Ethics in health research

Not so long ago, human research subjects were colloquially referred to as guinea-pigs. These days, health research ethics requires that human subjects be called research participants - to emphasise that research is a partnership. And the Medical Research Council's Ethics Committee is keeping a beady eye on the process, as LORENZO RAYNARD discovered.

Health research can heal - but it also contains the potential for harm: harm to the research participant.

The only way health researchers can convince the public to let them continue with their research, is if they subscribe to a strict code of ethics, equal to the highest standard of respect for human rights.

The MRC is fortunate to have a highly respected Ethics Committee, which meets on a regular basis to revise and improve the ethical standards expected from researchers. So far, the MRC Ethics Committee has published five booklets on ethics, which have become standard reference works for universities and other research organisations.

Before researchers are allowed to go ahead with any new MRC-funded project, they have to receive clearance from either the MRC's own Ethics Committee, or a research ethics committee recognised by the National Health Research Ethics Council and operating in accordance with MRC and national ethics guidelines.

Worldwide, however, such systems haven't always been in place. Modern medical or health research ethics, often referred to as bioethics, began in the mid-1960s as a result of the pioneering work of H Beecher in the USA, and M Papworth in the UK, both of whom exposed medical research misconduct that did not respect the rights of research participants.

One such unethical research study was done by a United States geneticist who deliberately infected thousands of Yanomami Indians with measles, killing hundreds of them. The geneticist, James Neel, injected the South American Indian tribe in Venezuela with a virulent measles vaccine as an experiment to test the effects of natural selection on primitive societies.

Neel ordered his researchers to refuse help to those who were sick and dying, insisting that they were present only to observe and record what was happening.

'Bioethics is a relatively new philoso-phical discipline characterised by very rapid growth and interest,' says professor Danny du Toit, chairperson of the MRC's Ethics Committee.

'There is a growing concern about the power exercised by scientists and doctors. There is also a strain on the resources of medical care, accompanied by the question: "to what extent can or may limited resources influence moral decisions?"

'In addition, pharmaceutical companies and the supply of drugs have become a very big global business, which puts pressure on the research system,' he says.

One of the publications of the MRC Ethics Committee, Guidelines on Ethics for Medical Research: General Principles, notes: 'Research involving human subjects should be based on a moral commitment to advancing human welfare, knowledge and understanding. This must include the welfare, knowledge and understanding of the people being studied.'

This has indeed become a critical issue, especially where large-scale trials are conducted in developing countries. 'Increasing research activity, competition and an attractive research environment may sometimes result in dishonest and fraudulent practice,' said the Minister of Health, Dr. Mantombazana Tshabalala-Msimang, in her speech at the launch of the MRC's Guidelines on Ethics for Medical Research: HIV Preventive Vaccine Research.

In 2000, a South African scientist made himself guilty of such dishonest and fraudulent practice. He presented results at an annual meeting of the American Society for Clinical Oncology that compared conventional chemotherapy with a treatment programme of high-dose chemotherapy followed by a bone marrow transplant. He was one of five speakers on that subject, but the only one who showed positive results for the above treatment.

This was such a surprising result that a team of oncologists from the United States came to Johannesburg to find out what he was doing differently in order to get such good results. However, they were dismayed to discover that he had lied about the drugs received by the patients undergoing conventional chemotherapy and falsified the hospital clearance for the research.

This was not only unethical, but highly dangerous, as he was trying to convince his colleagues about the merits of doing an expensive, debilitating, but ineffective procedure on women with breast cancer.

Prof du Toit says: 'It is the duty of researchers to conduct scientifically sound research while acting in the participant's best interest and respecting and protecting the participants' free will.'

Guidelines used by the MRC's Ethics Committee include respect for human dignity, autonomy, informed consent, the rights of vulnerable persons, confidentiality, the lack of harm, maximum benefit, and justice.

Issues of informed consent are of particular importance, as specified in the Constitution of the Republic of South Africa. The Constitution states: ‘... everyone has a right to bodily and psychological integrity, which includes the right not to be subjected to medical or scientific experiments without their informed consent.'

Prof du Toit says, 'The intention of ethics is to safeguard human dignity and to promote justice, equality, truth and trust. It is a critical reflection on our morality and is surely a serious issue to consider.'

Guidelines for HIV vaccine research
As the numbers of those infected by HIV and dying from AIDS increase dramatically, the need for a vaccine becomes ever more urgent.

Several candidate HIV vaccines are at various stages of development, since the successful development of effective HIV-preventive vaccines requires that many candidate vaccines be researched simultaneously in different populations around the world.

On 22 April 2005, the South African Medical Research Council (MRC), in conjunction with the National Department of Health, launched the fifth book in their ethical guidelines series, called Guidelines on Ethics for Medical Research: HIV Preventive Vaccine Research. The book is intended to highlight some of the critical elements that must be considered in HIV vaccine development activities in South Africa.

The book has come a long way. The process began in 1999, with the establishment of the South African AIDS Vaccine Initiative (SAAVI), whose aim is to accelerate the development of safe and effective HIV vaccines for South Africa. In addition to funding these and related activities, SAAVI funded the HIV/ AIDS Vaccines Ethics Group (HAVEG), whose task it is to undertake research and training in the ethical aspects of HIV vaccine research.

In 2000, the MRC approached HAVEG to coordinate the development of ethical guidelines for HIV vaccine research in South Africa. HAVEG agreed to do so in consultation with national resource persons and ethics structures, which included the UNAIDS guidance document Considerations in HIV preventive vaccine research.

Stigmatisation, because of the association with blood, sex, and illegal activities such as commercial sex, discrimination, marginalisation and even violence, are all factors increasing the risk of social and psychological harm for people participating in HIV vaccine trials.

The book outlines the additional efforts that researchers must make to minimise these risks, and to ensure that the risks are justified by the benefits.