Deputy Director of the Food and Drug Administration: Ensure the safety and effectiveness of drugs from the source

Source: People's daily 2015-12-31 authentic, standardized and complete clinical trials are the source guarantee of drug safety and effectiveness If there are problems in clinical trial data, it will not only bring hidden dangers to the safety of drug use for the common people, but also seriously affect the healthy development of China's pharmaceutical industry Since July 22, the State Food and drug administration has carried out the self-examination and verification of drug clinical trial data What is the progress of this so-called "most stringent" clinical trial data verification? How to deal with data fraud? In response, the reporter interviewed Wu Zhen, deputy director of the State Food and drug administration Some clinical trial data are untrue, incomplete and other problems reporter: why do we carry out self-examination and verification of clinical trial data? Wu Zhen: the data of drug clinical trials is an important basis for judging the effectiveness and safety of drugs It is a legal procedure before drug approval and marketing to verify the data In view of the untrue or even falsification of clinical trial data in some drug registration applications, the State Food and Drug Administration issued a notice on July 22 to comprehensively start the self inspection and verification of clinical trial data of drugs, with the purpose of standardizing the clinical trial of drugs in China and even the whole drug research and development, production and operation, and promoting medicine Industrial restructuring, transformation and upgrading to better meet the public drug demand This is also the key task of the State Council to reform the drug review and approval system Reporter: how is the progress of self inspection and verification of clinical trial data? What problems were found? Wu Zhen: the self-examination and verification of drug clinical trial data involves 1622 pending drug registration applications received by the general administration before July 22 In the stage of enterprise self-examination, 317 applications for registration have been withdrawn Since November, the General Administration has organized forces to verify part of the bioequivalence test projects with doubtful authenticity in two batches 24 registration applications of 22 enterprises with untrue and incomplete clinical test data have been rejected As of December 14, the total number of applications for voluntary withdrawal of drug registration was 727 From the verification of two batches of clinical trial data, there are two types of problems: one is authenticity, the other is standardization and integrity The authenticity problems mainly include fabricating data, tampering with data, concealing data, the original data can not be traced, and the test drug is not authentic Most of these behaviors have obvious subjective intention, which seriously endangers the effectiveness and safety of the drugs on the market The problems of integrity and standardization are mainly due to the lack of some clinical data, which is not enough to make the validity and safety judgment; the behaviors violating the relevant provisions of GCP affect the judgment of drug validity and safety made by the review organization Reporter: what are the causes of these problems in clinical trials? Wu Zhen: the main reasons for the problems are as follows: first, the applicant failed to fulfill the supervision responsibility for the clinical trial behavior in accordance with the relevant provisions of GCP The clinical trial contract organization (CRO) entrusted by the applicant failed to perform the corresponding supervision responsibility for the trial behavior Second, the clinical trial researchers violated the regulations, did not load the clinical trial data into the medical records and case tables, did not fill in the relevant data truthfully, or even tampered with the data Third, the clinical trial institutions do not review and check the research results The fourth is that some drug regulatory departments only conduct on-site clinical trials Clinical trial data is not true and complete, which has profound historical and social reasons China's modern pharmaceutical industry started late, with a serious shortage of drugs in history Since the reform and opening up, the pharmaceutical industry has developed greatly, which has basically solved the problem of drug accessibility In the past decade, China has taken many measures to improve the quality of drugs, but there is still a big gap between the quality and efficacy of some drugs and the original products This is not only the problem of the development of the pharmaceutical industry itself, but also related to the social environment of the whole society's lack of respect for intellectual property rights, the lack of respect for the labor of drug clinical experimenters, the expulsion of "good money" from "bad money" in the field of drug marketing, and the "supplement of medicine with medicine" by medical institutions Reporter: how to deal with the behavior person of clinical trial data fraud? Wu Zhen: if there is any authenticity problem in the clinical trial data, it is necessary to file a case for investigation and clarify the responsibilities of all parties In principle, the applicant for drug listing shall bear all legal responsibilities for the data registered and declared; the project researcher and cro of the drug clinical trial institution shall bear direct responsibility for the authenticity and integrity of the data; the drug clinical trial institution shall be indirect responsibility In principle, applicants and clinical trial institutions that have been found to have authenticity problems in multiple varieties will not be reviewed and approved for their application or other application items they undertake If the applicant or clinical trial institution believes that the data can be guaranteed to be true and reliable after self inspection, they can apply for on-site verification by the regulatory authority If there are still authenticity problems in the verification, they shall be given heavier punishment 。 Reporter: what are the policies and measures for self inspection and verification? Wu Zhen: first, we should be lenient in self-examination and strict in handling If it is withdrawn before the inspection of the General Administration, the list of responsible units and responsible persons shall be published, but the responsibility shall not be investigated; if it is verified that there are problems affecting the judgment of drug safety, effectiveness and quality controllability, it shall not be approved; secondly, intentional fraud shall be severely punished, and normative correction shall be allowed For the problems found in the verification, it is necessary to strictly distinguish the two types of problems with different natures: the untrue data, the irregular data and the incomplete data If the data is untrue and is subjective and intentional, it must be investigated and dealt with seriously, the relevant personnel shall be investigated for responsibility and released to the public; if the applicant, drug clinical trial institution or contract research organization has evidence to prove the authenticity of the data, and the data is verified to be true after investigation, it shall not be deemed as intentional fraud In case of falsification of drug clinical trial data, it is not allowed to mix the non-standard and incomplete problems, and make the matter smaller and attach more importance to the matter rather than the matter; in case of non-standard and incomplete problems, it is necessary to prevent misjudgment as data falsification The third is not to pursue the withdrawal quantity, only to see whether the data is true and complete Whether to withdraw or not shall be decided by the applicant or the medical institution on the basis of self-examination No unit may compel the applicant to withdraw It is not advisable for individual medical institutions to stop purchasing drugs from enterprises and force them to withdraw Strengthen the verification of clinical data to become a normal reporter: is the drug listing application submitted after the announcement on carrying out the self inspection and verification of drug clinical trial data subject to self inspection and verification carried out? Wu Zhen: strengthening the verification of clinical data should be the norm Data verification shall be conducted for the registration application not listed in the verification list in the Announcement No 117 of the General Administration on July 22 and the application for registration after July 22 In particular, if there is still data fraud in the registration application after Announcement No 117, the relevant responsible units and personnel shall be reprocessed All drugs to be reviewed and marketed must be subject to on-site verification of clinical trial data one by one The drug audit center and the verification center of the State Food and Drug Administration will timely communicate the variety information and verification results that enter the review procedure, and make the drug review conclusion in time Reporter: what are the considerations for further strengthening the management of clinical trials? Wu Zhen: we will cooperate with relevant departments to carry out clinical trial training and improve clinical trial management and R & D level According to the relevant provisions of China's GCP, starting with strengthening the construction of institutional offices and implementing the responsibilities of major researchers, we should ensure the scientific, authentic and reliable drug research and development data from the source Clinical research is a necessary ability for a medical college, especially for a large public medical institution Drug clinical research is the scientific research behavior of medical scientists, which has high risk and takes up medical resources, and needs reasonable remuneration Clinical research should be developed as a science and technology industry to fundamentally solve the problem of insufficient clinical resources We hope that drug manufacturers, drug clinical trial institutions and cros can consciously correct the untrue and incomplete clinical trial data It is hoped that the punishment, warning and education for the few persons responsible for the falsification of clinical data will help rebuild a good ecological environment for drug research and development, promote the healthy development of the pharmaceutical industry, and ensure the effective and safe use of drugs by the public.