| BackgroundThe establishment of a multi-stakeholder involved and multi-dimensional,and comprehensive drug value evaluation system has become a trending topic for drug management decision-making both domestically and internationally.Such a system would support the reasonable pricing and compensation based on drug value in China.Chinese patent medicine is a crucial component of the pharmaceutical system and plays a significant role in maintaining population health.Because of imprecise clinical positioning,broad indications,lack of highquality evidence,and unclear clinical efficacy,rational application of many post-marketing Chinese patent medicines and scientific decision-making of management departments face significant barriers.Meanwhile,Chinese patent medicine is a unique medicinal product that is developed based on traditional Chinese medicine theory and using Chinese medicinal materials as raw materials.When conducting a value evaluation,it is important to consider factors such as the sustainability of Chinese medicinal material resources,the fluctuating prices of medicinal materials,the clinical use of add-on drugs,and the existence of syndrome drugs for multiple indications.Therefore,it is not appropriate to simply rely on existing frameworks used for western medicines when evaluating the value of Chinese patent medicine.Instead,it is necessary to develop a transparent,quantitative index system that reflects the distinctive characteristics of traditional Chinese medicine based on existing research methods,the unique qualities of Chinese medicinal materials,and the conditions present in China.However,an evaluation index system that is tailored specifically to Chinese patent medicine has yet to be established.Multi-Criteria Decision Analysis(MCDA)has numerous advantages,such as its ability to incorporate multiple types of data(such as qualitative or quantitative data),its flexible selection of evaluation criteria,its structured and transparent evaluation process,and its potential to quantify evaluation results.It is widely utilized in multiple fields of research,including public health,medical and health-related policy-making,and value evaluation.In particular,MCDA is increasingly recognized as an efficient tool for conducting comprehensive evaluations of varied types of evidence.MCDA has become a possible alternative or supplement to traditional health technology assessment and is expected to solve some limitations in traditional health technology assessment.Hence,we propose to establish a systematic,quantitative,and transparent index system using MCDA that evaluates various criteria of drug value in post-marketing settings.This approach aims to encourage innovation and drug utilization of Chinese patent medicine,and foster rational use of clinical and medical resources.ObjectiveUsing MCDA model,we constructed a quantitative,structured,and transparent postmarketing value evaluation index system that covers multiple drug value criteria.This approach was exemplified through the comprehensive value evaluation of Danhong injection(DHI)in treating Chronic Stable Angina(CSA).We utilized literature research,Analytic Hierarchy Process(AHP),and Delphi methods to establish this system,which aims to elucidate the value connotation and advantages of Chinese patent medicine.Methods and ContentBased on MCDA model,the following methods were comprehensively applied to construct the evaluation index system of post-marketing Chinese patent medicine.1 Documentary analysis methodDuring the index system construction stage,we searched the databases of PubMed,CNKI,and the websites of regulatory bodies such as the US Food and Drug Administration,European Medicines Agency,US Institute for Clinical and Economic Evaluation,and UK National Institute for Health Clinical Excellence.We comprehensively and systematically analyzed relevant domestic and foreign literature and guidelines.Additionally,we employed content analysis to systematically sort out the constituent elements,core points,methods and steps of evaluation,evaluation result grading,assessment index and application of evaluation frameworks.Then,we made a preliminary evaluation index pool and interpretations of the indexes.We further improved our evaluation framework by investigating and demonstrating it to experts.Eventually,we determined the core index pool and index interpretation for the value evaluation of post-marketing Chinese patent medicine.Moreover,we established an evidence matrix for DHI in the treatment of CSA based on documentary analysis,which serves for validation evaluation.2 Analytic hierarchy processWe utilized the AHP to establish the layers of our evaluation framework,including the objective layer(value evaluation of