Since the State Food and Drug Administration started the self-inspection and verification of drug clinical trial data for one year, it has been found that over 80% of the clinical data of new drugs are involved in fraud, and the regulatory links behind them have fallen behind, and the violations of relevant subjects such as pharmaceutical companies, intermediaries and doctors are prominent.
Some people in the medical field believe that with the advance of the verification storm, negative arguments such as "too advanced" and "one size fits all" have risen. The state should adhere to zero tolerance for clinical fraud and reverse the medical ecology of bad money expelling good money with stricter supervision.
The enterprise intentionally concealed and omitted the records of adverse reactions.
The results of the verification of the authenticity and standardization of the data of 1622 drug clinical trial projects to be produced by the Food and Drug Administration caused a shock in the whole industry. Some people in the medical field revealed that with the deepening of self-examination and verification, more problems of untrue and irregular clinical trial data of drugs have been exposed. At present, over 80% of new drug applications have been withdrawn by pharmaceutical companies or rejected by the State Food and Drug Administration.
A staff member of the food and drug department said that during the verification, it was found that the clinical trial data of many drugs were incomplete, the analysis data had no differential trajectory, and some data could not be traced back. Other companies deliberately concealed or omitted the adverse reaction records, and revised the test data that failed to meet expectations.
"Before this round of self-examination and verification storm, clinical data fraud was an open secret in the industry." The dean of a top-three hospital in the west said that pharmaceutical companies randomly combined old drugs and found several hospitals to do clinical experiments. Of course, they all reported according to the expected results. Finally, the State Food and Drug Administration approved the new drugs. "How can this stew-style drug research and development model ensure the quality and safety of drugs?"
"The direct consequence of clinical data fraud is poor efficacy." A person in charge of research and development of a pharmaceutical company in Nanjing said that in a clinical trial, the company replaced the domestic anti-diabetic drug metformin taken by the subjects with the original drug Gehuazhi. Unexpectedly, after taking it for four weeks, the blood sugar of the subjects actually dropped to the level that they could not be enrolled in the group. Previously, the subjects had been taking domestic metformin, but their blood sugar could not be lowered.
According to insiders, most domestic generic drugs can’t meet the original research standards. In order to pass the evaluation, it is very common to conceal the discarded data and selectively use the data in clinical experiments. In this regard, the state launched the consistency evaluation of generic drugs’ quality and efficacy this year, requiring all generic drugs approved for marketing before October 1, 2007 to complete the consistency evaluation before the end of 2018, among which clinical effectiveness tests and varieties with special circumstances need to be carried out, and consistency evaluation should be completed before the end of 2021; If it is not completed within the time limit, it will not be registered again.
Yu Dechao, Chairman of Cinda Bio-Pharmaceutical, predicted that with the consistent evaluation of generic drugs’ quality and efficacy, more than 50% of the existing generic drugs will be eliminated, and the phenomenon of "bad money driving out good money" in the pharmaceutical field is expected to be initially reversed.
Absence of intermediary supervision encourages clinical fraud
In 1998, the relevant departments of the state promulgated the "Management Standard for Drug Clinical Trials (Trial)" (GCP for short), which was revised and implemented in 2003. The reporter’s investigation found that the binding force in the implementation of GCP is not strong, and the violations of relevant subjects such as pharmaceutical companies, intermediaries and doctors are prominent.
Driven by interests, some pharmaceutical companies have launched generic drugs, and the important and necessary link of clinical trials has been "ignored". The person in charge of a large pharmaceutical company in Jiangsu said that he had participated in the research and development of new drugs in a pharmaceutical company, in fact, he copied the newly developed innovative pharmaceutical materials from abroad. This pharmaceutical company spent a week preparing materials, and did not conduct clinical trials for six months at all. It even got the approval of "exclusive innovative drugs" very quickly. As a result, the effect of five domestic generic drugs is not obvious, but one foreign original drug is effective but can’t get in, which is a typical phenomenon of "bad money driving out good money".
