Clinical Trials

❘❙❚■ Chapter 9 | Sample Size and PowerWhat is ‘sample size’ for a randomized study?The sample size of a randomized controlled trial (RCT) is the number of subjectsthat are to be enrolled in the study. Choosing the right sample size is critical for astudy, and is based on key assumptions: the size of the benefit we anticipate withthe new treatment compared to standard (or placebo) treatment (the ‘expectedtreatment effect’); and the amount of certainty we wish to have with which tocapture the treatment benefit (the ‘power’ of the study).The larger the sample size, the better the power with which to detect a treatmenteffect, which means that smaller treatment effects can be detected as statisticallysignificant. In the same way, the smaller the sample size, the less power we havewith which to detect a treatment effect, meaning that the effect must be greater inorder to be detected as significant. The calculation used to find the required samplesize for a trial is also influenced by the trial’s design, so the method by which theprimary outcome is to be determined must also be clarified in advance ofdetermining the sample size.Why do we have to choose a sample size?When resources are limited we must decide how best to invest them in order tomaximize the benefits received. For example, should we use treatment X ortreatment Y? To answer this question, we need to decide how hard we will lookfor the answer. Until we do, people will continue to be given or refused atreatment without evidence. We might decide that it is only worth looking at thequestion if we are fairly likely to detect a 10% improvement with the newtreatment. To improve the chance that such a difference is detected (if it exists)we have to choose the sample size wisely, based on realistic initial assumptions.More importantly, it is unethical to carry out a study that is unlikely to capture areal difference since we will have spent precious resources on performing a studyfor no gain. From this, we can appreciate that choosing an appropriate sample sizefor a study is dependent on good judgment, which is critical to a trial’s success.What factors determine the sample size?Several factors are considered when determining the appropriate sample size touse for an RCT [1,2]:• the expected summary measure of the primary endpoint (such as eventrate) in the control or standard treatment arm of the trial82