Friday, August 08, 2014

Thoughts about the ethics of bio-medical research in Africa.

The fundamental point I would make is that it takes thought and care to do bio-medical research in Africa ethically. For example, since African research capacity is rather limited, and a great deal of the research is done through international collaboration, research efforts should meet the ethical standards of the different societies from which the participants are drawn. Such standards differ from society to society. Some are cultural and implicit rather than explicit. I would not take it for granted that the way an African doctor would interact with a patient would be accepted by a European colleague, nor that an African doctor would think that a European doctor's interaction with an African patient was proper. Medicine is an art as well as a science, and products of different medical schools practice differently; moreover, the interaction between doctor and patient is social as well as professional.

Indeed, projects may often have to meet the legal standards of medical ethics of the countries in which the field work is actually done, and the legal standards of the countries that fund the research, and the legal standards of the institutions outside of Africa involved in the research. Thus, when I managed the U.S. Israel Cooperative Development Research Program for some time, in which USAID funded a number of projects in which Israeli and African researchers collaborated, all three legal standards had to be met.

I seldom see the point made, but the first requirement for ethical bio-medical research is that it be done well. Almost invariably such research deals with people at risk  sometimes people in such projects get sick, sometimes they suffer permanent disabilities, and sometimes they die. Putting people at risk to do research badly seems fundamentally unethical. Thus it seems to me that such research should be done by well qualified people with adequate support, and it should be peer reviewed. All American medical research goes through an ethical review process, which seeks to assure among other things that the risks involved are justified by the results that can be expected. It seems to me that there should always be a supervision mechanism, and that mechanism should be prepared to investigate any complaints about the research. When I was responsible for the funding of international research networks on rapid epidemiological assessment and on the etiology of acute respiratory infection, I found that meetings of the chief scientists from the various projects (with international experts who volunteered their advice) was an excellent approach to assure quality. The researchers would very seriously debate how best to carry out their projects and to assure that their results were comparable.

The current Ebola epidemic in Africa reminds us that it is not only the community that is at risk, but also (and perhaps especially) the health care providers, and even the researchers themselves. Thus there must be containment of infectious agents and vectors, and appropriate protection of care providers and researchers if a project in such an epidemic is truly to be ethical. I remember that we had to ship materials internationally in some projects -- samples from the field would have to be analyzed in laboratories in other countries; there are specific rules for such shipments.

It seems obvious that people who get sick during a medical research project should be cared for. Yet that turns out to be a difficult issue in many projects. Should an foreign researcher get more and/or better care than his/her national collaborator? Does the guarantee of care to poor African patients create an inappropriate incentive to accept the risk of participation? The time to address such questions is before the issue arises, not after someone gets sick.

A key concern in the choice of medications and treatments is whether the risk of side effects is more than balanced by the probable benefits of that their use would confer. It should be obvious that the calculus is different in different populations. A drug that would not be approved for a communicable disease in the United States, where the incidence of the disease is low and the alternatives for treatment many and effective, might be appropriate in Africa if the incidence was higher and the alternatives few. Moreover, there is an argument that it is most ethical to leave the decision on use of a drug or treatment to the society involved, that an African government should not be barred from using a drug because the FDA did not approve its use in the USA. But how are medical researchers to deal with such an issue for an emerging disease such as Ebola. (Indeed, there is a current controversy as to whether an experimental drug which has been used for two sick health workers should be used more widely in the Ebola epidemic.)

Of course, scientific misconduct is never ethical. Thus falsification of data, misreporting results and similar failures must be fought against. So too, doing medical research without sharing the findings with the medical research community can be a problem; if people are put at risk for the purposes of the research, then the ethical response to that risk is to maximize the benefits that can be drawn from the research. As a consultant to governments in Latin America, I found that providing incentives to researchers to publish the results of government funded research works; publication rates go up!

The sine qua non of bio-medical research is that research subjects freely give their informed consent to participate in the research. The term "free" is important -- the subjects should not be pressured into the research. In Africa, financial or other pressures might sometimes be applied. and should be guarded against.

Getting informed consent is not always easy. How do you do so when prospective participants in a project do not share a common understanding of the disease process and/or will not have the background to easily understand the treatment, its potential benefits and its potential risks? How do you proceed when the prospective participants trust neither the foreign researchers, nor the medical elites from their own country, and especially not the government: if potential subjects think they are being lied to, what does their written consent really mean?

