Clinical trials
What is a clinical trial?
A clinical trial is a scientific study, or an organised test of medicines and new treatment options, involving patient and non-patient human volunteers.
Clinical trials confirm whether medicines are safe and effective to introduce as new treatments for a particular disease or condition.
Clinical trials may also be used to determine whether an existing medicine can be used safely and effectively for other diseases and/or conditions.
Why are clinical trials so important?
While medicines are extensively tested in laboratories, these tests can only predict how a medicine will act. To thoroughly understand how a new medicine actually works in humans, it needs to be tested on people affected by the disease the medicine is designed to help. These human tests (clinical trials) help doctors to assess if the new medicine is more effective or safer than old medicines or treatments, and to determine the correct dosage of the medicine.
Clinical trials are needed to collect data required by the Australian government to demonstrate that the medicine is safe and effective. It is not until this data has been assessed by the Australian government’s Therapeutic Goods Administration (TGA) that new medicines are approved for prescribing by your doctor or hospital and made available for sale at the pharmacy.
Results from clinical trials can lead to the development of medicines that can prevent thousands of deaths each year and also improve the lives of thousands more people suffering from various medical conditions.
How are clinical trials approved?
In Australia, clinical trials must conform to the Ethical Principles of the Declaration of Helsinki and to international Good Clinical Practice guidelines.
Before a trial can go ahead it needs to be approved by independent ethics committees that operate according the guidelines issued by the National Health & Medical Research Council (NHMRC Guidelines).
Who runs a clinical trial?
Each clinical trial is led by a doctor. The clinical trial team includes doctors and nurses as well as pharmacists and other health care professionals.
The clinical trial team is responsible for checking the health of the participants at the beginning of the trial, monitoring them during the trial, and staying in touch with them for a period of time after the clinical trial has been completed.
Are all clinical trials the same?
There are 4 different types of clinical trials, each one associated with a different phase in the development of a new medicine or treatment.
- Phase I clinical trials involve the first administration of the medicine to humans, usually to small numbers of healthy volunteers. Phase I clinical trials determine the safety of the medicine, how it works and how well it is tolerated. These clinical trials also identify preferred routes of administration (e.g. tablet, liquid or injection) and help determine the appropriate doses for later studies. Phase I clinical trials are usually undertaken in centres appropriately equipped for the specialised monitoring and the high degree of surveillance needed.
- Phase II clinical trials are normally the first trials of the medicine in patients suffering from the condition for which the medicine is intended. The principal aim of these clinical trials is to determine effectiveness and safety. These clinical trials are undertaken in a small number of closely supervised patients and conducted by researchers regarded as specialists in the particular disease or condition and its treatment.
- Phase III clinical trials involve greater numbers of patients and are undertaken for the purpose of determining whether the medicine confers clinical benefit in the disease/s for which effectiveness was demonstrated in Phase II clinical trials. They also determine the nature and likelihood of any side effects. Phase III clinical trials are undertaken if the Phase II clinical trials indicate the medicine has potential benefit that outweighs the hazards.
- Phase IV clinical trials are those clinical trials undertaken after the medicine has been approved for the treatment of a particular disease. Phase IV clinical trials are undertaken to compare a new medicine to a wider range of existing medicines/therapies. Such clinical trials are used to establish where, in the range of treatment options, the new medicine is best used. Phase IV clinical trials are also undertaken to investigate further the use of the medicine in the normal clinical setting of the disease, as this may differ quite markedly from the conditions under which the other clinical trials were conducted. This includes post marketing surveillance studies.
Do all participants receive the new trial medicine?
In order to determine objectively the benefits of a new medicine it is necessary to remove any subjective bias. This is particularly the case in Phase III and IV clinical trials where participants are normally divided into 2 or more groups.
One group (the test group) is given the trial medicine while the other group (the control or reference group) is given the standard treatment for the disease or condition. Where there is no pre-existing standard treatment, a placebo — a look-alike or dummy medicine containing no active ingredient — may be given to the control group instead. Participants are randomly assigned to either group.
Ideally, neither researchers nor participants should know which group a particular patient is in. Clinical trials where this occurs are referred to as double blind trials. However, safety does come first. Should a participant develop an unexpected or serious side effect the blinding of the trial can be broken so that appropriate action can be taken.
Why participate in a clinical trial?
There are a number of possible advantages of participating in clinical trials. These can include:
- gaining early access to new medicines not otherwise available;
- obtaining the clinical trial medicine at no cost, at least during the trial;
- receiving extensive medical care associated with the clinical trial; and
- contributing to the development of future life-saving or life-enhancing treatments.
Participation in clinical trials is not, however, without its downsides. For example:
- there may be unexpected side effects from the trial medicine;
- the trial medicine may not work;
- you may be placed in the control or reference group and may not receive the trial medicine until after the clinical trial has finished; and
- you may need to visit the hospital or doctor’s room more frequently or stay there longer.
Becoming a clinical trial participant
Eligibility
Depending on the type of clinical trial (Phase I, II, III or IV) and the medicine being trialled it may be necessary for participants to have been previously diagnosed as having the disease or condition for which the trial medicine is intended to treat.
Enrolling
Before making this important decision a person must be given a full written plain-English explanation of the clinical trial by a doctor. Only after carefully considering this document should a person provide their written consent to participate.
