Principles for Writing Clinical Trial Summary Reports on Traditional Chinese Medicine and Natural Drugs

Principles for Writing Clinical Trial Summary Reports on Traditional Chinese Medicine and Natural Drugs
(Draft 2)

March 18, 002

Principles for Writing Clinical Trial Summary Reports on Traditional Chinese Medicine and Natural Drugs

   1. Overview

A clinical study report is a summary document that reflects the design and implementation of drug clinical trials, analyzes and evaluates the results. It serves as critical evidence for assessing whether a drug has clinical value (efficacy and safety) and is an essential technical resource required for drug registration. Report authors bear professional and legal responsibilities.
Clinical trial reports must thoroughly analyze results and comprehensively describe the study design, management, and execution to establish a scientific basis for conclusions. Only through clear, rigorous reporting can well-designed and properly managed trials yield accepted findings. In drug clinical research, errors in writing or presentation can directly compromise evaluations of safety and efficacy. Therefore, mastering proper report-writing methodologies is essential.
Accurately describing facts, scientifically analyzing data, and objectively evaluating outcomes are the fundamental principles of writing clinical trial reports. Only reliable and authentic conclusions can withstand repeated verification, which is a core characteristic of scientific integrity.
This guideline applies to the preparation of clinical summary reports for Chinese medicine and natural drugs. Clinical trial reports for Chinese medicines should analyze and emphasize the distinctive features of TCM in terms of disease syndromes, target populations, and usage methods for the investigational product.
The goal of new drug development is to safeguard human life and health. Clinical trials must adhere to ethical standards, reflecting respect for life. Ethical considerations in clinical trial reports must be given due attention.
This guidance aims to provide writing conventions and regulatory direction for clinical trial reports on traditional Chinese medicines and natural drugs, facilitating the preparation of complete, clear, and evaluable reports.
This guidance document outlines the structure and key content elements of a general clinical trial report. Due to the complexity of clinical research, the summary report's structure and content may require adjustments based on the specific circumstances of each study. Furthermore, as the standards for clinical trial research continue to advance, the methods for drafting these reports will also be continuously improved and refined.
   II. Structure and Content
(I) Report Cover
Follow the format requirements for drug registration submission materials as specified by the National Medical Products Administration.
(II) Signature Page
1. Report Title
2. Signature of author.
3. Principal Investigator's declaration on the clinical trial report.
I have read this report and confirm that it accurately describes the test procedures and results.
4 Principal Investigator's signature and date. (Include statisticians.)
(III) Table of Contents
Page numbers for each chapter, attachment, and appendix table.

(IV) Abbreviations
Abbreviations should be written out in full at first mention, followed by the Chinese full name in parentheses. A list of abbreviations, special or uncommon terms, and measurement units used in the report should be provided.
(V) Ethical Issues
1. Confirm that the trial implementation complies with the Declaration of Helsinki and ethical principles.
2. Composition of the Ethics Committee and approval of the clinical trial protocol, with a table of independent Ethics Committee members provided in the appendix.
3 Describe how and when informed consent will be obtained for subject eligibility, and provide a sample in the attachment.
(VI) Executive Summary
The report summary should concisely and clearly address the following key points, typically within 1500 words.
1. Test Title.
2 Clinical Approval Number.
3. Principal Investigator and Clinical Trial Site.
4. Trial start and end dates (from the first visit of the first subject to the last visit of the last subject).
5. Objectives and Observation Metrics.
6. Description of the drug's class and therapeutic indications.
7. Provide a brief description of the study design, including the design type (parallel, crossover, group-sequential, etc.), blinding level (double-blind, single-blind, or open-label), randomization method, control type (placebo, active comparator, dose-controlled), and treatment duration.
8. Study Population.
9. Dosing regimen (including control group).
10. Evaluation Criteria (Effectiveness and Safety Metrics).
11. Statistical analysis methods or models (including baseline assessment, between-group comparisons, covariate analysis, network meta-analysis, etc.).
