Under China’s Order 818, only high-level hospitals will be able to conduct investigator-initiated trials (IITs).Credit: Xinhua/ShutterstockIn the past two months, reports that two children died after receiving gene-editing treatments in separate clinical trials in China have put a spotlight on the country’s fast-track trial pathway.Investigator-initiated trials (IITs) are a popular way that researchers and biotech companies test new therapies. Trials are much faster than those required by China’s drug-approval system, which is supervised by the National Medical Products Administration and roughly equivalent to the US Food and Drug Administration (FDA).IITs are widely considered to be a driving force behind China’s rising competitiveness in biomedicine, particularly for cell and gene therapies, with the number of annually registered IITs in this area growing 11-fold to 207 between 2015 and 20231. These trials also exist in the United States, although they require approval from the FDA.News of the deaths comes only months after the government introduced stricter rules for IITs of new biomedical technologies. Researchers and industry insiders say that the regulations are designed to spur innovation while increasing government oversight. The regulation, called Order 818, went into effect on 1 May.What are fast-track trials?IITs often provide safety and efficacy evidence that shows whether larger, more expensive clinical studies are worth pursuing, says Dai Jialing, president of PharmaDJ, a Shanghai-based company which provides business intelligence on the biopharmaceutical industry.Rules governing these trials already existed, but these weren’t strictly enforced or overseen, say researchers. For instance, previous rules required IITs for stem-cell therapies to be conducted at sanjia — China’s top research and training hospitals. However, Iris Zhang, a lawyer at Han Kun Law Offices in Shanghai, says that a good deal of cell-therapy activity took place in non-sanjia institutions, private clinics and hospital-affiliated ventures because supervision at those sites was inconsistent.This led to a grey market in which companies and hospitals sometimes charged large sums of money for unauthorized or fraudulent therapies. In some cases, this led to medical accidents and even deaths.What are the new rules?Order 818 governs the IITs that use new biomedical technologies, such as cell therapies, brain implants and treatments made using gene editing, among others. The purpose of the order is to increase regulatory oversight of these kind of trials, says Hao Bin, an economist at Xi’an Jiaotong-Liverpool University in Suzhou, China.Under Order 818, only sanjia hospitals are permitted to conduct IITs for all new biomedical technologies. “These hospitals have the best clinicians, the best researchers, the greatest access to patient populations. They are the most reliable, trustworthy institutions to deliver research, adding safeguards for patients,” says Ruby Wang, a physician based in London who is also a China health-policy consultant.Under the previous rules, an IIT could start if it passed scientific and ethical assessments by the hospital and was registered with the National Health Commission (NHC), the authority in charge of health policy and reforms. Under Order 818, the NHC might organize a second round of assessment for registered trials. It also has the power to order that trials be suspended, altered or cancelled if there are technical or ethical concerns. The new filing system is expected to operate “somewhat like a de-facto approval process” and adds a meaningful extra layer of regulatory oversight, says Aaron Gu, a lawyer at Han Kun Law Offices.For the first time, regulations also include penalties for hospitals or companies who violate the rules. For instance, a company or hospital can be fined millions of yuan for submitting a technology to clinical trial without authorization. The company and hospital would also be banned from carrying out clinical trials on new biomedical technologies for three years, and physicians leading the trial could have their medical licences revoked.Lizzi Lee, a researcher of China’s economic and technological policies at the Asia Society Policy Institute, a think tank in New York City, says that the real impact of the rules will depend on implementation. If the order is enacted inconsistently, it will not build trust and accountability among the public, she says, but if governments and institutions are too strict, it could slow the innovation that China is trying to promote.Gu says the policy change that allows companies in China to initiate IITs for the first time will make industry collaboration more practical. Previously, such a trial could only be launched by a clinical researcher, whom companies had to work with.