HONG KONG – The sheer speed of growth of the biotech and med-tech industries in China has easily outpaced the development of regulation and has led to concerns that too many of the ballooning number of clinical trials in the country fail to meet enrollment targets.

In a Feb. 17 report, intelligence provider Globaldata analyzed the enrollment efficiency of 324 oncology clinical trials launched between Jan. 1, 2012, and Dec. 31, 2017. The findings showed that a majority of the trials failed to meet enrollment targets.

Globaldata found the greatest discrepancies between planned targets and actual enrollments in phase II trials, with an average enrollment efficiency of 87.8 percent. Phase I oncology trials typically failed to meet planned enrollment targets.

Those theoretical findings matched the practical experience of drug companies and clinical research organizations (CROs).

Chinese drugmaker Chiatai Tianqing Ltd., which is currently holding 23 trials in China, has found that planned enrollment targets were unmet, though Xu Zhongnan, a researcher at Chiatai Tianqing, provided BioWorld Asia no further explanation.

On the other hand, some maintain the rate of enrollment may be high enough for the needs of the industry and comparable to global averages.

Lei Lyu, a spokesman at drug developer Beigene Ltd., told BioWorld Asia that the company's "average enrollment efficiency values stay at a high range" and "trials are mostly in smooth progress" but would not provide actual figures. Beigene has conducted 16 clinical trials in China over the past five years.

Despite those statistics, experts suggest that what is happening in China is hardly unique. Challenges enrolling patients can be seen elsewhere but in other areas the solution is often to extend timelines rather than just carry on with fewer patients. What's more, protocols often mean that trials cannot move forward until a certain number of patients have been recruited.

"Over the last eight to 10 years we have seen pharmaceutical companies actively developing oncology drugs, so the competition is fierce. When the number of patients is the same for many candidates out there, the enrollment process will inevitably meet hindrances," said Henry Yau, managing director of the clinical trials center at the University of Hong Kong. "This is simply an issue of supply not meeting demand."

Yau added the challenges enrolling patients for oncology trials are global.

The Tufts Center for the Study of Drug Development conducted a study in 2013 and found that "enrollment achievement rates vary by region, ranging from 75 percent to 98 percent of targeted levels, with Asia and the Pacific and Latin America achieving the highest rates."

Irish drug development consultant Icon in a report in 2013 cited U.S. FDA numbers that suggested only 6 percent of trials would be completed on time. At the same time, the National Cancer Institute in the U.S. said in 2010 that 40 percent of oncology trials failed to achieve the minimum patient enrollment and more than three out of five phase III trials failed to do so.

'Not as easy as it seems'

There have been studies worldwide on how to improve enrollment efficiency. In China, the problem is exacerbated by the rapid growth and the relative youth of drug developers and CROs. According to Yau, drug companies often overlook the difficulty of enrolling subjects.

"When they prepare the research protocols, they aim to recruit a certain number of subjects within a certain period of time. But when they actually start enrolling, they will find this is not as easy as it seems. This will prolong the development timeline," Yau said.

Altogether, the findings of the Globaldata report coupled with the experience of companies suggest that the challenges for Chinese pharmaceutical companies recruiting patients for trials may continue and that the barriers may stem from institutional issues. Those issues range from regulations to the way CROs compensate patients who experience serious adverse events during clinical trials. Neither regulations nor processes are particularly well-developed.

Processes that are well-established elsewhere are barely common practice in China.

"The idea of institutional review boards [IRBs] for regulating medical experimentation is a relatively new one in China," Hallen Stevens, an anthropologist at Singapore's Nanyang Technological University who studies China's bioscience field, told BioWorld Asia. "Many hospitals that conduct experimentation have IRBs, but some other scientific institutes do not. China is now realizing the need for more oversight and regulation, partly because it wants to conform to international standards."

Stevens added that patients must provide informed consent, but the procedures to secure that consent are not quite in place yet.

Adding to the challenges is the uneven nature of educational levels in China and the fact that knowledge of modern Western medicine is often low.

Cao Ye, director of the Clinical Research Department at the National New Drug Evaluation Institute of the Cancer Center at Sun Yat-sen University, told BioWorld Asia that enrollment used to be difficult in China from a policy level but conditions have improved.

"Before 2016, the process of gaining approval [to start clinical trials] was complicated in China and the process might take as long as nine months. This left insufficient time for the pharmaceutical companies to enroll patients," Cao said.

That practical experience is somewhat counterintuitive. There are several reasons to think that China should see higher enrollment efficiency than Western countries.

"There are certain contributing factors in China," Yau said. "First, is its huge population that can draw a sizable pool of patients. Second, is the lack of free health care in the country, unlike the Western countries. Not everyone can afford the high treatment costs, hence taking part in the clinical trials is one way to alleviate the financial burden," he added.

Experts have said they believe that enrollment efficiency values should continue to stay high in China as the CFDA works to speed up the process of approvals for trials, given that the number of oncology clinical trials conducted in China has been growing at a double-digit rate, according to Cao.

Last December, the CFDA sought out opinions on a policy that could see applicants have the ability to start trials in accordance with their protocols if no objection or inquiries are raised within 60 days of the application being received. Cao said that will greatly shorten the wait times for companies to launch trials and, in turn, speed up drug approvals.