化学药物综述资料撰写的格式和内容的技术指导原则——临床研究资料综述－EN

The Format and Content of Chemical Pharmaceutical Application Materials Technical Direction Principles -- --The Format and Content of Clinical trial Overview (The Second Draft) March 2005 Contents 3I Abstract 4II. The Format and Content of Clinical trial Summary 4( I ) Clinical literature summary and Clinical trial summary 41. Clinical literature summary 52. Clinical trial summary 52.1.Biopharmaceutics research result 52.2.Clinical pharmacology research result 62.3 Clinical pharmacodynamics result 62.3.1 Subject groups of the trial 72.3.2 Results and comparison of pharmacodynamics research 72.3.3 Comparison between different subject groups 82.3.4 Clinic information related to recommended dose 82.3.5 Long-term curative effect and toleration 82.4 Clinical safety result 82.4.1 Drug-taking /exposure conditions 92.4.2 adverse events 112.4.3 evaluation of the lab examining index 122.4.4 the physical conditions related to the safety and other discoveries. 122.4.5 the safety of the special group 132.4.6 the data after coming into the market 132.5 the conclusion of the bio-equivalent effects 13(Ⅱ) the general evaluation of the clinical trial 131 Topic analyses 142. the total evaluation by biopharmaceutics 143. the total evaluation by clinical pharmacology 144. the general evaluation by the effectiveness 155. the total evaluation of safety 166. Gain and Risk Evaluation 17III. Terms and Definitions 17IV. References 18V. Draft Specifications 19VI. Complier I Abstract According to Appendix II of Pharmaceutical Registration Management Measure, the 28th material to be submitted for a chemical pharmaceutical registration application is the “related Clinical trial materials summary internal and external ” which is compiled by the applicant. In order to guide and standardize the application of the summary, taking reference from the relevant technical requirements of the clinical part of application materials CTD of ICH and giving full consideration to the current condition of domestic pharmaceutical registration, we issue The Format and Content of Clinical trial Summary guidelines (following referred as Guidelines in short), the format and content of which is compatible with two guide principles of the Format and Content of Chemical Pharmaceutical Application Materials series: the Compilation Format and Requirement for Major Research Results Summary and Evaluation guidelines and the Format and Content of Clinical trial Report guidelines Clinical trial materials summary is the clinical information summary and evaluation necessary for registration, including Clinical trial and literature review and Clinical trial general evaluation. Clinical trial and literature review refers to the complete and detailed factual summary of Clinical trial and literature information related to the pharmaceutical under research. Based on the reality of domestic registration, Clinical trial and literature review is divided into two parts: 1) clinic literature review for pharmaceutical research and 2) Clinical trial summary. Depending on the different categories of pharmaceuticals, the content of Clinical trial literature review differs: 1) for pharmaceuticals that have come into neither the domestic market nor the international market, the complete and detailed Clinical trial literature review should be provided if there is any related clinic literature. If there is no related clinic literature, necessary explanations should be made and Biopharmaceutics research or literature closed related to Clinical trial should be made available; 2) for pharmaceuticals that have come into the international market but not the domestic market, international and domestic Clinical trial literature review as complete and detailed as possible should be provided together with clinical usage information if possible; 3) for pharmaceuticals for which there have already been national pharmaceutical standards, Clinical trial literature review should be provided together with clinical usage information after marketing if possible. Clinical trial general evaluation is the conclusion from analysis and evaluation based on Clinical trial summary, Clinical trial literature review and Clinical trial reports, which is combined with non-Clinical trial information. At different stages of application, the content of Clinical trial summary is different. When applying for clinical use, Clinical trial literature review and Clinical trial general evaluation should be provided. When applying for manufacturing, in addition to Clinical trial literature review and Clinical trial general evaluation, Clinical trial summary should be provided. Applicant should compile this summary in a scientific, precise and factual manner to provide a complete clinic information summary and evaluation, so as to demonstrate fully the systemic features of the research and development of the pharmaceutical. The summary should be logical, clear and concise. II. The Format and Content of Clinical trial Summary ( I ) Clinical literature summary and Clinical trial summary Clinic literature summary and Clinical trial summary should be compiled according to the following framework and logic. · Biopharmaceutics general evaluation · Clinical pharmacology general evaluation · Clinical Pharmacodynamics general evaluation · Clinical Safety general evaluation · Research Report List and Literature In addition, this material should provide relevant evidence for Clinical trial plan and menu. 1. Clinical literature summary This part should be compiled based on relevant literature (domestic and international). The format and content should be the same as those of Clinical trial Summary. 