Summary
Foreign collaborators participating in joint U.S.-China research projects need to carefully protect the safety and privacy of human research subjects. Ensuring project safety is more difficult in a developing country like China than it is in the United States.
Historically and particularly during the past decade, collaboration with foreign scientists has helped the Chinese government and Chinese researchers to improve their standards and practices in the area of medical ethics and patient and human research subject protection. But researchers must keep in mind the risks inherent in conducting research in today's China, such as:
In this message, Embassy Beijing provides suggestions that may help reduce the likelihood of future problems.The spread of disease through unsafe injections; The widespread sale and use of unsafe medical supplies (including the re-use of "disposable" needles); Substandard medical practices in many areas; and The difficulty that Chinese government entities at all levels experience when enforcing rules and standards.
Research Subject Protection in China: Potential Dilemmas
Collaborations between U.S. and Chinese researchers, some funded by NIH grants, address many kinds of health problems. These problems include HIV/AIDS, air pollution and health, and the relationship between genes and conditions such as high blood pressure and diabetes.
Some research involves the collection of blood from thousands of people. In such cases, foreign researchers working in China should be cognizant of the widespread unsafe injection and poor sterilization practices prevalent in Chinese health care, which have contributed to the spread of hepatitis and to China's very high liver cancer death rate. Recognizing that blood-borne diseases such as hepatitis are being spread through the blood supply, the Chinese Ministry of Health and the World Health Organization (WHO) view improving injection safety as essential to improving the health of the Chinese people.
Just under 10% of the Chinese population (120 million people) are believed to be Hepatitis B carriers. One result is 300,000 deaths each year due to liver cancer, the leading cause of cancer death in China. Some 20 million Chinese are infected with Hepatitis C. Many Chinese experts believe that most of those infected got the disease from unsafe injections. One of the main income sources of China's poorly paid health workers is to make money by giving injections. One result is a tremendous number of unnecessary and sometimes unsafe injections.
Many collaborative research projects involving foreigners in China actually depend upon local health workers to carry out the studies. Where these projects involve drawing blood, very close supervision with regular oversight from higher levels is absolutely essential so that everyday bad practices are not carried over to research work. In a sense, ensuring human research subject safety is more a management issue than a health issue. Good practices are widely understood by Chinese researchers, but the lack of accountability and poor supervision can mean that good practices are not followed on the front lines of research projects.
Chinese Views on Human Subject Protection in China
Many Chinese consider foreign concerns about human research subject protection in China to be overwrought. Allegations of inadequate research subject protection in several human genetic research projects in China, drawn from an August 1 Boston Globe article, were recently discussed in the Chinese Academy of Sciences newspaper "Science Times." The Science Times article argued that many years of collaboration between Chinese and Harvard researchers had resulted in 100 research papers, and that numerous research subjects had enjoyed significant health benefits. For example, some participants in a study of possible genetic links to high blood pressure discovered their high blood pressure for the first time.
Other Chinese point out that the situation for human research subject protection is improving in China, and emphasize the progress that has been made in writing new laws on the subject. Chinese bioethicist Qiu Renzong stated in late August that the allegations reported in the Boston Globe article were overblown. Qiu explained that China actually set up its first human research subject protection rules in the 1990's when doing so became a requirement for collaboration with some foreign organizations. Collaborating with foreign partners has been a major force in pushing forward Chinese thinking on research subject protection, Qiu added. (Qiu, the author of several books on medical ethics, is on the ethics advisory committee to the Chinese Ministry of Health.) In addition, Qiu said that China currently is studying a new round of human research subject protection regulations and draft rules. An English translation of these rules provided by Professor Qiu is available on the U.S. Embassy website, and noted at reference 1 below.
Qiu said that the Medical Ethics Committee of the PRC Ministry of Health is determined to make efforts to apply international ethical guidelines on human research in research conducted in China. The Committee welcomes any reports of any harm being done to patients or research subjects anywhere in China at any level. See the contact information below.
Qiu believes that since Chinese culture and customs are different, the way that truly informed consent is obtained may be different in China that in the United States. Fully literate farmers may not be willing to sign a document, but in some cases are willing to participate in a study, he said. Qiu agreed with Embassy EST officer's suggestion that China's history of frequent political campaigns and reversals in political direction might make some people unwilling to put anything down on paper. Qiu's books on medical ethics refer frequently to World Health Organization publications and international norms. There are not many China-specific questions or examples as, for example, one would expect many U.S. examples and discussions of the U.S. context in a book by a U.S. researcher. This reinforces our impression that bioethics and patient protection are newly born or newly reborn fields in China.
At the same time as emphasizing improvements in Chinese law and practices, the whole issue of foreign exploitation of Chinese research subjects remains a sensitive topic in China. Allegations of foreign exploitation or misdeeds are taken up quickly, and sometimes overblown, as seen in 1998 media charges that foreign corporations are trying to drain China's gene pool (see reference 4 below).
Many Chinese researchers are also concerned about the issue that some of them call "colonial science" -- the practice of some foreign researchers of just collecting samples and going back home without training or sharing authorship with Chinese collaborators. To deal with this concern, Chinese collaborative research contracts often require that a certain proportion of the value-added research work be done in China, that research equipment be provided to help upgrade Chinese research capacity, and that the Chinese side have a share in any resulting intellectual property rights.
Barriers to Overcoming Potential Problems
Research subject safety in China is both a management issue and an information issue. The information and knowledge needed to do research properly, while protecting the rights of research subjects, exists in China. But there are many barriers to the circulation of information within each level of society, as well as up and down various government hierarchies. This means that the central government -- in particular, the Ministry of Health -- has a very difficult time implementing health laws and regulations and finding out what really goes on at the grassroots level. The 300 professional staff persons who work at the Ministry of Health headquarters in Beijing necessarily depend upon provincial and local officials to tell them what is going on.
While provincial health departments are nominally subordinate to the Minister of Health under the "dual leadership" system, in practice they may pay far more attention to maintaining ties to their provincial leaders -- who have the ability to hire and fire, and make budget decisions for the local health authorities. This same loose center-to-province relationship is duplicated again in the relationship between provincial governments and prefectural governments, and then once again between the prefectures and the counties (there are ten or so counties to a prefecture).
Local officials are often unwilling to report problems to higher level officials, especially when it is very easy to hide the truth. As a result, the honesty and effectiveness of local government varies widely from place to place. The more prosperous provinces along the coast have the best educated and most efficient governments in China, but even within these provinces, the coastal areas are more prosperous and progressive while the interior is sometimes much less so. For example, Jiangsu Province is very prosperous generally, but the dry northwestern part of the province is much poorer than average.
Doing Research More Cheaply is No Justification for Working in China's Poorer Regions
A prominent Chinese epidemiologist told the Embassy that he believes that human subject research should be conducted in the poorer regions of China only if the people there will clearly and directly benefit from participation. Research should not be done in poorer regions "merely because it is cheaper." "Let me tell you how this often works in the interior of China", the researcher went on. "If the foreigner and Chinese research collaborator pay the county money to do research, the county officials might very well keep the money to buy a car, and just send an order to health workers in the villages to do the work without compensation." When local governments give orders, subordinate staff persons rarely fail to go along. "But matters are very different in the most prosperous regions of China along the coast," added the researcher. "There the heads of townships are often college graduates, and they don't merely accept orders from above. They tell the country magistrate, 'You have to explain this to me so that I can persuade the local people to go along.'" Research done in more developed areas, he said, can be considered to involve truly informed consent, and effective supervision of research projects is much easier to accomplish.
Foreign researchers interested in conducting health research collaborations in China should keep in mind the development levels of Chinese provinces and regions. The ability of Chinese provinces to address health issues correlates closely with their development and educational level. The coastal cities rank highest, followed at a considerably lower level by the first- tier eastern provinces (for example, Jiangsu, Zhejiang and Guangdong) and the second tier (such as Henan and Anhui). Much poorer again than these are the true western regions such as Qinghai, Tibet, Gansu and Xinjiang. U.S. Embassy Beijing does not recommend any research at all involving invasive procedures (including drawing blood) or privacy issues in Qinghai, Tibet, Gansu, and Ningxia unless under exceptionally tight supervision by the U.S. contracting entity.
Local Institutional Review Boards: Weak Links?
Provincial health departments reach judgments on the ethics and safety of research projects in their jurisdictions, with the help of their own ethics advisory bodies. The Ministry of Health Advisory Committee is now training local public health staff, and hopes that gradually all provinces will have their own local medical and ethics advisory committees. But as of today, some provinces may not yet be prepared to adequately supervise research collaborations, or to establish adequate institutional review boards.
Systemic management weaknesses can result in the failure to sterilize needles, dental equipment, and other medical supplies. The result can be the spread of hepatitis, STD's, HIV or other blood-borne diseases. While the Embassy has not heard of major problems erupting specifically from human subject research in China, the same management problems that endanger Chinese patients generally are also of great concern when considering the protection of research subjects. To date, the Embassy has heard no allegations of patients suffering seriously from research conducting in collaboration with foreign researchers in China. But given the problems with poor information availability in China -- vertical and horizontal disconnects in government and society hinder the flow of information and especially bad news -- that is no cause for complacency.
Current Rules for Collaboration with Foreign Researchers
Research collaborations involving foreign researchers in China must be approved by the central and/or local governments, and by an institutional review board (IRB) as those agencies direct. Research projects relating to the Ministry of Health or financed by the Ministry of Health are handled through the Department of International Cooperation of the Ministry of Health. The Ministry of Health relies on its Medical and Ethics Committee to supervise projects. For collaboration on genetic research, additional rules apply to protect Chinese intellectual property rights. Those rules were published internally in spring 1998, and released to foreigners in fall 1998 (see reference 3 below).
Shortcomings in China's Healthcare System
China is far from alone in facing the challenges of corruption and government ineffectiveness as it tries to make improvements in health care, the environment and other fields. An extremely strict construction of human research protection rules might make it impossible to do collaboration with researchers in any developing country. And international collaboration, as Professor Qiu Renzong argues, actually raises standards and brings more developing country researchers and officials into contact with foreign colleagues who adhere to international norms.
Higher incomes have brought improvements in nutrition and living standards that have greatly improved the health of the Chinese public. Yet the end of communal agriculture has disrupted the structure of health care provision in rural areas, and even in the cities an effective plan for financing and delivering health care in a market economy has not yet been realized. Some experts point to a sharp decline in the reach of the Chinese health care system since the mid- 1980s. One result is greater inequity in health care access, as underlined in the recent World Health Report 2000 in which China ranked 177 out of 191 countries in terms of the equity of access to health care. In other words, China's impressive health gains have largely resulted from rising incomes, and have come despite serious systemic shortcomings, some outlined above, in the Chinese health care system. Researchers who come to China must keep these shortcomings in mind for they are part of the social, economic and political environment in which research is conducted.
Professor Li Zhu of the National Center for Maternal and Infant Health of Beijing University told the Embassy that the presence of a CDC representative in China has been important in maintaining high quality of data in the project. Elaborate data collection and management systems were necessary to assure the accuracy and correct linking of patient records. To ensure participant safety and confidentiality of records, project organizers spent a full year teaching local health workers about research involving human subjects and the informed consent process, as well as educating the local people so that they would have sufficient information available to them to make an informed decision regarding participation. Professor Li and his colleagues visit all the project sites many times each year to check on the accuracy of reported data, such as death rates, where some underreporting was known to have occurred in the past, as well as to visit randomly selected study subjects to verify the accuracy of collected data, and to conduct special surveys, when indicated. Investigators examine data collection booklets to ascertain whether booklets appear to have actually been filled out during sequential visits (as determined by wear and tear on the booklet, different individuals' handwriting, etc.) and to verify the existence of equipment reported to be available at an individual project site. Strict criteria were established for ensuring data quality; project areas that were unable to meet these criteria, or whose reports or facilities did not meet project requirements were not allowed to continue as study sites.
U.S. Embassy Beijing Recommendations for Foreign Collaborators
Below are some suggestions from Embassy Beijing on ways that foreign collaborators can ensure human research subject protection.