post-marketing Chinese patent medicine),criterion layer(effectiveness,safety and risk management,cost,innovation,suitability,and accessibility),subcriterion layer(specific evaluation indicators under each evaluation dimension),and scheme layer(Chinese patent medicine under evaluation).Based on the importance score of the evaluation dimensions by experts in Delphi method,the judgment matrix of each evaluation dimension in AHP is constructed,and the consistency test is carried out to determine the weight value of each evaluation dimension.3 Delphi methodIn the optimization phase of evaluation indicators,we employed Delphi method,inviting experts to anonymously rate the importance of each evaluation dimension and indicator using the 5-level Likert scoring method.Additionally,they indicated their level of familiarity with each dimension and indicator,scaling from very familiar to unfamiliar,and provided the judgment basis.Furthermore,we gathered their response of the evaluation dimensions and indicators via open-ended questions.Examples included whether to delete,add,or modify the specific interpretation of an indicator.Following two rounds of Delphi,we determined the final index system for assessing post-marketing Chinese patent medicine.In the stage of determining evaluation index weights,we calculated each index’s weight by considering the importance scores and authority of the experts who participated in the Delphi process.By synthesizing the evaluation dimension and index weight,we obtained the final weight value of each evaluation index,constructing the value evaluation index system of post-marketing Chinese patent medicine with index’s weight.4 Empirical analysisUsing DHI as an example in the treatment of CSA,we conducted an empirical analysis to validate the established post-marketing value evaluation index system of Chinese patent medicine through direct(index system verification)and indirect(cost-effectiveness analysis)validation,emphasizing the operability and strengths of the sy stem.The direct verification involved adapting the system based on specific drug characteristics and building a matrix of evidence for evaluating the value of DHI.This was followed by two rounds of expert evaluation to rate the performance of DHI in the matrix table of evidence,which helped to confirm the availability of evidence indicators and the operability of the index system as a whole.We then used the expert scores and weight of each evaluation dimension and index to calculate the overall value score of DHI in the treatment of CSA and the contribution score of each evaluation dimension or index.In the indirect verification,the CUA was applied to evaluate the advantages of DHI in the treatment of CSA from a societal perspective.Based on phase Ⅳ clinical trial data for DHI for CSA and other published literature,as well as open database information,we established a Markov disease state transition model according to the natural history of CSA.We then used Quality-adjusted life years(QALY)as a health outcome index to assess the economic advantages of DHI.The results of direct and indirect verification were compared and analyzed to further verify the rationality of the comprehensive value score of DHI,and clearly verify the operability and advantages of the evaluation index system.Results1 Evaluation index system for post-marketing Chinese patent medicine valueThis study used Delphi method to optimize the evaluation index pool that has been constructed.The positive coefficient of experts,expert authority level,coefficient of variation score,Kendall coefficient of consistency in the two rounds of Delphi surveys can meet the needs of the research,and expert opinions can be adopted.The study ultimately constructed an evaluation index system for the value assessment of Chinese patent medicine,which includes 6 dimensions and 35 indicators with weight values.The specific dimensions,indicators,and weights are as follows:Evaluation dimensions:effectiveness(28.76%),safety and risk management(37.60%),cost(4.69%),innovation(6.86%),accessibility(12.15%),suitability(9.94%).Evaluation indicators:there are 7 indicators to evaluate effectiveness(Severity of the disease(4.12%),number of people affected by the disease(4.16%),proportion of people suitable for the drug(4.16%),type of benefit(4.02%),size of comparative benefit(3.89%),consistency of clinical efficacy(4.04%),quality of evidence(4.37%));9 indicators to evaluate Security and Risk management(Incidence of adverse reactions(4.37%),incidence of serious adverse reactions(4.62%),incidence of suspicious and unexpected serious adverse reactions(4.24%),severity of adverse reactions(4.44%),toxic medicinal materials(3.95%),risk control of toxic medicinal