Glossary of Clinical Trial Terms
Clinical trials often use lots of technical terms when describing study design, research outcomes and phases. Below is a glossary for some of the most commonly used terms. An extensive glossary of terms can also be found on ClinicalTrials.gov.
Adverse Event - an unfavourable change in health that occurs in trial participants during the clinical trial or in a set time frame following the trial. These can include abnormal laboratory findings (e.g., reduced white blood cell counts) and/or physical medical events experienced by participants (e.g., diarrhoea, hair loss, muscle cramps). A serious adverse event includes those that result in death, significant disability, hospitalisation and/or prolongation of hospitalisation. Adverse events are recorded during clinical trials to determine the safety profile of the intervention being investigated.
Basket Study - Also known as a bucket trial this is a type of clinical trial in which a new drug/intervention is tested on patients who have different types of cancer (e.g., stomach, breast, lung) but these cancers all share the same mutation or biomarker. The novel drug/intervention targets this specific mutation or biomarker that is shared amongst many different cancer types. Basket studies enable a new drug to be tested and approved more quickly than doing individual clinical trials on each different cancer type at different time frames.
Clinical Trial - a type of research study that investigates and evaluates a new test, drug, intervention or treatment on human health outcomes in volunteers. Clinical trials need to obtain ethical approval before they start and adhere to guidelines in the way they are designed and conducted. Clinical trials are divided into four phases - you can find out what the different phases are within this glossary of terms.
Clinical Benefit Rate - Abbreviated to CBR, this is the percentage of patients who achieve a complete response, partial response, or at least six months of stable disease as a result of the treatment they are receiving. A complete or partial response means either a complete or partial removal of the cancer.
Double-blind - This means that neither the trial participants, research team or doctors monitoring the participant know which treatment or intervention the participant is receiving until all data is collected and the trial is over. This method of concealing groups is used to reduce bias which can influence the results of the trial.
Duration of Response - the length of time that a tumour continues to respond to treatment without the cancer growing or spreading.
ER - The Estrogen Receptor (ER) is a type of receptor that can be present on breast cancer cells. If the ER is found to be expressed by breast cancer cells, the breast cancer will be termed ER positive (ER+). If the breast cancer doesn’t express the ER it will be termed ER negative (ER-). This criteria (ER+ or ER-) can be used to determine if a patient can take part in a breast cancer clinical trial.
Exclusion Criteria - specific characteristics that disqualify volunteers from taking part in a clinical trial (e.g., having high blood pressure). These characteristics can include medical conditions or comorbidities, other treatments a patient is currently taking or has taken and other factors that could mask the effect of the intervention under investigation.
First-in-human study - A clinical trial in which a new drug, procedure, or treatment is tested in humans for the first time. These can be called an FIH study. Before treatments or drugs can be tested on humans in clinical trials extensive laboratory testing and animal studies are conducted to initially test safety and effectiveness. These types of clinical trials would be Phase I clinical trials.
HER2 - Human Epidermal Growth Factor receptor 2 is a receptor that is found on the surface of normal breast cells. However, in some breast cancers HER2 is found in an abnormally high amount and contributes to the growth of breast cancer. If HER2 is found in substantial amounts in breast cancer cells the cancer will be referred to as HER2 positive (HER2+) and if HER2 is lacking in breast cancer cells the cancer will be referred to as HER2 negative (HER2-). Being HER2+ or HER2- can be used as a criteria to determine which patients can take part in a breast cancer clinical trial.
HR - Short for Hormone Receptor and refers to the estrogen receptor (ER) and progesterone receptor (PR). Both of these types of HR can be found to be expressed by breast cancer cells, if the breast cancer cells expresses one or both of the ER or PR then the breast cancer will be termed HR positive (HR+). If the breast cancer cells do not express a HR they are referred to as HR negative (HR-). Being HR+ or HR- can be used to identify who can take part in a breast cancer clinical trial.
Inclusion Criteria - these specify the specific characteristics that are required for entry into a clinical trial. It can include a variety of different aspects, such as the stage of breast cancer, the molecular type of breast cancer, the health status of the patient and what other treatments the patient has received.
Informed Consent - this is the term used to describe the formal decision, which must be written, dated and signed in which a patient decides to take part in a clinical trial. Before informed consent can be given a patient must be told the nature of the trial, its significance, implications and risks of taking part. You can remove consent if you decide you no longer want to take part in the trial.
Interventional Model - for a clinical trial this means that participants are assigned into groups that will receive one or more treatments under investigation (this is the intervention group). This intervention group will be compared to a group that receives either no treatment (i.e., no intervention) or the currently available standard treatment option (which is what usually occurs in secondary breast cancer clinical trials).
Maximum Tolerated Dose - the highest dosage of the drug or treatment that does not cause unacceptable side effects. This will typically be established in a Phase I clinical trial.
Non-randomised - In this type of clinical trial participants are not assigned at random into the different treatment groups of the clinical trial. A participant may be able to choose the group they want to be in, or they might be assigned to a group by the research team or doctor.
