Benefit-risk evaluation technology system suitable for Chinese patent medicine on market

Abstract

The invention provides a benefit-risk evaluation method and a technical system for Chinese patent medicines after marketing. The method aims at solving the limitation of an existing medicine benefit-risk evaluation method in evaluating the Chinese patent medicine and comprehensively reflecting the benefit and the risk of the Chinese patent medicine in clinical application. A perfect benefit-risk index system is constructed by adopting a qualitative and quantitative combined evaluation mode, and factors such as multiple indications and treatment based on syndrome differentiation of the Chinese patent medicine are fully considered. According to the technical scheme, the method comprises the following steps: a benefit-risk evaluation strategy after the traditional Chinese medicine is marketed, qualitative and quantitative benefit-risk evaluation, and establishment and implementation of a key technology. According to the method, the value of the Chinese patent medicine in clinical treatment can be evaluated more scientifically and comprehensively, powerful support is provided for clinical value evaluation of the Chinese patent medicine, and the accuracy and reliability of evaluation results are improved. The implementation of the method provides a reference basis for clinical decision making.

Description

Technical Field

[0001] The present invention relates to the field of evaluation methods, and particularly to a benefit - risk evaluation technical system applicable to traditional Chinese patent medicines after market approval. Background Art

[0002] In the field of drug research and evaluation, especially for traditional Chinese patent medicines, scientifically and comprehensively evaluating their value in clinical treatment has always been the focus of the industry. As an important part of the treasure house of traditional Chinese medicine, traditional Chinese patent medicines have characteristics such as multiple indications and syndrome differentiation treatment, and play an irreplaceable role in clinical applications. However, the existing drug benefit - risk evaluation methods have certain limitations when evaluating traditional Chinese patent medicines, and it is difficult to comprehensively reflect the benefits and risks of traditional Chinese patent medicines in clinical applications.

[0003] Specifically, the disadvantages of the existing technologies are mainly reflected in the following aspects: First, the existing evaluation methods mainly rely on clinical trials and literature research in terms of data sources, and these data may not fully cover the usage of traditional Chinese patent medicines in the real world, resulting in certain one - sidedness of the evaluation results; Second, the existing benefit - risk index systems are often not perfect enough to comprehensively reflect the benefits and risks of traditional Chinese patent medicines. Especially when considering the characteristics of traditional Chinese medicine, such as the theory of drug properties, compatibility taboos, syndrome differentiation treatment, etc., the existing index systems often fail to give full expression; In addition, the imperfections in data sources and index system construction of the existing evaluation methods also limit their extensive application and in - depth development in the evaluation of traditional Chinese patent medicines.

[0004] Therefore, in view of these disadvantages of the existing technologies, the industry urgently needs a benefit - risk evaluation method for traditional Chinese patent medicines after market approval, which can fully consider factors such as multiple indications and syndrome differentiation treatment of traditional Chinese patent medicines, adopt a combination of qualitative and quantitative evaluation methods to improve the objectivity of evaluation results, and construct a perfect benefit - risk index system to comprehensively reflect the benefits and risks of traditional Chinese patent medicines. The proposal of the present invention is precisely to solve this technical problem and provide new ideas and methods for the scientific evaluation of traditional Chinese patent medicines.

[0005] To solve the above problems, the applicant proposes a benefit - risk evaluation technical system applicable to traditional Chinese patent medicines after market approval. Summary of the Invention

[0006] The purpose of the present invention is to provide a benefit - risk evaluation technical system applicable to traditional Chinese patent medicines after market approval to solve the problems in the existing technologies.

[0007] To achieve the above purpose, the present invention provides the following technical solutions: A benefit - risk evaluation method for traditional Chinese patent medicines after market approval, the method comprising the following steps:

[0008] Clinical value confirmation: Each indication of the target traditional Chinese medicine (TCM) is evaluated separately to determine whether the benefits in the treatment of a specific disease outweigh the risks. This process can refer to existing treatment guidelines or placebo treatment;

[0009] Clinical value comparison: A comprehensive analysis is conducted on the target TCM and other similar drugs to evaluate the overall performance of their benefits and risks compared to other drugs, including comparison with other TCMs for treating specific diseases (indications) to identify its relative clinical advantages;

[0010] Clinical positioning and value maximization: Compare the benefits and risks of the target TCM in different clinical application scenarios to determine the optimal usage plan in clinical practice, ensuring that while achieving the maximum therapeutic benefits, the risks are minimized.

