What are clinical trials?

The World Health Organization defines clinical trials as:

‘any research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. Clinical trials may also be referred to as interventional trials. Interventions include but are not restricted to drugs, cells and other biological products, surgical procedures, radiological procedures, devices, behavioural treatments, process-of-care changes, preventive care, etc.’

How important are clinical trials?

Clinical trials are important to allow new interventions to become available and improve health outcomes. Clinical trials are designed and conducted in a group of human subjects in order to develop new interventions to show the benefits and identify any possible adverse effects related to the interventions.

How clinical trials work

Before a clinical trial is initiated, researchers may first test new interventions in laboratory and animal studies. When the results are promising, the next step is conducting clinical trials in humans, which will help to collect more information about the effectiveness and safety of a new intervention.

Clinical trials in Australia are governed by national ethics guidelines in the National Statement on Ethical Conduct in Human Research and codes of conduct in the Australian Code for Responsible Conduct of Research. Clinical trials of any unapproved substances and devices must also comply with the Therapeutic Goods Administration. Any participants in a clinical trial must give informed consent. They must be fully informed of the objectives, risk and benefits of the study.

All clinical trials are conducted according to trial protocols. A protocol consists of a list of measures for clinical trials teams to follow to ensure the study is performed correctly and participants’ safety. The protocol includes the type of subjects who are eligible to take part in the study; the study objectives; the study design, tests and procedures; number of subjects and length of study; preparation and administration of the investigational product; etc. Control groups are used in clinical trials to compare against a new intervention that is being assessed. A control group can be an existing treatment or a placebo. Randomisation is one of the ways used to avoid bias in a study. A computer system is normally used in this process to allocate human subjects to a control group or to a group using the new intervention. Blinding is another way to eliminate bias in a clinical trial. A single-blinded study means the clinical trial team knows which treatment is assigned to which participants. In this type of study, the human subjects in the trial do not know if they are receiving control drug or investigational drug. In a double-blinded study, both the clinical trial team and the participants do not know if a control drug or investigational treatment is given to which participant. In some situations where certain criteria outlined in the study protocol are met, a participant may need to be unblinded. This may occur if a patient experiences severe adverse effects and the practitioner needs to know the actual type of treatment given to the patient.

Phases of clinical trials:

Clinical trials are commonly conducted through four to five phases:

Phase 0 clinical trial or pilot study

In this phase, small doses of the experimental drug are given once or for a short time to a very limited number of humans (about 10 to 15 people) to test how a drug is processed in the body and how the body responds to the drug.

Phase I clinical trial

The main purpose of a Phase I trial is to test the safety and tolerability of an intervention at the best dose with the fewest side effects. The lowest dose is given and increased until side effects become too severe or the desired effect is seen. The number of human subjects usually ranges between 20 to 80 people and the study is normally conducted over several months. The information gathered in this phase is used to design Phase II trials.

Phase II clinical trial

Phase II studies aim to assess whether an intervention works and to provide additional safety data. The information gathered in this phase is used to develop research methods and design Phase III study protocols. Phase II clinical trials involve up to several hundred human subjects and may take several months to two years.

Phase III clinical trial

Phase III clinical trials involve several hundred to several thousands of human subjects, and the length of the study may take one to four years. As it involves a larger population and longer duration, the results of the studies will show long-term or rare side effects, and treatment benefits of the intervention studied.

Phase IV clinical trial

Phase IV trials are conducted after an intervention has been marketed. Several thousands of human subjects are recruited in the study for a longer duration. The study is designed to monitor the effectiveness of the approved intervention. The studies are also used to gather information about any adverse effects related to the approved intervention. It may also assist in investigating the potential use of the intervention in a different condition or in combinations with other therapies.