-SAT was regarded as alternative dominant strategy because its ICER compared with untreated was 2797.27yuan/QALY,which was lower than 3 times GDP per capita.3HP-DOT was regarded as dominant strategy based on preference for effectiveness because its ICER compared with 3HP-SAT was 40000.44 yuan/QALY,which was lower than 3 times GDP per capita.4.While comparing untreated,6H-SAT and 6H-DOT,6H-SAT was regarded as dominant strategy because its ICER compared with untreated was 9910.46 yuan/QALY,which was lower than 3 times GDP per capita.6H-DOT was always regarded as dominated strategy and its incremental cost was unworthy of paying because its ICER compared with 6H-SAT was 293730.94 yuan/QALY,which were higher than 3 times GDP per capita.5.Sensitivity analysis showed that the discount rate,the annual QALY of untreated and the start age of LTBI treatment have a great impact on the results of the model operation.The start age will change the comparison results of the dominant strategy,especially.At the start ages of 5 to 39 years old,the cost-effectiveness of 3HP-SAT and 3HP-DOT were high and 3HP-DOT was more advisable for its high effectiveness.At the start ages of 40 to 65 years old,the cost-effectiveness of LTBI treatment was no longer high and its advantage was no longer significant because the mortality of TB and no TB markov states depending on age changed dramatically.Conclusion1.Compared with untreated,the costs of 3HP-SAT,3HP-DOT,6H-SAT and 6H-DOT increased sequentially.2.Compared with untreated,four preventive strategies of treat group can improve effects,reduced TB cases and averted TB deaths.3.While comparing untreated,3HP-SAT,3HP-DOT,6H-SAT and 6H-DOT,3HP-DOT and 3HP-SAT are available in cost-effectiveness but 3HP-DOT is the dominant in the view of effects.4.While comparing untreated,6H-SAT and 6H-DOT,6H-SAT is dominant.5.It is more cost-effective to perform preventive treatment for LTBI in the young than the elder.