Adherence means sticking to the treatment prescribed, or allocated in a clinical trial and, if appropriate, finishing the course.
Adverse events are undesired effects that may or may not be related to treatment such as dizziness, stomach ache or a rash. A symptom caused by the treatment is a side effect. Serious adverse events in trial participants are reported to the national regulatory authority (MHRA in the UK).
This is a type of study that investigates the cause of a specific disease or tries to understand why a disease gets worse or better. Aetiological studies do not have to be clinical trials. Sometimes they can involve following up participants for a long time to see who develops the disease and what factors may have caused the disease to get worse or get better.
Bias results when a particular design or analysis is likely to favour a particular outcome and would, therefore, make those results unreliable. It is important to avoid bias in health research as it can distort the results and could lead to unsafe or ineffective treatments being licensed for use, or useful treatments being overlooked. One way to avoid bias is by using randomisation and by 'blinding' participants and their carers.
Blinding means that trial participants do not know which treatment they are receiving. This helps prevent bias. Double blinding refers to the participant, their doctor and researchers running the trial not knowing which treatment is received by each group until all data have been recorded.
When Trial Set-up has been completed, hospitals or recruitment centres need to ensure they have completed all the necessary paperwork before they can recruit any patients. This means checking they understand the trial and trial procedures, they have the correct protocols, participant information sheets and consent forms and that all involved staff are aware of their responsibilities. Once this has been checked, the centre is activated and they can start to recruit participants.
A case report form (CRF) is a printed, optical, or electronic document designed to record all of the protocol-required information to be reported to the sponsor on each trial.
Clinical trials are research studies that compare different treatments and treatment strategies. They test whether one treatment is better or, at times, at least as good as another. No matter how promising a new treatment or treatment strategy may appear, it must go through clinical trials before its benefits and risks can really be known.
Trial closure generally occurs in two phases. Recruitment closure occurs when a trial stops recruiting new participants but existing participants who are already in the study continue to be followed up as part of the trial. This follow-up can continue for many years if the study has been designed to look at long-term results. Follow-up does not necessarily mean that participants are seen by the researchers. In some trials, data from GP practices, hospital admission databases or death registers may be used. Follow-up closure occurs when the study investigators stop collecting any data on the participants and the data collected up to the point of follow-up closure are used to analyse the trial results. Usually, when a trial has closed to both recruitment and follow-up, no more information is collected on the participants unless specific ethical approval is granted for the researchers to do so.
In cross-over trials participants cross over and follow the same treatment as the other group they are being compared to after a certain period of time.
Independent data monitoring committees oversee the progress of trials. They are made up of experts who are independent from the trial and who examine its findings while the trial is still recruiting or in follow-up. If they see evidence that participants are experiencing serious or unexpected side effects, or if it emerges that one treatment being compared is clearly better or worse than the others, they can advise that a trial is stopped.
Disease progression refers to the course that a disease takes over time. This type of wording causes confusion sometimes. Generally, we tend to think of 'progress' as a positive thing. But unfortunately, when doctors talk about the 'progress of a disease' they mean it has got worse, so it is not good news.
These are clearly-defined criteria of who is eligible to take part in a study and who is not as given by the inclusion criteria and exclusion criteria of the study.
An epidemiological, or observational, study examines data on individuals with a specific condition and does not intervene in their care, as a clinical trial would. Epidemiological studies examine the effect of certain exposures (e.g. tobacco smoke, long duration of HIV infection) on health outcomes (e.g. cancer).
An ethics committee is a committee made up of healthcare professionals and lay people who review funded studies in order to ensure that they are conducted to appropriate ethical standards. Study participants cannot be approached about joining a clinical study until it has been approved by an ethics committee.
The event rate describes the number of people who experience a particular event or outcome measure (e.g. tumour recurrence) over a given time period.
A collection of the best available scientific research currently available about a health condition. This is used to make decisions about how best to treat and provide care for individuals with that condition, or to prevent it.
These determine who is not eligible for a clinical study. For example, many trials exclude women who are pregnant, or who may become pregnant, to avoid any possible danger to a baby, or people who are taking a drug that might interact with the treatment being studied. (See also eligibility criteria and inclusion criteria.)
This is an international quality standard for the conduct of clinical studies. Randomised Clinical Trials are required by law to conform to GCP.
