Glossary - Terms and definitions used in clinical trials
Adverse events, or adverse reactions, are unwanted, caused by a drug or other treatment. For example, if you are given a drug to treat a headache and it makes you sick, the sickness would be described as an adverse effect.
Arms
An arm is one of the treatment groups in a trial. If a trial is testing 2 treatments, there will be 2 ‘arms’.
An arm is one of the treatment groups in a trial. If a trial is testing 2 treatments, there will be 2 ‘arms’.
Baseline measures
At the beginning of a trial you may have to answer questions about your medical history, or how you are feeling now, or have some tests before being given the treatment. These are called baseline measures. These measures will allow the researchers to know where you started, so they can tell at the end of the trial whether there has been any improvement.
At the beginning of a trial you may have to answer questions about your medical history, or how you are feeling now, or have some tests before being given the treatment. These are called baseline measures. These measures will allow the researchers to know where you started, so they can tell at the end of the trial whether there has been any improvement.
Bias
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. Researchers try to avoid bias by using randomisation and by blinding those assessing the results of treatments.
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. Researchers try to avoid bias by using randomisation and by blinding those assessing the results of treatments.
Blinded or blinding: A method used in a clinical trial to prevent participants and/or researchers from knowing whether the patient is receiving the experimental or control treatment in a trial. Also referred to as “masking.” Single blinding is when only the patient does not know which treatment he or she is receiving. Double blinding is when both the patient and researcher do not know which treatment the patient is receiving.
Chronic condition
A chronic condition is an illness you have for a long time. For example, rheumatism or diabetes are both chronic conditions. A common cold is not.
A chronic condition is an illness you have for a long time. For example, rheumatism or diabetes are both chronic conditions. A common cold is not.
Studies performed in humans that are intended to increase knowledge about how well a diagnostic test or treatment works in a particular patient population.
A prospectively planned scientific study of the effects of a diagnostic test or treatment on selected patients, usually with respect to safety, efficacy, and/or quality of life.
In a clinical trial, a situation in which the interests of the researcher or institution are at odds with their professional obligation to the patient.
A company with whom a drug or device manufacturer or sponsor contracts to perform clinical trial related activities. CROs may contract to develop protocols, recruit patients, collect and analyze data, and prepare documents to submit marketing applications to FDA.
In a clinical trial, the patient group(s) that does not receive the experimental treatment. The control group receives the standard treatment,
placebo, or no treatment in accordance with the trial design, and the results of the control group(s) are compared to the results from the experimental group.
A prospective clinical trial comparing two or more treatments, or placebo and treatment(s) in similar groups of patients or within patients. A controlled trial may or may not use randomization to assign patients to groups, and it may or may not use blinding to prevent them from knowing which treatment they get.
Cross-over trials
If you take part in a crossover trial, your treatment will change partway through the trial. So if a trial is comparing the effectiveness of 2 different sorts of exercise for lower back pain, you might take part in exercise A for the first part of the trial and then exercise B for the second, then perhaps back to A again - and so on. You cross over from one treatment group to the other, and comparisons are then made between how you were during the different periods. Often there will be several cross-overs in a cross-over trial.
If you take part in a crossover trial, your treatment will change partway through the trial. So if a trial is comparing the effectiveness of 2 different sorts of exercise for lower back pain, you might take part in exercise A for the first part of the trial and then exercise B for the second, then perhaps back to A again - and so on. You cross over from one treatment group to the other, and comparisons are then made between how you were during the different periods. Often there will be several cross-overs in a cross-over trial.
Recorded observations about patients in a clinical trial.
Data monitoring committee
Most trials have a data monitoring committee that follows the progress of the trial and makes sure it is being run properly. The people on the data monitoring committee are independent. If they think that people are experiencing serious or unexpected side effects, or if evidence has emerged that one of the treatments being compared is clearly better than the others, they can advise that a trial is stopped.
Most trials have a data monitoring committee that follows the progress of the trial and makes sure it is being run properly. The people on the data monitoring committee are independent. If they think that people are experiencing serious or unexpected side effects, or if evidence has emerged that one of the treatments being compared is clearly better than the others, they can advise that a trial is stopped.
Double-blind trial
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.
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.
The degree to which a diagnostic test or treatment produces a desired result in patients in the daily practice of medicine.
The degree to which a diagnostic test or treatment produces a desired result in patients under the idealized circumstances of a clinical trial.
Eligibility criteria
All trials have guidelines about who can take part. These are called 'eligibility criteria', consisting of inclusion criteria and exclusion criteria. For example, the eligibility criteria for a lung cancer trial 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.
All trials have guidelines about who can take part. These are called 'eligibility criteria', consisting of inclusion criteria and exclusion criteria. For example, the eligibility criteria for a lung cancer trial 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.
