Clinical endpoint
Clinical endpoints or clinical outcomes are outcome measures referring to occurrence of disease, symptom, sign or laboratory abnormality constituting a target outcome in clinical research trials. The term may also refer to any disease or sign that strongly motivates withdrawal of an individual or entity from the trial, then often termed a humane (clinical) endpoint.
The primary endpoint of a clinical trial is the endpoint for which the trial is powered. Secondary endpoints are additional endpoints, preferably also pre-specified, for which the trial may not be powered.
Surrogate endpoints are trial endpoints that have outcomes that substitute for a clinical endpoint, often because studying the clinical endpoint is difficult, for example using an increase in blood pressure as a surrogate for death by cardiovascular disease, where strong evidence of a causal link exists.
Humane endpoint[edit]
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.[4] 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[edit]
A surrogate endpoint (or marker) is a measure of effect of a specific 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".[5][6][7]
Combined endpoint[edit]
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 infarction, 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. Overall Treatment Utility is an example of a multidimensional composite endpoint in cancer clinical trials.[8]
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.
Response rates[edit]
The response rate is the percentage of patients on whom a therapy has some defined effect; for example, the cancer shrinks or disappears after treatment.[9]
When used as a clinical endpoint for trials of cancer treatments, this is often called the objective response rate (ORR).[10][11] The FDA definition of ORR in this context is "the proportion of patients with tumor size reduction of a predefined amount and for a minimum time period."[10]: 7 Another criterion is the clinical benefit rate (CBR), "the total number (or percentage) of patients who achieved a complete response, partial response, or had stable disease for 6 months or more".[12]
Each trial, for whatever illness or condition, may define what is considered a complete response (CR) or partial response (PR) to the therapy or intervention. Hence the trials report the complete response rate and the overall response rate which includes CR and PR. (See e.g. Response evaluation criteria in solid tumors, and Small-cell carcinoma treatment, and for immunotherapies, Immune-related response criteria.)
Consistency[edit]
Various studies on a particular topic often do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. The Core Outcomes in Women's Health (CROWN) Initiative is one effort to standardize outcomes.[13]