There are four different stages of clinical drug trials - each of these are called "phases". 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 Therapeutic Goods Administration (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.