Chinese Regulators, Pharma Industry Address Ethics Committee Challenges
A workshop held recently in Beijing presented an overview of the current ethical considerations and procedures for effectively designing, conducting and registering clinical trials in China. A key focus was clarifying the working procedures and challenges for ethics committees, also called institutional review boards, in China.
The workshop, called “Ethics in Chinese Clinical Trials: A Roadmap for Sponsors and Researchers” was part of the Impact China: Pharmaceutical R&D Global Summit. The workshop was co-organized by Professor Yali Cong of the Medical Ethics Program at the Peking University Health Program; Dr. Haitao Liu, who is the International Officer of the Forum for Ethical Review Committees in China (FERCIC) and Francis Crawley, executive director of Brussels, Belgium-based Good Clinical Practice Alliance, which he founded in 2005.
Most of the participants were from the Chinese pharmaceutical industry. The discussion during the workshop addressed the procedures and issues that arise when developing applications to ethics committees in China alongside the primary application for approval to the State Food and Drug Administration (SFDA), China’s drug regulatory agency.
Two major challenges in conducting clinical trials in China are that China has one of the longest application review times in the world and that the SFDA needs to approve the application first before it goes to the ethics committee.
“The ethics committees are in a bit of a peculiar situation because they come under the direction, in a regulative sense, not under the SFDA but under the Ministry of Health. But they also come under the direction of the institution they’re part of. And my sense is that the Ministry of Health hasn’t really tackled the question of ethics committees or how they should be operating, how things should be going on,” said Crawley.
The responsibility for regulating drugs has undergone a lot of changes in the past decade in China. Originally the purview of the Ministry of Health in 1998, a separate bureau, called the State Drug Administration (SDA) was formed in 1999. The agency’s name was changed in 2003 to the State Food and Drug Administration (SFDA) and was still separate. In July 2007, the head of SFDA was executed for taking bribes that called China’s drug manufacturing practices into question. In March of this year, the SFDA is again situated within the Ministry of Health.
“I think right now there’s a strong tendency toward the focus on the quality in manufacturing, so something like GMP [Good Manufacturing Practice] standards is really where the focus is because that’s where they had the problems. So, I think that’s a major issue for them. And the clinical trials I think will come on once they get more settled inside the MoH [Ministry of Health] and inside the re-structuring of the SFDA. That’s my guess,” said Crawley.
Clinical trials in China can only be conducted at SFDA-accredited sites. According to the SFDA web site, as of April 2007, there were 251 sites—hospitals and universities—that were permitted by the SFDA to conduct clinical trials. Each site is required to have an ethics committee.
“Most of the clinical trials going on in China are not in rural China. We’re not dealing with really developing country issues here. We’re dealing with a very, very modern population,” said Crawley.
He did add, however, that some patients from rural areas also came to sites in the major research centers, which include Beijing, Shanghai, Guangzhou and Chengdu.
SFDA has shown great interest in Good Clinical Practice [GCP] and guidelines for ethics committees since its inception. In 2005, a delegation from the SFDA came to Europe on a trip organized by Crawley during which the they spent an intense 10 days traveling to Brussels, Geneva and London to meet with the European Commission, the European Medicines Agency (EMEA), the World Health Organization (WHO), the World Medical Association (WMA), hospitals, clinical trial units and ethics committees. The trip was organized principally so that the SFDA delegation could learn about GCP inspections.
In August 2005, the delegation organized a meeting in Shanghai, which Crawley attended, to demonstrate what they had learned and what they were doing with their knowledge.
“They did talk about inspections, but it was interesting when they came to that meeting they actually presented a draft guideline for ethics committees in China. But it was a bit strange, and they knew it too, because they really don’t have the authority over the ethics committees in the administrative sense. It belongs more to the Ministry of Health. And at that time they were outside the Ministry of Health. So, now that guideline has remained draft and has not been developed further. And now the question for the ethics committees is really how to organize themselves,” said Crawley.
There was quite a bit of discussion during this month’s workshop about how to expedite ethical review. One suggestion was to form a central ethics committee. Given the fundamental structure of China’s ethical review system now and the fact that each site in China is required to have its own ethics committee to make its own separate decision about an application, this suggestion was deemed unlikely to be able to be carried out. Fortunately, there were other suggestions that had a good chance of being put into practice.
“One of the ideas that was put forward was to try to come up with a common application form and also a common decision form, which would go a long way actually in harmonizing practices and would still leave the autonomy of decision making to the individual companies,” said Crawley.
Even if common application and decision forms were implemented, the ethics committees would still be in the position of having to review the application after the Ministry of Health had approved it. The question that hung over the room was: how would an ethics committee dare to disagree with an SFDA decision? This was not discussed during the workshop, but Crawley conceded, “I think that’s one of the issues that’s there.”
Workshop attendees generally expressed satisfaction with how ethics committees are working and with their quality. Crawley has worked with ethics committees through the Strategic Initiative for Developing Capacity in Ethical Review (SIDCER) training program. He has also helped create standard operating procedures (SOPs) that have been introduced to many ethics committees in China.
“The ethics committees that are functioning well are functioning well and are reliable, even demonstrably reliable in some cases. But, it’s still new. The clinical trial market in China is developing but developing very, very quickly—even with the difficulties up front. People in the U.S. and Europe can say, ‘Thank goodness’ for the moment that it’s nine months to get regulatory approval because once they shorten that, it’ll be really a lot of trials going on there,” said Crawley.
The focus for the future of ethics committees in China is on more training, continued adoption of SOPs and more harmonization, and guidelines down the road. Crawley was emphatic that his role was to participate in the discussion by offering an outsider’s perspective and that the responsibility for moving the process forward rested with China.
“The Chinese very much want to work with their government, so a lot of it is trying to see, how can we help government move this forward or what kinds of contributions can be made that would bring the way forward? Training is still a major area of interest, and there are a number of groups in China carrying out training now for the ethics committees. There’s also a need to find a more harmonious approach across ethics committees in China and also in relationship to the researchers, the sponsors, the trial sites and the regulatory authorities. This would tend to go, on the one hand, in the direction of guidelines, and on the other hand, standard operating procedures that were shared where the common application and common decision forms would help increase the regularity, let’s say, across committees,” Crawley said.
“We just want to be more or less part of the dialogue, part of the discussion with them and try to give some outside perspective on it, but this is something that happens inside the country and this is something that we want to happen inside the country.”