Comparison of transradial versus transfemoral percutaneous coronary intervention in routine practice: Evidence for the importance of 'falsification hypotheses' in observational studies of comparative effectiveness

摘要

To the Editor: There has been growing interest in the use of the transradial approach for percutaneous coronary intervention (PCI), supported by randomized clinical trials involving experienced transradial operators (1,2). However, the assessment of transradial PCI in routine practice has necessarily relied on observational comparisons (3), which may be susceptible to confounding even with modern statistical methods. In any observational study, there is always the possibility that unmeasured confounders bias the intended comparison regardless of the statistical approach used, including the use of advanced multivariable modeling or propensity score methods. Also, observational methods are limited in their inability to demonstrate causality.Recently, the use of "falsification endpoints" has been highlighted as an underutilized method to assess for residual confounding in observational studies (4). A "falsification hypothesis" is a claim, distinct from the main hypothesis being tested, that researchers believe is highly unlikely to be causally related to the intervention under study, similar to a "negative" control experiment in a laboratory. Most observational studies, including those focused on this clinical question (3), have not reported falsification endpoints. Despite the common parlance of the word "falsification," the term ?"falsification endpoints" or "falsification hypothesis" does not imply data falsification or attempts on the part of the investigators to mislead the reader. Rather, these endpoints are intended to test, within a single study, whether significant associations between a treatment and outcome are susceptible to residual confounding.