12. Subject enrollment and baseline demographic characteristics by group.
13. Efficacy results by group (primary and secondary endpoints).
14. Safety results by group (adverse events and serious adverse events).
15. Conclusions (conclusions on efficacy and safety).
(VII) Report Body
1. Introduction
Typically includes: background on the investigational drug; study site and investigators; target indication and study population; intervention measures; sample size; trial start and end dates; NMPA approval number for the clinical trial; principles and design rationale followed when developing the protocol; and any agreements or meeting minutes between the sponsor and the clinical research site related to the specific trial. A brief summary of the clinical trial process and results should also be provided.
2. Objective of the test
Provide a statement of the specific trial objectives (including primary and secondary objectives). Clearly specify the intervention, study population, and outcomes for this trial. Define the key research questions to be addressed and clarify the clinical positioning of the drug.
3. Test Method
3.1 Experimental Design
Description of the overall study design and plan (including a flowchart of the clinical trial). If the protocol is amended during the trial, provide the reasons, details of the changes, and the rationale.
Discuss the rationale and justification for the overall trial design, with specific points tailored to the design features. If a single-blind or open-label design is used, provide the rationale.
Provide the specific formula, calculation steps, and the estimated values with sources for all statistical parameters used in the sample size determination.
Describe the interim analysis plan.
3.2 Randomized Design
Provide a detailed description of the randomization methods and procedures, including how the random allocation sequence is concealed. Specify the allocation method used (e.g., centralized allocation or allocation within each trial site). Attach the randomization codes; for double-blind trials, include blinding records, and for multicenter studies, list codes separately by center.
3. 3Blinding Level
Clearly specify the rationale for and implementation steps of the blinding method. Describe specific operational procedures (e.g., drug bottle labeling, labels indicating broken blind codes, sealed coding lists or envelopes, double-dummy techniques). Define conditions for unblinding (e.g., serious adverse events, accidental disclosure), outline the unblinding procedure, and identify personnel authorized to know patient codes. If non-blinded investigators are required (e.g., to adjust medication), describe measures to maintain blinding among other study staff. Detail measures taken to ensure the investigational product matches the placebo or comparator in appearance, shape, size, color, odor, and taste. Confirm that labeling and packaging comply with blinding requirements, including drug packaging and numbering. Explain emergency letter preparation and emergency unblinding protocols. Describe procedures to maintain blinding during data monitoring or interim analyses. State whether data review and biostatistical analysis at trial completion were conducted under blinded conditions; include this information in the summary report and provide a blinded audit report as an attachment.
Additionally, in trials where blinding is difficult to maintain, describe the measures taken to minimize bias and ensure reliable assessment of the investigational product's clinical efficacy, as well as the steps implemented to keep personnel responsible for endpoint evaluations blinded to information that could reveal treatment allocation.
3.4 Research Subject
Describe the eligibility criteria for selecting subjects, including the diagnostic criteria used and their rationale. Specify inclusion and exclusion criteria, as well as withdrawal criteria. Address protocol-specified disease conditions such as severity thresholds or duration requirements, specific laboratory results, staging, or physical examination findings. Include relevant clinical history features, such as prior treatment failure or success. Discuss other potential prognostic factors, including age, sex, or race, and their relevance to subject suitability for the study.
For indications of new Traditional Chinese Medicine (TCM) drugs, the "disease-syndrome combination" approach is currently most common. In this context, both Western diagnostic criteria and TCM syndrome diagnostic criteria must be specified. If the target disease includes subtypes, stages, degrees, or grades, the corresponding classification standards must also be listed.
Details on conditions for subject withdrawal from the trial, among others, shall be described based on the specific product and indication.
3.5 Reference Method and Basis
Describe the type and method of control used, and justify their rationale.
The control drugs include positive controls and placebos. When justifying the selection of a positive control, explain the comparability between the investigational product and the control drug in terms of function and indications. The trial report appendix must include copies of the quality standards and package insert for the control drug.
