The importance of well designed research in rare cancer

By Professor Andy Hall on 1st February 2023

Modern medicine is built on the foundations of research. Without well-designed and carefully performed research projects and clinical trials we cannot be sure that new understandings of how diseases occur or ways in which they may be treated are correct.

Most of us aren’t very good at keeping an open mind. We tend to latch on to an idea and then stick with it even when the evidence begins to stack up that we are mistaken. In science this is called “confirmation bias” and it is almost impossible to eliminate. Take the example of astronomy- until Copernicus “everyone knew” that the sun rotated around the earth and astronomers concocted ever-more complex, and now obviously false, explanations as to why this was true.

The importance of well designed research

In order to overcome confirmation bias in medicine scientists lay great importance on the use of carefully chosen “controls”. Using an example relevant to rare cancers, let’s assume that we have found a promising new drug in the laboratory. All our tests indicate that it is likely to stop the growth of cancer cells but not affect normal cells to the same extent. The drug has taken many years to develop and it has cost a lot to get it to the point where it can be given to patients. Although we try to be objective, we really want it to work- and so do the patients who have agreed to help us prove that it does. The stage is set for us to unconsciously favour results that suggest that our promising new drug will be a success. To avoid this we need controls to ensure that we maintain our objectivity.

In most cases the best design for a clinical trial is a “placebo controlled, double-blind” study. What does this mean? A placebo is an inert substance, often a sugar pill, which looks exactly like the new drug to be tested. In a “double blind” study the placebo and new drug are coded so that neither the doctor who gives it nor the patient knows which is which. Patients are allocated one or the other at random-in effect by the toss of a coin. The code is only broken after all the patients to be included in the study have finished their treatment and the size of the anticipated effect of the new drug has been assessed in everyone. If the desired effect with the new drug is greater than that of the placebo then it really is an advance- if not, it isn’t.

This design works really well in conditions which are not life-threatening- for example migraines or moderate increases in blood pressure. In cancer unfortunately this is not always the case so instead of using a placebo the study uses the current standard treatment so that treatment is not suspended during the trial.

Many patients with cancer are keen to receive new drugs and are reluctant to take part in a study where there is only a 50:50 chance they will get them. To overcome this the control (the standard treatment) and the new drug may be swapped over during the study so that everyone gets both the control and the new treatment. This is a “cross-over” study.

In recent years there have been many discoveries which have suggested new ways of treating rare forms of cancer but proving that they are effective has been difficult because it has been hard to find enough patients to take part in properly designed clinical trials. RareCan has been set up to speed up this process by helping to find patients who are open to the idea of taking part in these essential research projects.