2. Clinical trial summary This is the summary of the Clinical trial and relevant research for the pharmaceutical under research. 2.1.Biopharmaceutics research result The purpose is to provide the evidence for dosage form design. Firstly, list experiment results, including: 1) dissolution in vitro research; 2) BA or BE research. A summary should be made based on the researches above, with emphasis on: · Evidence to show the influence of prescription and techniques on dissolution in vitro, BA and BE. · Evidence to show the influence of food on BA and BE. · Evidence to show the relations between dissolution in vitro and BA. · Comparison between BA and Be of different dose types. At last, base on the analysis of dissolution in vitro research, BA research and BE research, the logic and evidence for dose type should be provided. 2.2.Clinical pharmacology research result The purpose is provide guidance for Clinical trial. Firstly, list the experiment results based on human body bio-material , human body PK and PD researches and analyses, directive suggestions should be made towards Clinical trial. Content: (1) Human body bio-material research emphasizes permeability research (such as enteric absorbability, permeability of blood-brain barrier )，protein combination, liver metabolism and the interaction between the pharmaceutical and metabolism. (2) Human body PK research and PD research summarize the influence of intrinsic factors and extrinsic factors on PK and PD among different experiment subject groups so as to provide evidence for the design of dose, dose adjustment and drug-taking intervals among different target groups (such as children, old patients and liver- and kidney-mal function patients). (3) Bridging research: summarize and analyze effective information across regions and races so as to provide evidence to bridge international experience. 2.3 Clinical pharmacodynamics result List the pharmacodynamics for each symptom respectively. List Clinical trial results that are related to pharmacodynamics (including dose- pharmacodynamics relations research, pharmacodynamics comparative research, long-term pharmacodynamics research and pharmacodynamics research among different groups). Analyze the focus and particularity of the experiment design, including randomization, double blind method，selection of contrast pharmaceuticals and reasons, selection of experiment subject groups, particularities of the experiment design, research ends (primary and secondary), research duration and pre-decided results analysis methods. If necessary, non-Clinical trial data and clinic pharmacology data can be quoted as evidence, such as supporting the evidence for drug-taking method and dose. Appropriate measures (words, figures and tables) should be taken during compiling. For pharmaceuticals which are tested in more than one Clinical trial, all effective data, including supportive and disapproval data, should be summarized. There are usually two analysis methods: 1) Pooled Clinical trial results analysis; 2) comparison between Clinical trial results. For pharmaceuticals which are tested in just one Clinical trial, effective data from this one experiment should be summarized. The detailed content of the summary include: 2.3.1 Subject groups of the trial Briefly describe the baseline demographic and other features, including disease characteristics (seriousness, duration), treatment, inclusion and exclusion criteria; baseline differences between different experiment subject groups; difference between experiment subject groups and target groups after coming into the market; evaluation of the number, time and reasons of deciduous disease. 2.3.2 Results and comparison of pharmacodynamics research The emphases should be: (1). Analyze and compare all Clinical trial results (including positive results and negative results) that will be used for pharmacodynamics evaluation, with emphasis on research end point, contrast groups, research duration, statistical methods, experiment subject groups and dosage. (2). The comparison between Clinical trials should focus on research end point. When research end point involve different parameters and time points, comprehensive comparison of important information from all Clinical trials should be conducted. (3). Provide pharmacodynamics confidence interval. (4). When major differences arise between Clinical trials of the same design, descriptions and discussion should be made. (5). If Clinical trial assemble analysis is conducted, it should be made clear whether this kind of analysis is conducted according to a pre-decided analysis plan or an analysis plan designed after the experiment. The emphasis of this kind of analysis should be the differences between designs, experiment subject groups and pharmacodynamics evaluation so as to facilitate the evaluation of the relations between Clinical trial results and conclusions. (6). Bridging research: summarize and analyze effective information across regions and races so as to provide evidence to bridge international experience. 