My colleagues and I were dumbstruck with this headline from Science Alert: 80% of Data in Chinese Clinical Trials Have Been Fabricated.
This information is deeply disturbing on so many levels. For one, having clients in the medical field, I know just how important clinical trials are–without them, we are all dead in the water. Secondly, as a Chinese translator and someone with a great many friends in China, it is truly saddening to hear that they may unknowingly be taking ineffective or even dangerous drugs.
The Science Alert article was based off on an article originally published in the Economic Information Times, but at the time the Science Alert published the article, there was no full translation available. In order to benefit medical industry insiders and China-watchers alike, I decided I would make a project out of this translation, allowing interested parties could get a closer look.
With that, please continue to read below my translation below:
80% of New Pharmaceutical Clinical Data Suspected of Fraud
Background Oversight Failed at Many Levels
9 September 2016 07:06:41 Source: Economic Information Daily
In the one year since the China State Food and Drug Administration has begun its self-investigation of pharmacutical clinical trial data, 80% of new pharmacutical clinical data is suspected of fraud, background oversight has failed at many levels, and corruption in pharmacutical enterprises, intermediaries, doctors, and other major bodies presents an obvious problem.
Some in the medical field believe that negative arguments will rear their ugly heads following the violent advance of the efforts to check clinical studies, in that they will suggest policies that are “too advanced” or that take a “one size fits all” approach. The Chinese government should persist in taking a zero-tolerance attitude towards fraud in clinical trials to strictly supervise and turn around the current medical climate, where currently “bad money drives away good money.”
Enterprises Have Purposefully Hidden and Left Out Records of Adverse Events During Reporting
The results discovered by the State Food and Drug Administration regarding the truthfulness and lawfulness of pharmacutical clinical trial data from 1622 different medications which are currently pending production have shocked the entire industry. Some industry insiders have said that even more pharmacutical clinical trial data will be exposed as untruthful and unlawful following the countinuously deepening self-examination efforts. Presently, over 80% of new pharmacutical applications have been withdrawn by the applicant or denied by the CFDA.
An employee from the Food and Drug Departments said that during the inspection, they have discovered that many pharmacutical clinical trial data sets are incomplete and the origin of some data was untraceable. Some enterprises had even deliberately hidden or excluded records of adverse effects from reports and had made changes to clinical data which did not reach their expectations.
“Prior to the explosive results discovered during this round of self-investigation, the fabrication of clinical data was an open secret in the industry.” The hospital director at Sanjia Hospital in the western region of the nation said that the pharmacutical industry combines old medications, finds a few hospitals to carry out clinical trials, reports are written according to their anticipated results, and in the end, undergo review by the China Food and Drug Administration as a new drug. “This smorgasbord of pharmacutical research and development is unable to garuantee the quality and safety of pharmacutical products.”
“The direct consequence of fabricated clinical data is poor drug efficacy.” A supervisor at a Nanjing pharmacutical R&D enterprise said that during one clinical study, the anti-diabetes drugs the company administered to patients were switched from domestic Metformin to the drug that was originally researched, Glucophage. After taking GLucophage for four weeks, the patients’ blood sugar levels unexpectedly decreased so much that they were outside of levels specified in the inclusion criteria and were unable to be admitted into the study. Prior to this, patients had been taking domestic Metformin, but their blood sugar had never come down.
Industry insiders revealed that the majority of domestic generic drugs are unable to reach that standards of the originally researched drug. In order to pass reviews, it is extremely common to hide discarded data from clinical trials and to selectively use data. This year, China has begun a conformity evaluation for the quality and efficacy of generic drugs, requiring all chemical pharmacutical generics approved and on sale before 1 October 2007 to complete a conformity evaluation before the end of 2018. Drugs still requiring clinical efficacy trials and products with special situations must complete the conformity evaluation before the end of 2021. Those who do not submit the data on time will not be able to reapply.
The chairman of Innovent Biologics, Inc., Yu Dechao, estimates that 50% or more of generic drugs will be out following the developments of quality and efficacy conformity evaluations, making it possible to reverse the phenomenon of “bad money pushing out the good money” currently present in pharmacutical industry.
The Lack of Intermediary Regulation Fosters Clinical Fraud
Related departments in the State enacted the Guideline for Good Clinical Practice (Draft) in 1998 (also known simply as GCP) and released and enacted a revised edition in 2003. During implementation of GCP, restraints are not strong enough and through research and investigation, reporters found that remarkably, pharmacutical enterprises, intermediary bodies, doctors and related organizations are circumventing regulations.
