Efficacy,Safety And Economic Evaluation Of Two Chinese Medicine Injections In Treatment Of Hand-foot-mouth Disease

Objective(1)To evaluate the clinical efficacy and safety of Xiyanping injection and Reduning injection in treatment of hand-foot-mouth disease in children,promoting drug used rationally and providing an evidence-based basis for diagnosis and treatment of hand-foot-mouth disease as well as supplement and amendment to the package inserts.(2)To evaluate the economic significance of Xiyanping injection and Reduning injection through establishing the decision tree model and conduct cost-effectiveness.Through this study,it could control the drug cost,improve the utilization of medical and health resources,and provide a scientific basis to select pharmaceutical pricing and health insurance directory.Methods(1)Randomized or quasi-randomized controlled trials on Xiyanping injection or Reduning injection in treatment of hand-foot-mouth disease were retrieved from CNKI,VIP,Wanfang Data,Cochrane Library,PubMed from their inceptions to August 2015.Study selection was conducted using EndNote X7.Data was extracted and methodological quality evaluation was assessed by using risk of bias assessment tool after study selection.Meta-analysis of time for fever recovery,time for rash disappearance,time for mouth ulcer disappearance,the total effective rate,length of hospital stay,total course,incidence of adverse effect were conducted by using Review Manager 5.3.(2)Direct cost and indirect cost were adopted to calculate the total cost.Based on the result of meta-analysis,the decision tree was established with TreeAge Pro 2011 to conduct cost-effectiveness analysis.Sensitivity analysis was conducted through Tornado Diagram analysis,one-way and two-way sensitivity analysis.Results(1)Eighteen literatures about Xiyanping injection in treatment of HFMD were analyzed,including six literatures about Xiyanping injection comparing with Ribavirin injection and twelve about Xiyanping injection combined with Ribavirin injection comparing with Ribavirin injection.The result of meta-analysis revealed that the difference of time for fever recovery between Xiyanping group and Ribavirin group(WMD=-1.41,95%CI:-2.60 to-0.22,P=0.02<0.05)and between the combined group and Ribavirin group(WMD=-1.58,95%CI:-1.95 to-1.21,P<0.00001)were statistically significant.The difference of time for rash disappearance between Xiyanping group and Ribavirin group(WMD=-1.58,95%CI:-2.42 to-0.74,P=0.0002<0.01)and between the combined group and Ribavirin group(WMD=-1.54,95%CI:-1.91 to-1.17,P<0.00001)were statistically significant.Only one literature reported the time for mouth ulcer disappearance between Xiyanping group and Ribavirin group,which couldn’ t conduct meta-analysis.The difference of time for mouth ulcer disappearance between the combined group and Ribavirin group(WMD=-1.22,95%CI:-1.75 to-0.69,P<0.00001)was statistically significant.The total effective rate of Xiyanping group(OR=3.51,95%CI:2.08 to 5.92,-P<0.00001)or combined group(OR=3.83,95%CI:2.68 to 5.46,P<0.00001)showed increased comparing to Ribavirin group.The difference of length of hospital stay between the Xiyanping group and Ribavirin group(WMD=-1.87,95%CI:-3.16 to-0.58,P=0.004<0.05)and between the combined group and Ribavirin group(WMD=-2.01,95%CI:-2.71 to-1.31,P<0.00001)were statistically significant.Two literatures reported no adverse effect between the Xiyanping group and the Ribavirin group.The incidence of adverse effect between the combined group and the Ribavirin group(OR=5.05,95%CI:0.58 to 43.57,P=0.14>0.05)had no statistically significant.(2)Fifteen literatures about Reduning injection in treatment of HFMD were analyzed,including ten literatures about Reduning injection comparing with Ribavirin injection and five about Reduning injection combined with Ribavirin injection comparing with Ribavirin injection.The result of meta-analysis revealed that the difference of time for fever recovery between Reduning group and Ribavirin group(WMD=-O.96,95%CI:-1.09 to-0.82,P<0.00001)and between the combined group and Ribavirin group(WMD=-1.45,95%CI:-2.33 to-0.56,P=0.001<0.01)were statistically significant.The difference of time for rash disappearance between Reduning group and Ribavirin group(WMD=-1.57,95%CI:-1.73 to-1.42,P<0.00001)and between the combined group and Ribavirin group(WMD=-1.46,95%CI:-1.68 to-1.25,P<0.00001)were statistically significant.The difference of time for mouth ulcer disappearance between Reduning group and Ribavirin group(WMD=-1.75,95%CI:-2.12 to-1.38,P<0.00001)and between the combined group and Ribavirin group(WMD=-1.77,95%CI:-2.05 to-1.48,P<0.00001)were statistically significant.The total effective rate of Reduning group(OR=5.16,95%CI:3.49 to 7.46,P<0.00001)or combined group(OR=4.73,95%CI:2.47 to 9.03,P<0.00001)showed increased comparing to Ribavirin group.The difference of total course between the Reduning group and Ribavirin group(WMD=-2.22,95%CI:-3.40 to-1.05,P=0.0002<0.01)and between the combined group and Ribavirin group(WMD=-2.14,95%CI:-2.54 to-1.74,P<0.00001)were statistically significant.The incidence of adverse effect between the Reduning group and the Ribavirin group(OR=0.45,95%CI:0.21 to 0.97,P=0.04<0.05)was statistically significant.The incidence of adverse effect between the combined group and the Ribavirin group(OR=0.97,95%CI:0’:31 to 3.05,P=0.96>0.05)had no statistically significant.(3)Economic evaluation of Xiyanping injection:The total costs of the experiment group and the control group were 2887.53 RMB and 3058.72 RMB,respectively.The effective rates were 92.49%and 78.12%,respectively.The results of sensitivity analysis revealed that the outcome was stable within the range of the course of treatment of the control group or when the course of treatment of experiment group was less than 6.9 days or when the length of hospital stay of experiment group was less than 5.9 days or when the length of hospital stay of control group was greater than 6.1 days.(4)Economic evaluation of Reduning injection:The total costs of the experiment group and the control group were 2769.35 RMB and 3062.98 RMB,respectively.The effective rates were 95.00%and 78.70%,respectively.The results of sensitivity analysis revealed that the outcome was stable regardless of the changes of total effective rate of the control group or the length of hospital stay of the experiment group or the course of treatment of the experiment group or when the length of hospital stay of the control group was greater than 5.49 days.ConclusionIn terms of efficacy,Xiyanping injection and Reduning injection are better than Ribavirin injection in treatment of hand-foot-mouth disease in children.In terms of safety,Xiyanping injection is equal to Ribavirin injection and Reduning injection is safer than Ribavirin injection.In terms of economy,Xiyanping injection and Reduning injection are more cost-effective than Ribavirin injection in treatment of HFMD.