2.3.3 Comparison between different subject groups The purpose is to decide whether the effects of different sub-groups are the same. Conduct the parallel comparative analysis of multiple Clinical trials and evaluate the influence of demographic factors and other pre-decided or relevant intrinsic and extrinsic factors on pharmacodynamics. 2.3.4 Clinic information related to recommended dose Refer to non-Clinical trial results, summarize pharmacokinetics research, toxicology research and contrast Clinical trial and non-contrast Clinical trial data and provide evidence for the recommended dose (the first dose, maximum dose and patient-oriented dose). 2.3.5 Long-term curative effect and toleration The purpose is to understand the long-term curative effect and detect whether there is the problem of toleration。 Provide the number of patients with long term curative effect data and clinic information about the exposure duration and analyze the curative effect changes with the duration of drug-taking. This analysis is designed mainly for Clinical trials that have contrast groups, especially for those researches with the purpose of collecting long term curative effect. In long term effect observation Clinical trial, treatment pause in the early stage and other treatment measures should be considered to influence the curative effect. 2.4 Clinical safety result It summarizes all safety-related Clinical trial data and literature data. All experiment subject groups, even those who take the pharmaceutical under experiment for only once, should be listed in safety analysis. Safety-related data should be arranged by taking into the following three factors: · Drug-taking /exposure conditions (dose, duration and patient number) · Adverse events laboratory examination abnormity · Serious adverse events and important adverse events 2.4.1 Drug-taking /exposure conditions List safety evaluation data, including 1) non Clinical trial and literature; 2) clinical safety related clinical results; 3) special safety issues. 2.4.1.1 drug-taking/exposure levels Summarize the exposure levels at each stage of Clinical trial. During compiling, the following issues should be taken into account: (1). if there are different dosages and schedules , categorize and conclude the number of subjects according to the specific dose and schedule. (2). list the largest dosages and the dosage lasting the longest period of all the subjects. And list the per day dosage of the subjects, if necessary. (3). if the adverse events are related to the accumulated doses, the accumulated doses should be provided. (4). the calculation of the dosages according to the weight by kilograms or to the surface area can better imply the relationship between the dosages of the medicine and the adverse events and the lab abnormalities. 2.4.1.2 the characteristics of the subjects To briefly describe the related characteristics of the subjects, including the seriousness of their illness, whether there is any treatment in hospital, whether there is any damage to the functions of livers or kidneys of the subjects, whether there is accompanied syndrome, the other medicine taken and where the subject lives. When cases in which the subject has the accompanied syndrome or becomes more serious or is provided other medicines in violation of the treatment plan are removed from the safety analyses, it should be specifically mentioned. 2.4.2 adverse events To sum up and compare the adverse events in the experimented medicine and the compared medicine: (1) the types of the adverse events; (2) the seriousness; (3) how long it lasts; (4) the treatment; (5) the transferences. The adverse events should include those cases that are related to or unrelated to the treatment. 2.4.2.1 the common adverse events The common adverse events, which are related to the provided medicine, are results of the following factors: the dosages, the dosages calculated according to the weight by kilogram or to the surface area, how to take the medicine, the treatment time, the aggregate dosages, the demographical characteristics such as the age, the sex, the race, the other medicine taken, and the basic functions of the liver and kidney, the effective results and the strength of the medicine. The relationship between the adverse events and the above factors should be analyzed. 2.4.2.2 death All the death cases should be listed according to type, including the death cases within a short term after the treatment and the death cases after treatment, which may be related to the clinical experiments. According to the death rates of the clinical experiments and pooled clinical experiments, the death cases should be examined and analyzed one by one. The total death rate and special death cases taken into consideration, the relationship between the death and the adverse events related to the provided medicine should be analyzed. 2.4.2.3 serious adverse events The relationship between the occurring rate of the serious adverse events and the treatment time should be analyzed, especially when the medicine is provided for a long term. The relationship between the serious adverse events and the adverse events related to the provided medicine should be analyzed. 