Methods for Evaluating Causality in Observational Studies

Abstract

Background: In clinical medical research, causality is demonstrated b controlled trials (RCTs). Often, however, an RCT cannot be conducted for ethical reasons, and sometimes for practical reasons as well. In such cases, knowledge can be derived from an observational study instead. In this article, we present two methods that have not been widely used in medical research to date.

Methods: The methods of assessing causal inferences in observational studies are described on the basis of publications retrieved by a selective literature search.

Results: Two relatively new approaches-regression-discontinuity methods and interrupted time series-can be used to demonstrate a causal relationship under certain circumstances. The regression-discontinuity design is a quasi-experimental approach that can be applied if a continuous assignment variable is used with a threshold value. Patients are assigned to different treatment schemes on the basis of the threshold value. For assignment variables that are subject to random measurement error, it is assumed that, in a small interval around a threshold value, e.g., cholesterol values of 160 mg/dL, subjects are assigned essentially at random to one of two treatment groups. If patients with a value above the threshold are given a certain treatment, those with values below the threshold can serve as control group. Interrupted time series are a special type of regression-discontinuity design in which time is the assignment variable, and the threshold is a cutoff point. This is often an external event, such as the imposition of a smoking ban. A before-and-after comparison can be used to determine the effect of the intervention (e.g., the smoking ban) on health parameters such as the frequency of cardiovascular disease.

Conclusion: The approaches described here can be used to derive causal inferences ies. They should only be applied after the prerequisites for their use have been carefully checked.

Figure 1

Age-standardized hospitalization rates for acute coronary events (ACE) in persons under age 70 before and after the implementation of a smoking ban in public places in Italy, studied with the corresponding methods (30). The observed and predicted rates are shown (circles and solid lines, respectively). The dashed lines show the seasonally adjusted trend in ACE before and after the introduction of the nationwide smoking ban.

Figure 2

The effect of a smoking ban on the incidence of cardiovascular diseases