Medical Policies Weekly ( Issue 22，2020）
1、 The CDE has issued Technical Guidelines on the Detection of Minimal Residual Disease in Clinical Trials for Acute Lymphoblastic Leukemia (ALL)drugs.
In order to encourage the development of new anti-tumor drugs and to further normalize the application of the detection of minimal residual disease in drug clinical trials for acute lymphoblastic leukemia (ALL), the CDE has recently issued Technical Guidelines on the Detection of Minimal Residual Disease in Clinical Trials for Acute Lymphoblastic Leukemia (ALL) drugs after soliciting the previous public opinions. In the guidelines on new drugs for ALL developed in China, opinions and suggestions were put forward for the detection of Minimal residual disease (MRD) in the clinical studies, especially in the key clinical studies for registration. It is applicable to the clinical studies for acute lymphoblastic leukemia among children and adults, and it is used as the reference by the applicants and researchers for drug research and development.
2、The CDE has issued a number of draft technical guidelines for comments.
（1）In Technical Guidelines on Clinical Trials for Influenza Antiviral Drugs(Draft for Comments), the main contents include overall consideration of clinical trial design, conditions for entry into clinical trials, early clinical trials, exploratory clinical trials, confirmatory clinical trials, and technical considerations in specific public health situations, etc. The guidelines are applicable to the clinical research of the drugs used to treat and prevent diseases caused by influenza A virus (H1N1) and influenza B virus (including seasonal and pandemic influenza, and acute simple influenza without complications and severe flu).
（2）Technical Guidelines on Clinical Research of Drugs for Myopia Progression Control (Draft for Comments) is mainly applicable to clinical research of chemical drugs and biological products for myopia progression control, with emphasis on design principles for key elements of confirmatory clinical trials. The myopia described in the guidelines refers to simple myopia, and mainly refers to the axial myopia in which the anterior and posterior diameter is too long (axial length is beyond the normal range) while the refractive power (refractive properties of cornea, lens and other refractive components of the eye) is basically within the normal range.
（3）Technical Guidelines on Clinical Trials for Human Stem Cells and Their Derived Cell Therapy Products (Draft for Comments) introduces general considerations about clinical trials for human stem cells and their derived cell therapy products and special considerations about individual therapy products, elaborate the research objectives, research methods and evaluation methods of exploratory clinical trials and confirmatory clinical trials of such products launch, and specify “how clinical stem cell studies are used in drug registration applications”, which is initiated by researchers and filed by National Health Commission of the PRC, in order to accelerate the clinical research of stem cell-related therapeutic products in China and improve the efficiency of registration.
（4）Technical Guidelines on Drug Immunogenicity Research (Draft for Comments) aims to put forward the proposal for immunogenicity studies. Immunogenicity research is based on the risk and the logical orders are as follows: immune risk prediction, immune risk identification and risk control. Immune risk recognition mainly focuses on the detection of anti-drug antibodies (ADA). Given the importance of the detection method of ADA, the guideline mainly emphasizes the development and validation of detection methods , which mainly suitable for the protein, peptides and their derivatives, as well as drugs containing such components, such as the coupling drugs.
（5）Technical Guidelines on Non-clinical Research of Radiopharmaceuticals for In vivo Diagnosis（Draft for Comments） applies to surface imaging, single photon emission computed tomography (SPECT), positron emission tomography (PET) and other radiopharmaceuticals for in vivo diagnosis used in nuclear medicine, and mainly describes the concerns of radiopharmaceuticals for in vivo diagnosis in non-clinical research.
（6）Guidelines for Clinical Trials of Biosimilars of Omalizumab Injection (Draft for Comments) puts forward the suggestions for the design of clinical trials, subjects selection, endpoints and equivalence partitioning of biosimilars of Omalizumab injection. In the part of clinical research pathway, common considerations for the development of biosimilars are introduced. In the part of key points of clinical trial design, suggestions like pharmacokinetic comparison study, clinical efficacy comparison study, subjects selection, endpoints selection, evaluation criterion and immunogenicity investigation are introduced in detail.
（7）Catalogs of Chemical Drugs with Clear Clinical Value and No Recommendation of Reference Preparation (first batch): according to Announcement on the Implementation of Quality and Efficacy Consistency Evaluation of Generic Drugs for Chemical Injections (no. 62 (2020) issued by the NMPA), the CDE recently published the first batch of catalogs of chemical drugs with clear clinical value and no recommendations of reference preparation, a total of 117 varieties involved. Among them, varieties which are not listed in China need to refer to Announcement No. 230 (2015) by the CFDA and other related requirements to carry out research. Drug generic names and dosage form are subject to the examination and approval of the Pharmacopoeia Committee.
（8）In the Guidelines on Enrichment Strategy and Design of Drug Clinical Trial (Draft for Comments), the key issues to be considered are illustrated in enrichment design from the aspects of definition, main types, application scope, main design types and result interpretation of enrichment strategies. Instructional suggestions are given about how to use the enrichment strategy to select a more accurate target population. The guideline mainly includes an overview, the applicability of enrichment strategies and designs, common enrichment strategies and design, related considerations about enrichment strategies and design, regulatory considerations as well as appendices.
（9）Guidelines on Multiplicity Problems in Clinical Trials (Draft for Comments) mainly elaborates common multiplicity problems and corresponding solution strategy, introduces common statistical methods of the multiplicity adjustments, aiming to provide guidance on how to control FWER in confirmatory drug clinical trials. The general principles discussed in the guidelines are also applicable to other types of clinical studies.
（10）Guidelines for Subgroup Analysis of Drug Clinical Trials (Draft for Comments) expounds the key issues to be considered in subgroup analysis from the aspects of definition and identification of subgroup, type and application scope, and general considerations of subgroup analysis. Instructional suggestions are provided on how to scientifically conduct subgroup selection, analysis and interpretation of results in confirmatory clinical trials. The guideline mainly includes an overview, subgroup identification and definition, types of subgroup analysis, general considerations, confirmative subgroup analysis, supporting subgroup analysis, other considerations and appendices.
