Observational studies: going beyond the boundaries of randomized controlled trials

Abstract

The term observational study describes a wide range of study designs including prospective and retrospective cohort studies, case-control studies, and cross-sectional studies, a defining feature of which is that any intervention studied is determined by clinical practice and not the protocol. Data from large, prospective observational studies provide information about the safety and efficacy of medicines in daily clinical use. Such observational studies are generally carried out once a medicine has received approval from regulatory agencies. Observational trials have inherent limitations in terms of their susceptibility to bias and confounding, restricting their ability to define causality. However, their strengths include that they reflect daily clinical practice more closely than randomized controlled trials (RCTs), both in terms of the heterogeneous patient populations that are included, and the medical interventions that they receive. Therefore, observational trials can provide clinically relevant information that is not necessarily provided by RCTs. Given the limitations of an observational study approach, it is important to optimize their study design to maximize their validity, and thus, in particular, known causes of bias and confounding should be measured. Medical investigators, health authorities, and the pharmaceutical industry all have important roles to play in designing, approving, and performing observational studies.