To consent to and enter a clinical trial.
Conforming to an accepted standard of human behaviour.
Ethics committee
The job of an ethics committee is to make sure that research carried out in the NHS respects the dignity, rights, safety and well-being of the people who take part in medical research. A trial that takes place within the NHS cannot go ahead if an ethics committee has not approved it, and the protocol for a trial cannot be changed without the approval of the ethics committee. Ethics committee members include researchers and health care professionals as well as members of the public.
The job of an ethics committee is to make sure that research carried out in the NHS respects the dignity, rights, safety and well-being of the people who take part in medical research. A trial that takes place within the NHS cannot go ahead if an ethics committee has not approved it, and the protocol for a trial cannot be changed without the approval of the ethics committee. Ethics committee members include researchers and health care professionals as well as members of the public.
An approach to practicing medicine that involves consideration of results of clinical trials that are relevant to the disease or condition being treated when making decisions about how to treat patients.
Factors used to determine whether an individual is ineligible for a trial. Exclusion criteria determine who won’t be able to join a trial – for example, many trials exclude women who are pregnant, or who may become pregnant. This avoids any possible danger to a baby. Trials will also exclude people who are already taking a drug that may interact with the treatment being studied.
Investigational, unproven.
The group that receives the investigational treatment in a trial; the group to which the control group results are compared.
Inclusion criteria help researchers 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. The factors used to judge a participant’s eligibility for inclusion in a trial. There is an underlying rationale for the criteria selected. The rationale relates to the questions that the researchers are trying to answer by conducting the trial.
Except in exceptional circumstances (for example, if you're admitted to hospital in an emergency and you're unconscious), you cannot be entered into a trial without signing a form saying that you have given your informed consent. If you sign this form, you are saying that you believe you have been given all the important facts about a trial, you understand them and that you have decided to take part in the trial of your own free will. A patient’s oral and written agreement to participate in a clinical trial. Consent is based on full disclosure about the treatment, its potential risks and benefits, alternative treatments, and any other information the patient needs to make the decision. Patients enrolling in clinical trials must sign a consent form that explains what will happen in the trial.
Clinician or nurse involved in a clinical trial.
Person participating in a clinical trial.
MRC - Medical Research Council
The UK Medical Research Council is a national organisation funded by the UK taxpayer. It funds and supports research in many areas with the aim of improving the health and quality of life of the UK public and contributing to the wealth of the nation.
The UK Medical Research Council is a national organisation funded by the UK taxpayer. It funds and supports research in many areas with the aim of improving the health and quality of life of the UK public and contributing to the wealth of the nation.
Meta-analysis
Small beneficial effects of treatments, rather than miracle cures, are often the best that can be hoped of new medical treatments. These small improvements can be very important. But many trials do not manage to recruit sufficient numbers of participants to detect these small improvements, so researchers cannot give an accurate answer about how safe or effective a new treatment is. In this case, researchers can bring together the results of a number of similar trials to give a more accurate answer about the value of a particular treatment. This method of combining results of more than one trial is called a meta-analysis.
Small beneficial effects of treatments, rather than miracle cures, are often the best that can be hoped of new medical treatments. These small improvements can be very important. But many trials do not manage to recruit sufficient numbers of participants to detect these small improvements, so researchers cannot give an accurate answer about how safe or effective a new treatment is. In this case, researchers can bring together the results of a number of similar trials to give a more accurate answer about the value of a particular treatment. This method of combining results of more than one trial is called a meta-analysis.
MHRA - Medicines Healthcare Products Regulatory Agency
The Medicines and Healthcare Products Regulatory Agency (MHRA) is a part of the Department of Health. Its job is to protect and promote public health and patient safety by ensuring that medicines, healthcare products and medical equipment meet appropriate standards of safety, quality, performance and effectiveness, and are used in the right way. National and international guidelines exist for clinical trials. There are regulations to ensure that trials in the UK are run properly. From 1 May 2004, all trials have to conform to new regulations set by the European Union.
The Medicines and Healthcare Products Regulatory Agency (MHRA) is a part of the Department of Health. Its job is to protect and promote public health and patient safety by ensuring that medicines, healthcare products and medical equipment meet appropriate standards of safety, quality, performance and effectiveness, and are used in the right way. National and international guidelines exist for clinical trials. There are regulations to ensure that trials in the UK are run properly. From 1 May 2004, all trials have to conform to new regulations set by the European Union.
The World Medical Association has also developed the Declaration of Helsinki. This sets the ethical standards for research involving human beings, human material or identifiable data. Most researchers will state that their clinical trial protocol has been developed in line with these ethical principles.
Is the process of checking a patients’ health status during a trial. Can also cover the activities taken to oversee the progress of a trial, which ensure researchers comply with regulatory requirements.
