Challenging issues in randomised controlled trials.

WHAT THIS TOPIC IS ABOUT: Randomised controlled trials (RCTs) are the most rigorous way of determining whether a cause-effect relation exists between treatment and outcome and are an integral component in the hierarchy of evidence which guide current clinical practice. Whether ensuring the success of a RCT or interpreting the medical literature, it is important to understand the key components of RCT design to assess their quality and therefore the weight which should be attributed to its findings. This article will highlight some of these key components by using a number of ongoing trauma studies being co-ordinated by the Australian and New Zealand Intensive Care Research Centre, Monash University. COMMON PROBLEMS AND CHALLENGES: The quality of many RCTs could be improved by avoiding some common pitfalls, such as (i) unclear hypotheses and multiple objectives, (ii) poor selection of endpoints, (iii) inappropriate subject selection criteria, (iv) non-clinically relevant or feasible treatment/intervention regimens, (v) inadequate randomisation, stratification, blinding, (vi) lack of stratification in small RCTs (vii) inadequate blinding of trials, (viii) insufficient sample size/power, (ix) failure to use intention to treat analysis and (x) failure to anticipate common practical problems encountered during the conduct of a RCT. TIPS FOR RESEARCHERS: The RCTs most likely to be funded and/or be of high quality always address these issues. Copyright (c) 2010 Elsevier Ltd. All rights reserved.