Choose candidate variables from subject-matter knowledge, measurement quality and the target question before screening on outcomes. For an adjusted-effect analysis, retain prespecified confounders and essential design variables even when their individual values are large. For prediction, consider reliable predictors available at the intended prediction time; do not include future information. Handle missingness transparently, using a justified multiple imputation strategy where appropriate rather than changing the analyzed population unpredictably as variables enter.
Encode a categorical variable with indicators relative to a stated reference category, and assess it as a group. Check multicollinearity, sparse categories and plausible interactions. The relevant information is chiefly the number and distribution of events, not merely the number of enrolled subjects: hundreds of correlated or rarely varying predictors cannot be supported by a small event count.
Compare prespecified nested models by a likelihood-ratio test based on the partial log-likelihood and the change in parameter dimension. Penalized methods such as ridge regression or Lasso regression applied to the Cox likelihood can stabilize many-variable models; choose tuning by suitable validation and account for mandatory variables. The Akaike information criterion or a limited, documented model-selection procedure can help balance fit and complexity. Unrestricted stepwise searches and repeated univariable screening invite unstable choices, omit joint confounding effects, and make naive post-selection intervals misleading. Prefer a defensible, validated covariate set to a collection chosen only for small values.
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