Guideline on Non-inferiority Clinical Trials (Draft for Public Review)临床试验数据监查委 员会指导原则（征求意见稿）.docx

PAGE 2 Guideline on Non-inferiority Clinical Trials (Draft for Public Review) Center for Drug Evaluation, NMPA September, 2019  Table of Contents TOC \o 1-3 \h \z \u 1. Overview 1 2. Application Conditions 1 2.1 Historical Evidence of Active Comparator’s Efficacy 1 2.2 Constancy Assumption 2 2.3 Good Trial Quality 2 3. Key Points in Trial Design 2 3.1 Statistical Hypothesis 2 3.2 Active Control 3 3.3 Analysis Population 3 4. Determination of Non-inferiority Margin and the Corresponding Statistical Inference 3 4.1 Fixed Margin Method 4 4.2 Synthesis Method 5 5. Other Considerations 6 5.1 Potential Benefits Relative to Loss of Efficacy 6 5.2 Conversion between Non-inferiority and Superiority 6 5.3 Three-arm Non-inferiority Design 6 5.4 Communication with Regulatory Agencies 7 Appendix 1: Key Formulas 8 A1.1 Fixed Margin Method 8 A1.2 Synthesis Method 8 Appendix 2: Example 9 A2.1 Fixed Margin Method 9 A2.2 Synthesis Method 9 PAGE 1 Guideline on Non-inferiority Clinical Trials Overview When confirming the efficacy of a drug, superiority trials (superiority of the test drug over placebo, the lower dose of the test drug, or the active drug) are commonly considered. Where superiority trials are not applicable, e.g., the use of placebo control might be considered unethical, consideration may be given to the use of non-inferiority trials. Non-inferiority trials were designed to confirm the clinical efficacy of the test drug, in the sense that the difference in treatment effect is within a clinically acceptable range even in case the test drug appears to be inferior to the active control. The purpose of this guideline is to describe the application, design elements, non-inferiority margins, statistical inference, and other regulatory considerations in order to guide clinical trial stakeholders to understand, conduct, and evaluate non-inferiority trials. This guideline applies primarily to confirmatory