A large portion of pharmaceutical enterprises are driven by interest and hasten to produce generic drugs, ignoring a critical phase of drug production—clinical trials. A supervisor at a large-scale pharmacutical enterprise in Suzhou said that he has personally participated in the research and development of new drugs, and in reality, the R&D project was just a copy of newly developed, innovative foreign drug. This pharmacutical enterprise purportedly spend one week preparing materials, essentially did not carry out a 6 month clincial trial, yet still suprisingly obtained the approval for “Independent Pharmacutical Innovation” rather quickly. The effects of domestic Chinese generics are unclear, whereas foreign, originally researched drugs are not allowed in, a classic case of “bad money pushing out the good money,” which is sure to bring consequences down the line.
Supervision from contract research organizations (CROs) is lacking, contributing to the problem of fraudulent clinical data. A supervisor from one CRO revealed that CROs should be acting as a third party supervisor for the purpose of controling quality standards during R&D for new drugs, but because the barrier to entry is too high and wayward enterprises compete using bad techniques, CROs are forced to become accomplices to forging data under the intrest of making money. “Some pharmacutical enterprises know that their CRO is perpetrating fraud, but considering that the CRO has distributed the cost and risk of the illegal actions, the enterprise usually chooses to turn a blind eye to the problem. Moreover, some drug companies say that the CROs are forced to commit fraud because if the clinical trial does not pass review, the drug company could refuse to pay.”
CFDA law enforcement said that during investigation, they discovered that although doctors should be the main agent of clinical trials, some CROs hired many assistant researchers instead. Task such as observation, statistics and quality audits should be carried out by a doctor, but instead are often carried out by research assistants, a major reason for fraudulent and unstandardized data.
Professional misconduct by clinical doctors opens the door for fraudulent data. The directing physician at Sanjia Hospital in Guangdong says that “real implementation was very unstrict” during past participation in a three-phase clinical trial for an obstetric drug at a different hospital. Although records are kept for drugs that have profittably gone to market, clinical records on research data for drugs that are not profitable are wiped out. Fraud is especially common in comparative drug studies. “Doctors are very busy, so they don’t take clinical trials seriously and don’t take detailed records, leaving the work to the CRO, naturally sacrificing truthfulness.”
Clinical oversight has become the weakest link in the chain of pharmacutical oversight system. Some industry insiders believe that supervisory personnel and technical teams with clinical backgrounds are lacking at each level of pharmacutical oversight. An employee from Jiangsu Drug Administration System said that the abilities of on-site GCP checking teams are lacking when compared with those of GMP (Good Manufacturing Practice) checking teams, as neither personnel nor technology can keep up with the present requirements.
Do Not Allow Negative Arguments to Weaken the Power of Oversight
Through investigation, reporters have discovered that in one year, the effect of self-investigation of clinical data from drug trials has applied an unprecedented pressure to pharmacutical enterprises, initially curbing large-scale data fraud.
“Before, there was basically no oversite in clinical, but today we suddenly have to carry out self-investigations, which has taken us by suprise.” The manager at one pharmacutical company in Inner Mongolia complained about this sudden requirement to verify clinical data, comparing it to “punishing people from the Qing Dynasty with laws from today.” National policies should not change frequently or unpredictably and the opinions, laws, or regulations of today cannot be used to evaluate actions of the past.
This manager questioned CROs, asking why have so many of them been approved? Why did the clinical data previously submitted by CROs pass audits? Why are government-approved clinical trial organizations not carrying out testing according to the regulations? Why should the applicant be responsible for the mistakes committed by one oversight department after the other? “This problem is pending the proper treatment and explanation by the related departments.”
Some industry insiders say that those interested should be cautious against two different negative arguments regarding this unprecidented battle over clinical oversight. New policies should accomodate China’s current state and should not be too cutting edge when addressing requirements for innovative medicines. Furthermore, policies should not be a “one size fits all” approach—although some clinical data is not standard, that does not mean that it is inherently fraudulent.
Yu Dechao says pharmaceutical governance is experiencing a crucial period in which “bad money pushes out the good money,” where we must use the strictest system possible in order to encourage real innovation. If we weave a web of fraud in clinical, it will “cause a small crack to become a cave.” “If we allow one pharmaceutical company to commit fraud, then other pharmacutical companies will follow. For this reason, there must be an unrelenting zero-tolerance policy towards clinical fraud.”
In fact, China’s pharmacutical oversight is still pending strengthening efforts, in contrast to the United States. The CFDA has made it clear that if clinical research data is fradulent, any future applications for new drugs from that applicant will not be processed for the following three years and clinical data submitted by the person directly responsible or organizations participating in research will not be accepted for the following ten years.
Liao Guojuan, Ph.D, CEO of Suzhou Genewiz, Inc. said that in the United States, once fraudulent data is discovered, the company and the researchers are blacklisted and will be under a lifelong ban.
Industry insiders advise that the nation should convene with pharmacutical enterprises and international bodies. Pharmaceutical companies will only be able to stand their ground among international competition if the pharmacutical oversight system creates competition through by promoting real innovation.
(Reporters: Ling Junhui, Xiao Sisi, Zhang Lina)
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