3.6 treatment process
Describe the investigational drug's name, source, specification, and batch number. Include packaging, labeling, and instructions for use.
Specify the dosing regimen (route of administration, dosage, frequency, duration, and intervals), including the rationale for determining the dose. Describe any restrictions on concomitant medications or therapies during the trial.
For medication management, ensure procedures are clearly defined for inventory counts, distribution, storage, and the collection and disposal of unused medications.

3.7 Efficacy Evaluation Indicators and Methods
Clearly describe the primary and secondary efficacy endpoints. For the primary endpoint, specify the rationale for its selection and the exact time point at which it was defined. Detail the required laboratory tests, including the testing schedule (assessment dates, times, windows, and their relationship to dosing and meals) as well as the measurement methods. A flowchart illustrating the frequency and timing of endpoint assessments is recommended in the appendix. Describe the technical measures implemented to standardize laboratory tests and other clinical assessments or to ensure result comparability.
If surrogate endpoints (laboratory tests, physical examinations, or signs that do not directly reflect clinical benefit) are used as study endpoints, this must be explicitly stated. For traditional Chinese medicine (TCM) studies, the methods and criteria for evaluating TCM syndromes should be clearly described.
Outline the follow-up plan, including objectives, target population, monitoring indicators, treatment protocols, follow-up schedule, and assessment visit timepoints.
3.8 Security Evaluation Metrics and Methods.
Clearly describe the metrics used to assess safety, including symptoms, signs, and laboratory tests with their schedules (measurement dates, times, time windows, and their relationship to dosing and meals), measurement methods, and evaluation criteria. A flowchart in the appendix illustrating the frequency and timing of metric measurements is recommended.
Clearly state expected adverse reactions; describe protocols for observing, recording, managing, and reporting adverse events in the clinical trial. Specify methods and criteria for assessing causality between the investigational drug and adverse events, as well as for determining the severity of adverse events.
3.9 Quality Control and Assurance
Rigorous quality control throughout the entire trial is essential. Adherence to GCP provisions is fundamental to ensuring this quality. A brief description of the quality control system and methods should be provided. Since bias-prone or error-prone stages and factors may vary across trials, focus on outlining the specific QC measures implemented for those areas. Submit the Clinical Research Associate's monitoring summary report in the Appendix.
3.10 Data Management
Clinical trial reports must clearly describe the measures or quality control systems implemented to ensure data quality, including data collection, verification, entry, blind review, and data lock processes. Submit monitoring/audit reports in the appendix.
3.11 Statistical Analysis
Statistical analysis plan and methods for obtaining final results.
Clearly specify the definitions of the statistical analysis sets (full analysis set, per-protocol set, and safety dataset) based on the intention-to-treat principle; define primary and secondary endpoints; describe accepted statistical methods and software for analyzing each endpoint; and outline the criteria for evaluating efficacy and safety.
Key areas include detailed descriptions of how to analyze, compare, and perform statistical tests, as well as the handling of outliers and missing data. This encompasses descriptive analysis, parameter estimation (point and interval estimates), hypothesis testing, and covariate adjustment (including methods for addressing center effects in multicenter studies). The document must specify the hypotheses to be tested, the treatment effects to be estimated, the statistical methods employed, and the relevant statistical models. Estimates of treatment effects should be accompanied by confidence intervals, with the calculation method clearly stated. Hypothesis testing must explicitly indicate whether a one-sided or two-sided test is used; if a one-sided test is selected, the rationale must be provided.
Explain and provide detailed reasons for any cases excluded during analysis. Any revisions to the statistical plan used in the study must be documented.
4. Test Results
4.1 Subject Population Analysis
Provide a chart summarizing the exact number of all enrolled subjects, including those randomized into groups, the number entering and completing each trial phase, and reasons for discontinuation after randomization.
