Clinical endpoint

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. 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. The primary endpoint of a clinical trial is the endpoint for which subjects are randomized and for which the trial is powered. Secondary endpoints are endpoints that are analyzed post hoc, for which the trial may not be powered nor randomized. 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 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. A clinical trial will usually define or specify a primary endpoint as a measure that will be considered success of the therapy being trialled (e.g. 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. Clinical endpoints can be obtained from different modalities, such as, behavioural or cognitive scores, or biomarkers from Electroencephalography (qEEG), MRI, PET, or biochemical biomarkers. 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. These are expressed as a period of time (survival duration) e.g., in months. Frequently the median is used so that the trial endpoint can be calculated once 50% of subjects have reached the endpoint, whereas calculation of an arithmetical mean can only be done after all subjects have reached the endpoint.