Speakers at the conference who talked about international expansion of research said that China was the next big thing and said that India has an odd and uncertain future as it matures in its international relationships.
Right now 95% of people in China are covered by at least some minimal type of health insurance policy. Currently 7% of China’s GDP is spent on health care; this compares with 16-20% that the United States spends and the 9-12% that all developed countries except the United States spend. By 2020 China will be the world’s largest pharma market and have 787 million people living in urban areas. Per capita healthcare in China is about $700 USD per person per year currently; in the United States the expense is currently $14,000 per person per year and that number will definitely rise due to the Patient Protection and Affordable Care Act, with the extreme estimate being 25,000 per person per year.
The players in the China game are multinational companies, hospitals, the Chinese government, the Chinese Food and Drug Administration, and both local and multinational clinical research organizations. Anecdotal reports about the quality of clinical research data coming from China suggest that the health demographic data, dosing adherence, and outcome data give results about clinical research in China which are comparable to the results gotten from anywhere else. Australia is perceived to be the local place in the region for getting Caucasian data when that is required. Small hospitals in China typically have 2000 beds; the largest hospitals in the United States have 2000 beds and average hospitals in the United States have 200 beds; the United States has 5000 hospitals. China has 500 hospitals which are certified to practice good clinical practices (GCP) but perhaps 50 of those are qualified to Western standards. China is one of two countries which requires any company marketing a drug to disclose their manufacturing process; Israel is the other. To go to market in China a drug has to be tested in China, and for this reason, corporate strategies which in the past did research in China to market a drug elsewhere are wishing to do research in China for the sake of China’s market. Other countries in Asia which demand this are Vietnam, India, Taiwan, and Korea, and since India is so problematic, industry is currently looking over their one billion people at looking at China’s billion. Only local organizations may initiate early phase studies in China as China wants lower risk and is willing to delay market entry to get it.
In China specifically it is difficult to find research sites with compliance to the International Conference on Harmonization or good clinical practices. English is not widely spoken in the study sites and fundamental tenets of Western ethics face challenges at the research sites. Also China has barriers prohibiting drug testing until a compound has had phase 2 testing in another country.
Adherence to good clinical practices in China is troublesome. All tools must be available in Mandarin, including all pharmacy and lab manuals. Additionally, foreign researchers must be ready to produce new advanced manuals native to the local language when study staff request learning or educational resources for staff which other countries and cultures have never before needed. All study sites in China should have a relationship with a GCP compliance advising center which facilitates communication among all research sites and empowers them to sort GCP compliance among themselves. Western organizations can be expected to have lots of cultural problems in China; a commonplace surprising problem to Western people is that there is no voicemail in China, and another one is that antibiotics are often delivered by IV to sell the drug and procedure for more money than pills.
Corruption is a problem in Chinese clinical research. Three problems causing this are problems with hospital organizational infrastructure which simply leave room for corruption to exist, a “red envelope” culture in which doctors and researchers feel comfortable accepting financial gifts and thus gaining conflicts of interest even when they mean well, and a cultural shyness leading to the underreporting of adverse events due to a perception that notice of the occurrence of adverse events would cause the loss of face to a doctor, researcher, or manager. All of these are causes of a range of problems including a failure to consistently obtain or use informed consent. One current strategy for mitigating corruption is doing research in second and third tier cities, such as Changchun, Chengdu, Hangzhou,Hefei, Kunming, Taizhou in Zhejiang, Taizhou in Jiangsu, Xi’an, Zhengzhou. The thought in going to cities relatively unknown to the Western world are that they get less business and are more eager to please, plus diversity in the geography of research spurs competition in raising research standards. Technological innovations which lower chances of study problems include implementation of RFID and electronic medical record systems, because technology raises chances of detecting crazy problems like studies with all fake data and just makes people more conscious of duty while preventing human error.
If any research participant has an adverse event in China it can be treated like a crime and any Western researchers are under heightened scrutiny, as are their local affiliates. China does not want corruption; note the case of former director of the Chinese FDA. Zheng Xiaoyu was executed for corruption and perhaps allowing bad drugs to enter the market. Observers from the West were said to have perceived this person as much less corrupt than his peers. If a patient dies in a research study in China for whatever reason it is completely necessary to pay off the family of the deceased, and for this reason, researchers should be risk adverse there and never do any research in which a patient may die. As an example, foreign companies never do cancer research in China since with or without treatment the patients are likely to die, and research would only assume blame. Another story of China’s attempts to reduce corruption in this sector is presented in the Forbes article “Three ways to understand GSK’s China scandal.”
One of the reasons there is so much hope for producing large amounts of high quality research in China is that in China, researchers can earn higher pay than doctors in a medical practice. This never happens in the Western world, where even mediocre doctors in a practice will make much more money for their time spent than a doctor doing any sort of research. To give an example of scale, in the United States an oncologist treating a patient for their lifetime will get on average $60,000 from that patient, whereas building a relationship with a research participant will only bring payment of about $2500. Still, just for cultural reasons and lack of organizational infrastructure, clinical research in China is mostly maintained by graduate students who are certain to leave their research site after graduation and be replaced with other fresh students in a 2 year cycle.
Some other peculiarities about research in China are that research participants often require family engagement stipends including travel and reimbursement. This is counterintuitive to Western thought because seemingly it is difficult to increase Chinese researcher engagement in the informed consent process, yet families in China are much more deeply engaged in the health care decision making process in other ways to the extent they they must be funded to be with research participants. In China the clinical research organizations own the relationship with the research site and thus are middlemen to the vendors; this is both odd and because they provide cultural mediation a necessity. The availability of any historical medical records for any patient is sparse as patients carry their own medical records on paper rather than having them stored with the institution as in Western culture. Their records will also note traditional Chinese medicine, and while China’s standards of care may be aligned with Western standards of care the application of traditional medicine is ubiquitous and thus usual care differs from the standard of care. Almost any research site in China is going to be new to research. Sites want to build relationships and establish themselves based on past experience, and for this reason, the need for long-term collaboration instead of short term contracting must be emphasized. Sponsor involvement at every level of leadership is necessary as the hierarchy is respected. In Western culture salary negotiations are done individually but in China people frankly discuss their pay and it is to be expected that before anyone is offered any salary that person will know exactly how much everyone in a comparable position is paid because the new hire will already have been told by multiple sources.