A Contentious Drug Trial in India

There is an interesting article in Frontline (a magazine published by The Hindu in India) on the ethics of a drug trial that was conducted in India in 2001, which involved Johns Hopkins University researchers, at least in the analysis of tissue samples from tumors injected with experimental drugs before being excised from the patients. It is charged that the experimental drugs had not been subjected to sufficient animal tests before being used in human subjects, that they in fact had serious side effects, that the consent obtained from the subjects was not informed, and that the research had not been subject to appropriate ethical review prior to the treatment of the human subjects. It is also suggested that there might be significant profits from the sale of pharmaceuticals resulting from this and follow on research, and that inappropriate statements of the distribution of such profits had been made suggesting that the Indian institution involved in the research would benefit significantly from those profits.

Here is a preliminary finding from NIH on the behavior of Johns Hopkins University requiring changes in university processes, and the later letter stating that the university had complied.

Comment: It is hard to figure out what actually happened from the material at hand. It seems likely that there were several real problems -- inadequately tested drugs, poor communication between physicians and patients and between JHU and Indian researchers, and inadequate ethical review of the research. It may well be the case that all of these problems occurred due to lack of experience and may represent uninformed rather than unethical behavior by the people involved. History if full of examples of people behaving in ways that now look unethical, but which they did not recognize as immoral at the time.

I spent a lot of time over 15 years trying to assure that research funded by my office was the subject of ethical review, and thus was to the extent possible to assure conducted ethically. We funded a lot of collaborative international research, and developed a policy that any research had to survive ethical review in both countries involved. We did so not only for research involving human subjects, but for research involving laboratory or wild animals or livestock, research involving dangerous substances, or research that might have environmental impacts.

This was during the period 1982 through 1998. We often had to get overseas organizations to set up review committees. We ourselves had to learn a great deal in the process. Of course, the ideas as to what is really "informed consent" and what risks are acceptable to obtain what potential benefits vary from culture to culture. Lots of researchers seem to feel assured of their own morality and saw our efforts as bureaucratic obstacles put in the way of expeditious conduct of their research.

There were some funny instances in my experience. For example, mosquito vector research often involve setting out people as baits for mosquitoes which are caught when they bite. We were assured by a number of investigators that they would follow WHO guidelines on the treatment of the human baits (presumably informed consent and provision of prophylactic and curative drugs) before learning that there were no such guidelines. Similarly, a researcher who had planned to collect samples of a dozen plant species from the wild for pharmaceutical screening, when asked noted that half of the species were endangered.

In my days working in a research lab many years ago, I recall a couple of colleagues who had been exposed to very high levels of radiation in their labs, a couple who were badly injured in a laboratory explosion, the release of gases from the lab that killed nearby livestock, and a gas cylinder tearing through a couple of walls and laboratories. In this country we have spent generations institutionalizing systems to reduce the dangers of research to the researchers themselves, to the people around the research, to the subjects of research and to the environment. We have worked hard to balance the safety requirements with the need not to hinder the conduct of important research with potential benefits to the public and society.

It is perhaps not surprising that poor countries, which have much less experience with the conduct of research, have not developed comparably extensive and effective institutions. Helping to build such capacity should be a significant part of donor assistance for science and technology capacity building.

In this respect, I find the action of UNESCO's programs in bioethics and the ethics of science and technology to be falling short. I would love to see UNESCO, the World Health Organization, the Food and Agriculture Organization and other UN agencies take on the job of helping developing nations to build the capacity for ethical review of research and development, and indeed to build the capacity to do R&D ethically.