What are clinical trials?

What are clinical trials and why are they important?

A clinical trial is any medical research study that involves people. Clinical trials are the only reliable way to test if a new treatment or procedure:

  • Is safe
  • Has side effects
  • Works better than current treatments/procedures
  • Helps patients feel better

Clinical trials provide the evidence that healthcare professionals and patients need to know which medicines or procedures work best in the treatment of cancer. Clinical trials are also crucial in helping to develop new and better treatments for people with cancer. Trials carried out at ECMCs are important building blocks to developing treatments of the future.

Clinical trials follow a set of rules, known as a protocol, to ensure they are well designed and as safe as possible, that they measure the right things in the right way, and that results are meaningful. A full protocol should be available to anyone who is considering taking part in a trial and wants to see it.

 

How are clinical trials carried out?

Clinical trials are usually carried out in different stages, called phases. There are generally four phases of clinical trials – phases 1 to 4 (also written as phases I - IV). But some trials will have an earlier stage – phase 0. Most of the trials carried out by the ECMC Network fall within Phases 0-3, or biomarker studies.

Phase 0 Small patient group, and a very small drug dose

To test: If the drug reaches the cancer; how the drug behaves in the body; how cancer cells in the body respond to the drug

Phase 1 Small patient groups (6-30 patients)

To test: Dose safety; side effects

(NB: Patients on Phase I trials often have advanced cancer and have received all possible current treatments)

Phase 2 20-150 patients To test: Effectiveness balanced to side effects; if the new treatment works better for particular cancer
Phase 3 100s-1000s patients

To test: New versus current treatment (might become new treatment); may include 'quality of life' study

Phase 4 >1,000 patients

To find out more about the side effects, long term risks and benefits of current treatment

 

What to expect

Phase 0 trials

Althought Phase 1 trials are usually the earliest trials of drugs in people, a doctor might ask their patient if they would like to join a phase 0 study. These trials aim to find out if a drug behaves in the way researchers expect it to from their laboratory studies.

The main aim of these studies is to speed up the development of promising new drugs. Testing them in very small doses in humans rather than in animals can be more reliable and means scientists get useful information more quickly.

Phase 0 studies usually only involve a small number of people and they only have a very small dose of a drug. The dose of the drug is too small to treat your cancer, but the types of things researchers are looking for include whether the drug reaches the cancer and how cancer cells in the body respond to the drug

If you are partipiating in a Phase 0 study, you might have extra scans and give extra samples of blood and cancer tissue (biopsies) to help researchers work out what is happening. As the drugs dose used in phase 0 trials isso small, you won’t benefit from the drug, but this also means that you are less likely to have side effects.  

Phase 1 trials

Phase 1 trials are usually small trials, recruiting only a few patients. They may be open to people with any type of cancer.

When laboratory testing shows that a new treatment might help treat cancer, phase 1 trials are done to find out: The safe dose range; What the side effects are; how the body copes with the drug; and if the treatment shrinks the cancer.

Patients are recruited very slowly onto phase 1 trials. So although they don't recruit many patients, they can take a long time to complete. The first few patients to take part (called a 'cohort' or group) are given a very small dose of the drug.

If all goes well, the next group have a slightly higher dose. The dose is gradually increased with each group. The researchers monitor the effect of the drug, until they find the best dose to give. This is called a dose escalation study.

In a phase 1 trial, you may have lots of blood tests, as the researchers look at how the drug is affecting you. They also look at how your body copes with, and gets rid of the drug. They record any side effects.

People taking part in phase 1 trials often have advanced cancer and have usually had all the treatment available to them. They may benefit from the new treatment in the trial, but many won't. Phase 1 trials aim to look at doses and side effects. This work has to be done first, before we can test the potential new treatment to see if it works. 

Phase 2 trials

Not all treatments tested in a phase 1 trial make it to a phase 2 trial. These trials may be for people who all have the same type of cancer, or who have several different types of cancer.

Phase 2 trials aim to find out: If the new treatment works well enough to test in a larger phase 3 trial; which types of cancer the treatment works for; more about side effects and how to manage them; more about the best dose to use.

Phase 2 trials are often larger than phase 1. There may be up to 100 or so people taking part. Sometimes in a phase 2 trial, a new treatment is compared with another treatment already in use, or with a dummy drug (placebo). If the results of phase 2 trials show that a new treatment may be as good as existing treatment, or better, it then moves into phase 3.

Although these treatments have been tested in phase 1 trials, you may still have side effects that the doctors don't know about. Drugs can affect people in different ways.

Phase 3 trials

These trials compare new treatments with the best currently available treatment (also called the standard treatment). These trials may compare: A completely new treatment with the standard treatment; different doses or ways of giving a standard treatment; a new way of giving radiotherapy with the standard way.

Phase 3 trials usually involve many more patients than phase 1 or 2. This is because differences in success rates may be small, so the trial needs many patients to be able to show the difference. Sometimes phase 3 trials involve thousands of patients in many different hospitals and even different countries.

Phase 4 trials

Phase 4 trials are done after a drug has been shown to work and has been granted a licence. The main reasons for running phase 4 trials are to find out: More about the side effects and safety of the drug; what the long term risks and benefits are; how well the drug works when it’s used more widely.

Trials covering more than one phase

While most trials are just one phase, some trials cover more than one phase. For example, the same trial can include both phase 1 and phase 2. The aim of phase 1 might be to work out the highest safe dose of a new drug, and the aim of phase 2 might be to see how well that dose works. So you may see trials written as phase 1/2 or phase 2/3. 

 

Additional categories - randomised trials, blind trials, controlled trials

Phased trials may also have an additional category:

Randomised trials

In randomised trials, patients are allocated at random to treatment groups in the trial. This is usually done using a computer programme so that neither the patient nor the doctor will be able to influence the selection.

It is important that comparison is made like-with-like between each treatment group - each treatment group needs a similar mix of people of different ages, sex and state of health.

Blind trials

In blind trials, patients are not told which treatment group they are in. This is to avoid any influence that knowing which treatment they are receiving might have on a patient's reaction or how they report the symptoms.

A double blind trial is a trial in which neither the patient nor the doctors treating them know who is receiving which treatment. This is to prevent possible influence from the doctor's expectations.

All treatments in blind trials are made to look as similar as possible.

Controlled trials

These types of trials compare different treatments, usually comparing a new treatment with a standard/usual treatment. Controlled trials involve setting up two groups:

  • Trial/intervention group - given the new treatment.
  • Control group - given the standard/usual treatment. When there is no standard treatment, this group may be given a placebo. 

By comparing the results achieved by both groups, researchers are able to find out if a new treatment is more effective than the standard/usual treatment.