Clinical endpoint
Encyclopedia
In a clinical research trial
, a clinical endpoint generally refers to occurrence of a disease
, symptom
, sign
or laboratory abnormality that constitutes one of the target outcomes of the trial, but may also refer to any such disease or sign that strongly motivates the withdrawal of that individual or entity from the trial, then often termed humane (clinical) endpoint.
For example, a clinical trial investigating the ability of a medication
to prevent heart attack
might use chest pain as a clinical endpoint. Any patient enrolled in the trial who develops chest pain over the course of the trial, then, would be counted as having reached that clinical endpoint. The results would ultimately reflect the fraction of patients who reached the endpoint of having developed chest pain, compared with the overall number of people enrolled.
When an experiment involves a control group, the proportion of individuals who reach the clinical endpoint after an intervention is compared with the proportion of individuals in the control group who reached the same clinical endpoint, reflecting the ability of the intervention to prevent the endpoint in question.
In clinical cancer research, common endpoints include discovery of local recurrence, discovery of regional metastasis, discovery of distant metastasis, onset of symptoms, hospitalization, increase or decrease in pain medication requirement, onset of toxicity, requirement of salvage chemotherapy, requirement of salvage surgery, requirement of salvage radiotherapy, death from any cause or death from disease. A cancer study may be powered for overall survival, usually indicating time until death from any cause, or disease specific survival, where the endpoint is death from disease or death from toxicity.
(or marker) is a measure of effect of a certain treatment that may correlate with a real clinical endpoint but doesn't necessarily have a guaranteed relationship. The National Institutes of Health
(USA) define surrogate endpoint as "a biomarker intended to substitute for a clinical endpoint".
, or death. An example of a cancer study powered for a combined endpoint is disease-free survival (DFS); trial participants experiencing either death or discovery of any recurrence would constitute the endpoint.
Regarding humane endpoints, a combined endpoint may constitute a threshold where there is enough cumulative degree of disease, symptoms, signs or laboratory abnormalities to motivate an intervention.
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
, a clinical endpoint generally refers to occurrence of a disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...
, symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
, sign
Medical sign
A medical sign is an objective indication of some medical fact or characteristic that may be detected by a physician during a physical examination of a patient....
or laboratory abnormality that constitutes one of the target outcomes of the trial, but may also refer to any such disease or sign that strongly motivates the withdrawal of that individual or entity from the trial, then often termed humane (clinical) endpoint.
In general sense
In a general sense, a clinical endpoint is included in the entities of interest in a trial. The results of a clinical trial generally indicate the number of people enrolled who reached the pre-determined clinical endpoint during the study interval compared with the overall number of people who were enrolled. Once a patient reaches the endpoint, he or she is generally excluded from further experimental intervention (the origin of the term endpoint).For example, a clinical trial investigating the ability of a medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
to prevent heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
might use chest pain as a clinical endpoint. Any patient enrolled in the trial who develops chest pain over the course of the trial, then, would be counted as having reached that clinical endpoint. The results would ultimately reflect the fraction of patients who reached the endpoint of having developed chest pain, compared with the overall number of people enrolled.
When an experiment involves a control group, the proportion of individuals who reach the clinical endpoint after an intervention is compared with the proportion of individuals in the control group who reached the same clinical endpoint, reflecting the ability of the intervention to prevent the endpoint in question.
In clinical cancer research, common endpoints include discovery of local recurrence, discovery of regional metastasis, discovery of distant metastasis, onset of symptoms, hospitalization, increase or decrease in pain medication requirement, onset of toxicity, requirement of salvage chemotherapy, requirement of salvage surgery, requirement of salvage radiotherapy, death from any cause or death from disease. A cancer study may be powered for overall survival, usually indicating time until death from any cause, or disease specific survival, where the endpoint is death from disease or death from toxicity.
Clinical trial endpoints
A clinical trial will usually define or specify a primary endpoint as a measure that will be considered success of the therapy being trialled (eg. in justifying a marketing approval). The primary endpoint might be a statistically significant improvement in overall survival (OS). A trial might also define one or more secondary endpoints such as progression-free-survival (PFS) that will be measured and are expected to be met. A trial might also define exploratory endpoints that are less likely to be met.Humane endpoint
A humane endpoint can be defined as the point at which pain and/or distress is terminated, minimized or reduced for an entity in a trial (such as an experimental animal), by taking action such as killing the animal humanely, terminating a painful procedure, or giving treatment to relieve pain and/or distress. The occurrence of an individual in a trial having reached may necessitate withdrawal from the trial before the target outcome of interest has been fully reached.Surrogate endpoint
A surrogate endpointSurrogate endpoint
In clinical trials, a surrogate endpoint is a measure of effect of a certain treatment that may correlate with a real clinical endpoint but doesn't necessarily have a guaranteed relationship...
(or marker) is a measure of effect of a certain treatment that may correlate with a real clinical endpoint but doesn't necessarily have a guaranteed relationship. The National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
(USA) define surrogate endpoint as "a biomarker intended to substitute for a clinical endpoint".
Combined endpoint
Some studies will examine the incidence of a combined endpoint, which can merge a variety of outcomes into one group. For example, the heart attack study above may report the incidence of the combined endpoint of chest pain, myocardial infarctionMyocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
, or death. An example of a cancer study powered for a combined endpoint is disease-free survival (DFS); trial participants experiencing either death or discovery of any recurrence would constitute the endpoint.
Regarding humane endpoints, a combined endpoint may constitute a threshold where there is enough cumulative degree of disease, symptoms, signs or laboratory abnormalities to motivate an intervention.