Methodological issues in randomized controlled trials

Abstract

There is increasing emphasis on the need to practise evidence-based medicine and the strongest evidence comes from well designed and well-conducted randomized controlled trials. Every component is important for the success of a clinical trial; if the design or sample size is inappropriate, then the results of the study will be unreliable, however well the study is conducted. Conversely a well-designed study may founder because of poor outcome measurement or unacceptably high subject loss. The advantages of a well-designed trial apply equally to studies with short term outcomes and to those requiring long-term follow up. This paper therefore focuses on general methodological issues with a discussion, where appropriate, of the special considerations associated with long-term follow-up. This emphasis is motivated by the belief that a trial with methodological weaknesses is both a waste of resources and unethical. Anyone planning to undertake a randomized controlled trial should consult a more comprehensive text [1–4]. Here, some selected issues are highlighted with the choice of topics reflecting the experience and interests of the authors.