SA tightens its grip on ethics

Scandal over falsified breast cancer trial results has led to new ethical guidelines for researchers. Karen MacGregor reports from Durban

South Africa is to monitor medical research more carefully to ensure that proper controls are in place and ethical practices are followed, following the scandalous discovery earlier this year that a professor had misrepresented the results of a clinical trial for breast cancer treatment.

The health department is considering creating an oversight body to monitor medical research, and it has produced draft guidelines on how clinical trials should be conducted based on the international document Good Clinical Practice, which is already adhered to by drug companies.

The document is being adapted to circumstances in South Africa, which has a large disadvantaged population. It will guide the work of researchers and drug companies.

The department is also looking at screening medical trials for the affordability of the treatment they test. There is concern about "guinea pig" trials being conducted by pharmaceuticals companies on patients who cannot afford to continue treatment once trials end.

All new drugs used and clinical trials conducted in South Africa first have to go through ethical committees at universities and hospitals, and South Africa's Medicines Control Council has to approve or reject all new drugs.

"We have mechanisms in place and clear guidelines on research," said Peter Cleaton-Jones, chair of the Medical Research Council ethics committee and the University of the Wi****ersrand (Wits) committee for research on human subjects.

Wits has had an ethics committee since 1966 - it was the first university in South Africa and one of the first in the world to create one - and the MRC has had clear ethics guidelines since 1977.

"The problem here and elsewhere is that researchers don't always adhere to the rules. Institutions can only act against unethical research if they know it is happening."

Wits's ethical committee had no record of the clinical trials that disgraced Werner Bezwoda, head of its haematology and clinical oncology department and a respected cancer researcher.

Dr Bezwoda faked results he presented to a major conference of the American Society of Clinical Oncology last May, which showed ultra-high dose chemotherapy combined with bone marrow transplants to be more effective than standard doses in treating 154 South African women with high-risk breast cancer.

His paper sparked great interest, but investigation revealed that Dr Bezwoda had misreported the drugs he gave women in the control group, which were experimental and not standard as claimed, and that there were no records on or consent forms from most of the patients - including some 100 poor black women.

On March 10, following a disciplinary hearing, Wits fired Dr Bezwoda for scientific misconduct and for failing to obtain ethics approval from the university before a trial that violated clinical research standards.

Dr Bezwoda had earlier admitted "a serious breach of scientific honesty and integrity" motivated by "foolish desire to make the presentation more acceptable". But by then he was under pressure from American scientists coming to South Africa to verify his results for what is a controversial breast cancer treatment, before conducting further research based on them.

Wits has been applauded for acting speedily to suspend Dr Bezwoda, audit his research and then fire him. But this is the second case of misdirected medical research in South Africa in recent years that has managed to circumvent ethical mechanisms.

A highly suspect drug called Virodene was promoted as a cure for HIV-Aids, with its University of Pretoria "inventors" bypassing the ethics committee and gaining credibility with the government before being rejected by the MRC (which came under political pressure to look again at already rejected applications to develop the Virodene concoction).

South Africa does not want more fraudulent and embarrassing research incidents, so the health department is speeding up investigations that began last year into effective ways of ensuring that all projects are properly authorised and monitored.

There are also, said Professor Cleaton-Jones, behind-the-scenes negotiations to form a national research ethics body for South Africa that oversees all ethics committees in the country. Whether such a body would focus on medical or all research involving ethical issues has not been decided.

A possible model would be the national medical ethics committee in Denmark, which oversees all ethics committees on research. Each year the national committee investigates 5 per cent of research projects.

"But Denmark is a small country with lots of money, and we're the opposite," said Professor Cleaton-Jones.

At Wits, clinical trials are reported to the ethics committee twice a year. Some 500 projects are approved a year, and since they take on average four to five years, there are some 2,000 projects under way at any one time. "It is impossible to monitor them all," said Professor Cleaton-Jones.

Nevertheless, Wits is looking to tighten procedures "so that nobody escapes the net". For example, the ethics committee is considering making researchers declare annually that all work involving humans will first be signed by the committee, and it wants duplicate data from all trials to be stored with the university to allow rapid auditing and to ensure that no trials escape it.

"We cannot allow a Bezwoda incident to happen again," said Professor Cleaton-Jones.