materials(4.08%),incompatibility contraindications(3.91%),completeness of drug instructions(4.09%),drug safety notification information(3.90%));3 indicators to evaluate cost(comparative net cost(1.68%),other medical cost(1.54%),non-medical cost(1.47%));8 indicators to evaluate innovation(Irreplaceability(0.99%),accuracy of clinical indications(0.94%),specificity of drug action mechanism(0.80%),discovery of new indications(0.89%),specificity of drug use for special population(0.88%),development of new dosage forms(0.78%),improvement of quality standards(0.79%),improvement of production process(0.79%));6 indicators to evaluate accessibility(inclusion of relevant directories(2.12%),availability of drugs(2.07%),price level of drugs(2.05%),out-of-pocket payment ratio of patients(1.95%),proportion of daily treatment costs in household disposable income(1.95%),sustainability of medicinal materials resources(2.01%));2 indicators to evaluate suitability:drug maturity(4.84%)and patient compliance(5.10%).2 Value assessment of Danhong Injection based on MCDA evaluation systemThe comprehensive value score shows that the final value score of DHI plus standard treatment for CSA is 80.18(out of 100),indicating a good value of DHI in treating CSA.Among the 6 evaluation dimensions,"safety and risk management" contributes the most to the final value score,with a value score of 30.37,followed by "effectiveness" with a value score of 23.74,indicating significant clinical value advantages of DHI in treating CSA.The innovation contributes the least to the final value score,with a value score of 3.28,suggesting that there is a need to strengthen innovation research in post-marketing Chinese patent medicines.From the perspective of evaluation indicators,the top 10 evaluation indicators with significant contributions to the final value score of DHI plus standard treatment for the treatment of CSA are patient compliance(4.59),drug maturity(4.49),risk control of toxic medicinal materials(4.38),severity of adverse reactions(3.99),incidence of severe adverse reactions(3.91),incidence of adverse reactions(3.88),completeness of drug instructions(3.85),number of people affected by the disease(3.79),toxic medicinal materials(3.78),and severity of the disease(3.71).3 Value assessment of Danhong Injection based on cost-utility analysisBased on Markov model,the CUA results show that 1 year after the model simulation,the average cost and health outcome per patient in the "DHI plus standard treatment group" were 23,505.38 yuan and 0.81898 QALYs,respectively,while the "standard treatment group" was 17,670.06 yuan and 0.78841 QALYs.Compared with the "standard treatment" group,the cost of obtaining one additional QALYs in the "DHI plus standard treatment group"is 190,848.46 yuan.At a WTP of 242,928 yuan,compared with standard treatment,the "DHI plus standard treatment" has a certain cost-effectiveness advantage(190,848.46 yuan<242,928 yuan).Conclusions(1)This study constructed a set of quantitative,structured,and transparent value evaluation index system with MCDA model covering 6 dimensions and 35 indicators for post-marketing Chinese patent medicines.(2)Through the direct verification of DHI in the treatment of CSA,it was found that the availability of each indicator was generally good,proving that the MCDA-based evaluation index system for the value assessment of post-marketing Chinese patent medicines is operable in the specific drug value assessment.(3)Through the indirect verification of the CUA in the treatment of CSA with DHI,it was proved that the direct verification results were reasonable,further proving the strong operability of the index system.(4)By comparing the direct and indirect verification results,it was found that the MCDAbased multi-dimensional and multi-indicator value evaluation index system has two advantages:first,the value score of the evaluated Chinese patent medicine is more comprehensive.Second,the value score is highly structured and transparent,and the contribution of specific dimensions or indicators to the total value score can be compared to highlight the value advantages of Chinese patent medicines.Innovations(1)A Chinese patent medicine value evaluation index system that covers 6 evaluation dimensions:effectiveness,safety and risk management,cost,innovation,suitability,and accessibility,with distinct Chinese medicine characteristics and flexible applications,has been constructed.(2)By combining direct and indirect verification methods,the reliability and operability of the index system are ensured,further highlighting the value connotation and advantages of Chinese patent medicines under the multi-dimensional value evaluation index system. |
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