Objective Response Rate - this is defined as the proportion of patients who have a partial or complete response to a therapy, meaning that the cancer either gets less severe or fully disappears. It does not include stable disease and is regarded as a measure of the ability of the therapy to destroy cancer cells.
Observational study - this type of study does not involve any intervention. Typically, participants are monitored on their current treatment plan and health outcomes are tracked. This kind of study would not involve any patient taking a new drug or therapy.
Open Label (i.e., no masking or blinding) - this means that both the participant and the research team know what treatment is being given and this information is not withheld.
Overall Survival - Abbreviated to OS, this describes the length of time participants are still alive after they started the treatment being investigated in the clinical trial. Overall survival is often referred to as the gold standard endpoint for a secondary cancer clinical trial.
Parallel Assignment - This means that the different groups in the clinical trial only receive one type of drug or treatment. For example, one group will receive the new treatment of interest and the other group will receive the current standard of care (or placebo) and there is no overlap of these different treatments between the different groups.
Phase I Clinical Trial - Usually a Phase I clinical trial (sometimes called Phase Ia or Ib) is testing a new drug for the first time in a small group of patients to evaluate the safe dosage range and to identify side effects. Typically these are small studies recruiting ~20-50 people.
Phase II Clinical Trial - Usually a Phase II clinical trial (sometimes called Phase IIa or IIb) is testing a drug that has been found to be safe in Phase I trials but requires further study to further investigate potential adverse effects and further check the correct dosage. Typically these are medium size studies recruiting ~50-100+ people.
Phase III Clinical Trial - Usually a Phase III clinical trial will compare the new drug against the standard treatment or a placebo (a dummy drug) to determine how well the new treatment works in a larger group of patients. Typically these recruit hundreds of patients (sometimes over a thousand patients) and can take place in many different locations around the world. A Phase III clinical trial is required before a new treatment can get approved to be used in the NHS.
Phase IV Clinical Trial - A Phase IV clinical trial typically takes place after the drug has been approved from the beneficial results of a Phase III trial. The aim of a Phase IV clinical trial is to monitor the drug as it gets used in a wider population of patients over a longer timeframe to further investigate the long term benefits and potential side effects of the new drug.
Placebo - Sometimes referred to as a “dummy drug” a placebo is used in some, but not all, clinical trials and is intended to have no treatment effect. Typically in a placebo controlled trial, one group will be given the treatment of interest and another group will be given the placebo. This enables a fair comparison to measure the health outcomes of those receiving the treatment compared to those that don’t receive the treatment.
Progression-Free Survival - Abbreviated to PFS, this describes the length of time after treatment has started until there is the first evidence that the disease has got worse or spread. For a clinical trial, measuring progression-free survival is one of the common ways in which a treatment is investigated for how well it works.
Prospective study/cohort - this type of study follows participants through time and investigates what health outcomes occur. Usually two groups are monitored (e.g., people who smoke vs those who don’t).
Quality of Life/QoL - Clinical trials will typically not only measure the disease progression outcomes of patients when they take part in a clinical trial, but also measure what impact treatments have on the patients quality of life. Quality of life is typically measured by clinical trial participants completing questionnaires that ask about how the treatment is impacting the patients day to day life and any side effects they are experiencing such as pain, anxiety, stomach distress, impact on mobility, lethargy and sleeplessness. These side effects may not cross the threshold for being diagnosed as a medical condition but still have a notable impact on the patients life, so it is important that they are investigated in a clinical trial.
Randomised - Randomised Controlled Trials (RCTs) are studies in which participants are randomly assigned into the different groups in the study (i.e., the group that may receive the experimental treatment and the group that receives the current standard of care). By randomising participants it enables researchers to make a fair comparison of the health outcome results of the different groups.
Retrospective study/cohort - this type of study looks at past data collected on patients after the clinical event of interest or drug exposure has occurred. Typically this involves looking back at patients' medical notes. For example, researchers might look back at the medical records of a cohort of patients who received an already approved medication and see what health outcomes they experienced at different time points after starting this drug.
Sequential Assignment - this means that groups of participants in the clinical trial will receive two or more interventions in a specific order.
Single-Group Assignment - in this type of clinical trial all participants will receive the same treatment or intervention.
Sponsor-blind - This means that the company/group who is funding the clinical trial does not know what treatments each group received. This can help reduce bias and enable the company to make an independent review of the data.
Time to Progression - the length of time from either the date of diagnosis or the start of treatment in the clinical trial until the cancer starts to get worse or has spread to other parts of the body.
TNBC - Triple Negative Breast Cancer is a term used to describe breast cancer that does not have any of the three receptors (ER, PR & HER2) that are commonly found in breast cancers that are typically used to classify breast cancer. TNBC accounts for ~15% of all breast cancer cases and around 8,000 women are diagnosed with TNBC in the UK each year. TNBC status can be used to classify patients if they can take part in breast cancer clinical trials.