Phases of clinical trial
A clinical trial is a controlled test of a drug or device. New drugs and devices are tested in
the laboratory before being trialled in humans. Laboratory testing can only tell us how a
drug/device will act. To know if it is safe and effective for the treatment of a medical
condition, we need to test it in people.
Why are clinical trials so important?
All drugs and medical devices used in Australia must be approved by the Australian
Governments’ Therapeutic Goods Administration of Australia (TGA). The TGA requires
extensive testing of the effectiveness and safety of new drugs and devices before it will be
allow the product to be made available to Australian patients.
Therefore without clinical trials we will not have access to new and better treatments.
Results from clinical trials lead to new medicines being made available that can prevent
deaths and improve the lives of those suffering from disease such as cancer, heart disease
and diabetes.
How are Clinical drug trials done?
Clinical trials are done following strict methods to ensure that the results are true and
correct. There are 4 different types of clinical drug trials which are called phases ( Phase I,
II,III, IV). All new drugs must be tested in phase I, II and III studies before being approved
for use by the public.
Phase I trials
After extensive laboratory testing the drug is tested in a small group of people, for the first
time. The aim of these trials is to find out how safe the medicine is; how it works and how
well it is tolerated. Typically these trials are very short and very tightly controlled with a high
degree of monitoring of participants.
Phase II trials
Once a drug has been successfully trialled in a phase I study it is then tested again in a
small number of people who have the disease that the drug is being developed to treat. The
aim of phase II trials is to assess the best dose of the drug in regard to its effectiveness and
safety. Typically these trials are short and are closely supervised. Participants are closely
monitored.
Phase III trials
When a phase II trial of a drug shows that the drug has potential benefits that outweigh the
hazards (side effects) the drug is then tested in a phase III trial. The majority of trials
conducted at Royal Melbourne Hospital are phase III. These trials involve many participants
from around the world. The aim of phase III trials is to show that the new drug is effective for
the treatment of a medical condition and safe to use.
To ensure that the results of the trial are correct and free from bias it is necessary to include
two groups in the trial. The only difference between the two groups is that one group will
have the new drug and the other group will not. To do this a placebo may be used. The
placebo looks identical to the new drug but it does not contain any medicine. Participants
are randomly assigned to either of the groups. This is called randomisation. Neither the
participants nor the research staff know who is receiving the new drug or placebo as this
could cause bias. This is called blinding. Both groups of participants are then monitored
closely for a period of time (usually 3 months to 3 years) so that a scientific analysis can be
done to determine if the drug is effective.
Phase IV trials
These trials are done after the drug is approved by the TGA. The aim of these trials is to
obtain further information about the drug or to compare approved drugs to each other to find
out which treatment is better.
Monitoring of Clinical Trials
All clinical trials are conducted in accordance with the World Medical Association’s
Declaration of Helsinki and the International Conference on Harmonisation’s Good Clinical
Practice Guidelines. These guidelines state the requirements for documentation, protocols,
and indemnities, informing participants and obtaining consent and reporting of adverse (bad)
events. Additionally in Australia clinical trials are conducted in accordance with the National
Statement on Ethical Conduct in Human Research. This document provides guidance on
ethical issues in human research. All clinical trials must be approved by Human Research
Ethics Committee before they can commence.
Sponsors monitor clinical trials very closely to ensure that all procedures are being
completed correctly. Sponsors monitor the trial data to detect any potential side effects of
the new treatment as soon as possible. Most phase III studies have a Data Safety
Monitoring Board (DSMB) which is a group of independent experts whose role it is to
periodically review the trial data for safety, effectiveness and trial conduct and progress. The
DSMB make recommendations concerning trial continuation, modification or termination of
the trial.
The Melbourne Health Office for Research is responsible for the governance of all research
conducted at Melbourne Health. Investigators and Sponsors report regularly in regard to the
conduct of the trial and how it is progressing.