Demographics and other baseline characteristics (balance analysis). Comparative analyses are conducted using key demographic indicators and baseline characteristic data, typically including the Intent-to-Treat (ITT) population, Per-Protocol (PP) population, or subgroups defined by adherence, comorbidities, and baseline characteristics. Key analysis metrics include demographics (age, sex, race), target disease, inclusion criteria, syndrome criteria, disease duration, severity, clinical features and symptoms, laboratory results, critical prognostic indicators, comorbidities, medical history, other trial-influencing factors (e.g., weight, antibody levels), and related factors (e.g., smoking, alcohol consumption, special diets, menstrual status).
Number and reasons for subjects who violated the protocol (statistical description).
Compliance Analysis.
Analysis of concomitant medication and adjunctive therapy.

4.4 Efficacy Evaluation
4.2.1 efficacy analysis
Describe the datasets used for analysis, specifying both the full analysis set and the per-protocol population. Clearly define the participants included in the efficacy analysis (e.g., all subjects who received the investigational drug, all subjects who completed the study per protocol, or all subjects meeting specific adherence criteria). Generally, all randomized subjects who received at least one dose of the investigational product should be included in the analysis. Provide a detailed description of any subjects who received the investigational product but were excluded from the efficacy analysis dataset.
Perform within-group comparisons from baseline to treatment endpoint for all key efficacy endpoints (including primary, secondary, and syndrome-based endpoints), as well as between-group comparisons between the experimental and control groups. Analyses based on continuous variables (e.g., mean blood pressure or depression scores) and categorical variables (e.g., infection cure rates) are equally valid; if both analyses were planned and data are available, report both.
Traditional Chinese medicine should focus on syndrome-based efficacy analysis.
In confirmatory efficacy trials, results should include all planned analyses specified in the protocol and an analysis including all patients with post-treatment data. These analyses should quantify the magnitude of differences between treatment groups, present corresponding confidence intervals and hypothesis test results, and provide both statistical and clinical conclusions.
Analyze the impact of concomitant medications and background therapies on trial outcomes.
Follow-up result analysis.
Each site in a multicenter study should provide descriptive analysis results (site summary). When the sample size is small, hypothesis testing may be omitted. The site summary shall be prepared by the principal investigator of that site. The overall clinical study report must include an analysis of center effects.
4.2.2 Statistics and Analysis
The report text should describe the statistical analyses performed, including the statistical analysis plan and the statistical analysis report. Key features of the analysis should be discussed, such as specific methods used, adjustments for demographics or baseline characteristics or concomitant medications, handling of dropouts and missing data, adjustments for multiple comparisons, special analyses for multicenter trials, and modifications made for interim analyses. Any changes to the analysis made after unblinding must be documented.
4.2.3 Validity Summary
Provide a concise summary of key efficacy conclusions based on primary and secondary endpoints, planned and alternative statistical methods, and exploratory analyses.
4.5 Security Analysis
All subjects who received the investigational product more than once in the trial will be included in the safety analysis population. The safety analysis comprises three components: First, report the extent of drug exposure (dose, duration of treatment, and number of subjects). Second, describe common adverse events and laboratory abnormalities, categorize them appropriately, compare them across groups using suitable statistical methods, and analyze potential factors influencing the frequency of adverse reactions/events (e.g., time dependence, dose or concentration, demographic characteristics). Third, describe serious adverse events and other important adverse events. Special attention should be given to subjects who discontinued the study prematurely due to adverse events (regardless of whether they were considered related to the drug) and to any deaths that occurred.
The following content requires analysis and explanation of three types:
The report body should include summary data for (1), typically presented in charts or graphs.
Individual patient data listings for (2): Narrative descriptions of events with specific significance. All tables and analyses must clarify events related to the investigational drug and control treatment.
(3) All adverse events must be clearly linked to the drug. Summarize reported adverse events in tables or figures, and provide detailed descriptions for those of particular concern. Adverse events associated with both the investigational product and the comparator must be reported.
