Clinical Trials

❘❙❚■ Chapter 4 | EndpointsWhat is a clinical trial endpoint?A clinical trial endpoint is defined as a measure that allows us to decide whetherthe null hypothesis of a clinical trial should be accepted or rejected. In a clinicaltrial, the null hypothesis states that there is no statistically significant differencebetween two treatments or strategies being compared with respect to the endpointmeasure chosen. An endpoint can be composed of a single outcome measure –such as death due to the disease – or a combination of outcome measures, such asdeath or hospitalization due to the disease.Clinical trial endpoints can be classified as primary or secondary endpoints.Primary endpoints measure outcomes that will answer the primary (or mostimportant) question being asked by a trial, such as whether a new treatment isbetter at preventing disease-related death than the standard therapy. In this case,the primary endpoint would be based on the occurrence of disease-related deathsduring the duration of the trial. The size of a trial is determined by the powerneeded to detect a difference in this primary endpoint.Secondary endpoints ask other relevant questions about the same study; forexample, whether there is also a reduction in disease measures other than death,or whether the new treatment reduces the overall cost of treating patients.Occasionally, secondary endpoints are as important as the primary endpoint,in which case they are considered to be co-primary endpoints. When secondaryendpoints are also important then the trial must be sufficiently powered todetect a difference in both endpoints, and expert statistical and design advicemight be needed.What are the main types of endpoints?An endpoint may be based on [1]:• a binary clinical outcome indicating whether an event –such as death from any cause – has occurred• death from a disease-specific cause (eg, a fatal stroke for a trialcomparing blood pressure treatments)• the occurrence of disease signs or symptoms• the relief of symptoms• quality of life while disease is active• the use of healthcare resources (eg, the number of hospital admissions)38