The absence of supervision by CRO encourages the falsification of clinical data. A person in charge of a CRO revealed that CRO should be a third-party inspection agency, which plays a role in quality control of drug research and development, clinical application and approval. However, due to the lack of transfer threshold of domestic CROs and vicious competition of a large number of unscrupulous enterprises, many CROs have become accomplices in data fraud driven by interests. "Some pharmaceutical companies know that CRO is fraudulent, but considering that CRO shares the illegal costs and risks, they often turn a blind eye. What’s more, some pharmaceutical companies made it clear that if the test fails to pass the acceptance, it will not pay, forcing CRO to make fraud. "
A law enforcement officer of the food and drug supervision department said that during the inspection, it was found that the main body of clinical trials should be doctors, but some CROs hired a large number of assistant researchers instead of doctors to do clinical observation, data statistics and quality verification, which was an important reason for the irregular and untrue data.
Clinicians’ professional ethics is out of order, which opens the door for data fraud. The chief physician of a third-class hospital in Guangdong said that he had participated in the third-phase clinical trial of an obstetric drug under the leadership of another hospital. "The actual operation is not strict." Many records that are beneficial to the marketing of this drug have been saved, and adverse clinical cases or experimental data have been erased. Especially compared with similar drugs, the fraud situation is more prominent. "Doctors are very busy, clinical trials will not be done seriously, and there is no time to make such rigorous records. Many of them are done by CRO, and the authenticity is naturally greatly reduced."
Clinical supervision has become a weak link in the drug supervision system. Some people in the industry believe that drug regulatory authorities at all levels are generally short of regulatory talents and technical teams with clinical background, and long-term emphasis on system certification and neglect of clinical project process supervision, especially the safety and effectiveness evaluation of post-marketing drug clinical trials, and supervision is almost blank. A staff member of Jiangsu drug supervision system said that compared with GMP inspection team, there is a big gap in the ability of local clinical verification GCP team, and the personnel and technology can not keep up with the current requirements.
Beware of negative arguments weakening supervision.
The reporter’s investigation found that over the past year, the self-inspection and verification of drug clinical trial data has achieved remarkable results, initially curbing the situation of large-scale data fraud, and some pharmaceutical companies feel unprecedented pressure.
"In the past, there was almost no clinical supervision. Now we suddenly asked for self-examination and verification, which caught us off guard." A person in charge of a pharmaceutical company in Inner Mongolia complained that the storm of verification of clinical trial data was "a matter of punishing the Qing Dynasty with the laws of the Republic of China". The state’s policies can’t be changed constantly, and we can’t take the "opinions" and "regulations" issued today to consider what we did before.
The person in charge questioned why so many CRO companies were approved. Why did the test data provided by CRO company pass the review before? Why are clinical trial institutions approved by administrative departments not conducting regular trials? Why should the applicant bear most of the responsibility for a series of mistakes made by the regulatory authorities? "These problems need to be paid attention to by relevant management departments and explained reasonably."
Some people in the industry believe that there are two negative arguments to be vigilant against this unprecedented storm of clinical supervision. First, the introduction of policies should conform to China’s national conditions, and the requirements for innovation at this stage should not be too advanced; Second, the policy cannot be uniform, and some clinical data are just not standardized, not fraudulent, and should be allowed to exist.
Yu Dechao said that at present, it is a critical period to control "bad money drives out good money" in the field of drugs, and real innovation must be encouraged with the strictest system. Once the clinical fraud is spared, the result must be "a small gap becomes a big hole." "If a pharmaceutical company is allowed to falsify, then other pharmaceutical companies will follow suit. Therefore, we must adhere to zero tolerance and not relax about clinical fraud. "
In fact, compared with the United States, China’s drug supervision still needs to be strengthened. The State Food and Drug Administration has made it clear that if the clinical research data are fraudulent, the applicant’s new application for drug registration will not be accepted within three years, and the clinical trial data of the person directly responsible for participating in the research or organizing the research will not be accepted within ten years.
Dr Liao Guojuan, CEO of Suzhou Jinweizhi Biotechnology Co., Ltd. said that in the United States, once data fraud occurs, pharmaceutical companies and R&D personnel will be blacklisted and will not be allowed to enter related fields for life.
Insiders suggest that the country should actively integrate domestic pharmaceutical companies with the international market, establish an internal supervision system for pharmaceutical companies, and truly form core competitiveness through innovation in order to occupy a place in international competition.