2.4.2.4 major adverse events First it is presumed that the major adverse events resulting in stopping the medicine are related to the medical treatment, then analyze the reason why the medicine is stopped. Study should be conducted into the comparison of the rates of stopping using the medicine (between the treatment medicine and the consoling medicine or positive compared medicine). The relationship between the major adverse events and the adverse events related to the provided medicine should be analyzed. 2.4.2.5 categorizing the analyses of the adverse events according to the different organ systems The conclusions and analyses of the adverse events according to the different organ systems help to understand the relationship between the medicine and the cases. The names of the different organ systems should be given in these analyses, and should be listed from high occurring rates to low ones. If the adverse events are resulted in the form of syndrome, they should be concluded in particular forms. 2.4.2.6 the analyses of the adverse events All the adverse events of the trial medicine and the control medicine should be analyzed. The comparison of the occurring rates of the adverse events in both of the experimented group and of the control group should better be conducted separately with the combination of the seriousness of the cases and the reasons. If necessary, analyses should be done on the relatedness between the adverse events and the dosages, the medicine time, the basic characteristics and the demographical characteristics. The standard terminologies should be adopted in describing the adverse events. Pooled Safety Analyses is an often-adopted method of analyzing, which can be adopted in the cases when there are same subjects, experiment design, the medicine time and the method examining the adverse events. In some cases, using the combined safety analyses cannot provide valuable information, including the cases when the occurring rates are very different from the various clinical experiments and the cases when it is hard to explain them and use combined safety analyses may cover the true difference. When the cases appear other analyses should be adopted, such as individual study report. 2.4.3 evaluation of the lab examining index To briefly describe the major changes of the lab examining index in clinical experiments, including examining the blood cells, the blood biochemistry, the analyses of urine and the other suitable data, mainly from the following three aspects: · The number of the subjects with the abnormal lab examining index · The major abnormal lab index (including which lead to stopping using the medicine) · The major trends of the lab examining index, such as the average group figure or median. Among the above three, the evaluation of the first two may be more significant in clinical treatment. When the evaluation of the lab index is done, attention should be paid to the consistency of the different figures of lab examining, and explanation should be given to the combination cases. To analyze the relationship between the significance and the possibility of the change of the lab index and the research of medicine, such as to analyze its relationship with the dosages and the strength of the medicine, and to analyze whether it will become normal by continuing to use the medicine, or the risk increases or decreases in such cases and to analyze if it is necessary to use other medicines. To analyze the relationship between the abnormal lab index and the factors of the adverse events. 2.4.4 the physical conditions related to the safety and other discoveries. To provide the conclusion of the syndrome, the physical conditions, the cardiograph, and the video examinations, use the same analyses as the one used in the related part of the evaluation of lab examining. 2.4.5 the safety of the special group 2.4.5.1 internal factors To sum up the safety data whose internal factors are relative to individual treatment or patient management. 2.4.5.2 external factors To sum up the safety data whose external factors are relative to individual treatment or patient management. 2.4.5.3 the interaction of the medicine The interactions of different medicines or medicines and foods should be concluded in the clinical pharmacology part. But the part related to the safety should be concluded in this part. 2.4.5.4 pregnant women and feeding women To sum up the safety data of all the pregnant women and feeding women taking the medicine. 2.4.5.5 excessive dosages To sum up and discuss the information about the excessive dosages, including the symptom/the physical conditions, the discovery in the lab, the treatment measures and the antidotes etc. if possible, the treatment efficiency of using the antidotes and the dialyses should be provided. 2.4.5.6 the abuse of the medicine To sum up the possibility of the relationship occurring between the animals and human beings. To provide the data about the susceptible group. 2.4.5.7 stopping using medicine and rebound To sum up the clinical experimental results related to the stopping using the medicine and rebound, such as the illness becomes more serious, the analyses should be done on the possible relationship between it and stopping using the medicine. 