Sequential knockoffs for continuous and categorical predictors: With application to a large psoriatic arthritis clinical trial pool

Stat Med. 2021 Jun 30;40(14):3313-3328. doi: 10.1002/sim.8955. Epub 2021 Apr 25.

Abstract

Knockoffs provide a general framework for controlling the false discovery rate when performing variable selection. Much of the Knockoffs literature focuses on theoretical challenges and we recognize a need for bringing some of the current ideas into practice. In this paper we propose a sequential algorithm for generating knockoffs when underlying data consists of both continuous and categorical (factor) variables. Further, we present a heuristic multiple knockoffs approach that offers a practical assessment of how robust the knockoff selection process is for a given dataset. We conduct extensive simulations to validate performance of the proposed methodology. Finally, we demonstrate the utility of the methods on a large clinical data pool of more than 2000 patients with psoriatic arthritis evaluated in four clinical trials with an IL-17A inhibitor, secukinumab (Cosentyx), where we determine prognostic factors of a well established clinical outcome. The analyses presented in this paper could provide a wide range of applications to commonly encountered datasets in medical practice and other fields where variable selection is of particular interest.

Keywords: false discovery rate; knockoff filter; psoriatic arthritis; sequential knockoffs; variable selection.

MeSH terms

  • Algorithms
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Arthritis, Psoriatic* / drug therapy
  • Clinical Trials as Topic
  • Data Analysis
  • Humans

Substances

  • Antibodies, Monoclonal, Humanized
  • secukinumab