ReferencesResearch should be conducted primarily in the more prosperous parts of China, unless there is a strong justification for doing otherwise. (Chinese collaborators might well choose a district because it is their hometown or their friend's cousin is the county party secretary. Getting things done in China often involves "human connections (guanxi)" because rules are sometimes not followed. However, good connections should not be a reason for choosing a research site in a backward area where health care is poor and people are unable to protect their rights. Also, quality will probably be easier to maintain in relatively prosperous areas. The officials in these areas tend to better educated than their counterparts in poorer areas. In impoverished areas, the question of truly informed consent becomes more difficult. Local officials can sometimes have such great arbitrary power that a farmer may not want to say "no" to them.) Joint U.S.-China research studies should be done only in counties open to foreigners in order to make quality control easier. U.S. researchers in China need to have a practical plan for ensuring that their collaborators and collaborator's assistants are protecting their patients. This will often mean spending considerable time in China. Research involving drawing blood or invasive procedures should be undertaken with care in poorer regions. The Embassy recommends against any research at all involving invasive procedures or privacy issues in Qinghai, Tibet, Gansu or Ningxia unless under exceptionally tight supervision by the U.S. contracting entity. Research involving drawing blood should establish strict and closely-monitored controls to ensure that newly-manufactured disposable needles are used, and that the needles used on the project and not diverted for re-sale. U.S.-funded research projects might be located in villages with popularly elected village councils. These elected leaders may be relatively conscious of the rights and needs of their constituents. Comic book-style posters of the kind seen in many villages to tell people about law enforcement and their rights, can be used to help get essential information across to semi-literate or illiterate research subjects. (In some regions in China, there are many minority people who speak Chinese only very poorly. In other areas people speak Chinese but can't read well.) Research subjects should be educated about their legal rights under Chinese law before participating in a project. Chinese lawyers can give advice about how to do this. Research subjects should be given the names of non-local people to whom they can complain. They should be given the names, addresses and telephone numbers of people outside their village they might contact if problems develop. They should also be assured that their complaints will remain anonymous. (Only recently has the idea of individual privacy gained some currency in China. Privacy rules to protect the confidentiality of medical records are often ignored. Chinese people are accustomed to the idea of writing to and visiting higher level officials to complain. Therefore officials at the provincial health department might be able to give advice about how to set this kind of arrangement for specific projects.) Provincial, prefectural, and county level officials should be involved in project monitoring and in discussions about how to maintain standards. Discussions with central government officials are important, but Beijing officials often have great difficulty in imposing central government policy on the provinces and localities and finding out what is really going on. Involving provincial and county level officials is critical. U.S. researchers may find that their Chinese colleagues discourage them from broadening their circle of Chinese colleagues. There is a Chinese saying "Don't let your fertile waters flow into someone else's field" [Feishui bu liu waitian] . Particularly when they are in the provinces or near their field sites, U.S. researchers should try to make new professional and other contacts, to pick up information on local conditions. Researchers should take steps to support the growth of the nascent fields of sociology of medicine and bioethics in China. Chinese experts are working to improve the quality of Chinese textbooks and teaching in these areas and to integrate these fields into the medical education curriculum.
2) The WHO safe injection website Injection Safety (SIGN) Homepage at http://www.injectionsafety.org
3) New PRC Human Gene IPR Rules at http:// www.usembassy-china.org.cn/english/sandt/geneipr.htm
4) Alarm at U.S. Companies Draining China's Gene Pool at http:// www.usembassy-china.org.cn/english/sandt/generev.htm
5) "Protecting Human Research Subjects -- What Must be Done" Sounding Board -- NEJM 2000; 343: 808-810 by HHS Secretary Donna Shalala in the September 14 issue of the New England Journal of Medicine. http://www.nejm.org/content/2000/0343/0011/0808.asp
See also "Ethical Principles and Guidelines for the Protection of Human Subjects of Research" at http://ohrp.osophs.dhhs.gov/humansubjects/guidance/belmont.htm on the Office for Human Research Protections (OHRP) website at http://ohrp.osophs.dhhs.gov
See other reports on Health and HIV sections of
the U.S. Embassy Beijing webpage at US
Embassy-China/Environment, Science & Technology
http://www.usembassy-china.org.cn/english/sandt/index.html
Some recent information about health issues in China are also available in the weekly "Beijing Environment, Science and Technology Update and in the health press clippings at Sources for the Study of Environment, Science and Technology in the PRC
In particular see these Spring 2000 reports:
PRC Medical Care Uneven: American Visitors Should Buy Medevac Insurance PRC AIDS: Advice for U.S. Collaborators PRC Blood Donors and the Spread of Rural AIDS
Prof. Li Benfu
Deputy Director, Division for the Humanities and Social
Sciences
Health Science Center (Beijing Medical University) of
Beijing University,
Xueyuanlu No. 38,
Beijing, CHINA 100083
Office: 86-10-6209-1299
Email: ethics@sun.bjmu.edu.cn