Dishonest participants, another chapter of China’s fake data story

In China, data integrity has been a known problem in clinical trials. To make the situation more complicated, as a Chinese newspaper discovered, even trial participants themselves have a hand in the scandal.

A story published in Chinese by The Beijing News—a newspaper based in the country’s capital and famous for its investigative pieces—uncovered that many phase 1 clinical trial participants also play a key role in faking data.

It says that various tactics were used among those who want to get into phase 1 trials, studies which usually pick healthy participants to assess safety. The report said that during physical examinations, some used others’ urine sample, some said putting white vinegar in their urine samples can allegedly hide traces of smoking, while some used a chemical to cover abnormal transaminase caused by drinking or drug intake.

To guarantee the accuracy of trials and to protect participants’ health, local regulations ban participation of the same person in another trial within three months and decree that a candidate should wait five days before another physical exam, but some use fake IDs, or others’ papers, to get through.

In an undercover investigation, a nurse was found to have manually rigged the interval period to bypass the system, while in another case, one used several apparently tempered weight scales until a normal number showed for an overweight volunteer. Cosmetics were also used to hide needle pricks, which is evidence of recent med injection or blood withdrawal.

These techniques were said to be usually taught by so-called middle men who recruited participants for hospitals that actually conduct the tests. Commissions are said to be high for those middle men to take the risk—about 200 to 300 Chinese yuan per successful recruitment, and the number could reach 500 for a recruitment company, the story found. Neither those individuals nor the companies were properly regulated or equipped with medical expertise.

As for those participants, most of them also yield to the financial temptation. In the investigation, compensation for a five-day in-hospital trial on a heart failure injectable reached 5,500 Chinese yuan (about $945). To put that into context, according to data published by Beijing Municipal Human Resources and Social Security Bureau, the average monthly pretax salary for an employee in Beijing in 2015 was 7,086 Chinese yuan.

This is not the first time strong suspicions regarding China’s clinical trial data integrity were aroused. In July 2015, the Chinese FDA ordered companies to conduct self-examination of clinical trial data behind 1,622 drug applications. The companies were given the options to either submit a self-report for authority inspection or voluntarily withdraw their applications without penalty.

In what the CFDA sworn to apply “the most stringent criteria, the strictest supervision, the most powerful punishment and the most serious accountability,” about 80% of applications were voluntarily pulled. It looks as if this was only a glimpse of the entire picture.

Meanwhile, unlike the U.S., China implements a qualification verification system where only those organizations—mainly hospitals—approved by the CFDA can conduct clinical trials. In the CFDA database, as of Jan.17, all together 822 are listed, more than doubled from 2012. But since 2009, the CFDA has been approving 600 to more than 900 new drugs into clinical trials each year, except for a rare less than 400 in 2013; in 2015, that number was 606. Given the long life span of clinical trials, those organizations are still under a lot of pressure to conduct trials. Turning a blind eye to otherwise unqualified participants can almost ensure faster enrollment.

CROs are also said to have a share in the data-forging drama. As reported by financial news site Caixin in 2015, the country had about 400 CROs with "uneven qualities." An unnamed exec in a top CRO in China told Caixin that China lacked a certification and approval system for CROs which led to destructive competition. In an environment where supervision is inadequate and whoever gets the drug into approval at lower prices gets the deal, faking data appears to be an easier way. That exec also told Caixin that some pharma companies even made it clear in their contracts with CROs that no payment would be made without an approval. 

Clinical research associates, in many cases assigned by CROs, who are supposed to monitor clinical trials to ensure compliance with GCP guidelines are also compromised. The Beijing News story found that a CRA assisted the doctor in a trial on antimicrobial peptide PL-5 spray and recorded the data herself.

China’s regulators are not that tolerant. As specified in the trial data self-checking announcement sent out in July 2015, for applicants who are found to have faked clinical trial data, no applications from them will be accepted in three years, and trial conducting organizations' certificate will be revoked. But compared to the U.S.’ lifetime prohibition, the Chinese version is still lenient.

The Good Clinical Practice Regulations in China was most recently updated in 2003. Although it does decree “what should be done,” but nothing is said about consequences of violation.