In order to standardize the evaluation of the quality and efficacy consistency of generic drugs, the State Food and drug administration has formulated the general considerations of the clinical effectiveness test for the quality evaluation and the efficacy consistency evaluation of generic drugs.
This is the notice.
General Administration of food and Drug Administration
January 25, 2017
General consideration of clinical effectiveness test for evaluating the consistency of generic drug quality and efficacy
1. Scope of application
In order to implement the "State Council opinions on the reform of drug and medical device review and approval system" (Guo Fa 2015 No. 44), "the general office of the State Council regarding the development of generic quality and consistent efficacy evaluation opinions" (Guo Ban Fa 2016 No. 8) the spirit of the State Food and Drug Administration issued "on the implement the" Office of the State Council on matters relating to the quality of generic drugs and consistent efficacy evaluation opinions notice "(2016 106th). The above documents suggest that the evaluation method should be reasonably selected for the consistency evaluation of generic drugs. In principle, the method of bioequivalence test in vivo should be used to evaluate the consistency. The drug production enterprises can not find or determine the reference preparation, and the clinical effectiveness test is carried out by the pharmaceutical production enterprises.
The State Food and drug administration has issued guidelines for guiding the research of bioequivalence of chemical drugs based on pharmacokinetic parameters. This document is a supplementary document of the above guiding principles, which is mainly applicable to "generic drugs that need not be identified or unable to identify reference preparations, which need clinical effectiveness tests".
Two. General principles
First, we should consider and evaluate the actual clinical value of generic drugs, and make a preliminary judgement of clinical effectiveness based on their background information and evidence-based medical evidence. The general rule of generics quality consistency evaluation of clinical efficacy and validity of the test should comply with the clinical trials of drugs, at the same time according to generic background information (such as: domestic and international clinical research and application of information) and the evidence of evidence-based medicine to determine clinical trials, clinical trials so formulate follow-up programs and implementation.
In this document, there should be a comprehensive reference guide "drug clinical trials" principles of statistical principles and documents.
Three. Specific requirements
1. preliminary judgment of clinical efficacy
Generic drugs for clinical effectiveness trials should evaluate their clinical value in existing treatments, and make preliminary judgement on their clinical effectiveness based on their background information and evidence-based medicine. We should consider: (1) the clinical efficacy of the drug; (2) comparing the efficacy with other therapeutic drugs; (3) whether there are other factors that affect the efficacy of the existing therapeutic drugs, such as tolerance, compliance or patient orientation.
When considering the above problems, we should pay attention to whether the data are from the clinical trials of good control methods to make the conclusion scientific.
2. control drugs
The control drugs can be divided into placebo control and positive control drugs. In order to clarify the efficacy, we encourage the selection of placebo control for effective clinical trials. However, if the special conditions such as cytotoxic drugs are not suitable for the use of placebo control, the positive control drugs can also be selected for non inferiority clinical trials. The positive control medicine should be the same medicine with the same clinical effect. It is better to be the same drug as the experimental mechanism. The positive control drugs should be carefully chosen. A suitable positive control should be: (1) there is enough evidence supported by clinical data; (2) the curative effect is expected to be reproduced.
3. comparison type
The comparative types of clinical efficacy trials of generic drug consistency assessment mainly include both excellent and non inferiority trials.
The purpose of the effectiveness test is to show that the treatment effect of the test drug is better than that of the control drug, including whether the test drug is better than the placebo, and whether the test drug is superior to the positive control drug. The purpose of non inferiority test is to confirm that the efficacy of the test drug is at least not less than the positive control.
4. end point index
According to the characteristics of the generic drugs and the specific drug conditions, the appropriate end point index is selected. Evaluation of clinical effectiveness of generic conformance test is intended to evaluate the effectiveness of using clinical end point index generally accepted; can also use valuable biomarkers or surrogate end point, grasp the scientific, accurate, sensitive and efficient principle, realize the test objective.
Refer to "clinical trials" statistical principles about drug clinical trial end point index description, select appropriate end point indicator.
5 sample size estimation
Generally, the sample size estimation in the clinical effectiveness test is based on the effectiveness of the generic drug quality and efficacy consistency evaluation. Sample size estimation is influenced by factors such as disease, research design type, and research endpoint. The estimation of sample size should be based on the estimated therapeutic effect and the degree of variation, the statistical analysis method, the false positive error rate, the degree of research and the probability of missing visits.
Estimation of sample size specific statistical principles for clinical trials of the drug "reference".
Four. Reference literature
Statistical principles for clinical trials of 1.CFDA. drugs. 2016.
2.CFDA. based on pharmacokinetic parameters as a terminal evaluation index for bioequivalence of chemicals in pharmaceuticals. 2016.
3. chief editor of Qin Bo Yi. An introduction to the evaluation of new drugs. People's Health Press, Second Edition (1998).
4. Wei Shu Li editor. Biopharmacology and pharmacokinetics. Beijing Medical University Press, No. 1 (2001).
5. editor in chief of Zhao Xianglan. Clinical pharmacokinetics basis and application. Zhengzhou University press, first edition