Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘So is that it – just apply the formula?Statisticians have developed various methodologies for determining sample sizes,depending on the number of treatments compared, the type of primary endpointmeasured, the statistical analysis method used to analyze outcomes, and the designof the study. Detailed formulas for various endpoints can be found in reference [3].When determining the sample size it is wise to finalize the main objective of theprotocol and then to look at a range of assumptions by working with a medicalstatistician. This approach will suggest a range of sample sizes and a balance canthen be struck between the ideal statistical power, the available resources, and thelength of time before the sample size can be finalized. Even then, interim analysesof overall event rates during an RCT (at this point in the trial we are still unawareof event rates in each treatment group) will provide a guide as to whether thesample size needs to be altered as the RCT proceeds. If event rates are measuredby treatment arm during the course of a study, the data and safety monitoringboard might recommend the early termination of the study if a large benefit orelement of harm is seen with the new treatment.ConclusionThe sample size is the most important determinant of the statistical power ofa study, and a study with inadequate power is unethical unless being conducted asa safety and feasibility study. However, the calculation of sample size is not anexact science. It is therefore important to make realistic and well-researchedassumptions before choosing an appropriate sample size. This sample size shouldaccount for dropouts, and there should be a consideration for interim analyses tobe performed during the study, which can be used to amend the final sample size.References1. Pocock SJ. Clinical Trials: A Practical Approach. New York: John Wiley & Sons, 1983.2. Moher D, Dulberg CS, Wells GA. Statistical power, sample size, and their reporting in randomizedcontrolled trials. JAMA 1994;272:122–4.3. Chow SC, Shao J, Wang H. Sample Size Calculation in Clinical Research. New York: MarcelDekker, 2003.87