Trials are vital tool in research

One of the most important tools for testing new treatments is the randomised clinical trial or RCT. In an RCT, the new treatment is compared with the current standard treatment or a dummy pill. The important feature of an RCT is that each patient is allocated one of the two treatments at random using a process known as randomisation, similar to tossing a coin.

This process has the advantage that the groups taking one or other of the treatments will have the same numbers of patients with individual characteristics, for example older age that might influence the outcome. The beauty of randomisation is that it also matches the two groups of patients for characteristics that we can’t measure, such as their genetic make-up.

It was evidence from RCTs of a drug called alteplase that led to the clot-busting treatment for stroke known as thrombolysis. The commonest type of stroke is caused by a clot that blocks off an artery in the brain. Thrombolysis involves giving the patient alteplase into a vein to dissolve the clot and restore blood flow to the brain.

Thrombolysis can result in a patient, who would otherwise be paralysed for life, walking out of hospital within a day, but the trials showed the drug had to be given within a few hours of the stroke. Evidence that this was an effective treatment led to hyper-acute stroke units being set up to rapidly deliver thrombolysis and other evidence-based treatments.

Influential stroke research doesn’t always involve RCTs. GPs used to refer patients with transient ischaemic attack (TIA) and minor stroke to a weekly hospital clinic that had a long waiting list. The neurology department at Oxford University studied patients referred in this way and showed that more than 10 per cent of these patients had a recurrent stroke within three months while waiting for their appointment.

The researchers therefore set up a new daily clinic so that most patients were seen and started on treatment within 24 hours. The research showed that this new clinic reduced the rate of recurrent stroke by 2 per cent. As a result, most hospitals now have a daily TIA service.

Despite the evidence that trials have transformed the care of stroke patients, it is still difficult to raise the funds required

Sometimes, RCTs show that a new treatment is less good than the old. We conducted an RCT, known as the International Carotid Stenting Study, which included 1,713 patients who

had recently suffered a stroke or transient ischaemic attack caused by narrowing of the carotid arteries. These are the main blood vessels taking blood to the brain.

Early results of the trial showed that the traditional surgical treatment, which removes the fatty deposits causing the narrowing via an incision in the neck, was safer than the newer treatment of carotid stenting, in which a wire mesh stent is inserted across the narrow area to open it up.

The trial showed that stenting avoids the wound complications associated with an incision in the neck, but caused more minor strokes at the time of the treatment than surgery. We concluded that surgery should remain the treatment of choice. We also showed that stenting was a reasonable option for younger patients and those unsuitable or unwilling to have surgery.

One difficulty is that it is hard to identify which patient with disease of their arteries will have a stroke in the future. The five-year risk of future stroke in patients with severe carotid narrowing ranges from a high of 40 per cent down to a low of 5 per cent.

In the second European Carotid Surgery Trial we will test a score based on clinical characteristics and will use new techniques to image the carotid narrowing to see if we can predict which patients have a high or low risk. When this trial is finished, we should have much better ways of selecting patients for surgical removal of the narrowing and will know which patients need only take medication.

RCTs are expensive because they often need to recruit thousands of patients to get a result. However, despite the evidence that trials have transformed the care of stroke patients, it is still difficult to raise the funds required. The UK expenditure by the government and charities on stroke research in 2007-2008 was only £23 million in comparison to a staggering £590 million spent on cancer research.

The income of the main charity supporting stroke research, the Stroke Association, in one year is about £30 million. In contrast, the British Heart Foundation receives about £250 million, although it does support some stroke research. Other charities supporting stroke research have much smaller budgets. Hopefully, with increasing attention being paid to stroke, this will change. Undoubtedly, investment in research will result in further advances in treatment in the future.

Martin Brown is professor of stroke medicine at the Institute of Neurology, University College London, and consultant neurologist at University College Hospital and the National Hospital for Neurology and Neurosurgery.