Health: A risk worth taking

An increasing number of people want to take part in drugs trials in the hope of finding a cure. Roger Dobson reports

JAYNE Harrison was desperate to become part of a clinical trial. The 33-year-old dentist had been diagnosed as having breast cancer and was only too aware of the doubts about the effectiveness of existing drugs, particularly among women of her age.

"Being diagnosed at 33 as having cancer was pretty shitty, but I knew a lot of trials with new drug treatments were going on and, more than anything, I wanted to get involved, not just for myself, but in the hope that it could help others, too," she says.

Jayne is one of a rapidly growing number of patients who choose to take part in clinical trials - the main way in which drugs and some other treatments are tested before becoming generally available. But although new drugs offer the patient the possibility of a more effective treatment, they can also turn out to be worse or no better than existing treatments and may also have side effects. And for the doctors involved, trials can be a minefield of ethical problems and moral dilemmas.

Six days ago, doctors in the US blew the whistle on a study of the anti- breast cancer drug tamoxifen on the grounds that those women in the trial who had been taking it to prevent cancer were doing so well, it would be unacceptable to continue and deny the benefits to the women who had been taking a placebo. But critics of that decision say it means doctors and patients will not now get the long-term data they need from that study to establish the safety of a drug that would be taken by healthy women for many years.

The ending of the tamoxifen trial illustrates some of the dilemmas involved in the expanding area of clinical trials. It is estimated that there have now been around 400,000 trials since regulations on the safety of drugs were tightened in the aftermath of the thalidomide disaster. A single teaching hospital may now have up to 300 trials running at any one time and medical sites on the Internet are currently seeking volunteers for more than 5,500 trials, tackling a diverse range of diseases, from Alzheimer's and acne to vascular problems and vitamin deficiency.

Trials like these are the main examination that a new or improved drug has to undergo before it can be licensed for a specific condition. Before being trialled on patients, it will already have undergone tests on animals and small groups of healthy patients to identify any obvious side effects. In clinical trials, it is tested against a placebo or the best existing therapy and who gets what is usually determined by a random selection process.

But just who gets to participate in clinical trials remains something of a grey area, although the US National Cancer Institute recommends that they should be considered when there is no standard therapy available that works. Many patients, particularly those with advanced and life-threatening diseases, want to go on a clinical trial in the hope that they will be among those who get the new drug. Others do it for altruistic reasons, aware that while it may be too late for them it may help future sufferers. A few take part because they believe they will get better medical attention and observation, while others just want to get involved, to have a new hope.

Jayne enrolled because she felt she needed to do something after getting her diagnosis. "I am a dentist but I was also doing a PhD in clinical trials, so I was very genned up on the pros and cons," she says. "I knew there was uncertainty about the treatment of breast cancer, particularly among pre-menstrual women, and I had decided that if it was malignant I wanted to be in a trial.

"At the time, I would have gone on any trial which did not affect my fertility, because I have no children and I didn't want my ovaries to get zapped or anything like that. In the end, I was put on a trial involving tamoxifen as a treatment for breast cancer in the under-50s. It was a randomised trial which meant that the luck of the draw gave some people tamoxifen, others got nothing, and two other groups were given a combination of drugs or an injection. I got tamoxifen.

"I knew you had to accept what came along, whatever it was, but it was more important for me to be involved in a trial, any trial, than anything else. I felt that if some good came out of it, it was worth doing."

Jayne believes that everyone should be aware of trials before they need them. "I don't think that many know about clinical trials before they are ill, and I think people should be educated so they don't have to understand all the pros and cons at a time when they are also trying to come to terms with what is wrong with them."

Hazel Thornton, founder and chairman of the Consumer Advisory Group for Clinical Trials, says that giving people the right information is vitally important: "People need to be given enough information and be presented with the case as it really is. It is vital that people make the right, informed decision."

One of the dilemmas of the trials is that individuals who enrol often want a personal and immediate benefit while the trial itself will have wider goals. Professor Richard Lilford, adviser to the NHS on clinical trials, says: "Desperate patients will want something to be done even if it is not yet proved, but society has to follow a policy which enables the correct evidence to be selected in the long term.

"The way to reconcile the imperative to help patients and the imperative to provide society with knowledge is to make a distinction between the two kind of decision makers, the individual doctor who must do the best for the patient, and the state who must do the best for patients corporately."

A second dilemma for doctors is an ethical test known as equipoise: "A trial is ethical if there is genuine uncertainty as to what the best treatment is. If I embarked on a study when I had a good idea which was the best drug, that would not be equipoise. I could not expect a patient to accept randomisation if I had a good idea which was best," says Professor Kent Woods, professor of therapeutics at Leicester University.

Clinical triallists are also keen to point out that there is always a referee involved checking on progress, even when both doctor and patients do not know which patient has the drug under test - a so-called double blind trial. "Whenever a trial is going on, there will always be a group in the background who are not blind to the data and can see if one group is doing better or worse than another and can make a decision to stop the trial," says Professor Woods.

But he adds: "The decision to blow the whistle is a terribly difficult one. You are protecting the interests of the patients who agreed to take part, and at the same time there is the wider consideration about all the patients whose treatment in the future is going to be influenced by the result of that trial."

With the tamoxifen trial, the debate centres on whether it was the correct moment to stop that trial. Only time will tell if it was the right decision.