Understanding variation in the results of real-world evidence studies that seem to address the same question.

OBJECTIVES

Multiple database studies on the same question, conducted by different investigators using different approaches or different data sources, can be considered sensitivity analyses for the same causal treatment effect question. We evaluated the contribution of alternative study design parameters and analysis choices to variation in estimates of the risk of major bleeding with dabigatran compared with warfarin.

STUDY DESIGN AND SETTING

We followed a 7-step process: (1) identify published studies asking the same question, (2) independently reproduce selected studies in the same data sources as the original authors, (3) contact original authors, (4) evaluate validity, (5) document critical study parameter specifications, (6) implement a designed matrix of variations in study parameters based on the original studies, and (7) evaluate contributors to variation in results.

RESULTS

Most variation remained unexplained (60-88%). Of the explained variation, two-thirds were related to data and population differences, and one-third were related to the use of alternative study design and analysis parameters. Among these, the most prominent were differences in outcome algorithms and criteria used to define follow-up.

CONCLUSION

When making policy decisions based on database study findings, it is important to evaluate the validity, consistency, and robustness of results to alternative design and analysis decisions.