[0011] Optionally, this method also includes adopting an evaluation method combining qualitative and quantitative approaches, where:

[0012] Qualitative evaluation: Conduct a qualitative evaluation of benefits - risks following a structural framework, which includes four main parts: treatment background, benefits, risks and risk management, and benefits - risks conclusion;

[0013] Quantitative evaluation: Adopt a multi - criteria decision - analysis model as a quantitative analysis tool for drug benefits - risks evaluation.

[0014] Optionally, this method also includes constructing a complete benefits - risks index system, which includes:

[0015] Benefit indicators: Used to evaluate the positive outcomes brought by the drug to patients' clinical treatment, prognosis, quality of life, etc., covering the recognized efficacy indicators for the target indications or diseases of drug treatment, the unique syndrome efficacy indicators of TCM, patient - centered patient experience data and health benefits, as well as key characteristics such as the accessibility, appropriateness, and cost - effectiveness of the drug;

[0016] Risk indicators: Used to evaluate the clear or potential negative outcomes brought by the drug to patients, including adverse reactions, misuse, abuse, etc., considering the properties of traditional Chinese medicines, compatibility characteristics, clinical usage characteristics, and the characteristics of adverse reactions based on relevant traditional Chinese medicine theories.

[0017] Optionally, this method also includes determining the weights of benefits - risks indicators. Combining the opinions of health decision - makers, clinicians, pharmacists, patients, and health economists in relevant disease fields through the analytic hierarchy process, qualitatively and quantitatively, subjectively and objectively, to determine the relative importance of each indicator in the overall benefits - risks assessment and set the scoring weights.

[0018] Optionally, the method further includes determining criterion attributes, that is, setting performance reference levels for each benefit-risk indicator, which are divided into two types: quantitative and qualitative. At least two performance reference levels are set for each indicator, namely, the upper limit reference level that is most attractive and the lower limit reference level that is least attractive.

[0019] The evaluation method according to any one of claims 1 to 5, characterized in that the method further includes the following implementation steps:

[0020] Define the decision problem: Based on the benefit-risk assessment framework and the operation implementation steps of MCDA, defining the decision problem involves decision objectives, evaluation criteria, stakeholders, and output forms;

[0021] Obtain the data to be evaluated: Obtain relevant data through methods such as systematically searching Chinese and English journal databases, regulatory and medical data, and research interviews;

[0022] Benefit-risk evaluation: Based on the benefit-risk assessment framework and the MCDA model, conduct a detailed qualitative and quantitative analysis of traditional Chinese patent medicines;

[0023] Analysis of variability factors: Analyze the impact of variability factors on the target diseases treated by traditional Chinese patent medicines to clarify their clinical positioning;

[0024] Sensitivity analysis: Evaluate the stability of the benefit-risk evaluation results and the reliability of the evaluation indicators.

[0025] A multi-functional evaluation system based on the characteristics of traditional Chinese patent medicines, characterized in that the system adopts the evaluation method according to any one of claims 1 to 6 for conducting benefit-risk evaluation of traditional Chinese patent medicines after listing.

[0026] Beneficial effects: 1. Improvement in comprehensiveness and scientificity: The present invention fully considers the characteristics of traditional Chinese patent medicines such as multiple indications and syndrome differentiation and treatment. By constructing a complete benefit-risk indicator system, it comprehensively covers the positive results brought by the drug to aspects such as patients' clinical treatment, prognosis, and quality of life, as well as the clear or potential negative results such as adverse reactions, misuse, and abuse. This method not only improves the comprehensiveness of the evaluation but also makes the evaluation results more scientific and objective.

[0027] 2. Combination of qualitative and quantitative evaluations: The present invention adopts a combination of qualitative and quantitative evaluation methods. It not only follows a structural framework for qualitative evaluation of benefit-risk but also introduces a multi-criteria decision analysis (MCDA) model as a quantitative analysis tool. This combination reduces the subjectivity of the evaluation and improves the accuracy and reliability of the evaluation results.

