CLINICAL TRIAL PROTOCOLS
Clinical trials follow a plan, or set of rules, known as a protocol to ensure that they are as safe as possible, that they measure the right things in the right way and that the results are meaningful. For example, a protocol describes:
- Who is eligible to take part in the trial;
- The research methods, tests and procedures that will be used;
- The interventions that will be used and how they will be delivered; and
- The length of the study, what information will be collected and any follow up
If someone who is ill is given a medication and then gets better, it could be due to a natural recovery that would have happened anyway or to other factors. To determine if the intervention has worked, it needs to be compared to another intervention, non-interventional standard care or a placebo.
Participants in a clinical trial will therefore be put into one of two groups:
- a group that is given the new intervention being assessed; and
- a group that is given an established intervention that is already in use, other standard care or a placebo
The second group is known as the control group.
The aim of the trial is to compare what happens in each group. The results have to be different enough between the two groups to prove that the difference has not just occurred by chance.
If the individuals in the group being given the new intervention show a significant improvement, without any serious side-effects, over the control group, then the researchers may end the clinical trial early and seek to change the nature of the clinical trial to afford more patients the opportunity to receive the new intervention.
Comparing a new intervention with a standard intervention
A new intervention is often compared with a standard or commonly used intervention that is already known to be helpful. This makes it possible to determine whether the new intervention works better than one that is already being used.
Comparing a new intervention with a placebo
In some biomedical trials, a new intervention is compared with a placebo. A placebo is a ‘dummy’ treatment, such as a sugar pill, that looks the same or is used the same way as the interventional substance, but that has no known health effect. If the patients who received the intervention have a better outcome compared to patients who received the placebo, this suggests that the intervention was effective.
Placebos are not used if a patient would be put at risk, for example – in the study of treatments for serious diseases – by not being given effective treatment. Potential participants are told if placebos will be used in the trial before they agree to participate.
It has been shown that if you think and believe you are going to get better, you are more likely to do so. If you take something you believe to be an effective medicine, your symptoms may improve. Reassurance from a doctor or other health care professional also helps some people to feel better. This is known as the ‘placebo effect.’ It is an effect that is poorly understood but that can, nonetheless, be quite real and powerful.
In clinical trials where it is used, a placebo appears to be the same as the new medication being studied, so you don’t know which one you are taking. Some people may feel better after taking the placebo because they think they are being given real medication. Researchers take the placebo effect into account when designing clinical trials, usually by ensuring that the number of people involved in the trial is large enough to compensate for any possible placebo effects.
Number of people in a clinical trial
The effect of an intervention may vary between people. This means that promising interventions have to be tested on a large enough number of people to ensure that the results can be analysed using statistics to see if any differences measured are statistically significant (i.e. real) and not due to chance.
For example, if seven out of ten people improve with a new intervention, this could be due to chance. However, if 700 out of 1000 people improve, then researchers can be reasonably confident that the new intervention is effective. Researchers can work out how many people are needed for a particular trial and whether the results are statistically significant by using mathematical calculations.
Later phases of trials require larger numbers of participants.
Many trials compare the effects of an intervention using two groups of participants. The two groups need to be as similar as possible except for the intervention received (or not received), so that any differences in outcomes are due to the differences between interventions and not the differences between groups.
In order to ensure that there is no bias during the selection of the different groups for a clinical trial, participants are allocated to each group in a way that doesn’t involve a decision by anyone involved in running the trial. This process is called randomisation and is usually done by a computer.
If a clinical trial is ‘blinded’ or ‘masked’, it means that the participants and/or the researchers don’t know who is receiving the new intervention and who is not.
If a clinical trial is ‘single blind’, it means that the participants in the trial do not know which intervention they are receiving, but the researchers and medical staff do.If a clinical trial is ‘double blind’, it means that neither the researchers organising the trial nor those taking part in the trial know who is receiving which intervention.
Blinding helps to reduce the effects of bias when comparing the outcomes of the interventions. If either researchers or participants know who is receiving the new intervention, this knowledge can influence what they report. Participants who think that they are receiving a new intervention may be very hopeful about its effects or may not want to let down the researcher. For this reason, they may exaggerate benefits and minimise side effects. Likewise, researchers may allow their hopes for a new intervention to unconsciously influence how they record the effects.
In the event of an emergency where you doctor needs to know which intervention you are receiving to provide the care you need, the blinding can be ‘broken’ and they can find this out.