4.3.1 dosage level
Treatment duration shall be expressed as the mean or median of dosing time, reported as the number of subjects at specific time points. Subgroup counts by age, sex, disease, and other factors must also be provided.
Report dosing as median or mean, expressed as the number of subjects per average daily dose. Dosing can be combined with duration (e.g., for at least one month), showing the number of subjects in each dose group. Additionally, report subgroup counts stratified by age, sex, disease, and other relevant factors.
4.3.2 Adverse Event Analysis
Provide a summary of adverse events observed during the trial. Analyze all adverse events for both the investigational drug and the comparator, and present them visually in tables or figures showing incidence rates, severity, system organ classes, and causal relationship to treatment.
Compare the incidence of adverse events between the treatment and control groups, stratified by severity and causality assessment. When necessary, analyze associations with dosage, timing of administration, baseline characteristics, and demographic factors.
Serious adverse events (SAEs) and other important adverse events deemed reportable by the Principal Investigator shall be summarized and analyzed separately, with case reports attached. The appendix includes case reports for each subject who experienced an SAE or other important adverse event, containing the case number, demographic characteristics, details of the adverse event (onset date, duration, severity, intervention, outcome), and causality assessment.
In combination therapy, the rationale for conclusions regarding the safety of the investigational drug must be clearly stated.
Laboratory tests related to safety for 4.3.3
Based on professional judgment, meaningful laboratory abnormalities (excluding those that are clinically insignificant or unrelated to safety) should be analyzed and explained. Provide a summary table of abnormal findings and comparative statistical tables for the treatment and control groups. Discuss the clinical significance of these changes and their relationship to the investigational drug.
Clinical laboratory evaluation includes frequency tables of normal/abnormal changes for each laboratory test before and after treatment, and a list of individual cases showing clinically significant abnormal values measured before and after treatment.

4.3.4 Security Summary
Provide a summary of the overall safety profile of the investigational drug, with particular attention to: adverse events leading to dose modification or requiring treatment; serious adverse events; adverse events leading to discontinuation; and deaths. Identify potential high-risk populations for the investigational drug. Discuss the potential impact of safety concerns on the broad clinical use of the investigational drug.
5. Discussion
Briefly analyze and discuss the efficacy and safety results of the trial, along with the risk-benefit relationship. The discussion should not simply repeat the results or introduce new findings. Clearly articulate any novel or unexpected discoveries, comment on their significance, and address all potential issues, such as inconsistencies between assessments, considerations for the clinical use of the investigational drug, and limitations in the efficacy analysis. Evaluate the clinical relevance and importance of the results by referencing existing data. Explicitly state benefits for individual subjects or at-risk populations and outline special precautions, providing guidance for future research. Based on the therapeutic profile of the drug, draw possible conclusions regarding its development value and prospects, justify these conclusions, and discuss any issues encountered during the trial that may have impacted the results. For Traditional Chinese Medicine (TCM) studies, explore how TCM theory guides clinical efficacy and adverse reaction prevention.
6. Conclusion
The final conclusion of this clinical trial focuses on a comprehensive evaluation of safety and efficacy to determine whether further research or regulatory submission is recommended.
7. References
List references related to trial evaluation.
III. Attachments
1. Clinical Research Approval from the National Medical Products Administration.
2. Final Case Report Form (CRF).
3. Randomized drug code (if double-blind trial, provide blinding records).
4. Independent Ethics Committee Member List.
5. Investigative sites, including names, affiliations, roles in the study, and resumes of key investigators.
6. Instructions for use and quality standards for the positive control drug, and instructions for use for the investigational drug (if it is a marketed drug).
7. Blindness verification report and records of unblinding and emergency unblinding.
8. Statistical Plan and Statistical Analysis Report.
9. Final monitoring report by the Clinical Research Associate (CRA), audit report by the auditor.
10. Drug Lot Assignment Form (for multiple drug lots)
11. Case report of a serious adverse event and any other important adverse events deemed by the principal investigator to require reporting.
