Mail & Guardian (Johannesburg) - January 31, 1997
Lesley Cowling

IN 1960, a new drug meant to ease morning sickness for pregnant women hit the market. It was called Thalidomide and it gave its name to the babies who were damaged by it in the womb. This pharmacological disaster still haunts the medical profession.

The strict controls for developing new drugs are a legacy of that experience. It was this set of rules that researchers of the compound Virodene fell foul of when they tested it on a dozen Aids patients to see if it would kill HIV in humans. And it was the contravention of these rules that resulted in the Medicines Control Council suspending the trial, despite its positive results.

"Thalidomide was the watershed," says Damian Largier, medical adviser for Glaxo Wellcome pharmaceuticals. "Before that there were few controls. People didn't realise that you couldn't necessarily extrapolate small numbers to big populations."

"If one in a thousand women have a problem, or one in 5 000, it's only when you administer the drug to large numbers that you pick that up."

Regulatory bodies in most countries control the process of bringing a new compound on to the market. Largier says there are different phases to developing a drug:

* Phase one is experimental, when tests are done in laboratories, on cultures and animals. After some initial experimentation, a drug company, research institute or individual may register their compound with patent offices all over the world.

"It's uncommon for South African companies to develop a new entity because of the huge costs involved in bringing a drug through all the regulatory controls," says Largier. South Africa gets drugs after they have been through the process in other countries. Next come human trials, and it is here that regulatory bodies really get involved. "When you're giving the drug to volunteers, you must be reasonably sure it's safe," Largier says. "At this stage, you want to know something about the drug, its effects, what kind of dosage you should give."

It is tried first on healthy volunteers; when those trials are completed, it will be given to a small group of people suffering from the condition the drug is thought to treat, to make sure it has an effect.

In this country, no human trial can be conducted without the go-ahead from two bodies: the Medicines Control Council and an ethics committee. The council looks at how the study is designed and makes sure all the necessary preliminary work has been done. Ethics committees examine the researchers' relationship with their human volunteers, and make sure volunteers understand exactly how the trial works and what the consequences may be to them.

* During phase three the drug is given to large numbers of people, and the trials are designed to show specific things - for example, how it compares to other drugs and, especially, how it compares to placebos.Trials are conducted all over the world to make them statistically reliable.

"Once you have a group of two or three phase three trials, the compound is submitted to the local regulatory authority. They can ponder over it for more than a year before deciding it can be released," says Largier.

How human trials are conducted and their ethics is a subject constantly under discussion by medical scientists. The Pretoria scientists' decision to ignore the regulatory process is likely to add fuel to that debate, both here and internationally.

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