Clinical Trials

Non-randomised trial designs and other studies

Clinical trials are carried out in a number of stages. Early stage trials usually involve small numbers of patients. Particularly for drugs, early stage studies are needed to assess safety and unwanted side effects, after early laboratory testing has been completed. (See Resources).
Phase 1 trials usually involve a small group of healthy people, or sometimes patients. They are mainly aimed at finding out how safe a drug is. This is often the first time that a drug will have been tried in human beings.
By the time a drug reaches Phase 2, researchers will know more about it. In Phase 2 the aim is to test the new drug in a larger group of people to better measure safety and side effects, and see if it has a positive effect in patients. Sometimes Phase 2 trials may be randomised, but sometimes not. (See ‘Feelings about being allocated (randomised) to a treatment group’).
Tom, Anthea and Julian all understood that, especially with early phase trials, there are possible risks and side effects doctors may not yet know much about. (See also ‘Side effects and queries’). As with all trials, there was also no guarantee of benefit. But given that they all had advanced forms of cancer and other treatments were either not possible or had stopped working, they were keen to try anything that might help, as well as perhaps benefiting others. As Anthea says below, it was also a way for her to keep positive and feel she was doing something. (See also ‘Reasons for taking part in a clinical trial – personal benefit’ and ‘Reasons for taking part in a clinical trial – helping medical science and other people’).
These participants all described their own side effects as relatively mild, though some had met other people in the trial who had to give up because of side effects. All were impressed by the amount of monitoring and tests carried out. (See also ‘Appointments, monitoring and questionnaires’).
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Tom wanted to emphasise the difference between early phase trials in healthy volunteers compared to people who are seriously ill.
In Phase 2 trials we can start to get some idea of whether a treatment works for some people, and what kind of side effects they experience. But controls and larger numbers are needed in randomised Phase 3 trials, which compare new treatments with current standard treatments or placebos. Phase 3 trials can also find out more about how common and serious any side effects or risk are. Sometimes even when Phase 1 and 2 trials suggest a new drug is promising, when it is tested in Phase 3 trials the results do not show it makes a significant difference.
People in early phase trials can find it hard to accept this if they have personal experience that suggests the drug has worked for them, as Julian commented.
Some people we spoke to had been involved in other kinds of non-randomised study. Pam was given the cancer drug lapatinib which had not yet been licensed for use in the UK. (It was later licensed in July 2008). Women who were eligible could only be given the drug as part of a supervised study, monitoring effectiveness and side effects - an ‘open label expanded access’ study. (‘Open label’ means both the patient and doctor know what the drug is that is being taken).
Sometimes with diagnostic or surgical procedures non-randomised studies are done to check if the procedure is safe and effective.
Kate was unsure whether this type of surgery would eventually be tested in randomised controlled trials. She wondered if otherwise the type of patients selected might make the results look better than they would be for a wider group of people.
Unlike drugs, the success of a surgical intervention depends on the skill of the doctor as well as the type of procedure, so further studies may be needed to check that individual surgical teams have acquired the necessary skills to carry it out. Shirley was asked to take part in a study of a technique called sentinel node biopsy to check whether breast cancer has spread into the lymph nodes. The sentinel node is the first lymph node to be affected. If it can be found and removed, and is not cancerous, then other lymph nodes will not need to be taken out, avoiding some unpleasant side effects. The technique has already been found effective in randomised clinical trials, and many hospitals now want to offer it to their patients. But before they can do so the surgeons must demonstrate they can find the sentinel node accurately. The study Shirley was asked to join was part of a national programme to ensure local surgeons could perform the procedure and needed 30-40 women to join.

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Last reviewed September 2018.
Last updated July 2011


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