12. Medication Dispensation Registration Form.
13. Copies of the primary clinical research references.
14. Flowchart showing the frequency and time points for metric measurement.
 IV. Definitions:
Random allocation concealment: A method that prevents the allocator from knowing the upcoming treatment assignment during group formation, thereby preventing clinicians, nurses, or patients from selecting a desired treatment.
Follow-up: Follow-up refers to the continued monitoring of subjects after the completion of the trial treatment period until the follow-up endpoint is reached or the outcome is observed. It is a critical step in clinical trials, playing a vital role in objectively evaluating the efficacy and safety of the investigational drug.
Audit: A systematic examination conducted by individuals not directly involved in the trial to evaluate whether the trial's implementation, data recording, and analysis comply with the protocol, standard operating procedures, and applicable regulations for clinical trials.
  V. References
1 ICH Harmonised Tripartite Guideline: Structure and Content of Clinical Study Reports E3.Recommended for Adoption at Step 4 of the ICH Process on 30 November 1995 by the ICH Steering Committee
2. "Drug Registration Management Measures" (2002)
3. Good Clinical Practice (2003)
4. Zheng Xiaoyu. "Guiding Principles for Clinical Research of New Chinese Medicinal Drugs" (Trial Edition). China Medical Science and Technology Press, 2002,5, 1st ed., pp. 46–49.
  VI. Drafting Explanation:
1. The guiding principles for this document primarily emphasize: rigorous methodology, valid analysis of efficacy outcomes, and objective reporting of safety results to fully reflect the drug's unique characteristics; highlighting the distinctive features of traditional Chinese medicine; ensuring full consideration of ethical requirements; documenting the clinical trial process for new drugs with a focus on quality control and assurance measures; providing detailed explanations of safety studies. This guidance aims to improve the quality of clinical trial reports, ensuring they comprehensively, objectively, and accurately reflect the trial process and outcomes.
2. This guideline provides general requirements for writing clinical trial reports of new traditional Chinese medicines (TCMs) and natural drugs for reference only. Report authors should tailor the key points for each clinical trial summary report based on the characteristics of the drug and its indication, building upon these general requirements.
3. The second draft was developed based on the first draft, following the structure outlined in "Writing Clinical Trial Summary Reports" from the *Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs* (Trial), edited by Zheng Xiaoyu. It incorporates the structure and content recommended by ICH clinical trial reports, while considering the unique characteristics of new drug research for traditional Chinese and natural medicines as well as China's specific context. Each section was carefully reviewed, discussed within the research group, and revised into a finalized second draft after circulation to experts for feedback.
4. This guidance places significant emphasis on addressing issues such as the neglect of safety reporting in current research studies and is drafted by referencing the comprehensive safety reporting approach outlined in ICH guidelines.
5. While consensus was reached on the following discussion points, further attention from experts across all parties is still required:
To ensure the authenticity and integrity of clinical trial reports, it is recommended that the following items be included in the attachments:
In the appendix of the clinical trial report, 5.1 must provide copies of the quality standards and package insert for the comparator drug.
5.2 provides a flowchart indicating the frequency and time points for metric measurement.
5.3 submits the monitor's monitoring report in the Appendix.
5.4 Randomized drug code (provide blinding records if a double-blind trial).
5.5 Independent Ethics Committee Member List.
6. The research group identifies the following issues for further discussion, requiring attention and feedback from all parties.
6.1 Principal Investigator signature and date. (Signatories should include the sponsor, statisticians, etc.)
Does 6.2 provide an audit report?
Does 6.3 need to provide the medication distribution registration form?
Experts agree on the evaluation of TCM syndrome treatment efficacy for 6.4. Some experts suggested adding content on "the role and significance of the investigational drug in improving syndromes within disease efficacy assessment," leading to some disagreement. This point can be discussed further.

Authors: Research Group for the Study on "Principles for Writing Clinical Trial Summary Reports of Traditional Chinese Medicine and Natural Drugs"