[0028] 3. Prominent traditional Chinese medicine (TCM) characteristics: When constructing the benefit-risk index system, the present invention fully considers TCM-related theories, such as the theory of drug properties, compatibility taboos, syndrome differentiation and treatment, etc., so that the evaluation results can more accurately reflect the TCM characteristics of Chinese patent medicines. This helps to promote the modernization and internationalization process of TCM.

[0029] 4. Guiding clinical decision-making: Through the evaluation method proposed by the present invention, the benefits and risks of Chinese patent medicines in different clinical application scenarios can be compared and analyzed, so as to determine the best usage plan in clinical practice. This not only helps doctors make more scientific clinical decisions, but also maximizes patient benefits and minimizes risks.

[0030] 5. Promoting the development of the field of Chinese patent medicine evaluation: The proposal of the present invention provides new ideas and methods for the field of Chinese patent medicine evaluation, which helps to promote the in-depth development and wide application of this field. At the same time, this method also has high practicability and operability, and is convenient for popularization and application in various fields such as drug regulatory agencies, medical institutions, and pharmaceutical enterprises. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 It is a diagram of the benefit-risk index system for traditional Chinese medicines after marketing;

[0032] Figure 2 It is the setting of the performance reference level and the adjustment of the basic scale. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0033] The following introduces the preferred embodiments of the present invention with reference to the accompanying drawings of the specification, making its technical content clearer and easier to understand. The present invention can be embodied in many different forms of embodiments, and the protection scope of the present invention is not limited to the embodiments mentioned in the text.

[0034] Example 1

[0035] The present invention aims to propose a multi-functional evaluation system based on the characteristics of Chinese patent medicines, that is, a benefit-risk evaluation method and technical system for Chinese patent medicines after marketing. This method fully considers factors such as multiple indications and syndrome differentiation and treatment of Chinese patent medicines, adopts a combination of qualitative and quantitative evaluation methods, and constructs a complete benefit-risk index system to comprehensively reflect the benefits and risks of Chinese patent medicines.

[0036] Benefit-risk evaluation strategy for traditional Chinese medicines after marketing

[0037] Confirmation of clinical value: Evaluate each indication separately to determine whether the benefits of Chinese patent medicines in the treatment of specific diseases exceed the risks. Refer to existing treatment guidelines or placebo treatment to evaluate whether Chinese patent medicines have clinical value in the treatment of specific diseases (indications).

[0038] Clinical value comparison: Conduct a comprehensive analysis to compare the clinical value of traditional Chinese patent medicines with other similar drugs, and evaluate the overall performance of their benefits and risks compared to other drugs. This includes comparing with other traditional Chinese patent medicines for treating specific diseases (indications) to identify their relative clinical advantages.

[0039] Clinical positioning and value maximization: Compare the benefits and risks of traditional Chinese patent medicines in different clinical application scenarios, determine the optimal usage plan in clinical practice, ensure that while achieving the maximum therapeutic benefit, the risks are minimized, thereby enhancing their overall clinical value and practical applicability.

[0040] Qualitative and quantitative combined benefit-risk evaluation

[0041] Selection of qualitative evaluation framework: Follow the benefit-risk evaluation ideas in China and adopt a structured and step-by-step qualitative evaluation framework, including four main parts: treatment background, benefits, risks and risk management, and benefit-risk conclusion.

[0042] Selection of quantitative analysis model: Adopt the multi-criteria decision analysis (MCDA) model as the quantitative analysis tool for drug benefit-risk evaluation, integrate evidence from different sources, and improve the accuracy of decision-making.

[0043] Key technologies for post-marketing benefit-risk evaluation of traditional Chinese medicines

[0044] Establish a benefit-risk index system: Include benefit indicators and risk indicators, covering key features such as the target indications of drug treatment, syndrome efficacy indicators, patient experience data, drug accessibility, appropriateness, and cost-effectiveness, as well as the overall benefits and long-term efficacy brought to the patient's family and the relationship of the social group where they are located. At the same time, consider the risks related to traditional Chinese medicine theories such as the properties of traditional Chinese medicines, compatibility characteristics, and clinical usage characteristics.

[0045] Determine the weights of benefit-risk indicators: Based on the key role of clinical evaluation and the overall value of the drug, as well as the weights of evidence from different sources, use the analytic hierarchy process (AHP) to determine the relative importance of each indicator in the overall benefit-risk assessment and set standardized weights.

[0046] Determine the criterion attributes: That is, the performance reference levels of the indicators, which provide measurable standardized parameters for benefit-risk evaluation. Set two types of performance reference levels, quantitative and qualitative, and construct a piecewise linear function according to clinical actual needs.

[0047] Implementation steps for post-marketing benefit-risk evaluation of traditional Chinese medicines

[0048] Define the decision problem: Based on the benefit-risk assessment framework and the operation implementation steps of MCDA, define the decision problem, including decision objectives, evaluation criteria, stakeholders, output forms, etc.

[0049] Obtain data and information to be evaluated: Through methods such as systematically searching Chinese and English journal databases, regulatory and medical data, research interviews, etc., obtain clinical research literature, real-world data, investigation reports, etc. related to the target Chinese patent medicine, and extract and integrate relevant data information according to the type of benefit-risk indicators.

[0050] Benefit-risk assessment: Based on the benefit-risk assessment framework and the MCDA model, conduct a detailed qualitative and quantitative analysis of the Chinese patent medicine to clarify its clinical value.

[0051] Analysis of variability factors: By analyzing variability factors, clarify the clinical positioning of the Chinese patent medicine after marketing, and provide a scientific basis for clinical decision-making.

[0052] Sensitivity analysis: Evaluate the stability of the benefit-risk assessment results and the reliability of the evaluation indicators to ensure the stability and reliability of the evaluation results.

[0053] The present invention relates to a benefit-risk evaluation technical system for Chinese patent medicines after marketing, which can comprehensively reflect the benefits and risks of Chinese patent medicines in clinical treatment, and improve the objectivity and scientific nature of the evaluation results. At the same time, this method fully considers the characteristics of Chinese patent medicines, such as the theory of medicinal properties, compatibility taboos, syndrome differentiation and treatment, etc., and provides theoretical and practical support for the benefit-risk evaluation of Chinese patent medicines after marketing. In addition, through a combined qualitative and quantitative evaluation method, the accuracy and reliability of the evaluation results are improved.

[0054] Example 2

[0055] Implementation of the benefit-risk evaluation of a Chinese medicine injection after marketing

[0056] Hepatitis B virus (HBV) infection is a global public health problem that has a profound impact on human health and social economy. Existing treatment options mainly include nucleoside (acid) analogs (NAs) and pegylated interferon (PEG-IFN), as well as traditional Chinese medicine syndrome differentiation and treatment formulas and Chinese patent medicines. However, there are still some uncertainties in existing treatment options. A certain Chinese medicine injection is mainly used for the treatment of acute and chronic hepatitis B virus infection, and this drug is widely used in clinical practice. Taking the evaluation of the benefit-risk of this Chinese medicine injection in the treatment of hepatitis B virus infection as an example, the implementation steps of the benefit-risk evaluation strategy for Chinese medicines after marketing are described.

[0057] Define the decision problem

[0058] ① Clinical value confirmation: Evaluate the clinical value of this traditional Chinese medicine injection in the treatment of hepatitis B virus. ② Clinical value comparison: Compare this traditional Chinese medicine injection with conventional Western medicine treatments (such as NAs and PEG-IFN), and with other similar proprietary Chinese medicines, and compare their benefit-risk advantages. ③ Clinical positioning and value maximization: Define the optimal usage plan of this traditional Chinese medicine injection in the treatment of hepatitis B virus, and further optimize its clinical positioning.

[0059] Determine benefit-risk indicators

[0060] Through literature research, questionnaire surveys, and expert demonstrations, clarify the benefit and risk indicators. Benefit indicators include: liver function indicators, liver fibrosis indicators, virological indicators, and patient-centered evaluation indicators; risk indicators include: incidence of adverse reactions, incidence of allergic reactions, incidence of systemic damage, incidence of digestive tract reactions, incidence of neuropsychiatric system, incidence of circulatory system, and incidence of other adverse reactions.

[0061] Set index weights and criterion attributes

[0062] Select 6 authoritative experts in the field of liver diseases and use the back-to-back independent scoring method to assign weights to the benefit indicators and risk indicators based on clinical experience and professional knowledge, and calculate the arithmetic mean of the weight scores of each indicator as the initial weight; secondly, organize an expert demonstration meeting to determine the final weights of the benefit-risk indicators through structured discussions; finally, use the M-MACBETH software to generate the standardized weights of each indicator. Set performance reference levels for each benefit indicator and risk indicator. In binary variables, the optimal value of the effective rate is 1, and the worst value is 0; the optimal value of the risk indicator is 0, and the worst value is 1. For continuous variables, the optimal value is calculated by referring to the difference between the values of the control group in the included literature before and after treatment, and the best of them is taken as the optimal value of this indicator, and the worst value is 0.

[0063] Obtain evaluation data

[0064] Systematically collect the clinical research data of this traditional Chinese medicine injection. Among them, the benefit data comes from literature research, and the risk data comes from literature research, post-marketing safety re-evaluation research, hospital centralized monitoring, SRS feedback from the National Center for Monitoring of Adverse Drug Reactions, and PSUR independently collected by the marketing authorization holder. In binary variables, the event incidence rate is determined as the final reference value. For continuous variables, the difference between the value after treatment and the value before treatment is used as the final reference value.

[0065] Benefit-risk evaluation

[0066] Qualitative benefit-risk evaluation of the collected data was conducted according to the "Benefit-Risk Assessment Framework", and a quantitative evaluation system was constructed based on the MCDA model. The comprehensive benefit-risk scores of this traditional Chinese medicine injection, conventional Western medicine treatment drugs, and four similar traditional Chinese patent medicines were calculated respectively. Through the evidence integration of the qualitative evaluation conclusions and quantitative calculation results, the comprehensive benefit-risk evaluation results of this traditional Chinese medicine injection in the treatment of hepatitis B virus were formed.

[0067] Table 1 Example of benefit-risk scores

[0068]

[0069] Analysis of variability factors

[0070] With the help of RevMan software, the results of each subgroup of different combination medication methods, traditional Chinese medicine syndrome types, treatment courses, doses, solvent concentrations and doses, and types of adverse reactions were combined respectively. Using the M-MACBETH software, the benefit-risk scores of each outcome index and overall were calculated, the influence of variability factors on the benefit-risk evaluation results of this traditional Chinese medicine injection was analyzed, and its clinical positioning was clarified.

[0071] Sensitivity analysis

[0072] Since there are many included benefit and risk outcome indicators, only the outcome indicators with the largest weights after standardization are analyzed, that is, the weight sensitivities of TBil and the negative conversion rate of HBV-DNA. The current weights of TBil and the negative conversion rate of HBV-DNA are both 5.26%. By adjusting the weight of TBil, it is found that when its weight is lower than 21.6%, the benefit-risk score of this traditional Chinese medicine injection is higher than that of other traditional Chinese patent medicines, and when the weight is higher than 21.6%, the benefit-risk scores of other traditional Chinese patent medicines are higher than that of this traditional Chinese medicine injection; moreover, the change in the weight of TBil has no impact on the ranking of the two alternative treatment options of this traditional Chinese medicine injection and conventional Western medicine treatment. When the weight of the negative conversion rate of HBV-DNA changes from 0% to 100%, it has no impact on the ranking of all alternative treatment options.

[0073] This traditional Chinese medicine injection has significant clinical benefits in the treatment of hepatitis B virus, especially in improving hyperbilirubinemia, inhibiting the process of liver fibrosis, inhibiting virus replication, and significantly improving the quality of life of patients. Although there are certain risks, most of the adverse reactions are allergic reactions and digestive tract reactions. The clinical monitoring and management of adverse reactions / events are relatively easy, and the impact on drug compliance is small. Most of the potential outcomes are improvement or cure. During the clinical use process, strictly use the medicine according to the usage and dosage in the instructions, and conduct close monitoring and management in a hospital environment. The clinical benefits of using this traditional Chinese medicine injection in the treatment of hepatitis B virus are greater than the risks.

[0074] The foregoing has shown and described the basic principles, main features and advantages of the present invention. For those skilled in the art, it is obvious that the present invention is not limited to the details of the above-described exemplary embodiments, and without departing from the spirit or basic features of the present invention, the present invention can be implemented in other specific forms. Therefore, in any aspect, the embodiments should be regarded as exemplary and non-limiting. The scope of the present invention is defined by the appended claims rather than the above description. Therefore, it is intended to embrace all changes that fall within the meaning and scope of the equivalent elements of the claims in the present invention. Any reference signs in the claims should not be construed as limiting the claims involved.

