Clinical Trials

What are clinical trials and why do we need them?

Clinical trials are research studies involving patients, which compare a new or different type of treatment with the best treatment currently available (if there is one). Some clinical trials look at possible ways to prevent illnesses, for example by testing new vaccines. No matter how promising a new drug or treatment may appear during tests in a laboratory, it must go through clinical trials before its benefits and risks can really be known. Trials aim to find out if treatments are safe, what side effects participants might experience, and if the new therapies work better than the treatment used currently.

Clinical trials are the most reliable and best way of testing treatments. A new treatment is not always better, and can sometimes be worse than existing treatments. Trials are therefore very important to find out whether one treatment is safer and more effective than another, or sometimes to find out if it is just as good.

New treatments usually have to go through a series of clinical trial phases to test whether they are safe and effective. New drugs go through a number of different phases of a trial:

• Phase I trials aim to test the safety of a new treatment. They look at side effects of a treatment – for example, does it make people sick, raise their blood pressure and so on. Phase I trials involve only a small number of people, who are often healthy volunteers.
• Phase II trials test the new treatment in a larger group of people who usually have the condition for which the treatment is to be used, to see whether the treatment is safe and has some effect on that condition. Usually less than one hundred people are involved at this stage.
• Phase III trials involve larger numbers of patients (hundreds or sometimes thousands), who are usually randomised to receive the new treatment or the best available current treatment (or sometimes a placebo). They aim to assess how well the new treatment works, and take longer than Phase I or II trials to run.
• Phase IV trials are done after the drug has already been approved by drug regulatory authorities. They are carried out to gather information on the drug's effect in various populations and any side effects associated with long-term use.

What is a randomised controlled trial?

Randomised controlled trials (RCTs) are a type of clinical trial. RCTs, like STAMPEDE2, aim to make a fair comparison between a new treatment and the existing treatment, or between two (or more) existing treatments, to see which one works best.

A controlled trial compares two or more groups of people: one or more experimental group(s) who receive a new treatment, and a control group, who receive the current standard treatment (which might be the best existing treatment, no treatment or a placebo). Information from the follow-up of the control group allows the researchers to see whether the new treatment(s) they are testing are any more or less effective than the existing treatment.

The decision about which treatment each participant in a randomised controlled trial receives is made at random – based on chance, rather than decided by the doctor or participant. This process is called randomisation.

Randomisation ensures that the two (or more) groups of people in a trial are as similar as possible, except for the treatment they receive. This is important because it means that researchers can be sure that any differences in outcomes between the groups are therefore only due to the treatment received.

Randomisation is the best way of ensuring that the results of trials are not biased by the way participants in each group are selected. For example, if a doctor chose which treatment a patient should receive as part of a trial, she or he might give the new treatment to sicker patients, or to younger patients. This would make the results of a trial unreliable, as it could exaggerate or hide the effects of the treatment.

Randomised controlled trials are the most reliable way to compare treatments.

What is a multi-arm multi-stage (MAMS) trial?

A clinical trial known as a multi-arm multi-stage (MAMS) trial enables the evaluation of several potential therapies simultaneously. The MAMS design aims to maximise the efficiency of testing treatments. It offers flexible features, including:

• Testing multiple treatments at the same time and comparing them with a common control group, reducing the required number of patients.
• Adding the flexibility to drop treatments that don’t show promise, and allow the addition of new treatments as they become available.
  
  MAMS trials have been successful in improving treatments for cancer and infectious diseases.

How do we make sure a trial is safe?

A lot of care is taken to ensure that clinical trials are as safe as possible. Some of the things that go into making a trial safe are detailed as follows;

Independent Scientific Review

All trials conducted at the MRC Clinical Trials Unit at UCL are scientifically reviewed before the trial can start. The plan for the trial (called the protocol) is sent to a number of independent scientists for comment. The protocol may also be sent to patients, to ask for their comments. Both patients and researchers must be independent of the trial.

Ethics Committees

All our trials have to be examined and approved by an ethics committee before they can start, to make sure the planned research is ethical and as safe as possible. This committee usually includes members of the public, researchers and health care professionals. Any changes that are made to the trial protocol while the trial is running also have to be examined and approved by the ethics committee. Researchers must tell the ethics committee if people experience unexpected and serious side effects during the trial.

Data Monitoring Committees

Most trials have a data monitoring committee that looks at how the trial is progressing. The people on the data monitoring committee must be independent of the trial. An independent group of people like this is able to look at the interim results of a trial and decide if a clear result has been reached. Their aim is to ensure that the trial is safe. If the data monitoring committee sees any information or data to indicate that a trial should not continue, perhaps because people are experiencing serious side effects that were not expected, this committee can recommend that a trial is stopped.

National and International Guidelines

There are guidelines to ensure that trials are run properly. European and UK laws agreed in 2004 mean that all organisations that run trials must ensure there are arrangements in place in case people are harmed during a trial of a drug. You can read more on this in the guidelines from the Department of Health & Social Care on Good Clinical Practice (GCP) in non-commercial trials. The Research Governance Framework developed by the Department of Health & Social Care sets out standards of good practice in the conduct of health research. Ethics committees check these arrangements are in place when they make decisions about whether to agree that a trial can go ahead.

Informed Consent

Before a participant joins a trial, the researcher must explain the trial and get the person’s agreement to take part. The researcher must explain:

1. The aim of the trial – why is it taking place?
2. The treatments that are being compared.
3. What the trial involves for participants.
4. Possible benefits and risks involved.

All participants should receive a patient information sheet explaining these things. Participants are asked to sign a form giving informed consent to take part in a trial. Informed consent means that participants have been given the important facts about a trial, understand them and have decided to take part in the trial of their own free will. Participants can change their mind after signing the informed consent form, and can withdraw from a trial at any stage.

Confidentiality

Confidentiality of patient data is very important in clinical trials. In a trial, all medical records are confidential. This information is kept securely, and only a very limited number of people have access to it. Participants’ names, or details that could help others identify individual participants, are not used in any reports about the trial.

Your hospital will use your name, NHS number and contact details to contact you about the research study, and make sure that relevant information about the study is recorded for your care, and to oversee the quality of the study. Individuals from UCL and regulatory organisations may look at your medical and research records to check the accuracy of the research study. Your hospital will pass your name, postcode and NHS number to UCL along with the information collected from you and your medical records. The people who analyse the information will not be able to identify you and will not be able to find out your name, NHS number or contact details.

The Medical Research Council is the sponsor for this study, based in the United Kingdom. University College London (UCL), through the MRC Clinical Trial Centre at UCL, will be using information from you and your medical records in order to undertake this study and will act as data controller for this study. UCL will be responsible for looking after your information and using it properly. UCL will keep identifiable information about you for 25 years after the study has finished.

You can find out more about how we use your information by viewing the UCL Privacy Policy.