Pitfalls in clinical trial design and methodology

Large clinical trials have become important tools for determining the benefits and risks of therapies for acute coronary syndromes. Understanding clinical trial methodology is important both for trial design and interpretation of trial results. Conducting large trials, and overviews of large trials, involves the collaboration of many health professionals and experts in trial design and methodology which, in turn, has major resource implications. Subjectivity may be introduced into clinical trials at many stages, and interpretation of trials may be biased, depending on the original viewpoint of the investigator or the audience. The rationale for conducting large, randomized trials involves the need to reduce bias and the requirement for large study populations to demonstrate small reductions when event rates are low. Potential sources of error in data interpretation are discussed. Overviews, or meta-analyses, of large trials addressing the same or similar questions may provide the best evidence for guiding the use of treatments, with the caveat that publication bias favours the reporting of positive trials results.