Clinical trials

We have made great progress in cancer care in recent years. There are many reasons for this, but the following are among the most important factors:

 

• The use of already established treatments in different ways, for example, by giving drugs or radiotherapy in addition to surgery (adjuvant therapy).
• Technological development, including scanners, lasers and improved radiotherapy machines.
• The development of better anti-cancer drugs and drugs capable of reducing significantly the side effects of some treatments.
• Greatly increased understanding of the fundamental nature of the disease.

 

These developments have resulted in a large number of promising or proven new approaches, many of which are now part of routine care. The speed of change is accelerating: there is an ever-increasing number of new drugs, technologies and concepts arriving on the scene. Unfortunately, however, some new treatments don’t live up to their initial promise. What seems to work in the laboratory sometimes has a frustrating tendency not to work in real people. Sometimes a new treatment appears initially to be an improvement, but is found eventually to be no better than that which was previously available.

 

Why trials are done

 

There is of course only one way to evaluate a new treatment, and that is to try it out on volunteers. It is only because entirely new and experimental treatments were tried out on patients in the past that we are where we are now, but all such research must be conducted and planned meticulously.

 

A totally new treatment is first evaluated in a fairly small number of patients who are observed very closely indeed, with particular attention being paid to detecting any side effects. It is at this stage that a drug may be tried at varying dosages, with the aim of discovering the optimum dosage. This is sometimes called a ‘phase I’ trial.

 

At a later stage, if the new treatment is showing some possibly useful effect, it may be tried out in a greater number of patients with particular cancers. They are closely monitored to detect both the advantages and disadvantages of treatment in ‘phase II’ trials.

 

At a still later stage the value of a promising new treatment for patients with a particular cancer may be assessed in what is known as a ‘randomised controlled’ or ‘phase III’ trial. This usually involves comparison of the new treatment with what has hitherto been the standard treatment.

 

In a randomised trial usually half the patients will receive the standard treatment and half the experimental treatment. Who gets what is decided at random, in a process similar to tossing a coin. Sometimes the proportions are slightly different and sometimes more than two treatments are compared, with patients being divided into three or four groups. Everyone involved in a trial gets potentially effective treatment for their illness, but at this stage it will not be clear whether or not the new treatment is better than the standard approach.

 

It is important that neither the patient nor the doctor decides which treatment the patient will receive. If there was an element of choice some types of patients might opt for – or be advised to receive – one treatment rather than another. As a result, the two groups might end up being not exactly comparable. Then it might not be possible to tell whether any differences in the response to treatment in the different groups were caused by the particular treatment they had received, or by differences between the patients, or by a mixture of the two.

 

The underlying principle behind a randomised controlled trial is that different treatments are given to groups of patients that are very similar, so that any differences in the way the two groups respond can reasonably be put down to the treatment that they have received.

 

The similarity between the groups is ensured partly by the random allocation of patients to the different treatments and partly by having large numbers of patients, usually at least hundreds, in the trial. By having large numbers, any differences occurring by chance in the make-up of the patient groups will tend to be ironed out.

 

As an analogy, it wouldn’t be surprising to find a variation in height of several inches within a first form class of secondary school children. However, it would be very surprising if the average height of all first form children in one city was three inches less than in another city not many miles away.

 

In the not so distant past only a fairly small percentage of patients were entered into trials. This was a pity because there can be no doubt that progress in treatment would have been made more quickly if more people had been included in trials. The entering and monitoring of patients in trials can be time-consuming and the resources available have not always been sufficient to cope. But since the millennium national cancer research networks have been established within each of the countries of the United Kingdom, backed by substantial governmental investment intended to provide much better support for trials. A major aim has been to increase the recruitment of patients to those carefully chosen and meticulously designed trials which seem most likely to lead to yet further improvements in what can be offered to future patients. The results have been impressive and approximately 20% of new cancer patients are now being entered into trials.

 

Ethical considerations

 

A clinical trial can be conducted only with the approval of the local ethical committee, comprising non-medical people and doctors who are not immediately involved in the treatment of the people being entered into the trial. The committee must satisfy itself that there is no evidence that patients will be disadvantaged if entered into the trial.

 

It is unethical for doctors to invite patients to enter a trial if they already believe that one of the treatments being assessed is superior. Thus, a randomised clinical trial can proceed only if there is genuine uncertainty about which of the treatment options being assessed, if any, is superior. It is quite common for new treatments to be found to be no better than or not as good as already existing treatments, when compared with them in a randomised trial. It is a mistake to assume that all new treatments are better. The progress of trials is kept under close review and you can be reassured that the trial will be stopped if one treatment is clearly turning out to be better.

 

Taking part in a trial

 

Patients who take part in a trial may have to attend clinics more often and for longer than if they were not in a trial. This is because very thorough assessments are being made of both treatment efficacy and any side effects, which would not otherwise be quite so necessary or perhaps even feasible.

 

It has been claimed that patients treated in trials (whatever treatment they receive) tend to do rather better than those treated outside trials. While the evidence for this is somewhat controversial, it does seem clear that patients treated within trials are in general likely to fare at least as well as those treated outside trials. Certainly patients in trials tend to have their progress monitored more closely. There is probably also a tendency for treatment centres and units with particular expertise to be more enthusiastic about entering their patients into trials.

 

The choice is yours

 

If you are invited to join a trial you are under absolutely no obligation to accept and your refusal will have no effect on the standard of your care: you will still receive the best available conventional treatment. You should not feel that you are under any pressure to join a trial and you must have enough time to make the decision that is right for you.

 

Some people are happy to make their mind up one way or another almost straightaway, but others will want to take away written information about the trial and think about it over a few days.

 

You can be included in a clinical trial only with your written consent, having received all the information you require about it beforehand, and you are entitled to leave it at any time if you wish.

KEY POINTS

• Progress in the fight against cancer depends on patients being treated in clinical trials

• All clinical trials are very carefully vetted

• Patients in a trial cannot receive any treatment that is known to be inferior

• Patients treated in trials fare in general at least as well as those treated outside trials

• A patient can be entered into a trial only with his or her informed consent