Principles of Valid Clinical Research

Abstract

In clinical studies, errors are usually categorized into systematic errors (bias, confounding) and random errors. Systematic errors are of particular concern because they lead to over- or under-estimation of effects. Bias is a systematic error that distorts the relationship between exposure and outcome. As a general rule, it is not possible to mathematically adjust for biases once they have been introduced. Confounding is a special case when the distorted relationship between cause and effect is caused by a third factor. Confounding can be neutralized using careful study design or statistical methods. Validity is the opposite of bias, and is usually divided into internal validity and external validity. A study is internally valid if the estimates drawn from the study population are free of confounding and bias. A study is externally valid if its results can be applied to a separate population. Internal validity is a prerequisite for external validity.