[0075] In addition, it should be understood that although this specification is described in terms of embodiments, not every embodiment only contains an independent technical solution. This narrative manner of the specification is only for clarity. Those skilled in the art should regard the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A benefit-risk assessment method for a post-marketing Chinese patent medicine, characterized in that: The method comprises the following steps: Clinical value confirmation: Each indication of the target Chinese patent medicine is evaluated separately to determine whether its benefits outweigh the risks in the treatment of a specific disease. This process can refer to existing treatment guidelines or placebo treatments; Comparison of clinical value: Conduct a comprehensive analysis of the target TCM and other similar drugs to evaluate its overall benefits and risks relative to other drugs, including comparison with other TCMs for treating specific diseases to identify its relative clinical advantages; Clinical positioning and value maximization: Compare the benefits and risks of the target Chinese patent medicine in different clinical application scenarios, determine its optimal use plan in clinical practice, and ensure that the risks are minimized while achieving the maximum therapeutic benefit.

2. The evaluation method according to claim 1, characterized in that: The method also includes the use of a combination of qualitative and quantitative evaluation methods, including: Qualitative evaluation: Follow the structured framework for qualitative benefit-risk evaluation, which includes four main parts: treatment background, benefits, risks and risk management, and benefit-risk conclusions; Quantitative evaluation: A multi-criteria decision analysis model is used as a quantitative analysis tool for drug benefit-risk evaluation.

3. The evaluation method according to claim 2, characterized in that: The method also includes building a comprehensive benefit-risk indicator system, which includes: Benefit indicators: used to evaluate the positive results that drugs bring to patients in terms of clinical treatment, prognosis, quality of life, etc., covering the industry-recognized efficacy indicators of the target indications or diseases of drug treatment, syndrome efficacy indicators unique to Chinese patent medicines, patient-centered patient experience data and health benefits, as well as key features such as drug accessibility, suitability, and cost-effectiveness; Risk indicators: used to evaluate the clear or potential negative consequences of drugs to patients, including adverse reactions, misuse, abuse, etc., taking into account the medicinal properties of traditional Chinese medicine based on relevant theories of traditional Chinese medicine, compatibility characteristics, clinical use characteristics and characteristics of adverse reactions.

4. The evaluation method according to claim 3, characterized in that: The method also includes determining the weights of benefit-risk indicators. Through the analytic hierarchy process, the opinions of health decision makers, clinicians in related disease areas, pharmacists, patients and health economists are combined to determine the relative importance of each indicator in the overall benefit-risk assessment by combining qualitative and quantitative methods, and subjective and objective weighting, and set the scoring weights.

5. The evaluation method according to claim 3, characterized in that: The method also includes determining the criterion attributes, namely setting a performance reference level for each benefit-risk indicator, which is divided into two types: quantitative and qualitative. Each indicator sets at least two performance reference levels, namely the most attractive upper limit reference level and the least attractive lower limit reference level.

6. The evaluation method according to any one of claims 1 to 5, characterized in that: The method also includes the following implementation steps: Define decision problems: Based on the benefit-risk assessment framework and the operational implementation steps of MCDA, define decision problems involving decision objectives, evaluation criteria, stakeholders, and output forms; Obtaining data to be evaluated: Obtain relevant data through systematic searches of Chinese and English journal databases, regulatory and medical data, and research interviews; Benefit-risk assessment: Based on the benefit-risk assessment framework and MCDA model, conduct a detailed qualitative and quantitative analysis of Chinese patent medicines; Variability factor analysis: Analyze the impact of variability factors on the target diseases treated by Chinese patent medicines and clarify their clinical positioning; Sensitivity analysis: evaluate the stability of benefit-risk assessment results and the reliability of evaluation indicators.

7. A multifunctional evaluation system based on the characteristics of Chinese patent medicine, characterized in that: The system adopts the evaluation method described in any one of claims 1 to 6 to perform benefit-risk evaluation on post-marketing Chinese patent medicines.

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