Understanding clinical trials

Some of the strongest evidence about the effects of medicines comes from clinical trials, which are research studies to find out how well treatments work and what side effects they have. Read more about what clinical trials tell us, and why they are important.

Evidence-based medicine

Theories are important, and without them we wouldn’t have much progress in medicine — but they aren’t always right. This is why evidence from scientific studies to test theories is essential. If a health professional practices evidence-based medicine, it means they base their treatment decisions on evidence from scientific research, as well as their clinical experience and the needs of the individual person they are treating.

However, not all scientific research is created equal, and not all evidence is totally reliable. The strength of the evidence depends on the type of research and how well it is conducted. This means that finding a ‘scientific study’ to support an idea or a treatment is not enough.

What is a clinical trial?

Some of the strongest evidence about the effects of medicines comes from clinical trials.

Clinical trials are experiments to find out how well medicines work and what side effects they have. They are essential for proving whether medicines are actually effective or not.

Clinical trials are carefully designed to judge the medicine on a level playing field. To do this, researchers have two groups of people who are the same in every way (or as close they can get to it); the researchers give one group the medicine in question, and they give the other group either a placebo (a dummy treatment) or another medicine for the same illness.

A good clinical trial will have similar types of people in each group to avoid any bias. For example, having people who are much sicker in one group could make the medicine look either better or worse than it really is.

Tip: The best way to make the groups similar is to randomly put people into groups, so randomised clinical trials are considered better in general than non-randomised trials. If you are looking at the results of a study, check if it is a randomised trial.

oranges and lemons

The sailors given citrus fruit made a speedy and dramatic recovery. Image: Shutterstock.com

The first clinical trial gave us a cure for scurvy

James Lind, a doctor in Britain’s Royal Navy, pioneered the idea of the clinical trial in 1747 by testing his theories on how to cure scurvy in 12 sailors.

He divided the sailors in to six groups of two and gave each group a different treatment. The lucky ones were given orange and lemons, the others were given cider, elixir vitriol (sulphuric acid), vinegar, nutmeg or sea water. The sailors given citrus fruit made a speedy and dramatic recovery, and anyone else with scurvy could then be cured with a treatment Lind knew would work.

Nowadays there are very strict rules to make sure clinical trials are ethical, and no one would be given sulphuric acid!

Randomised trials and a cautionary tale of medically-caused blindness

Read a story from Informed Health Online about how one of the earliest randomised trials helped solve a fierce debate about what was causing blindness in premature babies in the 1950s.

What is the placebo effect?

When people take a medicine, it is not just the active ingredient or chemical in the medicine that makes a difference to how they feel — the expectation of getting better also has an effect. When people are given a dummy pill, or placebo, but think they may be taking a real medicine, up to one-third of those taking it will feel some improvement.

There are other factors that can contribute to people in the placebo group feeling better. People in clinical trials are monitored closely and have regular assessments and check-ups. They will be talking to a health professional more regularly and perhaps taking better care of themselves than usual. Also, sometimes people just get better because that is the nature of their illness.

People taking placebos can also experience 'side effects' that they think might be due to the medicine. Being able to compare the number of side effects experienced by people taking a placebo compared with those experienced by people taking the medicine helps to establish if the medicine is the likely cause.

Why does this matter?

If a clinical trial has a comparison (or control) group who have taken a placebo, we can be more confident that any differences in the results were actually due to the medicine, and not to other factors.

Tip: When you hear about the results of a study, check what the medicine in the study was being compared to. If there is no comparison group, you can’t really be sure that any changes reported in the trial were due to the medicine. The comparison group used in trials may be either a placebo or a medicine that is known to work for the same condition. A trial with a placebo group is called a ‘placebo-controlled trial’.

The best clinical trials will make it difficult for both the person taking the medicine and the health professional monitoring them to know which treatment they are taking. For example, placebos are made to look exactly the same as the real medicine, and doctors are not told which treatments patients are taking. This is called ‘blinding’, and it aims to get rid of any unintended influence, or bias, caused by the patients’ and doctors’ expectations of the medicine. Surprisingly, it can make a big difference to the results of a clinical trial.

Tip: When you read the results of a clinical trial, see if it mentions blinding. If the study is not blinded, the results might be overstated. A ‘double-blinded trial’ means that both the participants and the people assessing them were ‘blind’ to the treatment being used.

If you are thinking about going into a clinical trial, the researchers must tell you if there is a chance you will be given a placebo.

Putting it all together

Not all research studies are equally reliable. Different types of studies can actually be given a rating to say how good the overall scientific evidence they provide is. A properly designed randomised controlled trial, particularly if it is blinded, provides one of the highest levels of evidence available and gives health professionals a good basis for making decisions.

A review of multiple randomised controlled trials examining the same medicine, which combines the trials’ results, provides the strongest kind of scientific evidence.

Read more information provided by the Royal Melbourne Hospital about how different types of studies rate.

What clinical trials tell us about medicines

New medicines are first tested on animals to determine whether they appear to be safe enough and effective enough to justify clinical trials in people.

A medicine's journey from the laboratory to the public

A medicine's journey

A medicine must pass a series of experiments, trials, and approval processes before it is available for sale.

The first clinical trial (Phase I) is small, with only 20–80 healthy volunteers. This trial will work out how the human body reacts to the medicine, and what is a safe dose. The next trial (Phase II) involves 50–100 people who have the target illness, and gives information about how well the medicine works and more information about dosage.

If the medicine still looks promising after these early trials, it will be tested in a bigger trial (Phase III). This phase usually involves 1000–3000 people with the target illness. The Government regulatory body, the Therapeutic Goods Administration, looks at the results of Phase III trials when deciding whether to approve a new medicine for use in Australia.

Only a small percentage of new medicines make it through the entire testing process.

All new medicines are monitored after being approved for use. Some also undergo further Phase IV clinical trials. This type of trial may follow thousands of people to get a better picture of the medicine’s effects over a few years.

Phase IV testing allows researchers to learn more about the medicine and helps them to resolve uncertainties about the medicine's safety, side effects and most appropriate use. For example, Phase IV trials may be used to determine whether the medicine should be the first treatment tried for a condition, or whether it should be used only if other treatments have not worked.

Useful links

If you are thinking about going into a clinical trial, the following may be helpful:

For more information on the different types of clinical trials and how to evaluate their results, see: