Single-arm Trials With External Comparators and Confounder Misclassification: How Adjustment Can Fail.

ABSTRACT:

Background

"Single-arm trials" with external comparators that contrast outcomes in those on experimental therapy to real-world patients have been used to evaluate efficacy and safety of experimental drugs in rare and severe diseases. Regulatory agencies are considering expanding the role these studies can play; guidance thus far has explicitly considered outcome misclassification with little discussion of misclassification of confounding variables.

Objectives

This work uses causal diagrams to illustrate how adjustment for a misclassified confounder can result in estimates farther from the truth than ignoring it completely. This theory is augmented with quantitative examples using plausible values for misclassification of smoking in real-world pharmaceutical claims data. A to

SUBMITTER: Webster-Clark M 

PROVIDER: S-EPMC7665993 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature