"Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version 2021)" Released

The General Office of the National Health Commission issued the "Notice on Standardizing the Development of Comprehensive Clinical Evaluation of Drugs", accompanied by the "Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version 2021)", and made detailed arrangements for the comprehensive clinical evaluation of drugs nationwide

In order to further implement the decision and deployment of the Party Central Committee and the State Council on improving the drug supply guarantee system, and promote the return of drugs to clinical value, in accordance with the National Health Commission's "Notice on the Implementation of Drug Use Monitoring and Comprehensive Clinical Evaluation" (National Health Drug Administration Letter [ 2019] No.

1.

Comprehensive clinical evaluation of drugs is an important technical tool for drug supply assurance decision-making

The National Health Commission organizes the comprehensive clinical evaluation of drugs in accordance with its responsibilities, promotes the construction of a national comprehensive clinical evaluation system for drugs focusing on essential drugs, and mainly guides relevant technical institutions or commissioned institutions to carry out comprehensive evaluations and coordination of basic drugs for the prevention and treatment of major diseases.

2.

Encourage medical and health institutions to independently or take the lead in building work teams, establish technical consultation and special training systems, and organize comprehensive clinical evaluation of drugs

Scientific research institutes, colleges and universities, industry associations, etc.

3.

Medical and health institutions at all levels and at all levels should focus on strengthening the coordination of comprehensive clinical evaluation of drugs, explore the construction of a cross-regional multi-center comprehensive clinical evaluation mechanism for drugs, and coordinate the promotion of national basic drugs for the prevention and treatment of major diseases, and regional (provincial) basic drugs for the prevention and treatment of important diseases.

All localities shall adhere to the principle of “who is in charge, who is authorized, and who uses who is responsible” in accordance with relevant laws, regulations and standards for cybersecurity and data security, and strengthens the collection, storage, use, processing, and processing of data in the evaluation process.

No unit or individual is allowed to illegally obtain or disclose data and information on comprehensive clinical evaluation of drugs, and shall not use or release data and information related to comprehensive clinical evaluation of drugs at the national and provincial levels without authorization by the national and provincial organization and management departments

All localities are requested to promptly report the problems encountered in the standardized comprehensive clinical evaluation of drugs and related work suggestions to the Department of Pharmaceutical Affairs of the Commission

Attachment: Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs (Trial Version 2021)

General Office of the National Health Commission

July 21, 2021

(Information Disclosure Form: Active Disclosure)

Appendix

Guidelines for the Management of Comprehensive Clinical Evaluation of Drugs

(Trial for 2021 version)

Foreword

1.

In accordance with the "Basic Medical Hygiene and Health Promotion Law of the People's Republic of China", "The Drug Administration Law of the People's Republic of China", "Healthy China 2030" Planning Outline, "Opinions of the General Office of the State Council on Improving the National Essential Drug System" (issued by the State Council (2018) No.

Second, the formulation process

In order to accelerate the establishment of a unified, scientific and practical comprehensive drug clinical evaluation standard, implementation path and work coordination mechanism, coordinate the development of drug decision-making evidence integration, scientific analysis and accurate evaluation, guide and standardize the comprehensive clinical evaluation of drugs, the National Health Commission The Department of Pharmaceutical Affairs entrusted the National Center for Comprehensive Evaluation of Medicines and Health Technologies (linked to the National Health Development Research Center of the National Health Commission, hereinafter referred to as the Evaluation Center), the National Health Commission’s Drug Management Center (hereinafter referred to as the Center for Medical Devices), the United Nations National Cardiovascular Center, National Cancer Center, National Children's Medical Center, and related medical and health institutions, etc.

Three, drafting ideas

This guide mainly focuses on the basic drug requirements for the prevention and treatment of major clinical diseases in China, based on China’s drug clinical application practice and drug supply guarantee policy status, referring to beneficial international practices and experience, and focusing on clarifying the purpose, principles, organization and management, and standardized procedures of comprehensive drug clinical evaluation.
Content methods, quality control, results application, etc.
, aim to guide and promote relevant subjects to conduct comprehensive clinical evaluation of drugs, continue to promote the standardization, standardization, scientification, and homogeneity of comprehensive clinical evaluation of drugs, and better serve the national drug policy Decision-making needs, help improve the quality of pharmaceutical services, ensure the supply and standardized use of clinical basic drugs, control unreasonable drug expenditures, and meet the people's drug needs with higher quality
.

Fourth, the main content

This guide includes 4 chapters
.

The first chapter proposes the purpose, basic principles and the scope of application of this guideline for comprehensive clinical evaluation of drugs
.

The second chapter introduces the evaluation process, content and dimensions
.
It defines a comprehensive drug clinical evaluation work process including three basic links including subject selection, evaluation implementation, and result application transformation
.
Focusing on the two main lines of technical evaluation and policy evaluation, the management requirements for scientific and standardized clinical comprehensive evaluation of drugs from the six dimensions of safety, effectiveness, economy, innovation, suitability, and accessibility are put forward
.

The third chapter introduces the evaluation and application of evidence
.
Clarified the requirements for establishing and improving the basic information platform for the national comprehensive clinical evaluation of pharmaceuticals, making full use of real-world data, and gradually forming a national comprehensive clinical evaluation model, index system and standardized decision-making framework for the national pharmaceutical clinical evaluation, and strengthening data information security
.
Proposed guidance on evaluation quality control and results application, carried out key quality control work around the qualifications of relevant entities, organizational process compliance, methodological rigor, etc.
, and proposed that the organization implementing agencies should carry out evaluation results transformation and application according to the process, and continue to track The application situation of medicines, continuously accumulating data to verify the evaluation results and other requirements
.

The fourth chapter puts forward the requirements of the guideline management
.
It is clear that this guideline and the relevant disease-specific technical guide jointly constitute a comprehensive clinical evaluation guide system for drugs, and it is proposed that this guideline accepts social opinions for a long time and is regularly revised and improved
.

Five, special instructions

This guideline is compiled based on the cognition level and technical ability of the implementation of comprehensive clinical evaluation of drugs under the current circumstances in China, and is intended for reference by relevant subjects involved in the research and implementation of comprehensive clinical evaluation of drugs
.
With the deepening of theoretical research, the progress of scientific and technological development and the accumulation of practical evidence, this guide will be continuously updated and improved
.

Chapter 1 Overview

First, the purpose

The comprehensive clinical evaluation of drugs is centered on people’s health and guided by the clinical value of drugs.
It uses real-world data and information from all aspects of drug supply to carry out comprehensive analysis of drug practical applications, explores and establishes and gradually improves it based on policy coordination and information sharing to meet multiple subjects Participation and multi-dimensional analysis of the needs of the national drug clinical comprehensive evaluation mechanism to provide evidence-based evidence and professional health technology evaluation support for improving the national drug policy, ensuring the supply and rational use of clinical basic drugs
.

2.
Basic principles

(1) Demand orientation
.
Focus on the major issues in the governance decision-making needs of China's health care and the implementation of the drug supply guarantee system in the new era, adhere to correct value guidance and evidence-based judgments, focus on optimizing the dynamic management mechanism of clinical basic drugs, and promote the coherent coordination of national drug policies
.
(2) Overall planning and coordination
.
Adhere to the concept of co-construction, co-governance and sharing of overall planning, multi-party participation, and coordination of technology and management, give full play to the advantages and information technology of all parties, and explore the establishment of comprehensive clinical evaluation standards, pathways and working mechanisms with Chinese characteristics
.
(3) Scientific norms
.
Based on the actual situation of the country, highlighting the evidence of drug efficacy and drug supply guarantee policy evaluation, summarizing and referring to international beneficial experience and successful practices, rationally drawing on evaluation models, methods, technical processes and tools, integrating multidisciplinary professional knowledge systems, and establishing and improving evaluation rules and technical standards Guide the development of comprehensive clinical evaluation of drugs in an orderly manner
.
(4) Fairness and transparency
.
Insist on the joint participation of stakeholders, establish information disclosure and data sharing evaluation implementation, quality control and application transformation mechanisms to prevent potential conflicts of interest, ensure that the evaluation organization, management, implementation process and results are fair and just, and open in accordance with laws and regulations
.

3.
Applicable reference range

This guide is mainly used by national and provincial health departments to organize and carry out comprehensive clinical evaluation of drugs based on the decision-making purposes of selecting basic drugs for disease prevention and treatment, formulating basic drug policies for the prevention and treatment of major diseases, and strengthening drug supply management
.
At the same time, it provides management practices and process guidelines for medical and health institutions, scientific research institutes, universities, colleges, and industry (association) associations to carry out comprehensive drug clinical evaluation activities
.

Chapter 2 Evaluation Process, Content and Dimensions

The comprehensive clinical evaluation of drugs focuses on the key decision-making elements of the drug use and supply guarantee system, focuses on the actual clinical use of drugs and the related drug policy decision-making issues, selects appropriate evaluation theoretical frameworks, methods and tools, and collects and analyzes the use and supply of drugs.
Link data and information, comprehensively evaluate the clinical use of drugs and the actual implementation effects of drug policies
.
1.
Evaluation process The complete process of comprehensive drug clinical evaluation includes three basic links: subject selection, evaluation implementation, and result application transformation.
Evaluation implementation includes project commission, quality control, result submission and acceptance (pictured below)
.

Schematic diagram of the evaluation process

The organization and management of comprehensive drug clinical evaluation and technical implementation agencies shall coordinate to strengthen work coordination, information communication and technical exchanges, promote the establishment of work systems such as subject selection, quality control, expert consultation and result transformation, and organize the specific evaluation tasks undertaken in accordance with local conditions
.
Give full play to the professional advantages of various types of medical and health institutions, scientific research institutes, colleges and universities, and industry (association) associations, develop evaluation technical specifications, strengthen business training, and explore the establishment of cross-provincial, multi-center real-world data collection and standardization Parallel technology evaluation mechanism
.
The evaluation themes mainly include national basic drugs for the prevention and treatment of major diseases, regional basic drugs for the prevention and treatment of important diseases, and drugs for medical and health institutions, taking into account other themes such as special drugs
.
The theme of the national basic medicine for the prevention and treatment of major diseases is selected by the Joint Evaluation Center of the Center for Medicine and Tools, and the theme of the basic medicine for the prevention and treatment of regional important diseases is selected by the provincial health department
.

Encourage national medical centers, national regional medical centers, provincial regional medical centers, and medical and health institutions to independently or take the lead in building work teams, establish technical consultation and special training systems, and organize comprehensive clinical evaluation of drugs
.
The lead unit relies on the evaluation and collaboration network, combined with basic accumulation and technical expertise, to summarize comprehensive information such as disease burden, basic drug needs, drug costs, and hierarchical diagnosis and treatment service system impact, and link with national and regional themes to determine the main topics and their corresponding topics The reference object, after the approval of the participating medical and health institutions, starts the evaluation theme project and evaluation work according to the procedures
.

2.
Evaluation content

The comprehensive clinical evaluation of drugs is a comprehensive evaluation of multi-dimensional and multi-level evidence carried out by the evaluation subject using a variety of evaluation methods and tools
.
The evaluation mainly focuses on major technical and policy issues in the clinical use of drugs.
It focuses on the two main lines of technical evaluation and policy evaluation, and conducts science from the six dimensions of safety, effectiveness, economy, innovation, suitability, and accessibility.
Standardized qualitative and quantitative data integration analysis and comprehensive research and judgment, and put forward policy recommendations on the supply and use of basic drugs for disease prevention and control such as national, regional, and medical and health institutions
.

The main contents of evaluation subjects include: conduct, drug policy information collection and comprehensive analysis of clinical evidence of drug use, organization and implementation of technology assessment, evaluation of drug policy evaluation and written reports
.

Three, evaluation dimensions

(1) Safety evaluation
.

Comprehensive analysis of the results of safety information before and after the drug is launched
.
The included evaluation information includes: drug clinical trial data, drug label content, adverse reactions, adverse events and other information, relative safety (compared with similar products), drug quality, drug efficacy stability and other information
.

