This section aims to provide patients, their family and friends, and the general public with information about clinical trials, how they are carried out and what it is like to take part in a trial.
Clinical trials are studies which require human participants to test new treatments, or make changes to existing ones, by comparing one type of treatment with another before these treatments can be approved for use.
There are many things to think about when considering taking part in a clinical trial. These include the need to travel to the centre running the trial and the need to join a waiting list for some trials. Therefore, if you are considering taking part in a clinical trial we would encourage you to use this information, and contact us directly, to discuss current clinical trials.
Clinical trials aim to determine if a new treatment or procedure is safer and/or more effective than the currently available standard of care for a particular disease or condition. They are crucial to improve the knowledge of a specific medical area while improving treatment options for patients.
There are numerous questions clinical trials aim to answer, such as:
- Is this treatment safe?
- Does this treatment have any side-effects?
- Is this treatment more effective than the currently available treatment?
- Is there a better way to administer a particular treatment?
- Does using a combination of existing treatments make therapy more effective?
- Are there any ways to improve the services and care patients are receiving?
Clinical trials may also test a new diagnostic procedure, a disease screening method, if a life-style change can improve outcomes or if an intervention can improve quality-of-life for patients.
Clinical trials aim to compare a new treatment to the best currently available treatment method or, occasionally, to a placebo drug. A placebo drug is a drug containing no active ingredient and therefore it has no effect on the body. Placebos are useful in determining if the beneficial effect of treatment is really occurring, or if the advantage being experienced by the patient is due to the psychological effects of taking a medication.
The larger a clinical trial is, the more reliable the results will be. Therefore, in rarer diseases, such as primary bone cancer, the trial may be an international study in order to recruit enough participants to ensure the trial is reliable enough.
A large multi-disciplinary team of healthcare professionals will also be involved in the trial, including researchers, doctors, nurses and social workers who will help patients participate in clinical trials.
Although there are different ways to design clinical trials, the simplest design involves separating the participants into two groups.
- One group receives the best treatment currently available (or a placebo where there is not yet an available treatment).
- The second group receives the new treatment, test or procedure under investigation.
Where possible, both the participant and the doctor are unaware of which group the patient is in. This is known as a ‘double blind’ design and helps to ensure that the results are not biased. Often, a computer programme is used to randomly allocate participants into one group or the other. This is known as ‘randomisation’ and is used to reduce the chances of the results being biased.
To begin with, new treatments are investigated in the laboratory during experiments known as ‘preclinical studies’, which can take around 3 to 4 years to complete. Following this, clinical trials are carried out in human participants.
Clinical trials are separated into stages which are known as ‘phases’. Phases tend to go from 1 to 3, but some trials may also have a phase 0 and a phase 4. Earlier phases ensure the safety of the new treatment, while the later stages assess the effectiveness and benefit of the treatment in comparison to the best currently available standard of care.
The phases of clinical trials are:
- Phase 0: This phase is also known as an investigational new drug (IND) phase. Phase 0 is a relatively new concept and so is not as commonly used as the other phases. These studies are very small, around 10-15 people, and use a tiny amount of the drug (less than 1%). This tiny amount of drug will not treat the cancer but it allows researchers to determine if the drug is behaving in the way they were expecting.
- Phase 1 (I): Following on from a successful ‘phase 0’ trial, ‘phase 1’ trials can begin. This phase is carried out in a small number of participants* to assess the safety, side-effects and behaviour of the drug in the human body, rather than the effectiveness of the drug for treatment. Very low doses of the drug are administered to patients and if deemed safe, another group of patients will receive a slightly higher dose of the drug; this process continues and is known as a ‘dose-escalation’ study. As this study is assessing the safety of the drug, the doses used may not be high enough to expect the drug to help the trial participant at this stage.
*As phase I trials recruit a small number of participants, who often need to be observed for some time after treatment to make sure the drug does not have too many side effects, there is a possibility that patients wishing to take part in such trials will be placed on a waiting list. This may not be suitable for all patients and so is best discussed with your oncologist.
- Phase 2 (II): Phase 2 trials are carried out on a larger group of around 100 patients and aim to determine if this treatment works well enough to test in a larger trial group. The effectiveness of the drug, its effect on the cancer, the safety of the dose and the best way to deliver the drug are all being assessed during this phase.
- Phase 3 (III): Phase 3 trials determine if the trial treatment works as well as, or even better than, the currently available treatment method. These trials include a larger group of people to ensure the results seen are reliable, accurate and the trial drug is beneficial to patients. This phase will usually test the new treatment against an existing treatment or a placebo drug, which is called a ‘randomised phase 3 trial’.
