1. Introduction 1. Introduction 2. Two reasons for... 3. Fulfilling the promise... References Many important questions in medicine involve questions about causality. For example, do low levels of high-density lipoproteins (HDL) cause heart disease? Does high body mass index (BMI) cause type 2 diabetes? Or are these traits simply correlated in the population for other reasons? The gold standard study design for answering this type of question is the randomized controlled trial, which requires identifying an intervention that influences the potential causal factor (for example a drug), randomly assigning individuals to receive the intervention, and monitoring outcomes. In this study design, the use of randomization allows one to isolate the causal effect of a single variable (e.g. the drug) from the effects of potential confounding variables. However ...