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| About Clinical Trials |
What is a Clinical Trial?
Medical research studies involving people are called clinical trials. Clinical trials look at
• Preventing disease - using drugs, vitamins, foods to reduce risk
• Treatments - new drugs or combinations of drugs; new ways of giving treatment, new types of treatment
• Diagnosing disease - new tests or scans
• Controlling symptoms - new drugs or complementary therapies
Trials aim to find out if a new experimental drug or procedure
• Is safe
• Has side effects
• Works better than the currently used treatment
• Helps you feel better
New treatments have to be thoroughly tested. A new drug, for example is investigated first in the laboratory. If it looks promising, it is carefully studied in people.
Phase 1, 2, and 3 Trials
There are three different types of clinical trials. These are called phase 1, 2 and 3.
Phase 1 (phase I)
These are the earliest trials in the life of a new drug or treatment. They are usually small trials, recruiting anything up to 30 patients (often a lot less). The trial may be open to people with any type of disease.
When laboratory testing shows a new treatment might help treat a particular disease, phase 1 trials are done to find out
• The safe dose range
• The side effects
• How the body copes with the drug
• If the treatment treats the disease
The first patient to take part will be given a very small dose of the drug. If all goes well, the next person will get a slightly higher dose. With each patient taking part, the dose will gradually be increased and the effect that has will be monitored. Any side effects will be recorded. In a phase 1 trial, you may have lots of blood tests, as the researchers look at how the drug is affecting you. And at how your body copes with, and gets rid of the drug.
People entering phase 1 trials are often healthy individuals. The aim of the trial is to look at doses and side effects as well as the pharmacodynamics and pharmacokinetics of the drug (how the body metabolizes the drug and how the drug affects the body). This work has to be done first, before we can test the potential new treatment to see if it works. Phase 1 trials are important because they are the first step in finding new treatments for the future.
Phase 2 trials (phase II)
About 70 out of every 100 new treatments tested at phase 1 make it to phase 2 trials. These trials may be done on people who all have same type of disease, or with several different types of a particular disease. Phase 2 trials are done to find out
• If the new treatment works well enough to test in phase 3
• Which types of disease it is effective against
• More about side effects and how to manage them
• More about the most effective dose to use
Although these treatments have been tested at phase 1, you may still have side effects that are not known about. Drugs can affect people in different ways.
Phase 2 trials are often larger than phase 1. There may be up to 50 people taking part. If the results of phase 2 trials show that a new treatment may be as good as existing treatment, or better, it then moves to phase 3.
Phase 3 (phase III)
These trials compare new treatments with the best currently available treatment (the standard treatment). They may compare
• A completely new treatment with the standard treatment
• Different doses or ways of giving a standard treatment
• A new radiotherapy schedule with the standard one
Phase 3 trials are usually much larger than phase 1 or 2. This is because differences in success rates may be small. So, you would need very many results to show the difference.
Sometimes phase 3 trials involve thousands of patients in many different hospitals and even different countries.
Randomization
Phase 3 trials are usually randomized. This means the researchers put the people taking part into 2 groups at random. One group gets the new treatment and the other the standard treatment. There is more about randomization and types of trials on the next page in this section.
How do I know it's safe?
Treatments have been thoroughly tested in laboratory trials before they are ever tested with groups of patients. Then, treatments must get through patient trials at phase 1 and 2 before they can be used in phase 3 trials. Clinical trials are research as they aim to answer a question regarding an experimental drug, and are not considered treatments.
There are many other safeguards for patients taking part in trials
• The trial plan (protocol) is inspected and must be approved by an ethics committee
• The running of the trial is supervised by a data monitoring committee (During the Trial)
• Insurance for patients must have been arranged
• Your privacy is protected
• You must be told all about the benefits and risks before you agree to take part
Insurance
This is indemnity insurance. It pays out compensation to you if any harm should come to you because of the trial. The organization or drug company funding the trial has to take out the insurance. If they do not, the ethics committee may not approve the trial.
If a trial is investigating drugs already licensed for treating cancer, there may not be extra insurance. The drugs have already been tested and found safe to use, so extra insurance is not thought necessary. You would be covered by the insurance held by the doctor and hospital where you are treated. You can ask your doctor or research nurse about trial insurance if you are worried.
The researchers and organizations funding the trial do not want any harm to come to the people taking part. They want better treatment for people with diseases. If something goes wrong, their reputations would suffer which would make their future projects much harder to carry out.
The advantages (benefits) of being in a trial
When deciding whether to participate in a clinical trial it is vital to evaluate both the risks and benefits.
The main advantages (benefits) of being in a trial are
• You may get a new treatment that works, that you could not get outside the trial
• You could be helping to improve treatment for future patients
• You will get closer monitoring
• You may receive compensation for your participation in the trial.
Throughout the trial, you will have check-ups more often than usual. You may have more blood tests or CT scans. Many people find this reassuring. Some people find it makes them more nervous and preoccupied with disease. Only you know how you feel about this. The tests and check ups you need to have will be explained to you before you decide to enter the trial.
