Two-Phase Sampling Designs and Analysis Approaches for Ordinal Outcomes
Modern clinical trials and cohort studies gather low-cost data on all participants but may have limited resources to assess expensive exposures such as biomarkers or genomic data. When interest lies in associations involving expensive exposures, two-phase designs provide a cost-effective framework by using information available on all participants to guide the targeted selection of a subset for additional measurements. We extend this framework to studies with ordinal outcomes, a common yet previously unexplored setting. We propose three outcome-informed phase 2 sampling designs -- outcome-dependent sampling (ODS), covariate-stratified ODS, and residual-dependent sampling -- that leverage phase 1 data to enrich phase 2 selection with informative subjects. We then develop analysis methods for valid and efficient estimation/inference, including conditional likelihood methods with ascertainment-corrected maximum likelihood estimation, multiple imputation, and a full likelihood method using sieve maximum likelihood estimation. Across a range of scenarios, simulation studies show that the proposed methods substantially improve efficiency over simple random sampling with standard maximum likelihood estimation. We further demonstrate their practical utility by examining the association between interleukin-6 and a four-level clinical status outcome -- discharged, hospitalized but not in the ICU, hospitalized in the ICU, and death -- 14 days after randomization into the Crystalloid Liberal or Vasopressors Early Resuscitation in Sepsis trial.