No one really wins in this life-and-death lottery

Randomised clinical trials of new medicines present a dilemma for doctors, who want results, and patients, who just want to be cured
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The Independent Online
Are you willing to be a guinea pig? Perhaps, in some circumstances, for the sake of the public good, you might agree to take part in a clinical trial. But would you agree if you or your child had a life-threatening condition? More and more patients are now refusing and, as a result, a large number of Medical Research Council-backed clinical trials are being abandoned. The money is there, the doctors are keen, the statisticians are standing by their computers - but the patients will have none of it.

Professor David Machin, one of the MRC's chief statisticians, says many trials are collapsing because patients want treatments, not experiments. In the old days before ethics committees obliged doctors to get genuinely informed consent from patients, the issue was often fudged. Nowadays, patients read about treatments and they know what they want. They may be wrong, but they have opinions.

Examples: a trial of brain tumour treatment has been abandoned because only one patient in two years was willing to enter it. The trial was designed to find out whether cutting out a cancerous tumour made a difference or might even do more harm. Patients were to be chosen randomly by computer either to have their tumour removed or to have no treatment and to be closely observed. But they all demanded that the tumour be taken out.

It was not a question of allowing them to choose which they had. To make the trial properly scientific, their treatment had to be selected by computer. It was this element of luck they couldn't abide. But if they had been allowed to choose or if their doctors had chosen for them, then the statisticians would have declared the trial invalid.

Another trial is collapsing: doctors suspect that conventional chemotherapy may be as effective in treating childhood leukaemia as bone marrow transplants, which are more painful and expensive. They asked parents to allow their children to go into a random trial, but the parents refused. They want the transplant, not the chemotherapy, because they've read about it as a successful treatment. The same is happening with prostate cancer trials - men are demanding to have the cancer removed and are refusing a random trial that might select them to have no treatment at all. They are insisting on surgery even though for older men, operating may be much more dangerous than the cancer.

Doctors' powers of persuasion are considerable. If a doctor recommends one or other course of action, the patient would probably accept it. What patients don't like, quite rightly, is for a doctor to refuse to give an opinion and to offer them a random trial instead.

The offer to join a trial can be singularly uninviting. I have twice refused, though I admit I felt ashamed at doing so. It is part of one's civic duty to help medicine along, but when your own life is on the line, science takes a back seat.

As I had a high family risk of breast cancer, I was asked to join a trial to see if the drug tamoxifen prevented high-risk women from getting cancer. First, the doctor had to persuade me that tamoxifen looked like a good bet. It might have some side-effects, but early indications suggested it also might prevent cancer.

Now that is a clear choice. But when the doctor goes on to say: "Ah, but I'm not offering tamoxifen. I'm offering a randomised trial, so neither you nor I will know if you are getting it or a sugar pill," then that is deeply disturbing. You screw up your nerve to accept a treatment - then you don't know if you are getting it or not. Are you having side- effects or is it imaginary? I said no, and I had nothing. (This may have been a mistake, but how am I to know?)

I am not alone. In the early days of AZT in America, a group of Aids patients were offered AZT only if they entered a double blind trial. When they realised half of them were getting sugar pills, they rebelled. Secretly, they ganged together and pooled all the pills so that they could all get at least some of the AZT. The trial was wrecked. Random trials make a lottery of life, but then unscientifically proven medicine is anyway a lottery.

Later I did develop breast cancer. Once it was chopped out, I was offered another randomised trial. I would be allocated tamoxifen, tamoxifen and radiotherapy, just radiotherapy or nothing. I was sure my distinguished specialist had a hunch which treatment he thought best. He might not prove it scientifically, but he must have an idea and I demanded the benefit of his experience. He would not give it. At this point, any patient wonders whether the imperatives of science are interfering with the doctor's imperative to do the best possible for his patient.

So I went for a second opinion from a specialist not engaged in this trial. I gleaned from him the general view that tamoxifen was a pretty good bet and radiotherapy in my case was probably not necessary. Armed with this reassuring advice, I returned to my own doctor, refused the trial and requested the treatment I wanted. This was, I am afraid, anti- social behaviour. The more of us who behave like that the more impossible it becomes to find out which treatments work. And yet for a doctor to withhold his opinion in order to coerce you into a trial seems to me to verge on the unethical, where scientific ends justify the dubious means.

The reason we need trials is that cancer treatment is an absurd lottery anyway, with doctors up and down the country doing quite different things. We may beg a doctor to give his best advice, but his hunches may be no better than a randomised trial. Without trials, no one knows what works, but there are good reasons why patients say no.

I have spoken to many doctors and researchers over the last few days. Some are crisply scientific - the trials must continue on the old basis. Others hope the statisticians will come up with better ways to assess outcomes while letting patients make choices for themselves. Professor Machin says that can't be done: if doctors advise patients which treatment to take, the trials would be fatally flawed.

Professor Ian Kennedy, leading medical ethicist, thinks this is an intrinsic ethical problem: if doctors suppress their own advice, they compromise their duty to patients. "They may justify it by claiming a higher morality. Or else they just say, 'I'd like to do this trial, I've got the money, sod the ethics.' If research is an imperative, that way lies Nuremberg". Another leading cancer doctor said: "Oh God, don't talk to the ethics people. What do they know about science?" Another pointed out wryly that doctors and nurses are the hardest to persuade into randomised trials.

This issue produces not just a conflict of interest between the individual and the general good. It reveals a fundamental divide between a vision of medicine as cold science and medicine as art, a healing magic to make us feel good. No one knows the answer to this dilemma - but it is making the onward march of medicine considerably harder.