(2) Effectiveness evaluation
.

Through quantitative analysis, the population measurement of the clinical effects of the drugs to be evaluated and the reference drugs is carried out to determine whether important health benefits are obtained
.
The core indicators mainly include survival time and quality of life.
The related indicators of survival time include survival rate, disease control rate, and other measurable indicators that can reflect disease progression; quality of life related indicators include health-related quality of life and health utility value.
The quality-adjusted life year (QALY) can be used for further evaluation
.
According to different diseases or treatment fields, core indicators for targeted effectiveness evaluation can be set
.
The data for clinical effect analysis should be derived from all currently available relevant research evidence and real-world data of the best quality.
If necessary, the effect data of subgroups of patients should be analyzed.
At the same time, attention should be paid to the selection of reference drugs and comparative analysis of effects
.
Comprehensive use of existing national, regional or provincial large-scale databases and other real-world data resources, standardize the analysis and measurement based on real-world data research, and use standardized and rigorous methods to achieve clinical actual medication effects within acceptable uncertainties Measurement and judgment
.

(3) Economic evaluation
.

Comprehensive use of epidemiology and health statistics, decision science, economics and other multidisciplinary theories and methods to analyze and calculate the cost, effect, utility and benefit of medicines
.
At the same time, strengthen incremental analysis and uncertainty analysis, and perform health-related budget impact analysis when necessary to comprehensively judge the economic value and impact of the clinical application of drugs
.
According to the specific needs of drug decision-making, you can choose to carry out cost-effectiveness analysis (CEA), cost-utility analysis (CUA), cost-benefit analysis (CBA), minimum cost analysis (CMA), etc.
, and give priority to recommendations when conditions permit Carry out cost-utility analysis
.
Make full use of the results of systematic reviews based on second-hand evidence and real-world treatment models to construct analytical models, attach importance to economic research based on evidence-based results of the Chinese population, and select the best available data as model parameters
.

(4) Innovative evaluation
.

Through analysis to determine the extent to which drugs and reference drugs meet clinical needs, encourage domestic original research and innovation, etc.
, conduct drug innovation evaluation
.
Carrying out innovative evaluation should highlight the filling of clinical treatment gaps, address unmet clinical needs, meet the urgent needs of patients for diagnosis and treatment, and promote innovative value judgments such as domestic independent research and development
.

(5) Suitability evaluation
.

The focus of suitability evaluation includes the suitability of the technical characteristics of drugs and the suitability of drug use
.
The suitability of the technical characteristics of drugs can be evaluated from the aspects of drug labeling, drug inserts, storage conditions, etc.
; the suitability of drug use mainly includes whether the indications are appropriate, whether the interval between patients' medications is appropriate, and whether the length of treatment is consistent with patients, diseases, and drug pharmacology.
characteristics, compliance with medication guide clinical use norms
.
At the same time, from the perspective of the hierarchical diagnosis and treatment and other health service systems, the impact of drug connection, patient welfare and social value of lower and lower medical and health institutions is studied and judged
.

(6) Accessibility evaluation
.

With reference to the WHO/HAI standardization method for drug accessibility, it mainly involves three aspects: drug price level, availability and affordability
.
The drug price level can be obtained by comparing the domestic drug purchase price with the international drug price of the same type in the last year.
If necessary, the medical insurance reimbursement situation should be understood to determine the actual payment level of the patient
.
Availability can be reflected by the availability of medicines in medical and health institutions or whether there is a shortage or not
.
Affordability can be reflected by the percentage (%) of the annual per capita treatment cost of medication in the annual disposable income of urban and rural households
.
Relevant supporting information can be obtained from different channels according to the needs of the evaluation, such as information on the production and supply of medicines, data on the use of medicines in medical and health institutions, and opinions from residents and patient representatives
.

Chapter III Evaluation and Application of Evidence

1.
Evidence information and security protection

(1) Basic information platform
.

The assessment center makes full use of the data resources of existing national, regional and provincial databases, including population health data, health information system data, procurement and circulation and other market data, national and local drug use monitoring data, and clinical diagnosis and treatment service standard guide data to establish and improve National Basic Information Platform for Clinical Comprehensive Evaluation of Drugs (hereinafter referred to as information platform)
.
The information platform has established a complete data co-construction and sharing mechanism, and relevant provincial-level institutions have established a data and work collaboration mechanism with the national platform in combination with local data resources
.

The information platform covers the key links of the whole business process such as subject selection, evaluation research design, data analysis and evaluation, and result evaluation, and has the function of providing information support for key tasks such as data interaction management
.
Medical and health institutions and third-party evaluation institutions are conducting independent topic selection evaluation projects, encouraging them to exchange results on information platforms on a voluntary basis, and promote the sharing of data and information resources related to the industry-wide clinical comprehensive evaluation of drugs
.

For national and provincial-level drug clinical comprehensive evaluation projects involving cross-provincial, multi-center real-world data collection, relevant provincial-level organization and management agencies should study and formulate the overall planning of residents’ health data and medical and health institutions in their jurisdictions in accordance with collection specifications and data security requirements The data collection plan for diagnosis and treatment-related data provides data and information support for the smooth development of the evaluation work
.
At the same time, strengthen network information security and privacy protection matters
.

(2) Real world data
.

Comprehensive clinical evaluation of drugs should make full use of real-world data
.
Real-world data is derived from various data related to patient health status and/or diagnosis, treatment and health care generated daily by medical institutions and other related professional institutions
.

The current real-world data sources related to the clinical application of drugs in China mainly include, but are not limited to: health information system data such as medical and health institution information systems, patient electronic medical records, personal health records, and expense settlement; birth and death and disease registration system data; drugs Adverse reaction monitoring data; medical research cohort data; social drug service data and health-related data self-reported or self-evaluated by patients
.
The acquisition of real-world data is mainly realized through data exchange and sharing
.

Before using real-world data to carry out comprehensive clinical evaluation of drugs, the applicability of the data should be fully evaluated, and scientific research design and rigorous organization and implementation should be carried out around clinical and health policy questions that can be answered by real-world evidence to obtain relevant, reliable, and Appropriate real-world data, after proper, sufficient and accurate analysis, will form relevant evidence for the safety, effectiveness, and economics of the clinical application of drugs
.

Focusing on the basic medication decision requirements, combined with clinical reality, standardized, scientific and reasonable design and implementation of clinical research, promote the use of real-world data in clinical comprehensive evaluation and give full play to its advantages
.
With reference to the recommendations of the practical trial research design, observational research design and other non-experimental designs related to the real-world research of drug review, define the real-world data sources and classification standards closely related to the disease group and the drug characteristics, and compile standardized drug clinical trials comprehensive evaluation data sets, the scope of the definition of acquisition, the acquisition variable, like the acquisition mode
.
Fully rely on the hospital's existing electronic information system to collect data to ensure the accuracy, authenticity and completeness of data collection
.

Encourage medical and health institutions and other drug clinical comprehensive evaluation entities to establish relevant review and supervision systems, conduct quality control evaluations on key links such as data acquisition, data quality, analysis process, and result interpretation, strengthen scientific research ethics management and patient privacy protection, and try to avoid data collection and Analyze bias and effectively support the comprehensive clinical evaluation of drugs
.

(3) Data method model
.

Form data modules based on drug technology evaluation and policy evaluation objectives, give full play to the technical advantages of big data, blockchain, etc.
, to ensure the standardization, completeness, traceability and consistency of the data flow between various source levels, and to carry out the quality of the data Verification provides data and evidence guarantee for scientific evaluation and decision analysis
.
Relying on the evaluation center, other technical guidance units and key medical and health institutions, classification and standardization of data elements, integration of multi-source, multi-type, and multi-center data and evidence, establish national drug clinical comprehensive evaluation standards and methods, and gradually form a national drug clinical Comprehensive evaluation model, index system and standardized decision-making framework
.

(4) Data and information security
.