We read in the papers about immunization campaigns, using techniques of well established safety and effectiveness, being targeted by terrorists. Such things happen in Africa as well as Asia. They happen because of mistrust for modern medicine as well as out of a desire to do mischief. I recall a friend and colleague telling me that he was having great difficulty in his research which involved drawing blood samples from immunized children; the rumor had spread that he was doing so not for the benefit of the children and the research, but to feed a colony of vampire bats being studied in the same research institution. Ethical conduct of bio-medical research requires cultural sensitivity, and it sometimes requires working with communities as well as with patients.

Who gives the consent? The "age of consent" differs from country to country. In some countries a 17 year old patient would be considered of age, in others a 17 year old would not be of age and a parent's consent would be required; in some countries both the consent of the 17 year old and the parents would be required. In other cases, other consents might be needed  (e.g. the consent of a village chief for a member of an African village, the consent of a superior officer for involvement of military subjects, the consent of prison officials for participation of prisoners).

The standards for  the ethical treatment of animals must be considered. In the United States these are quite complex. There are different standards for different kinds of laboratory animals. There are different standards for animals bred for the laboratory, livestock (as might be involved in the study of a disease such as swine flu, which is transmitted from pigs to humans), and wild animals (such as the primates and bats implicated as reservoirs for Ebola). Incidentally, sometimes there animals must be shipped between countries in research done primarily in Africa. This requires special treatment to assure the welfare of those animals. (I remember a colleague bringing his colony of vampire bats from South America to the United States telling me that in order to assure the were kept suitable warm and the journey was suitably quick, be bought the bats an airline ticket. The animals were put in boxes and the boxes tied into the seat next to him. Imagine explaining to the airline attendants not to worry about the boxes, that they only contained live vampire bats! Think about bringing them through the airport agricultural inspection process!)

An especially worrisome possibility would be the use of Africans as guinea pigs for research on drugs and treatments intended to be sold in wealthier countries, say thosecountries of the OECD. This was the subject of a popular film some years ago, The Constant Gardener. Since sometimes it is easier to find subjects with the medical conditions to be studied in Africa than in rich countries, and since sometimes it is less expensive to do the research in a poor country than in rich one, companies have sometimes found it tempting to do bio-medical research in Africa even for products that they expect to be so expensive as not to be affordable in Africa. However, ethically the subjects of medical research should be drawn from the population that would be expected to benefit from success of the research. Using poor Africans to develop interventions that would only be used in rich countries is problematic. Yet research on diseases must be carried out where the diseases exist (and indeed where their incidence is high). Considering the ethics in advance may help to avoid ethical failures in the conduct of such research.

A related issue is the sharing of intellectual property rights that arise from research done in Africa. Sometimes commercial firms are involved, planning to patent technology arising from or proven in the research; sometimes those firms cooperate with academic and/or government researchers in Africa and outside Africa; how are the profits from the commercialization of such technology to be shared with the researchers? Is there an appropriate formula for the participation of the communities that took risks and the subjects who participated in the research. Again, forethought can help assure ethical distribution of benefits resulting from the research.

In short, there is no substitute for careful consideration of ethical issues in planning bio-medical research in Africa.


John Daly said...

In the monitoring and evaluation of projects involving bio-medical research, assuring the ethical conduct of the research is especially important, and is sometimes not addressed specifically in M&E guidelines. When the projects involve field work in a developing nation and international collaboration, the issues to be addressed to assure ethical conduct are especially complex and difficult.

John Daly said...

"The World Health Organization (WHO) is to meet on Monday to discuss ethical issues surrounding experimental treatments being given to people with Ebola, a virus that has claimed the lives of 932 people in West Africa so far in this outbreak."

John Daly said...

From the New York Times:

"In Geneva, the World Health Organization convened an ethics panel on Monday to debate the broader use of untested drugs. In a statement on its website on Tuesday, it said that given “the particular circumstances of this outbreak,” the panel had reached a consensus that “it is ethical to offer unproven interventions with as yet-unknown efficacy and adverse effects, as potential treatment or prevention.”

"The panel said the use of untested drugs should be guided by ethical criteria, including transparency about all aspects of the care provided, informed consent of the patient, freedom of choice and patient confidentiality."