Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Ideally, a trial should have a single endpoint based on just one outcome measure.However, as the art of trial design has evolved, most large trials have a primary(composite) endpoint consisting of multiple outcome measures.An endpoint can also be the time taken for an event to occur. For such an endpoint,the events of interest for which a time is to be recorded – such as stroke or heartattack – must be predefined. Trial endpoints can also be a quantitative measurementof a biochemical or socioeconomic parameter such as cholesterol level or qualityof-lifescore. Therefore, there are a number of different outcomes – which can beevaluated both individually and in combination – on which the primary endpointof a trial can be based.How are clinical endpoints chosen?When choosing endpoints for a clinical trial, it is important to ensure that they:• are clinically meaningful and related to the disease process• answer the main question of the trial• are practical so that they can be assessed in all subjects in the same way• occur frequently enough for the study to have adequate statistical powerIf the endpoint to be measured consists of more than one outcome, then theseoutcomes should be easily differentiable from each other so that the events maybe quantified independently. For example, in a cancer treatment trial, good outcomesto choose would be the primary tumor size and the number of new tumor metastases.Why is death or time to death not always the best endpointto measure?Although death is the ultimate clinical endpoint and probably the best yardstickto judge treatments by, it may not be the best endpoint to measure in all studiesfor the following reasons:• Death may be a rare event within the timeframe of the trial.• Following all patients until a significant difference is seen in thenumber of deaths or the time to death may take many years offollow-up, so substantial resources may be required.• Death may result from causes other than the disease being treated(eg, deaths due to car accidents, assuming that the disease processdoes not impair driving ability).39