Adhere to the principle of “who is in charge, who is responsible for authorization, who is responsible for who uses, who is responsible for use”, and strengthen the safety management of data collection, storage, use, processing, transmission, provision, and disclosure in the evaluation process
.
Each evaluation task-bearing institution shall establish and complete relevant information network security management systems, operating procedures and technical specifications, strictly implement patient privacy protection and national confidentiality regulations, and build a credible network security environment
.
No unit or individual may illegally obtain or disclose data, and shall not use or release data and information related to the comprehensive clinical evaluation of national and provincial drugs without authorization by the national and provincial organization and management departments
.
Each evaluation implementing agency and personnel shall bear the main responsibility for the data, network security, personal information protection and evidence quality within the scope of their organization and implementation of the evaluation tasks
.

2.
Evaluation of quality control and application of results

(1) Quality control
.

The focus of quality control includes, but is not limited to, the verification of relevant subject qualifications, organizational process compliance, methodological rigor, data reliability, and report quality
.
Promote the establishment of a sound quality control result feedback mechanism and industry-wide drug evaluation evidence joint construction and sharing mechanism, comprehensive use of existing drug evaluation data and policy information, and carry out evidence quality classification and verification
.

Give full play to the main role of quality control of medical and health institutions and their clinicians, pharmacists and other professional and technical personnel
.
Encourage medical and health institutions and third-party evaluation institutions that meet the requirements to implement rigorous and standardized quality control of key evaluation links in accordance with the needs of comprehensive clinical evaluation of drugs, and establish data quality evaluation and result quality control mechanisms
.

(2) Promote the application of evaluation results
.

The organization and implementation agency of comprehensive clinical evaluation of medicines transforms and applies the evaluation results in accordance with the evaluation plan and process
.

The results of comprehensive clinical evaluation of drugs in regions and medical and health institutions are mainly used to: 1.
Medical and health institutions drug procurement and supply guarantee; 2.
Promote the selection of drug catalogues of medical and health institutions and link up the drug catalogues of medical and health institutions at lower and lower levels to improve pharmaceutical services and safety Reasonable drug use level; 3.
Control irrational drug expenditures, improve the efficiency of health resource allocation, and optimize the structure of drug use; 4.
Provide reference for improving the national drug policy
.

The results of the comprehensive clinical evaluation of drugs by third-party evaluation agencies can be used to: 1.
Enrich the practice of comprehensive clinical evaluation of pharmaceuticals in the industry and expand the documentary evidence reserve; 2.
Promote the in-depth exploration of theories and methods of comprehensive clinical evaluation of drugs in the scientific research field
.

(3) The evaluation results are optimized and perfected
.

The implementation agency of comprehensive clinical evaluation of drugs should continue to track the actual supply and application of the drugs that have been evaluated, and continue to accumulate relevant data to verify the evaluation results
.
The continuous follow-up time of long-term medication depends on the disease or condition, usually not less than 1 year
.
In response to the comprehensive clinical evaluation results of national and provincial medicines with adjustment needs, the main project agency commissioned to carry out evidence optimization and results update in a timely manner based on the policy needs of specific fields and the update of evidence from domestic and foreign evaluation institutions
.

To optimize the evidence and update the results of the comprehensive clinical evaluation of drugs at the national and provincial levels, the relevant departments and medical and health institutions shall combine the clinical application monitoring of drugs and other relevant evaluation research data to submit a written request for evidence verification or update, and consult with the lead organization.
After the argumentation, it is determined whether to start the relevant work
.

Chapter 4 Guide Management

This guideline is the basis for the development of comprehensive clinical evaluation and management of drugs.
In actual application, it needs to form a systematic and complete evaluation guideline system with the professional technical guide for drug evaluation for related diseases
.
The formulation of the technical guidelines for clinical comprehensive evaluation of drugs for specific diseases is jointly organized by the Evaluation Center, the Center for Medical Devices and related technical guidance units in accordance with the procedures, division of labor, collaboration, writing by category, collective review, and on the basis of fully soliciting the opinions of all relevant stakeholders.
, Released after modification and improvement, and updated regularly according to procedures
.

This guide has been implemented since the date of its release.
It accepts social opinions and suggestions for a long time, and regularly organizes revisions and improvements
.