A clinical trial conducted at multiple sites using a common protocol (set of procedures).
NICE - The National Institute for Clinical Excellence
The National Institute for Clinical Excellence (NICE) is part of the NHS. NICE decides whether a new treatment should be made available on the NHS. NICE looks at the results of clinical trials and decides if there is enough evidence from trials to show that: a new treatment is better than existing treatments; the benefits of the new treatment outweigh the costs of its side effects and of making it available.
The National Institute for Clinical Excellence (NICE) is part of the NHS. NICE decides whether a new treatment should be made available on the NHS. NICE looks at the results of clinical trials and decides if there is enough evidence from trials to show that: a new treatment is better than existing treatments; the benefits of the new treatment outweigh the costs of its side effects and of making it available.
NICE takes all aspects of using a new treatment into account. For example, a new treatment may have fewer side effects than the standard treatment being used. Or it may allow people to be treated as outpatients rather than in hospital, reducing inconvenience and the overall cost of providing it.
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.
Outcome measures
The final results of a medical test or treatment/s given to a patient. During the trial you are likely to be asked questions and have examinations and tests to assess the effects of treatment. These are known as outcome measures. This may involve more visits to the clinic than normal, or more tests than normal - for example, extra blood might be taken when you give a blood sample. Sometimes the tests are carried out as part of your routine care.
The final results of a medical test or treatment/s given to a patient. During the trial you are likely to be asked questions and have examinations and tests to assess the effects of treatment. These are known as outcome measures. This may involve more visits to the clinic than normal, or more tests than normal - for example, extra blood might be taken when you give a blood sample. Sometimes the tests are carried out as part of your routine care.
The medical (e.g., disease, stage of disease, hormone receptor status, prior treatments) or demographic (e.g., age, sex, marital status, race) qualities or traits of a patient.
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 sick, raise their blood pressure etc? Phase I trials involve only a small number of people, who are more often than not healthy volunteers. Phase I or Healthy Volunteer Studies are non-placebo controlled, and the first test of a drug in humans. They are designed to Establish safe/tolerable levels, establish initial pharmacology in humans, and will usually pay volunteers reimbursement money for their time.
Phase I starts with the initial administration of an investigational new drug into humans. Studies in this phase of development usually have non-therapeutic objectives and may be conducted in healthy volunteer subjects or certain types of patients, e.g. patients with mild hypertension or asthma. Drugs with significant potential toxicity, e.g. cytotoxic drugs, are usually studied in patients. Studies in this phase can be open, baseline controlled or may use randomisation and blinding, to improve the validity of observations.
Studies conducted in Phase I typically involve one or a combination of the following aspects:
a) Estimating the intitial safety and tolerability levels
b) Pharmacokinetics
c) Assessment of pharmacodynamics
d) Early measurement of drug activity
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. Usually a few hundred people are involved at this stage. Phase II trials also look at safety. Phase II studies are non-placebo controlled or randomised studies. They are designed to provide evidence of activity and better evidence of safety, define dosage and regimen, and includes participants with the disease. Phase II is usually considered to start with the initiation of studies in which the primary objective is to explore therapeutic efficacy in patients. Does the drug or treatment actually help those people with the condition? Studies in Phase II are typically conducted in a group of patients who are selected by relatively narrow criteria, leading to a relatively homogeneous population and are closely monitored.
Treatments only move into a phase III clinical trial if phases I and II suggest that a drug 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 will be involved in a phase III trial. They may use different hospitals and live in different countries. Large numbers of people are needed because researchers have to be able to detect moderate but important differences between treatments. The smaller the difference between treatments, the more people are needed to produce meaningful statistics.
Phase III usually is considered to begin with the initiation of studies in which the primary objective is to demonstrate, or confirm therapeutic benefit. This stage of study is designed to confirm the preliminary evidence accumulated in Phase II that a drug is safe and effective for use in the intended indication and recipient population. These studies are intended to provide an adequate basis for marketing approval. Studies in Phase III may also further explore the dose-response relationship, or explore the drug's use in wider populations, in different stages of disease, or in combination with another drug. For drugs intended to be administered for long periods, trials involving extended exposure to the drug are ordinarily conducted in Phase III, although they may be started in Phase II. These studies carried out in Phase III complete the information needed to support adequate instructions for use of the drug (official product information).
Trials conducted after a drug has been approved and marketed for a particular disease or condition. Thois stage goes beyond determining a drug's safety, efficacy and dose definition. They are studies that were not considered necessary for approval but are often important for optimising the drug's use. They may be of any type but should have valid scientific objectives. Commonly conducted studies include additional drug-drug interaction, dose-response or safety studies and studies designed to support use under the approved indication, e.g. mortality/morbidity studies, epidemiological studies. Phase IV clinical trials are often undertaken to compare a new medicine to a wider range of existing medicines/therapies, and where it is best used.
