Controlled Trials of aspirin in Cancer - Can they still be done

Professor Elwood recently gave the Cochrane Lecture in Wales. Its subject was the studies he did with Archie Cochrane in the 60s and 70s. They could not be done now. The proposed EC directive on controlled trials is designed to bring all RCTs under the same umbrella whether pharmaceutical firms or academic units do them. The cost is around £2000 per patient. Pharmaceutical firms will not set up the trials - but who will? The new directive says the sponsor is responsible for the planning and breaches of the obligations will be a criminal effect.

Cardiovascular protection by aspirin is the best evaluated intervention today - 140 trials show overwhelming benefit in relative reduction and in most situations an absolute reduction. The position is different for cancer trials. The practice in clinical medicine is to target intervention in people with early disease or at risk of the disease, but in cancer this is not possible. If we do nothing and wait for the risk factors such as oncogenes to be identified. most of us will die from cancer before that happens. Or should daily aspirin be recommended for everyone over 55 or 60 when there will be substantial relative benefit and small absolute benefit? There will be an absolute reduction of cardiovascular disease, cataract and maybe Alzheimer's disease. We should discuss this before the situation becomes totally confused.

What is to be done to preserve some level of freedom to do trials? If we do no trials at all, but just give everyone a drug, no one would learn anything but no one will object. To give half of our patients a drug and the other half a placebo will attract attention and perhaps stop the trial. There are many people who would value the ability to take part in trials but are denied the right to do so because it is not possible to use their data for the greater good. The current rules are that confidentiality of records must be preserved at all costs.

Funding is becoming more difficult. The comparison between a drug and placebo is hard enough, but that between two active drugs is very much harder and needs many more patients. It is complicated by analysis of subgroups and comparisons between them.

Even when a result is beneficial, it is difficult to implement it. For example, after studies of diets have shown positive effects the advice to increase fruit and vegetable intake has little effect. Professor Elwood's department ran a trial, one arm of which was to give intensive advice to increase fruit and vegetable consumption. Follow up showed this had no effect on the poor eating habits of older men in Wales. Health screening has enormous difficulties and brings tremendous expectations on the part of the public. There will be false negatives, leading to claims of negligence.

Even with all these problems, we are left with the remarkable conclusion that the group of salicylates has so many effects on diseases such as cancers, cataracts, Alzheimer's disease and Hughes syndrome. Will there be more syndromes on which aspirin will have an effect?

The Welsh aspirin Group of epidemiologists, cardiologists and other interested doctors and scientists are planning a meeting on May 6, 2004, on the public health importance of aspirin. A current study is on aspirin use in general practice in Wales: in particular, how many people are taking it. So the debate on what should be done has started.

Bringing the meeting to an end, Professor McVie agreed that an aspirin summit is needed. It could provide important statements on age, doses, and high risk groups. He believed Professor Elwood could use his meeting in May for this purpose.