How Much Are We Reporting about Ethical Misconduct: A Critical Review of Cyranoski’s Article “Chinese Clinical Trials: Consenting Adults? Not Necessarily”
By Edward Chigwedere
David Cyranoski’s recent article in Nature, “Chinese clinical trials: Consenting adults? Not necessarily,” reveals how certain clinical research in China has violated ethical research regulations. In this paper, I briefly outline what the article reports, disclose Cyranoski’s sources of information and consider how authoritative they are, highlight significant omissions in the report, discuss how the report deals with controversial issues and their interpretations, and finally look at the implications of the report.
In 1999 China passed the Good Clinical Practice (GCP). This international standard demands a variety of regulations, including informed consent, approval of trial protocols by independent Institutional Review Boards (IRBs), and strict monitoring of trials. Despite these formal regulations, their enforcement is patchy. A classic example of a poorly regulated Chinese trial is the VGV-1 trial, which sought to study the effects of VGV-1 on participants who had never had antiretroviral therapy. Cyranoski reports a number of flaws with this trial, notably:
While the above list includes many significant flaws, one that Cyranoski fails to point out is the scientific justification for using research participants who had never been exposed to antiretroviral therapy. The only other VGV-1 trial that Cyranoski mentions relied upon participants who had previously been on antiretroviral therapy. Given that we do not have any information about the effectiveness (and the risks) of VGV-1 on people who had never taken AIDS treatment, I am unsure of what the scientific basis was for carrying out this trial.
In order to assess and critique this trial, Cyranoski draws from four distinct sources. First, he spoke to trial participants, quoting directly what they viewed as the flaws in the VGV-1 trial. Second, he communicated with Ruotao Wang, the IRB chairperson for the National Center for AIDS/STD and Prevention and Control. Wang states that rather than being cautious when making decisions about new drugs, many IRBs in China are ineffective due to “inexperienced members” with “little training in bioethics” and a tendency of getting “carried away with enthusiasm” (139). Third, Cyranoski got in touch with the public relations representative for Viral Genetics, the company that supplied the drugs. Fourth, Cyranoski sought information and perspectives from people not directly linked to the trial, like the director of the Aaron Diamond AIDS Research Center in New York who is conducting research in China on IRBs.
Despite consulting this wide range of sources, Cyranoski has two serious omissions in his method. First, he did not attempt to contact the Ditan Hospital IRB, which was the IRB that approved the VGV-1 trial. Second, given both the magnitude of the problems that the Chinese bioethics committees reported and how poorly the case was handled after reports were made to the National Center for AIDS/STD Prevention and Control IRB, Cyranoski should have sought independent legal views. I will return to this second point later.
Now that I have pointed out all these problems with this trial, what might explain them?According to Cyranoski, ethical misconduct in Chinese clinical trials is largely a function of two interrelated factors: first, an alarming lack of knowledge regarding ethical regulations; and second, ineffective IRBs—IRBs that rubberstamp proposals that come before them instead of enforcing bioethical standards. Despite the existence of these problems in the Chinese biomedical system, medical researchers are queuing for clinical trials in China. Indeed, among countries sponsoring research, China is a favorable destination in Asia. According to the National Institute of Health (NIH), China received the highest NIH award in international research for all Asian countries in 2003—an amount equivalent to 13.2 million American dollars (Bartlett 2005).
Why this level of interest and support for clinical research in a country with questionable ethical standards? Cyranoski believes that this interest is due to “plentiful clinical opportunities” as a result of a “debilitating” disease profile: infectious diseases (including AIDS), lifestyle ailments, and rare genetic disorders (138). Additionally, China is an attractive place for clinical research because of the sheer size of its population. Such a large population, especially one with chronic medical needs, translates into good business for the pharmaceutical industry. Specifically, China is an appealing open market for antiretroviral pharmaceutical companies given that it is estimated that approximately 10 million Chinese—almost the size of the Zimbabwean population and three times the size of the population in Botswana—will have AIDS by the turn of this next decade.
Some argue that developing countries attract clinical trials because conducting research in such countries (or countries in transition as is said to be the case with China) is less cumbersome than in developed countries (Angell 1988). Cyranoski’s article lends further support to this position, as he describes how Chinese IRBs typically approve proposals that come their way without adequate consideration to ethical standards. Cyranoski overlooks another reason why receiving research approval in developing countries is not as cumbersome—their IRBs are poorly staffed. Instead of a well staffed committee consisting of people from diverse backgrounds, and importantly including people who are not affiliated with or invested in the trial in any way, as is the model in developed countries, IRBs in developing countries are all too often one-person committees. There have been reports in developing countries of committee members with personal interests in the trial protocols, as well as of committees receiving a significant portion of their funding from protocols they approve, which means they benefit from approving rather than rejecting trials (Ndebele 2005).
In light of my discussion, it seems that the approval of the VGV-I trial was a result both of the aforementioned factors and of scientists’ limited knowledge of bioethical standards. As Wang observes, most IRBs in China consist of scientists who lack adequate substantive knowledge of bioethics. He asserts, however, that under normal circumstances they should still avoid using any drug whose profile is unknown. In other words, while serving on IRBs and working in clinical trials, they are still expected to abide by the Hippocractic oath of “do no harm.”
Cyranoski offers two recommendations for alleviating such ethical misconduct: first, provide bioethics training to all IRB board members and second, if they want to avoid tarnished reputations, international funding organizations need to be more cautious of where and whom they fund. While these recommendations are laudable, it is also important to note that they do not include a legal voice. This cogent omission implies that Cyranoski does not recognize the interconnected relationship between bioethics and the law. A legal perspective, for example, would be helpful in determining the legal obligations that both China and sponsoring countries have in ensuring ethical research trials. Moreover, by excluding a legal perspective, Cyranoski’s recommendations do not address the possible legal consequences of both physicians and investigators knowingly misleading VGV-1 research participants.
In conclusion, Cyranoski’s article sheds light on ethical misconduct in China, but still and yet it perpetuates a disturbing divide between bioethics and law particularly in the developing world. Ethical misconduct, especially in the research field, should necessarily attract attention within academic circles. However, such attention should also be inclusive of legal perspectives. This calls for vigilance on the part of bioethicists in developing countries and for support from their colleagues in the developed world.
References
Angell, M. 1997. The Ethics of Clinical Research in the Third World. Eng J MedVolume 337:847-849
Angell, M. 1988. Ethical imperialism? Ethics in international Collaborative Clinical Research. Eng J Med 319:1081-1083.
Cyranoski, David. 2005. Chinese clinical trials: Consenting adults? Not necessarily.Nature 435, 138-138 (12 May).
Bartlett, E.E. 2005. International Research: Promises and Pitfalls.Conference on Ethical Dilemmas in Human Subject Research, Michigan State University. October 28, 2005.
Ndebele P. 2005. The Problem of “False Confidence” in Microbicide Trials in Zimbabwe and Elsewhere. Invited lecture. Michigan State University. October 6, 2005.
Ndebele P. 2005 Health Research Oversight in Zimbabwe: Responding to International Developments and Current Challenges. Invited lecture. Michigan State University, October 7, 2005.