An inactive substance or treatment, such as a sugar pill, injection of sterile water, or sham medical device, that is given under the guise of treatment to separate the effects of the actual treatment being evaluated from psychological or other effects. A placebo is a fake or dummy treatment. It allows researchers to test for the 'placebo effect'. This is a psychological response where people feel better even though the treatment they are receiving is not working. By comparing people’s responses to the placebo and to the treatment being tested, researchers can tell whether the treatment is having any real benefit. Placebos are designed to be harmless, but they may make people feel better.
A laboratory or animal study of a drug, device, or procedure to find out if the new treatment shows enough promise to be studied in humans.
Principal investigator
The principal investigator is the researcher in overall charge of a trial. If you take part in a trial you may never meet the principal investigator, especially if the trial is very large and taking place in several countries. But this person is responsible for the design of the trial and how it is run, as well as for analysing the results. He or she is usually helped by a trial steering committee and a data monitoring committee.
The principal investigator is the researcher in overall charge of a trial. If you take part in a trial you may never meet the principal investigator, especially if the trial is very large and taking place in several countries. But this person is responsible for the design of the trial and how it is run, as well as for analysing the results. He or she is usually helped by a trial steering committee and a data monitoring committee.
The formal plan for the conduct of a clinical trial that defines the design, purpose, length, patient selection, methods, treatment, follow-up, clinical end points, and outcomes to be measured. A protocol is the plan for the trial, and it must include information on:
- What question the trial is asking
- How many people will be involved
- Who can take part in the trial - the eligibility criteria
- What treatments will be compared
- What tests people taking part in the trial will have and when they will have them
- Details about how and when information will be collected
Quality of life studies
As well as measuring the physical effects of a treatment, many trials now try to assess the impact of treatments on people’s quality of life. For example, a ‘quality of life’ study might ask you about:
- Your mood and general sense of well-being
- Whether you feel more tired than usual
- Whether you are managing to lead the life you would lead normally – going to work, looking after your family, or whatever you would normally do
Any of the many methods used to assign subjects to an experimental group or control group so that assignment is not influenced in any way by those making the assignments or by the researchers
conducting the trial. Random assignment reduces the potential for bias in a trial.
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, researchers 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 researchers need to ensure that clinical trials are not biased. It is quite easy for people to be biased without realising it.
For example, suppose a new treatment is being tested that has quite bad side effects. Without randomisation, researchers, doctors and the sickest patients might avoid the new treatment. As the trial continued, more and more of the sickest patients would join the comparison group getting the old treatment, so this group would then have more and more of the sickest patients in it. The people in the new treatment group might do better simply because they are not as ill when they started the treatment. These results could be interpreted wrongly – people might believe that the new treatment works better than the old one. Randomising patients to different treatment groups avoids biasing the results in this way.
Processes used to attract and enroll trial participants according to eligibility criteria. (See inclusion and exclusion criteria.)
With respect to clinical research, the federal statutes, codes, and laws that govern the conduct of federally funded clinical trials and privately sponsored clinical trials for new drugs, devices, biologics, and procedures.
In clinical trials, the group of healthcare professionals who conduct the trial; it typically includes a principal investigator and a clinical research coordinator.
Analysis of the data collected during a trial.
In a clinical trial, the probability of discomfort or harm to participants in a clinical trial.
An inactive device or device/procedure that mimics the actual device and can be used as a placebo in a clinical trial.
Undesired effect of a treatment. Investigational new drugs and devices are evaluated for immediate and long-term side effects.
Side effects, or adverse effects, are undesired effects of a treatment. For example, if you are given a drug to treat a headache and it makes you sick, the sickness would be described as a side effect. Trials will often look at short-term and long-term side effects of a treatment.
Side effects, or adverse effects, are undesired effects of a treatment. For example, if you are given a drug to treat a headache and it makes you sick, the sickness would be described as a side effect. Trials will often look at short-term and long-term side effects of a treatment.
An individual, company, institution, or organization that initiates, manages, and/or finances a clinical trial.
The treatment that is currently thought to be effective in medical practice.
Trial Steering Group
Most trials have a trial steering group or committee. This makes sure the trial is running well. In the UK, this committee often includes patient representatives as well as the researchers, doctors and nurses who are leading the trial.
Most trials have a trial steering group or committee. This makes sure the trial is running well. In the UK, this committee often includes patient representatives as well as the researchers, doctors and nurses who are leading the trial.
Free of coercion, duress, or undue inducement. In a clinical trial, refers to a participant’s decision to enrol.
In a trial, to end a patient’s participation before he or she reaches the designated end point.