The explanation of the study will include things such as the eligibility criteria; possible risks and benefits of the new medicine; the risks of any side effects; the type, frequency and risks of any medical tests or procedures that may be undertaken as part of the trial; and the person's rights and responsibilities.
Potential participants will be made aware that they can withdraw from a study at any time, without any effect on ongoing medical care and that their involvement is entirely voluntary.
Commencement
The clinical trial will commence when a sufficient number of people have been enrolled to participate in the clinical trial. This may take some time.
Important considerations
Who pays for clinical trials?
Clinical trials are conducted, or ‘sponsored’, by a wide range of organisations. They include:
- pharmaceutical companies, either solely or jointly with other research institutions such as universities and hospitals;
- private research organisations under a grant from the government’s National Health & Medical Research Council or from public donations; and
- publicly funded research organisations such as universities and teaching hospitals.
Regardless of the type of organisation sponsoring the clinical trial, the clinical trial must be approved and monitored under the ethical and good clinical practice guidelines set down by the Australian government.
What happens if there are side effects from participating in a clinical trial?
By the time a medicine reaches the clinical trial stage it has already been extensively tested in laboratories for likely side effects. However, part of the purpose of the clinical trials is to see what unexpected side effects emerge, and how severe or common they are. So as well as experiencing the benefits of a new medicine, there may also be side effects for some people. The doctor or study nurse will carefully record any problems or side effects you have, and these are relayed to the principal researcher to ensure that you are kept as safe as possible.
In company-sponsored clinical trials, compensation is available for participants who suffer personal injury (including death) caused by participation in clinical trials. Copies of the Guidelines for Compensation for Injury Resulting from Participation in Company-Sponsored Clinical Trials are available from Medicines Australia.
What happens with the results?
As well as being reviewed by the government authorities such as the Therapeutic Goods Administration, the results of the clinical trials may be reported in the medical press and are made available to doctors. The publication of results is done so that doctors can make scientifically valid assessments of the benefits and risks of a new medicine for their patients.
Although the results of the study may be published, nothing that identifies individual patients will be released. All details of a clinical trial participant’s treatment are kept confidential and patient anonymity is assured.
In addition, your doctor will be notified of the results of the study as soon as they are made available. Your doctor should be able to inform you of the outcomes of the clinical trial. If you participate in a study, it is recommended that you keep in touch with your doctor so that you can find out the results of the study when they become available.
Questions and answers
If you decide you would like to participate in a clinical trial you should discuss it with your doctor and other healthcare professionals to make an informed decision. You should also seek to understand the credentials and experience of the people and the company involved in the study. Discuss with them the trial and the implications it may have for you.
Below is a list of questions you might like to ask the clinical trial doctor before agreeing to participate in a clinical trial.
- What is the clinical trial about?
- Why are you doing the clinical trial?
- What do you expect to get out of the clinical trial?
- What will you do with the results?
- Have you or others done this type of clinical trial before?
- What did you learn?
- Who put this clinical trial together?
- Who are the researchers? Who do they work for?
- Have they done a clinical trial like this before?
- Is the government part of this clinical trial? Who else is part of this clinical trial?
- Who is paying for the clinical trial?
- Who will make money from the results of this clinical trial?
- Who can I go to with questions or complaints?
- Who is going to be in this clinical trial?
- What kinds of people are you looking for? Why?
- How are you finding people for this clinical trial?
- Can I quit the study after signing a consent form?
- What will I get out of the clinical trial?
- What are the benefits? What are the risks?
- Will I get treated the same as everyone else?
- What kinds of different treatments are offered in this clinical trial?
- Is there a trial and a control treatment?
- Is payment involved?
- Do I get reimbursed for my fares to and from the clinical trial centre?
- What do I have to do in this clinical trial?
- How much of my time will be needed?
- Will I need to take extra time off work?
- What extra tests or procedures will I be subjected to?
- How will I be protected from harm?
- Do I stand a chance of being harmed in the clinical trial? In the future?
- Does the clinical trial protect me from all types of harm?
- If I get harmed in any way, will I get all needed treatment and compensation?
- Who pays for the treatment?
- How will my privacy be protected?
- Who is going to see the information I give?
- Will my name be used with the information?
- What happens to the information I give if I quit the clinical trial?
- Is there a written guarantee of privacy?
- What progress has already been made?
- When did you start this clinical trial? How long will it last?
- How much of the clinical trial have you already done?
- Have there been any problems so far?
- What will be left behind after the clinical trial is over?
- What are you going to do with the results of the clinical trial?
- Will results be in places where the public can see them?
- Are you going to send me a copy of the results?
- Will I continue to get the clinical trial medicine after the study is complete?
Additional information on clinical trials can be obtained from the websites listed below.
Acknowledgements
This information was developed in consultation with the Australian Health Ethics Committee, the Consumer’s Health Forum of Australia, Alzheimer’s Australia, the Cancer Alliance Network, the Royal College of Nursing (Australia), SANE Australia, National Asthma Council Australia, and the National Association of People Living With HIV/AIDS with reference to material developed by Research Australia, the Central Sydney Area Health Service, the Cancer Council (NSW), the Cancer Foundation of WA and the Queensland Cancer Fund.
Last Reviewed: 16 July 2003
