痛泻宁颗粒治疗腹泻型肠易激综合征肝气犯脾证的临床综合评价

Clinical Comprehensive Evaluation of Tongxiening Granules in Treatment of Diarrhea-predominant Irritable Bowel Syndrome with Liver Qi Invading Spleen Syndrome

目的:系统梳理痛泻宁颗粒治疗腹泻型肠易激综合征(IBS-D)肝气犯脾证的现有证据,从“6+1”维度进行临床综合价值评估,为国家医疗决策、药品临床应用、药事服务等提供参考。方法:依据《药品临床证据和价值评估管理指南》相关标准,基于循证医学证据、问卷调查、药物经济学评价等定性与定量相结合的方法,利用多准则决策分析模型(MCDA),从有效性、安全性、经济性、创新性、适宜性、可及性、中医药特色“6+1”维度对痛泻宁颗粒治疗IBS-D肝气犯脾证的临床证据和临床价值进行综合评估。结果:(1)安全性:根据安全性证据的已知风险和证据充分性两方面评价结果,认为痛泻宁颗粒风险可控,安全性证据充足。(2)有效性:基于Meta分析,痛泻宁颗粒联合益生菌可以降低IBS-D患者肠道症状积分水平[均数差(MD)=-2.29,95%置信区间(95%CI)(-3.20,-1.38),P<0.01],痛泻宁颗粒联合常规治疗(双歧杆菌三联活菌片/匹维溴铵片/马来酸曲美布汀片)有效提高IBS-D患者的综合改善率[相对危险度(RR)=1.19,95%CI(1.14,1.25),P<0.01],痛泻宁颗粒能够显著提高IBS-D患者腹痛[RR=1.99,95%CI(1.62,2.44),P<0.01]及腹泻有效率[RR=1.56,95%CI(1.07,2.25),P<0.05],痛泻宁颗粒与匹维溴铵片在降低IBS-D患者HAMA评分[MD=0.29,95%CI(-0.30,0.88),P=0.34]、HAMD评分[MD=0.35,95%CI(-0.31,1.00),P=0.30],改善IBS-QOL评分[MD=0.28,95%CI(-1.70,2.26),P=0.78]方面疗效相当。根据有效性的证据质量和证据价值评价结果,认为该品种有效性证据充足。(3)经济性:痛泻宁颗粒为全国医保乙类产品,经过5年3种Markov模型模拟后,认为痛泻宁颗粒为优势治疗方案,且结果稳定,经济性较好。(4)创新性:痛泻宁颗粒守正创新,从临床应用、产品组分和生产工艺上进行研发,获得国家中药新药证书、中华中医药学会科学技术一等奖、中国专利优秀奖等,在临床、企业、产业三方面创新性证据充足。(5)适宜性:该药品中成药信息服务信息齐全,问卷调查结果显示该药品在个体依从性、体系、管理等多个维度对临床医生、护士、药师及患者适宜,综合评价该品适宜性证据充足。(6)可及性:痛泻宁颗粒限定日费用占城镇居民可支配日收入中位数的2.43%,占农村居民可支配日收入中位数的9.26%,与同类药相比,价格适中合理,可负担性证据充足,且销售覆盖全国31省市自治区,可及性证据充分、结果明确。(7)中医药特色:痛泻宁颗粒源于《丹溪心法》“痛泻要方”,为经典名方化裁而来,上市后开展了多项临床试验,总研究例数达5000余例,积累了一定的人用经验。基于中医药特色评定原则,痛泻宁颗粒中医药特色突出;综合“6+1”维度结果,运用CSC V2.0软件计算得出综合衡量价值为0.83分。结论:基于痛泻宁颗粒各维度评价结果及综合评价分数,认为痛泻宁颗粒治疗IBS-D肝气犯脾证的临床价值证据充足。可为临床决策和药事管理提供参考。未来建议进一步开展网状Meta分析,进行同类中成药治疗IBS-D的横向比较,提高循证证据质量,充分发挥痛泻宁颗粒的临床价值优势。

Objective:To systematically review the existing evidence of Tongxiening(TXN)Granules in the treatment of diarrhea-predominant irritable bowel syndrome(IBS-D)with liver Qi invading spleen syndrome,and evaluate the clinical comprehensive value from the 6+1 dimension,providing references for national medical decision-making,drug clinical application promotion,pharmaceutical services,etc.Method:Following the relevant standards of the"Guidelines for the Management of Clinical Evidence and Value Evaluation of Drugs",a combination of qualitative and quantitative approaches based on evidence-based medicine,questionnaire surveys,pharmacoeconomic evaluation,etc.,was employed.Multi-criteria decision analysis(MCDA)model was employed to comprehensively evaluate the clinical evidence and value of TXN Granules in the treatment of IBS-D with liver Qi invading spleen syndrome from the"6+1"dimensions of effectiveness,safety,economy,innovation,suitability,accessibility,and traditional Chinese medicine(TCM)characteristics Result:①Safety:Based on the evaluation of known risks and adequacy of safety evidence,TXN granules were considered to have controllable risks with sufficient safety evidence.②Effectiveness:Metaanalysis showed that TXN granules combined with probiotics could reduce the intestinal symptom score level of IBS-D patients[mean difference(MD)=-2.29,95%confidence interval(CI)(-3.20,-1.38),P<0.01],and TXN granules combined with conventional treatments(such as Bifidobacterium triple viable capsules,pinaverium bromide tablets,or trimebutine maleate tablets)effectively improved the comprehensive improvement rate of IBS-D patients[relative risk(RR)=1.19,95%CI(1.14,1.25),P<0.01].TXN granules significantly improved abdominal pain[RR=1.99,95%CI(1.62,2.44),P<0.01]and diarrhea efficacy rate[RR=1.56,95%CI(1.07,2.25),P<0.05]in IBS-D patients.TXN granules were comparable to pinaverium bromide tablets in reducing HAMA score[MD=0.29,95%CI(-0.30,0.88),P=0.34],HAMD score[MD=0.35,95%CI(-0.31,1.00),P=0.30],and improving IBS-QOL score[MD=0.28,95%CI(-1.70,2.26),P=0.78].Based on the quality of evidence and evidence value assessment of effectiveness,it was considered that there was sufficient evidence of effectiveness for this product.③Economy:TXN granules are a national medical insurance category B product.After 5 years of simulation with three kinds of Markov models,it was considered that TXN granules were the advantageous treatment option with stable results and good economy.④Innovation:TXN granules adhered to original innovation,conducting research and development from clinical application,product components,and production processes.They have obtained national TCM new drug certificates,first prizes from the China Association of Chinese Medicine for Science and Technology,and excellent awards for Chinese patents,providing sufficient innovative evidence in clinical,corporate,and industrial aspects.⑤Suitability:The information service of this drug is comprehensive.The questionnaire survey results showed that this drug was suitable for clinical doctors,nurses,pharmacists,and patients in terms of individual compliance,system,and management across multiple dimensions.The overall assessment showed sufficient evidence of suitability for this product.⑥Accessibility:The daily cost of TXN granules accounts for 2.43%of the median disposable daily income of urban residents and 9.26%of rural residents,which is moderate and reasonable compared to similar drugs.There is sufficient evidence of affordability,and it is sold nationwide covering all 31 provinces,municipalities,and autonomous regions,with full accessibility evidence and clear results.TCM characteristics:TXN granules originate from the prescription for treating diarrhea in Danxi's Experiential Therapy.They are derived from classical formulas and have undergone multiple clinical trials involving 5000 cases since their launch,accumulating a certain amount of human use experience.Based on the principles of evaluating TCM characteristics,TXN granules highlight TCM characteristics.The comprehensive value measured using CSC V2.0 software is 0.83 points based on the results of“6+1”dimensions.Conclusion:Based on the evaluation results of TXN granules in various dimensions and the comprehensive evaluation score,it is considered that there is sufficient clinical value evidence for TXN granules in treating IBS-D with liver Qi invading spleen syndrome,which can provide references for clinical decision-making and pharmaceutical management.It is suggested for future research to conduct network Meta-analysis,conduct horizontal comparisons of similar TCM treatments for IBS-D,improve the quality of evidence-based evidence,and fully leverage the clinical value advantages of TXN granules.