In Phase 1 and Phase 2 trials everyone taking part will get the treatment being evaluated. (See also ‘Why do we have clinical trials in children and young people?’
) However, many trials compare a new treatment with the standard or usual treatment by comparing two groups of people. People in one group are given the new treatment. Those in the other group are given a standard or existing treatment. (Sometimes you may hear the new treatment group called the ‘experimental group’, ‘trial group’ or ‘intervention group’. This can be confusing, as all the groups, including the control group, are part of the trial, and people in the control group may also be given an intervention, in the form of the standard treatment or placebo.)
To make sure that each group contains a similar mix of people, many trials are ‘randomised’. This means that people are allocated at random to one of the groups in the trial, often by using a computer programme. When people are randomised they have an equal chance of being in either trial group, and their personal characteristics are not taken into account when they are allocated. Random allocation helps ensure that two very similar groups of patients will be compared, so if one group does better than another, it is likely to be because the treatments being compared have different effects, and not because of differences between the people in the groups.
If no standard treatment is available, the control group may not be given any specific treatment, or may be given a placebo. A placebo is a treatment with no active ingredient, which is designed to appear very like the treatment being tested. By comparing people’s responses to the placebo and to the treatment being tested, researchers can tell whether the treatment is having any real benefit, rather than patients simply feeling better because ‘something is being done’.
There are several ways in which the results of trials can be made as reliable and accurate as possible. One of these is to make the trial a ‘blind trial’. In a blind trial the participants are not told which group they are in. This is because if they knew which treatment they were getting, it might influence how they felt or reported their symptoms. Some trials are double-blind, which means that neither participants nor the doctors and others treating them know which people are getting which treatments. This also avoids the doctors’ hopes and expectations influencing the results of the trial.
Some of the parents we talked to had enrolled their children in a double-blind, randomised placebo-controlled drug trial. This means that children were allocated randomly to either trial group and neither parents nor doctors or others treating them knew which group their children were in. However, all the parents we talked to were willing to accept this, though some were still hoping their child would get the new drug in case there was a chance their child would benefit. Some parents who had been in other types of trial were not sure they would be willing to enter a placebo-controlled trial.
During her stay on a neonatal unit, Catherine enrolled her son as a control participant in a study on gut deformities in unwell premature babies. She reflects on her own experience of being invited to join a placebo-controlled trial. She says that making a decision to take part in such a trial can be difficult, depending on the situation you are in.
Jo’s son is in a drug trial for the treatment of migraine in children. Not knowing whether her son is on a drug or a placebo has been difficult at times. Jo won’t know what her son has been taking until the end of the trial, but as she says there is nothing to lose because “You don’t know which one is going to come out on top.” She is pleased they are taking part if it can offer some help to her son and other children.
Randomised trials are done when we don’t know which treatment is best, in other words when the relative merits and disadvantages of different treatments are uncertain. It is important to realise that, on average, new treatments are as likely to turn out worse as they are to turn out better than existing treatments. This means that, going in a trial, everyone, regardless of which of the treatment groups the computer allocates them to, must have similar chances of a good outcome. If, in spite of the treatment uncertainties that the trial has been designed to address, people would strongly prefer one of the treatments being compared, they should not volunteer for the trial.
Lucinda’s son is also taking part in a double blind randomised placebo controlled drug trial for the treatment of migraine in children. Although this is the first time they have tested the drug in children, knowing that the drug was used to treat adults and children was reassuring to Lucinda. If it had been a new or untested drug she would not have agreed for her son to take part. Her son received his own information about the trial and the doctors talked to him to ensure that he understood about the different groups. (See also ‘Involving children in decisions’.)
Linda had also enrolled her daughter, soon after she was born with a serious heart condition, in a randomised trial that was double blind and placebo controlled. Linda couldn’t quite remember all the details but does remember the medication was marked ‘trial drug’. Linda was happy to take part as the drug had already been tested. She still does not know for certain which treatment her daughter received, but she is fairly certain that her daughter had the active treatment because she has done so well. Linda described this as like a lottery; others used terms such as ‘flipping a coin’ or ‘drawing it out of a hat’ to describe the way the decision is made.
Sometimes when people do not experience a change in symptoms they assume they must be taking the placebo. However, this is not necessarily the case, as not all drugs work on all patients in the same way. Equally, people who are taking a placebo may sometimes experience improvements in their health. This is known as the placebo effect or placebo response. We still do not understand exactly why this happens, but it seems that believing a treatment will help can result in real changes. This is why new drugs are often compared against a placebo – if the patients on the drug do significantly better than those taking the placebo, it suggests the new drug really has an effect. If people were only given the new drug, we could not be sure if improvements were simply due to a placebo effect.
Parents we talked to understood that they would not be choosing which treatment they would receive. Alison has experience of enrolling her son in different clinical trials in neonatal care and when he was older, a growth hormone trial. She understands that the decision is made by the trial design which treatment your child will get.
Rachel enrolled her three children to a swine flu vaccine trial. She didn’t mind not having a choice which vaccine her children were given. However, she feels that some people may have a preference. It is important that when parents agree to enrol their children to take part in any randomised trial they understand that they may not get their preference.
Some parents we talked to had a preference for which group their children would be in, even though they knew they might not get their preference. Lisa’s son was born prematurely, weighing 2lb 12oz (about 1.2kg). When he was 4 years old, she agreed to enrol him in a growth hormone trial in which he is still participating. She explains that the aim of the trial was to find the best dosage for different children.
Emma enrolled her son to a clinical trial to test different diets for children with epilepsy.
In Emma’s case, children would be randomised to one of the two diets or a control group (though the children in the control group would also get one of the diets after 3 months).
Vicky and her daughter took part in a randomised trial on the management of diabetes in children and young people. Although they were happy to take part, she admits that they were both a little disappointed to be in the standard treatment group.
A lot of the terms used in trials are quite complex and closely related to each other. Below are some brief definitions as a reminder of how they fit together. You may like to look at the UK Clinical Research Collaboration booklet on Understanding Clinical Trials and chapter 3 of ‘Testing Treatments’
Control group: a comparison group in which people often get a standard treatment. If no standard treatment exists the control group receives no specific treatment or a placebo. Comparing the results of people in the control group with people in the experimental group helps assess whether there are differences between the new treatment and the control treatment.
Randomisation: allocating people at random to one group or another, so that each group contains a similar mix of people. Random allocation helps ensure we are comparing two very similar groups of patients, so if one group does better than another, it is very likely to be because the treatments being compared have different effects, and not because of differences between the people in the groups.
Placebo: a treatment with no active ingredient which is designed to appear very similar to the treatment being tested. By comparing people’s responses to the placebo and to the treatment being tested, researchers can tell whether the treatment provides any additional benefit.
Double-blind: trying to ensure neither patients nor doctors or others treating you know which treatment each person is getting, so that this knowledge does not influence how patients feel or how doctors interact with their patients or interpret the results.