Medical network - February 8 to regulate quality of generic drugs and curative effect evaluation of consistency, total bureau of national food and drug supervision and administration organization developed the generic quality consistency and curative effect evaluation of clinical efficacy test general considerations, are hereby issued.
Please take note.
Attachment: generic quality consistency and efficacy evaluation of clinical effectiveness test general considerations
The food and drug supervision bureau
On January 25, 2017
The attachment
Generic quality consistency and curative effect evaluation of clinical effectiveness test general considerations
A, scope of application
To implement the state council about the opinions of the drug review of medical equipment examination and approval system reform "(guo fa [2015] 44), the state council general office on the evaluation opinions of generic quality and curative effect of consistency" (countries do hair [2016] no. 8), the spirit of the state food and drug supervision and administration bureau issued "on the implementation of the general office of the state council about to carry out the quality of generic drugs and curative effect evaluation opinion consistency > announcement of relevant matters of no. 106 (2016). The above-mentioned documents, generics consistency evaluation should select appropriate evaluation method. In principle should adopt the method of in vivo bioequivalence test consistency evaluation. Can't find or unable to determine the reference preparation, clinical effectiveness tests by the pharmaceutical producing enterprises.
State food and drug supervision and management of administration has issued the pharmacokinetic parameters for the finish evaluation index of chemical drugs generic human bioequivalence study technical guiding principles such as guiding principles. This document is a supplement to the above guidelines document, mainly is suitable for the "can't find or can't to determine the reference preparations, needs to carry out clinical effectiveness test of generics".
Second, the general principle
Generic drugs for clinical effectiveness and test the first thing to consider and evaluate the practical clinical value of generic drugs, based on the background information and evidence of evidence-based medicine to clinical effectiveness in preliminary judgment. Generic quality consistency and curative effect evaluation of clinical efficacy test shall comply with the general rule of drug clinical trials, at the same time, according to background information of generic drugs (such as: clinical research and application at home and abroad information) and evidence-based medical evidence to determine the purpose of clinical trials, in accordance with the formulate follow-up clinical trial scheme and implementation.
In addition to this document, it is should be comprehensive reference "guiding principles in biostatistics drug clinical trials and related guidelines and documents.
Third, the specific requirements
1. The clinical effectiveness of preliminary judgment
Generics should evaluate the clinical effectiveness of experiment in the existing treatment of clinical value, based on the background information and evidence of evidence-based medicine to clinical efficacy in preliminary judgment. The drug's clinical curative effect should be considered: (1); (2) compared with other treatment curative effect; (3) whether there is any impact to existing drug curative effect of other factors, such as tolerance, compliance, or patients.
Considering the problem above, should pay attention to is the data come from a good control method in clinical trials, in order to make the conclusion has the scientific nature.
2. The control medicine
Controlled drugs generally can be divided into placebo-controlled and positive control drug. For clear curative effect, encourage choice placebo-controlled clinical trials for optimal effectiveness. But such as is not suitable for the special situation of cytotoxic drugs etc application placebo-controlled, also can choose positive control drug in clinical trials the bad effect. Positive control medicine indications should be the same, the clinical efficacy of drugs. The best is the same as the test drug action mechanism of drugs. Positive control medicine to choose carefully, an appropriate positive control should be recognized: (1), have enough clinical data support; (2) the curative effect is expected to return.
3. Compare type
Generics consistency evaluation of clinical efficacy test comparison types mainly include the superior effect of experiment and the bad effect.
Optimum effect of test is to show the purpose of the test drug treatment effect is better than that of controlled drugs, including: experimental drugs is better than a placebo; If medicine is better than the positive control drug. Not bad effect test purpose is to confirm the curative effect of experimental medicine at least not worse than the positive control drug.
4. The finish indicators
According to the characteristics of generic drugs, combined with the specific situation to choose the appropriate drugs end target. Generics consistency evaluation of clinical efficacy test purpose is to evaluate the effectiveness, can be used universally accepted measure of clinical end point; Also can use valuable alternative destination or biomarkers, grasp the scientific, accurate, sensitive and efficient principle, realize the testing purpose.
Refer to the guiding principles in biostatistics drug clinical trials on drug clinical trial end point index, select the appropriate indicators.
5. Sample size estimation
Consistency under normal circumstances, the quality of generic drugs and curative effect evaluation of clinical efficacy test sample size estimation is based on the effectiveness of consideration. Sample size estimation by the study of disease, types of study design and study the influence of factors such as the end. Estimation of sample size should be according to the experimental group and control group treatment effect of forecast values and the corresponding variation degree, statistical analysis method, a false positive error rates, master degree, may be lost to follow-up rate to determine the parameters, such as.
Sample size estimation of concrete may refer to the guiding principles in biostatistics drug clinical trials.
Fourth, references
1. The CFDA. Drug clinical trials of biostatistics guidelines. 2016.
2. The CFDA. Pharmacokinetic parameters for the finish evaluation index of chemical drugs generic human bioequivalence study technical guidelines. 2016.
3. Qin Boyi Ed. An introduction to new drug evaluation. People's medical publishing house, second edition (1998).
4. Wei Shuli editor. Biopharmaceutics and pharmacokinetics. Beijing medical university press, (2001) the first edition.
5. Xiang-lan zhao Ed. Clinical pharmacokinetic foundation and application. Zhengzhou university press, (2003) the first edition.
6.FDA. Guidance for Industry Bioequivalence Studies with Pharmacokinetic Endpoints for Drugs Submitted Under an ANDA. 2013.
7.General Considerations for Clinical Trials（E8）.
8.Statistical Considerations in the Design of Clinical Trials（E9）.
9.Choice of Control Group in Clinical Trials（E10）.
10.Garbe E， Rohmel J， Gundert-Remy U， et al. Clinical and statistical issues in therapeutic equivalence trials[J]. Eur J ClinPharmacol， 1993： 45： 1-7. |