Risks and drawbacks
With an experimental treatment, there will be some risk. Not a great deal will be known about the treatment. You will be closely monitored and treatment will be stopped if anybody thinks there is a risk for you.
Remember - even in phase 1 or 2 trials, the treatment has been carefully researched in the laboratory before it is given to patients.
With phase 3 trials, more is known about the new treatment so there is less risk that there could be a harmful side effect.
There are other drawbacks. You may
• Have to make more trips to hospital
• Have unexpected side effects
• Have to do some paperwork
If you need more check ups and tests, you will spend more time at the clinic. This will cost you time and money. If you are one of those people who really don’t like seeing a doctor, you need to think about this.
For some people, more check ups means more reassurance. For others, it means more worry. Only you know how these appointments are likely to affect you.
Side effects
There is a chance you will get side effects you (and your doctor) were not expecting. If you are in a phase 1 trial, the researchers may not be able to tell you much about side effects. You will be told everything they do know before you agree to take part in the trial.
Remember - you can withdraw from a trial at any point. You do not have to give a reason. Withdrawing from a trial will not be held against you in any way.
You will be asked to report all your side effects to your doctor or nurse. You may be asked to keep a diary at home or fill in questionnaires about feeling sick or tiredness.
After the trial
Trials go on for several years after you have stopped having treatment. The researchers need to know what happens to you so that they can monitor the long term effects of the treatment they have given you.
Your doctor will send reports of your check ups to the trial centre. This is unlikely to make any difference to you. But you should understand that the results of your trial could take years to come out.
Questions you may want to ask before participating in a clinical trial.
• Can you tell me why this trial is being done?
• What are the advantages and risks of taking part?
• What are the treatment choices in the trial?
• What are the likely side effects?
• Would I be allocated a treatment by computer or do you and I have any choice?
• How many patients are being studied?
• How long will the study last?
• Will I be told about the results if I take part?
• Who will be allowed to see my medical records?
• What information about me will be on the computer?
• Who will be told I am in a trial?
• Will my General Practioner know?
• What treatment will I get if I decide not to enter the trial?
• Can I leave the trial if I want to?
• What will I have to do if I take part?
• What will happen if I get side effects?
• Who can I contact in an emergency?
• Who makes sure the trial is safe and properly run?
• Will I have to spend more time in hospital or having tests?
• What about my expenses, such as travelling costs?
• Am I covered by insurance if things go wrong?
• Is there anything I am not allowed to do while I am in the trial?
• Are there any drugs or medicines I shouldn't take while I am in the trial?
Steps of the FDA drug approval process:
1. Pre-clinical (animal) testing.
2. An investigational new drug application (IND) outlines what the sponsor of a new drug proposes for human testing in clinical trials.
3. Phase 1 studies (typically involve 20 to 80 people).
4. Phase 2 studies (typically involve a few dozen to about 300 people).
5. Phase 3 studies (typically involve several hundred to about 3,000 people).
6. The pre-NDA period, just before a new drug application (NDA) is submitted.
A common time for the FDA and drug sponsors to meet.
7. Submission of a new drug application is the formal step asking the FDA to consider a drug for marketing approval.
8. After an NDA is received, the FDA has 60 days to decide whether to file it so it can be reviewed.
9. If the FDA files the NDA, an FDA review team is assigned to evaluate the sponsor's research on the drug's safety and effectiveness.
10. The FDA reviews information that goes on a drug's professional labeling, guidance on how to use the drug.
11. The FDA inspects the facilities where the drug will be manufactured as part of the approval process.
12. FDA reviewers will approve the drug or find it either "approvable" or "not approvable."
Information gathered on fda.gov websites, please visit http://www.fda.gov/fdac/features/2002/402_drug.html for more information
The Common Rule and FDA Good Clinical Practice regulations:
-The Common Rule was created by the Department of Health and Human Services as a Federal policy to protect the confidentiality and rights of human trial subjects (45 CFR part 46).
-Good Clinical Practice is the standard that has been created for the design, conduct, monitoring, auditing, recording, analysis of results, and reporting of clinical trials. GCP guidelines are to be complied with in order to provide assurance that the final results that are reported are accurate and credible and that the confidentiality and rights of trial participants are protected (ICH guideline 1.24).
The Informed Consent Process:
Before beginning participating in any clinical trial the subject must undergo the Informed Consent process during which the study synopsis as well as benefits and risks are outlined. Subject is also instructed that they may cease participation in the clinical trial at any time before or during the trial period.
Role of IRB’s in protecting study subjects:
The role of IRBs is to ensure that human subjects used in any research projects are protected against undue risk and give informed consent to the research, as well as to ensure that research subjects' safety, rights, privileges, and privacy are protected.
Alternatives to participation in a clinical trial:
It is important to always consider alternatives to clinical trials, such as seeking a treatment that is already deemed safe and approved by the FDA, or seeking a treatment that does not involve medication at all.
Additional information regarding clinical trials:
Additional information can be found on the US Government’s clinical trials registry website at http://www.clinicaltrials.gov/ct/info/resources.
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