2.4.5.8 the influence on the control or the damage to the recognition ability. 2.4.6 the data after coming into the market If the medicine is already sold in the market, the register applicant should provide the conclusion of the clinical data after it has been sold in the market. 2.5 the conclusion of the bio-equivalent effects To sum up the main conclusion of bio-equivalent effects research , including the conclusion and the results with the method of methodological test, pharmacokinetics parameters and the equivalent effect evaluation. (Ⅱ) the general evaluation of the clinical trial When this part is written, attention should be paid to the following: · To describe and explain the process of the clinical experiments of the medicine resesch; · To evaluate the clinical design and its effects, including the implementation of the GCP; · To briefly describe the positive discoveries in the clinical experiment including the effective discoveries and the safety positive discoveries; · According to the conclusion of the clinical experiments, to provide the evaluation of the profit and risks; · To provide the questions related to the effectiveness or the safety and explain how the questions have been evaluated and solved; · To explore into the unsettled questions and explain the reasons why they will not influence the examination and evaluation, and to provide the plan in dealing with these questions; · To explain some important or uncommon prescriptions. 1 Topic analyses Its' aim is to provide the evidence to support the proposed presumption. The analyses and discussions should be mainly done on the following questions and provide the concluding evaluation of the medicine research proposal. (1). to study the verification according to the category of the medicine science; (2). to study the target adaptation cases in the simulation medical treatment, preventing and diagnosis; (3). to do research into the scientific background of the medicine (4). to briefly describe the items of the clinical trials, including the clinical trials in process or to be done and the applying basis, and the uses of the foreign clinical trials' data; (5). when the analyses are done to the research design and its implementation process, attention should be paid to the agreement between the existed theory and the development of the research. If they are in disagreement, analyses should be done on it. To state clear whether the regulations and laws and the suggestions of the register sections have been taken into consideration. 2. the total evaluation by biopharmaceutics Its aim is to provide the basis to decide the dosage form. As the medicine type design is directly related to the effectiveness and the safety, analyses should be done to the relatedness of the medicine type ready to be sold in market and the bioavailability, such as the dosage form, the dosage, whether the dosage form ready to be sold and the dosage form used in clinical trials are the same or not, and the effects of the food on the medicine. Also the related conclusion should be provided. As for the research on the bio-equivalent, whether there is an interchangeable result between the experimental medicine and the control medicine should be made sure through the methodological test and the analyses and evaluation of pharmacokinetics Parameters. 3. the total evaluation by clinical pharmacology Through the pharmacokinetics, pharmacodynamics and through the analyses and the evaluation of the related data in the clinical trials, evidence should be found to support the clinical trials, During the analyses, all the related data should be taken into consideration, and to what extent it can support the conclusion should be stated. 4. the general evaluation by the effectiveness To provide the analyses of the clinical effectiveness data of the researched medicine’s target group and to explain to what extent these data can support the target adaptation and the prescription. The following factors should be taken into consideration in the evaluation by the effectiveness: (1). the characteristics of the subjects, including the demographical conditions, the ranks of the illness, the other potential main mutation, the main groups excluded from the research, and the children groups and the elderly groups. Discussions should be given to the differences between the tested groups and the potential users after is has been sold in the market. (2). research design, including the chosen patients, research period, the compared groups and the destination. More attention should be paid when using the uncommon clinical trial destination. When the replaced research destination is used, proof should be given that the replaced destination in use is proper. (3). to adopt the examination by non-low-effectiveness so as to prove the effective experiment. During this process, analyses should be done on whether there is experimental test to judge the sensitivity and whether the defining figure of non-low-effectiveness is set up properly. (4). the calculating and analyzing method and any other questions which may affect the results and which needed to be explained. (5). when there are evident