Clinical Trials Explained

Medical research studies involving people are called clinical trials. Clinical trials look at:

Preventing a disease: using drugs, vitamins, foods to reduce risk
Screening: for people at higher than average risk, or for the general population
Diagnosing: new tests or scans
Treatments: new drugs or combinations of drugs; new ways of giving treatment, new types of treatment
Controlling symptoms: new drugs or complementary therapies

The aim of trials is to find out if a new treatment or procedure:

Is safe
Has side effects
Works better than the currently used treatment
Helps an individual feel better

New treatments have to be thoroughly tested. A new drug, for example is investigated first in the laboratory. If it looks promising, it is carefully studied in people.

Different types of trials

There are 4 phases of clinical trials. Each treatment being tested has to go through all these phases:

Phase I trials look at whether a trial treatment is safe or has any harmful effects. For trials of new drugs, the correct dose to give will also be tested.

Phase II trials look at whether a treatment works. Only a treatment that has got through these 2 phases will go into phase 3 testing

Phase III trials test a new treatment against the existing standard treatment. If it gives better results, it may become the new standard treatment. Phase III trials also look at how well the treatment works, and at the side effects. Researchers may look at the impact a treatment has on someone - how often they have to travel to hospital, for example. Studies of impact and side effects are sometimes called quality of life studies. Most well planned phase III medical research includes an investigation of quality of life.

Usually, a new treatment has to go through a few Phase III clinical trials before doctors are confident enough to accept it as the new standard treatment. One good trial result could happen by chance or because a trial was not very well designed. This is not likely if several trials have the same results.

There are now trials called Phase IV trials. These are carried out after a drug has been licensed. They collect information about side effects, safety and the long term risks and benefits of a drug.

Clinical trials will not all result in new and better treatment. Some will discover that the treatment being tested does not work. Or that it has side effects that are much worse than with existing treatments. But, to researchers and doctors, and in the end for patients, it is still useful to be able to rule something out.

Phases of Clinical Trials

Phase I

This is the earliest trial in the life of a new drug or treatment. They are usually small, recruiting up to 30 patients but often a lot less. If the trial is for a cancer drug for example the trial may be open to people with any type of cancer and would be targeted at finding out:

The safe dose range
The side effects
How the body copes with the drug
If the treatment is effective eg. shrinks the cancer

The first patient to take part will be given a very small dose of the drug. If all goes well, the next person will get a slightly higher dose. With each patient taking part, the dose will gradually be increased and the effect that has will be monitored. Any side effects will be recorded. In a Phase I trial, the researchers look at how the drug affects the patient, how their body copes with it and gets rid of it too.

People entering Phase 1 trials often have advanced form of the disease the new drug is designed to treat. This is because they may benefit from the new treatment in the trial, but many won't. The aim of the trial is to look at doses and side effects. This work has to be done first. Phase I trials are important because they are the first step in finding new treatments for the future.

Phase II

About 70% of new treatments tested at Phase I make it to Phase II trials. Although these treatments have been tested at Phase I, there may still be side effects that are not known about. Drugs can affect people in different ways. For example, these trials may be done on people who all have same type of cancer, or with several different types of cancer. Phase II trials are done to find out

If the new treatment works well enough to test in Phase III
Which types of the disease it is effective against
More about side effects and how to manage them
More about the most effective dose to use

Phase II trials are often larger than Phase I. There may be up to 50 people taking part. If the results of Phase II trials show that a new treatment may be as good as an existing treatment, or better, it then moves to Phase III.

Phase III

Phase III trials are usually much larger than Phase I or II. This is because differences in success rates may be small. So, you would need many patients in the trial to show the difference. These trials compare new treatments with the best currently available treatment (the standard treatment). They may compare:

A completely new treatment with the standard treatment
Different doses or ways of giving a standard treatment
A new radiotherapy schedule with the standard one

Sometimes Phase III trials involve thousands of patients in many different hospitals and even different countries.

Randomisation
Phase III trials compare one treatment with another, to find out which is better. Most Phase III trials are randomised. This means that there are at least 2 different groups in the trial and those taking part are put into one or other group at random. Each group in the trial will receive a different treatment. If there are 2 groups, one group will have the new treatment being tested and the other the standard treatment that they would have to treat their disease if not in the trial. Those having the standard treatment are called the 'control group'. A randomised trial that has a control group is called a 'randomised controlled trial'. There may be more than 2 groups. Some trials test more than one new treatment or they may test variations in one particular new treatment - for example different doses of a drug. There will still be a control group, who have the standard treatment that they would have if not in the trial. Sometimes control groups are given a dummy treatment, called a placebo. This is only done if there is no standard treatment available. Randomisation is done because researchers need to be sure that the results they get are correct and not biased for any reason.

The placebo effect
Patients can also be biased. Many of us feel better if we believe we have taken something to make us feel better. Even if we've only taken a tablet made of chalk or sugar. This is called the placebo effect. Phase III trials could compare a new treatment with no treatment at all. But then, the people getting the new treatment might feel better, even if the new treatment didn't work. They would be showing the placebo effect. Some trials compare a new treatment with a dummy treatment called a placebo. The two groups of patients cannot be biased, because they won't know if they are getting the placebo or the new treatment. It is not ethical to give a placebo to group of people who really needed a treatment for say cancer. So the research ethics committee would not give permission for a trial designed in that way. A placebo would only be used if there was no standard treatment and the patient would not receive any treatment if not in the trial.

Overviews
Trial overviews are studies that combine all the results from Phase III trials of a new treatment. They are sometimes called meta-analyses. The idea is to get a broader picture of how well a treatment works. The more data (information) you have, the more accurate the results are likely to be.

Phase IV

Phase 4 trials are done after a drug has been shown to work and has been granted a license. So they are looking at drugs that are already available for doctors to prescribe, rather than new drugs that are still being developed.

The main reasons pharmaceutical companies run Phase IV trials are to find out