Clinical trials

Written by: 
Toby Murcott, medical writer

Many people will be asked to take part in a clinical trial at some stage in their lives. Most often this will be a phase III clinical trial, one where a new treatment has already been tested in animals and in small-scale human studies and has been shown to be safe enough to test in large numbers of patients. You might be asked to take part because there is a new drug for your condition, or because you fit the profile of patients needed for a particular trial.

Types of clinical trial

In practice, clinical trials can take many forms.

Some are small-scale pilot studies aimed at working out whether a new treatment is worth developing further, while others are large-scale studies designed to establish whether a new drug is safe to release for more general use.

Three phases of a large-scale trial

Large-scale pharmaceutical trials are divided into three stages, phase I, phase II and phase III.

  • Phase I trials are mainly to determine the safety of the drug and are normally conducted on small numbers of people - perhaps as few as ten, who are often healthy volunteers. The point is to see whether the treatment is safe to administer to people
  • Phase II trials include a significant number (often hundreds) of patients. They are the first stages in working out how effective the drug is when given to real patients. If a drug passes this test, it moves on to phase III
  • In phase III trials the drug is given to much larger numbers (often thousands) of patients, who have been recruited from as wide a range of the affected population as possible, usually by involving patients from multiple different centres, often in several different countries.

Being in a clinical trial can deliver benefits, but it is not entirely without risk, so should not be entered into lightly. If you are asked to take part in a clinical trial, it is a good idea to discuss the matter very carefully with your own doctor.

Considerations if you are asked to take part in a clinical trial

If your doctor suggests that you might be suitable for a clinical trial appropriate for your condition, it is important that:

  • You understand what the treatment under trial is intended to do
  • You know whether the test treatment is being compared with a placebo (inert treatment) or with a known drug or procedure
  • You understand the risks and benefits of taking part
  • You are confident that the trial is properly regulated[1]
  • You know what type of trial you might be involved in
  • You are happy that you can comply with any restrictions that might be imposed, for example on diet or alcohol consumption.

Risks and benefits

The major risk in taking part in a trial is the possibility that a new treatment will cause unexpected complications or problems.

The benefits can be a little more subtle:

  • You may receive a more effective treatment for your condition - either during the trial or when it is  completed
  • You are likely to be monitored carefully over the course of the trial, and this in itself could improve your overall wellbeing
  • Even if you receive no direct benefit, your participation will almost certainly add to the body of knowledge about your condition. Helping others can be a powerful motivation.

How a clinical trial is carried out

The principle of a clinical trial is straightforward: give someone affected by a particular condition the test treatment to see if his or her condition improves.

However, some important questions arise:

  • Has the person been properly diagnosed?
  • Would he or she have got better regardless?
  • Is there something about this particular person that makes him or her more amenable, or more resistantA microbe, such as a type of bacteria, that is able to resist the effects of antibiotics or other drugs., to the treatment?

Modern clinical trials have developed techniques aimed at answering all these questions, and more. In the process they have become highly sophisticated, complex procedures. The key elements include:

The widely preferred type of trial for drug treatments, designed to produce the most reliable results, is the double blind randomised controlled trial.

The control group

An essential element of all clinical trials is the control group. One group of patients (the active treatment group) is given the test drug or procedure, while a second group (the control group) is given a known drug/procedure or a dummy (placebo). The treatment being tested is thereby compared with the control treatment.

This design, known as a controlled trial, aims to answer the questions:

  • Is the new treatment better than the current procedures?
  • Is the treatment better than doing nothing?

Random selection

Results obtained from a controlled trial are only useful if the two groups, the active group and the control group, contain the same mix of people. Putting the healthiest individuals in one group and the sickest in the other, for example, would bias the result.

To avoid this, the patients are divided into groups at random.

The size of the trial

The next step is to determine whether the treatment will work for all those who need it. The best way to answer this is by testing it on as many people as possible. The more people included in the testing, the more likely the results will reflect the range of different responses. How many people are needed to achieve a result that will be statistically meaningful depends on the type of response being sought and the likely scale of the difference that the new treatment may make. The more people that are included in the trial, the more likely it is that even rare side-effects may come to light.

Bias and 'double blinding'

It is well known that if you give patients a placebo treatment and tell them that this will make them better, the patients' health will usually improve. This phenomenon is known as 'the power of belief' or 'the placebo effect'. To avoid this effect influencing the results, in a clinical trial patients are not told whether they are receiving the control or the test treatment.

Bias can affect researchers as well as patients, however. If the person dispensing a treatment knows or believes that it is better or more effective, this too can influence patients' responses. For example, a doctor who is aware of the contents of pills might appear more confident when dispensing an active treatment than when giving a placebo.

In a well designed trial therefore, the doctors do not know which patients are receiving which treatment. In a trial of a drug, for example, neither doctors nor patients know what is in the bottle. This procedure is called 'double blinding'.

The double blind randomised controlled trial

The gold standard of modern clinical trials is the double blind randomised controlled trialA study comparing the outcomes between one or more different treatments for a disease (or in some instances, preventive measures against that disease) and no active treatment at all (the placebo group). Study participants are allocated to the various groups on a random basis. May be abbreviated to RCT., or RCTRandomised controlled trial. A study comparing the outcomes between one or more different treatments for a disease (or in some instances, preventive measures against that disease) and no active treatment at all (the placebo group). Study participants are allocated to the various groups on a random basis.. In this type of trial:

  • There is a control group as well as a test group
  • People undergoing the trial are randomly allocated between the test and control groups
  • Neither doctors nor patients are aware who has received the active therapy and who was given the placebo treatment.

Carried out properly, with a large number of patients, this type of trial is accepted as having the best chance of determining without bias how well a new drug or treatment works.

The double blind randomised controlled trialA study comparing the outcomes between one or more different treatments for a disease (or in some instances, preventive measures against that disease) and no active treatment at all (the placebo group). Study participants are allocated to the various groups on a random basis. May be abbreviated to RCT. cannot be used in all cases, however. Trials of many non-drug based treatments such as physiotherapyThe use of physical therapies such as exercise, massage and manipulation. or surgery cannot be designed to be double blind.

References: 
  1. The list of registered drugs trials worldwide. Link.