difference between the research results and the references, explanation of the influence on the effective data is needed. (6). among all the subject groups and the sub-groups, the relationship of every effect, dosage and the way to use medicine of the adaptation symptom should be stated. (7). how the clinical data from other areas support the research results. (8). in the case of the medicine of long term use, the effectiveness in the long run and the drug-toleration should be taken into consideration. (9). the data of blood medicine concentrate related to the effectiveness. (10). the clinical significance of the research (11). if the replaced destination is used, state the benefits in the clinical experiments. (12). if there is not enough proof in the clinical experimental effectiveness of the special subject groups, the effectiveness should be judged from the effectiveness of whole groups. 5. the total evaluation of safety The important safety analyses should take the following into consideration: (1). the pharmacology adverse effects related to the, medicines. (2). the special adverse effects, such as irregular cardiac rhythm, and the interim prolonging of QT. (3). the bad responses related to the animal toxicology and the product quality. (4). the exposure extent of the subjects’ conditions and the medicines of the experimental groups and the compared groups. Due to the limitation of the safety data, the proper evaluation should be done by the foreseen safety data after the medicine’s selling in the market. (5). in the cases of the common bad responses, discussions only be done about the frequently-occurring adverse events. If significant adverse response, important adverse response, and other clinically important lab index abnormity appear, analysis and evaluation should be conducted on absolute population and occurrence rate. (6). Relevant specifications given when the research result and references differ markedly. (7). Analysis of the difference of any adverse event’s occurrence rate among subgroup subjects (demographic factor, weight, complication, complication medication and genetic polymorphism). (8). Relationship between the adverse reaction on one side and medication dosage, interval and time limit on the other side. (9). Safety of long-time medication. (10). Methods of preventing, reducing and treating adverse reactions. (11). overdosage reaction, rebound phenomenon, medication dependence and medicine abuse. (12). Marketing experience: extent of clinical application in the world; any confirmed, new or different safety issue; administration department’s reaction to the safety issue. (13). Support of research data in other regions for this research. 6. Gain and Risk Evaluation Evaluation should be carried out on the overall gain and risk of medicine studied, with biopharmaceutics, clinical pharmacology, effectiveness and safety conclusion. In evaluation, the following issues should be given concerns: (1). Effectiveness of each target indication. (2). Obvious safety problems and preventive measures taken. (3). Relationship between quantity and effect, relationship between dosage and toxicity, appropriate dosage range and medication. (4). Safety effectiveness of different age groups (age, sex, ethnicity, organ function, disease seriousness and genetic polymorphism). (5). Safety data of children of different age group. (6). Any dangerous factor of known and potential food-medicine or medicine-medicine interactions and recommended methods of medicine research. (7). Effect on operational ability. III. Terms and Definitions 1. Ethnic Factors: factors related to a large number of people who live with their own ethnic people or live with the same characteristics and habits. 2. Intrinsic Factors: factors used to determine and verify a certain subgroup, which are likely to impact whether clinical data could be applied from one region to another. Intrinsic factors include genetic polymorphism, age, sex, height, weight, lean body mass (fat-free mass) and organ incompetence. 3. Extrinsic Factors: factors related to residence environment and culture, which include less genetic features and more cultural and behavioral features. Extrinsic factors include social and cultural features in the region (e.g. the current situation of medical treatment), food, smoking, drinking, pollution, illumination, social and economic situation, medication compliance, and more importantly, reliability of clinical tests in different regions, clinical test design and its actual implementation. 4. Serious Adverse Event: following unpredictable clinical events when any dosage is used: death; threaten to life; need for in-hospital treatment or extension of in-hospital treatment; leading to continuous or obvious dysfunction or leading to congenital malformation or birth defect. 5. Significant Adverse Event: adverse events which are caused by pertinent treatment measures taken (such as medication termination, dosage reduction and heteropathy) and marked anomaly in hematology tests and other lab tests, except significant adverse events. 