- Phase 4 (IV): Once the trial drug has been successful in phase 3 trials and it is licenced for use, a further trial known as phase 4 can be carried out. Phase 4 trials are very long-term, investigating how the drug effects a patients’ survival and any risks or benefits occurring when this drug is taken for long periods of time. Additionally, phase 4 trials assess the cost-effectiveness of the drug and the patients’ quality-of-life while undergoing this treatment.
As a patient, or parent of a patient, a trial may be suggested to you by your doctor or another member of your specialist cancer team. Additionally, you may find a clinical trial online yourself. Either way, you should always discuss the prospect of taking part in a clinical trial with your doctor to ensure this trial is suitable for you, or your child, and so you can receive the information you need in order to make an informed choice about taking part. Furthermore, in order to participate in a clinical trial you will require a medical referral from your doctor.
In order to join a clinical trial you must give ‘informed consent’. If a patient is under 16, this consent may be given by a parent/guardian. Before consenting to a clinical trial, you will be given information to read about the trial and time to think about whether you wish to take part. You must ensure you have been told everything you would like to know about the trial and understood all of the information before signing your consent. Furthermore, you are able to withdraw from a clinical trial at any point if you wish to do so, and this will have no effect on the care and further treatment you will receive.
Children’s Cancer and Leukaemia Group (CCLG) have produced a booklet called A Guide to Clinical Trials, which describes the process of taking part in a clinical trial in further detail.
Being Eligible for a Trial
Before looking into a clinical trial further, you must first determine if this trial is suitable for you and if you are able to take part. This information is known as ‘eligibility criteria’. Every trial has these criteria to ensure the participants of the trial are as similar as possible in order for researchers to compare the results accurately.
If you are interested in a clinical trial please confirm with your doctor first that you are eligible to take part.
Eligibility criteria may include:
- Type of cancer
- Stage of cancer
- Previous treatment received
- General health
In some cases, clinical trials may not be available for a particular tumour type. This may be due to the rarity of the cancer or due to a clinical trial just finishing or no longer recruiting patients. If this is the case, the doctor and nurses will follow the most appropriate treatment plan set out for your particular tumour type.
Providing Samples for a Clinical Trial
The analysis of biological samples, such as blood or a biopsy from the tumour or other tissues, may be an important part of the clinical trial and you may be asked to consent to these samples being used.
Samples may include the patients’ blood, saliva, urine or a small sample of their tumour. The doctor or nurse collecting the sample will firstly need your permission and signature of consent. All samples collected are put into a ‘biobank’; creating a library of patient’s samples which are all anonymous and identified by a unique barcode.
Results of a Clinical Trial
The results of a clinical trial can take a long time to be collected and analysed. This often takes 2-5 years but this time period can last up to 10 years or more depending on how many people have taken part in the clinical trial and what the trial is aiming to discover.
When identifying a new treatment it must pass certain levels of safety and effectiveness in order to be licenced for use. Before this can occur the results of the trial must be shown to other researchers so they can analyse and assess the validity of this clinical trial research. This is known as ‘peer review’ and can take several months to be carried out.
Following the clinical trial all participants will be made aware of the results by their doctor. If you do not receive this information, or want to find out more on the progress of the trial, feel free to ask your doctor for more information at any point.
There are many benefits to taking part in a clinical trial, but there are also some risks that need to be considered. Some patients find these risks to outweigh the positives, so it is important that you are fully aware of all aspects of the clinical trial before consenting to take part.
- Treatment is monitored more closely when you are taking part in a clinical trial, which is known to be beneficial
- Participating in a clinical trial can help find new treatment options for patients and improve that area of healthcare
- The treatment offered on the clinical trial may not be available as standard care and is therefore an additional treatment option for patients
- When beginning a clinical trial, you cannot be sure of the final outcome or the side-effects you may experience during the trial
- As treatment is monitored more closely during a trial, you are likely to undergo more tests and check-ups than usual. (This can be viewed as a positive or negative by different patients)
- Due to these frequent check-ups and tests, you may have to visit the hospital more often. Trials may cover the cost of travel for this, but it is worth confirming these details before consenting to take part
For more information on taking part in a clinical trial and the safety measures of clinical trials please visit Macmillan Cancer Support
If you are interested in taking part in a clinical trial the first person you should speak to is your doctor. Doctors can provide information on currently available clinical trials and whether or not you are eligible to take part.
If you do decide to participate in a clinical trial, there will undoubtedly be many questions you will want to ask. The Bone Cancer Research Trust have put together a list of just some of the important questions a patient should think about asking their doctor before consenting to take part.
- How long will this clinical trial last?
- What will I have to do to take part?
- What kind of tests will I need to have done during this trial?
- What is this trial trying to find out?
- What are the likely side-effects?
- What do I do if I experience any side-effects?
- Who can I contact in an emergency?
- How do I withdraw from the trial?
- Who will access my data?
- Can I talk to somebody else who has taken part in a trial?
- Is there anything I am not allowed to do while on this trial?
- Will costs, such as my travel to hospital, be covered?
- Will I have more check-ups after the trial is complete?
While looking into, or taking part in, a clinical trial you may come across certain words or phrases which can be difficult to understand. The Bone Cancer Research Trust have provided a list of the definitions of common phrases you may come across.
If you come across a term which is not on our list, or want to find out more about any of these terms, please feel free to contact us for more information.
Adverse Effect (Side-Effect): an adverse effect, also known as a side-effect, is an undesirable effect to healthy areas of the body which is caused by a treatment intervention. Common adverse effects include headaches and nausea
Arm of the trial: the grouping of participants to receive a specific intervention is referred to as the ‘arms of the trial’. Therefore, there are two or more arms to all trials (i.e. ‘arm receiving current standard treatment’ and an ‘arm receiving the new trial treatment’)
Baseline:data collected at the very beginning of the trial from all participants is known as the baseline data. This data includes age, gender, and medical measures specific to the trial, which may include blood pressure or previous medications
Bias:biasoccurs when there is a fault in the design of the clinical trial study which allows a result to be influenced towards a desired outcome of the research. Bias is controlled by ‘blinding’ and ‘randomisation’
Blinding:‘blinding’ a clinical trial is a design strategy in which the patients and doctors involved in the trial are unaware of the treatment assigned to each participant. ‘Blinded’ studies are conducted to prevent any unintentional bias that can affect subject data when treatment assignments are known
Clinical Investigator:a clinical investigator is the medical researcher in charge of carrying out the trial and ensuring the trial protocol is strictly followed
Complete Response: the term ‘complete response’ refers to the absence of detectable cancer cells after the patient has undergone treatment. Tumours are capable of returning at a later time (see Relapse/Recurrence) and therefore complete response does not always mean the cancer has been cured
Dose:the quantity of medication to be taken at one time is known as the dose
Dose-Escalation Study:A dose-escalation study (also known as a dose-ranging study) is carried out in Phase 1 or Phase 2 clinical trials to establish the best dose of treatment to use for patients that carries the least side-effects.
Efficacy: the power of the treatment in producing the desired result is known as the treatments’ efficacy or effectiveness
Endpoint: an endpoint is a measure of studying how well the trial intervention has performed. Examples of endpoints are overall survival, the relief of symptoms and the shrinkage of the tumour
Eligibility Criteria: requirements that clinical trial participants must meet to be included in a study are known as the ‘eligibility criteria’. This helps make sure that patients in a trial are similar to each other in terms of age, type and stage of cancer, general health, and previous treatments to ensure the results of the trial are as accurate and valid as possible
FDA (Food and Drug Administration): the FDA is part of the U.S Department of Health and Human Services responsible for ensuring drugs are safe before being licensed for public use
Good Clinical Practice:Good clinical practice, also known as GCP,is an international quality standard which ensure governments have set strict regulations to follow for clinical trials practice
Informed Consent: the process of understanding all the information, risks and benefits of a treatment option before the patient consents to undergo such treatment is called ‘informed consent’
Monitoring: the act of overseeing the progress of aclinical trial to ensure that it is conducted, recorded, and reported in accordance with the protocol and regulations is known as the monitoring of a trial
Partial Response: when the tumour decreases by at least a third of its original size following treatment this is known as a ‘partial response’
Peer Review: evaluation of scientific, academic, or professional work by others working in the same field is known as a ‘peer review’. Clinical trial results will be peer-reviewed by other researchers before released to the public and trial participants
Pharmacodynamics: pharmacodynamics is an assessment of the effect of drugs in the body and how they act on the cancer
Pharmacokinetics: pharmacokinetics is an assessment of how the drug is taken in by the body, how the drug moves around the body to get to the cancer and how the drug is processed by the body
Placebo: a substance that has no therapeutic effect and is used as a control in testing new drug is called a placebo drug
Protocol: a document that describes the objectives, design, methods and overall organisation of a clinical trial
Randomisation: there are two or more groups in all clinical trials. Participants are put into these groups at random to ensure there is no bias towards a certain outcome. This random grouping is called randomisation and is carried out using a computer programme
Relapse/Recurrence: A cancer is capable of returning at a later date following treatment and an improvement in the patients’ health. This is referred to as a ‘relapse’ or ‘tumour recurrence’ and can happen many years after finishing treatment
Stable disease: When a cancer neither decreases nor increases in size (and the severity of the cancer remains the same) following treatment, this is referred to as ‘stable disease’
Toxicity: the degree to which a drug or substance can harm the body is known as a toxicity
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