Basics
1. What is a “clinical trial”?
2. What are Phase I clinical trials?
3. What are Phase II clinical trials?
4. What are Phase III clinical trials?
5. What does “post marketing surveillance” – also known as Phase IV trials - mean?
6. What is a “placebo”?
7. What does “blinding” mean?
8. What does “bias” mean?
9. What are “randomized” trials?
10. What is an “open label” trial?
11. What are “eligibility criteria”?
12. What are “inclusion criteria”?
13. What are “exclusion criteria”?
1. What is a “clinical trial“?
A clinical trial is a research study in human subjects with the aim of answering specific questions about a new medical treatment (vaccines, new therapies or new ways of using known treatments). Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Pharmaceutical clinical trials are conducted in Phases. The trials at each Phase have a different purpose and each Phase looks at different areas (e.g. toxicity, dose finding etc).
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2. What are Phase I clinical trials?
Phase I trials (sometimes called early treatment trials) aim to test the safety of various doses of a new drug. This includes looking at the side effects of a drug – for example, does it make people feel bad, raise their blood pressure etc? Phase I trials involve only a small number of people, who are usually healthy volunteers. In exceptional cases, for instance in cancer or HIV, patients who are at a very advanced stage of the disease may participate.
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3. What are Phase II clinical trials?
Phase II trials test the new drug in a larger group of people who are ill, to see whether it has any effects suggesting that it might help them. As in Phase I, the number of participants is limited. Phase II trials also look at safety and at the right dose.
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4. What are Phase III clinical trials?
Treatments only move into a Phase III clinical trial if Phases I and II suggest that a substance might actually be useful in ways that patients would regard as important. Phase III trials test new drugs in larger groups of people who are ill.
Phase III trials compare the new drugs with whatever treatments are currently in use, or occasionally with a placebo. These trials look at how well the new treatment works in practice, and at any side effects. They usually last longer than Phase II trials – typically a year or more.
Often several thousand patients in different countries will be involved in a Phase III trial. A large amount of participants is necessary because investigators have to be able to detect moderate but important differences between treatments.
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5. What does “post marketing surveillance” – also known as Phase IV trials – mean?
Post marketing surveillance concerns the last and 4th Phase of a clinical trial. After a medicine has been launched, Health Authorities are often asking companies to provide additional data, collected from the actual use of the medicine in thousands of patients. Phase IV studies are designed to provide broader experience in evaluating the safety and effectiveness of the new medicine in larger numbers of patients, subgroups of patients, and to compare and/or combine it with other available treatments. These studies are designed to evaluate the longterm effects of the drug. Less common side effects may be detected at this stage.
Despite the vigilant tests carried out during clinical trials in the other three Phases, active post marketing surveillance of drug side effects is essential. Not all potential side effects of a medicine can be anticipated based on only several hundred to several thousand patients.
Therefore, clinical trial sponsoring enterprises maintain a system of risk assessment programs to identify side effects that did not appear during the other trials. Information on adverse events that have been brought to the attention of the marketing authorisation holder are collated. This is also called “Pharmacovigilance” (i.e. the safety of medicines).
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6. What is a “placebo”?
A placebo is a treatment that does not contain any active substance. It allows investigators to test for the ‘placebo effect’. This is a psychological response where people feel better even though they do not take a medicine with an active ingredient. By comparing people’s responses to the placebo and to the treatment being tested, the benefit of the treatment can be described.
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7. What does “blinding” mean?
Blinding means that whoever is assessing the effects of treatment will not know if they study patients on the treatment or patient on placebo. This helps to prevent bias. Sometimes patients will assess the effects of treatment, sometimes doctors will, and sometimes third parties will. Some or all of these people may be kept unaware of which treatment has been received.
If you take part in a ‘double-blind’ trial, neither you nor your doctor will know which treatment you are receiving. The aim is to make sure that nobody’s expectations affect the results of the trial.
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8. What does “bias” mean?
When prejudices lead to incorrect conclusions about the effects of treatment, this is bias. It’s really important to avoid bias in health research, as it can distort the results and could lead to unsafe or inefficient treatments being licensed for use, or useful treatments being overlooked. Investigators try to avoid bias by using randomisation and by blinding those administering the drugs and assessing the results of treatments.
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9. What are “randomised” trials?
Most clinical trials are randomised trials. If you take part in a randomised trial, a computer, not a doctor, will decide which treatment to give you. This decision will be random. It will be due to chance alone, and not based on your doctor’s decision.
Randomisation is the best way of ensuring that people in the different parts of a trial are broadly similar. By comparing similar groups of people, investigators can be sure that their trial is checking the difference between the treatments being studied, and not the differences between the people taking part.
Randomisation is important because investigators need to ensure that clinical trials are not biased. It is quite easy for people to be biased without realising it.
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10. What is an “open label” trial?
In an open label trial, both you and your doctor will know which treatment you are receiving. In other words, this is the opposite of a double-blind trial.
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11. What are “eligibility criteria”?
All trials have guidelines about who can take part. These are called ‘eligibility criteria’, consisting of inclusion criteria (i.e. who is suitable to participate) and exclusion criteria. Not anyone who suffers from a particular disease can take part in any trial that studies this disease: the eligibility criteria for a lung cancer trial for instance might say that the only people who can take part are people who are at the earliest stages of their condition, who are over 18 but under 80, and who have no other health problems.
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12. What are “inclusion criteria”?
Inclusion criteria help investigators decide who can join a trial. For example, some trials only include people of a certain age, or at a particular stage in their illness. You may have to have a medical examination before a trial (e.g. a blood test) to assess whether you are suitable to take part.
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13. What are “exclusion criteria”?
Exclusion criteria determine who won’t be able to join a trial – for example, many trials exclude women who are pregnant to avoid any possible danger for the baby. Trials may also exclude people who are already taking a drug that may interact with the treatment being studied.
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