6. Pooled Safety Analyses: a frequently used analysis method,which is applied when the same test method is used on group, test design, dosage, medication time limit and adverse event. The clinical test that can use pooled safety analyses includes: 1) control study where combination is the best information source of frequent adverse events and it can distinguish between medicine-related adverse events and spontaneous events; 2) all studies where combination is useful for evaluation of rare adverse events; 3) all studies about special medication channels and plans or special adjoint medication; 4) clinical tests of adverse events from volunteer questionnaires and direct inquiry; 5) clinical tests in the same region. The first two are most frequently used. IV. References The Common Technical Document for the Registration of Pharmaceuticals for Human Use Efficacy – M4e: Clinical Overview and Clinical Summary of Module 2. V. Draft Specifications 1. Background With the issuance and implementation of the revised Pharmaceutical Administration of the People's Republic of China，Implementary Ordinance for Pharmaceutical Administration of the People's Republic of China and Drug Register Administration（to try out）and China’s entry into WTO, it is necessary to issue a related instructional document in order to regularize and define the written format and content of the clinical test material overview. Consequently, Examination and Comment Centre for Drug is assigned by National Food and Drug Administration to draft the guideline of the Written Format and Content of the Clinical test material overview (the guideline hereafter). The purpose of this guideline is to provide ways to write the clinical test material overview. 2. Guiding ideology for drafting the guideline: (1). Understanding the current situation in China, with reference to success experience of ICH. (2). Taking into account the following issues in formulating the guideline: demonstrating systematicness of medicine R & D, systematicness and integration of medicine evaluation, and the EBM concept. 3. Structure of the Guideline The clinical test material overview should provide the clinical test summary and evaluation information. The overview should comply with Module 2 of Common Technical Document (CTD) of ICH. Module 2 includes Clinical overview and Clinical summary. With reference to the basic structure of Module 2 of ICH-CTD the guideline defines its basic structure as follows: clinical documentation and clinical summary and overall evaluation of the clinical test. In accordance with China’s actual registration situation, clinical documentation and clinical summary are divided into clinical documentation summary and clinical test summary. In clinical documentation and clinical test summary, the uniform structure framework is adopted. According to the suggestions of Examination and Comment Centre for Drug after the discussion of the project group and the actual registration situation in China, the clinical documentation summary should be placed the first and the clinical test summary the second in terms of the two’s logical order of appearance. There are also relevant specifications about the added item, “bioequivalence study summary” under “clinical test summary” and the added item, “overall evaluation of biopharmacy” under “overall evaluation of the clinical test” when only the bioequivalence study is conduced. The “clinical test summary” of the guideline contains the comparison among several clinical tests. Experts of the project group think that the clinical tests in different phases for registration is nothing but a study at present, so the comparison among several clinical tests cannot be included. After discussion, it is held that the “clinical test summary” should contain the comparison considering the prospect of the guideline, the development of new medicine in China and likely increase of clinical tests of new medicine. If only one clinical test carried out, only that clinical test need to be include without comparison with others. According to the actual situation of medicine registration in China, the guideline specifies requirements for overview materials in different applying phases. 4. Content of the Guideline The Guideline takes the following issues into considerations: (1). Compile the required content of each item in a scientific and cautious way. Since there is no relevant guidelines in China, the content of this guideline takes reference from CTD. By combining the pharmaceutical practice realities, we compile the guideline by making cautious selections. (2). We endeavor to demonstrate comprehensive and systematic evaluation. The guideline tries to demonstrate the systematic value of medicine development and evaluation both in the overall structure or technical requirements of specific projects. In analysis and evaluation of each clinical test, mutual support and verification between clinical tests are emphasized and pharmacy and non-Clinical trial results are taken into account. (3). We endeavor to demonstrate the comprehensiveness of data, and to reduce the bias in analysis and evaluation. For example, in pharmaodynamics summary, non-supportive or negative data should be analyzed. In pooled adverse events report, all adverse events should be provided, including those drug-taking and non-drug-taking related events. VI. Complier The project team for the Format and Content of Chemical Pharmaceutical Clinical Research Overview. 1