In some clinical trials the cost of all aspects of the treatments being compared is examined. This is particularly important when there is more than one effective approach to treating a condition.
These clearly indicate who can join a trial, e.g. the condition and stage of disease they are already at, and their age. (See also eligibility criteria and exclusion criteria.)
Individual participant data (IPD) meta-analyses tend to use standard systematic review and meta-analysis methods, but also involve the central collection and analysis of the original data from all the relevant trials worldwide, rather than just the published summary statistics.
This refers to a participant in a research study agreeing to take part of their own free will after being given all the important facts about that study, and after they have had the chance to ask questions and have them satisfactorily answered and understood.
An analysis of trial data which is undertaken before the end of the trial.
An intervention is a measure which is introduced and evaluated through a clinical trial with the aim of improving health. It could be a treatment (e.g. drug A vs. drug B), a treatment strategy (e.g. a drug vs. a surgical technique), a different screening approach, or prevention measure.
Meta-analysis is a means of quantitatively combining the results of several research studies to provide an ‘average’ estimate of the treatment effect.
Metadata is a formalised way to describe how to structure a database based on the requirements of the trial.
This is research activity carried out to improve the methods used in research.
See epidemiological study.
This refers to a trial which is still recruiting or following up participants. It may also refer to a trial where the participant knows which treatment (or treatment strategy) they are receiving, i.e. they are not blinded (see blinding). This is usually called an ‘open label’ trial.
In an open label trial, participants and their doctors know which treatment (or treatment strategy) they are receiving.
When Trial Set-up has been completed, any hospital or recruitment centre that has been activated can start to recruit participants into the trial.
Outcomes are measures of health, e.g. response to treatment, occurrence or recurrence of disease, a measure of well-being.
A placebo is a dummy treatment that is designed to be harmless and to have no effect. It looks, smells and tastes like the treatment being tested, so that trial participants do not know if they are taking the dummy treatment or the treatment itself (see blinding).
Prophylaxis is any measure to prevent a health condition, rather than curing or treating it, such as vaccination and use of anti-malaria drugs.
A protocol is the plan for a research study. Protocols need to be approved by an ethics committee before the study begins to recruit participants. They provide information on the question being addressed by the study, the eligibility criteria, and the visit schedule for trial participants.
As well as measuring the physical effects of a treatment (for example changes to blood pressure), 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 about:
- Participant's mood and general sense of well-being
- Whether participants feel more tired than usual
- Whether participants are managing to do more things than before
- Whether participants sleep patterns have changed
Randomisation means that a computer will decide at random which treatment or treatment strategy a trial participant will receive. This ensures that each participant has the same chance of receiving the treatments or strategies being compared and avoids one treatment being given to someone because they are, for example, a woman, are older or sicker. Randomisation ensures that the groups of people being compared in a trial are as similar as possible to start with except for the treatment they receive. This in turn ensures that differences seen between these groups after they have started their treatment are likely to be due to the treatments being compared.
Randomisation is central to randomised controlled trials (RCTs) and allows a fair comparison between trial groups to be made.
During Trial Set-up, all the processes for the trial are put into place. These include things like:
- writing protocols and working instructions for the researchers,
- writing the participant information sheets and consent forms,
- obtaining ethical approval and other regulatory approvals that are required.
It also involves deciding which hospitals or recruitment centres will take part and getting permission from them that they are happy to take part.
The organisation responsible for the trial.
Trial arm refers to one of the groups to which trial participants are assigned to in a randomised controlled trial. The group of people receiving the current standard of care are usually referred to as the control arm.
The Trial Management Group is the committee of trial researchers who are responsible for the trial set-up, the day-to-day running of the trial and the release of any trial results or publications. To ensure that the study is conducted safely and scientifically, the TMG should include members from all the necessary specialties, eg. doctors, nurses, trial and data managers, statisticians and patient/public representatives.
Clinical trials are conducted in phases:
Phase I: Aims to test safety and usually involve a small number of people.
Phase II: Aims to evaluate effectiveness, and usually involve a larger number of people.
Phase III: Aims to compare two or more treatments or treatment strategies and monitor side effects. Results from these trials allow drugs to treatment recommendations being made and drugs licensed.
Phase IV: Are post-marketing studies and collect further information on use of treatments in clinical practice.
A trial steering committee (TSC) usually oversees the conduct of a clinical trial and is made up of researchers, doctors and independent members.