/ 31 January 1997

Fear lurks behind the regulations

Lesley Cowling

IN 1960, a new drug meant to ease morning=20 sickness for pregnant women hit the market.=20 It was called Thalidomide and it gave its=20 name to the babies who were damaged by it=20 in the womb. This pharmacological disaster=20 still haunts the medical profession.

The strict controls for developing new=20 drugs are a legacy of that experience. It=20 was this set of rules that researchers of=20 the compound Virodene fell foul of when=20 they tested it on a dozen Aids patients to=20 see if it would kill HIV in humans. And it=20 was the contravention of these rules that=20 resulted in the Medicines Control Council=20 suspending the trial, despite its positive=20 results.

“Thalidomide was the watershed,” says=20 Damian Largier, medical adviser for Glaxo=20 Wellcome pharmaceuticals. “Before that=20 there were few controls. People didn’t=20 realise that you couldn’t necessarily=20 extrapolate small numbers to big=20 populations.”

“If one in a thousand women have a problem,=20 or one in 5 000, it’s only when you=20 administer the drug to large numbers that=20 you pick that up.”

Regulatory bodies in most countries control=20 the process of bringing a new compound on=20 to the market. Largier says there are=20 different phases to developing a drug:

* Phase one is experimental, when tests are=20 done in laboratories, on cultures and=20 animals. After some initial=20 experimentation, a drug company, research=20 institute or individual may register their=20 compound with patent offices all over the=20 world.=20

“It’s uncommon for South African companies=20 to develop a new entity because of the huge=20 costs involved in bringing a drug through=20 all the regulatory controls,” says Largier.=20 South Africa gets drugs after they have=20 been through the process in other=20 countries.

Next come human trials, and it is here that=20 regulatory bodies really get involved.=20 “When you’re giving the drug to volunteers,=20 you must be reasonably sure it’s safe,”=20 Largier says. “At this stage, you want to=20 know something about the drug, its effects,=20 what kind of dosage you should give.”

It is tried first on healthy volunteers;=20 when those trials are completed, it will be=20 given to a small group of people suffering=20 from the condition the drug is thought to=20 treat, to make sure it has an effect.

In this country, no human trial can be=20 conducted without the go-ahead from two=20 bodies: the Medicines Control Council and=20 an ethics committee. The council looks at=20 how the study is designed and makes sure=20 all the necessary preliminary work has been=20 done. Ethics committees examine the=20 researchers’ relationship with their human=20 volunteers, and make sure volunteers=20 understand exactly how the trial works and=20 what the consequences may be to them.

* During phase three the drug is given to=20 large numbers of people, and the trials are=20 designed to show specific things – for=20 example, how it compares to other drugs=20 and, especially, how it compares to=20 placebos.Trials are conducted all over the=20 world to make them statistically reliable.=20

“Once you have a group of two or three=20 phase three trials, the compound is=20 submitted to the local regulatory=20 authority. They can ponder over it for more=20 than a year before deciding it can be=20 released,” says Largier.

How human trials are conducted and their=20 ethics is a subject constantly under=20 discussion by medical scientists. The=20 Pretoria scientists’ decision to ignore the=20 regulatory process is likely to add fuel to=20 that debate, both here and internationally.