Performs biostatistical analyses specialized for clinical and biomedical research including survival analysis, Kaplan-Meier estimation, Cox proportional hazards regression, longitudinal data modeling, and diagnostic test evaluation; trigger when users discuss clinical outcomes, survival curves, or biomedical study statistics.
Performs biostatistical analyses specialized for clinical and biomedical research including survival analysis, Kaplan-Meier estimation, Cox proportional hazards regression, longitudinal data modeling, and diagnostic test evaluation; trigger when users discuss clinical outcomes, survival curves, or biomedical study statistics.
When to Trigger
Activate this skill when the user mentions:
Survival analysis, time-to-event, censoring
Kaplan-Meier curves, log-rank test, median survival
Cox regression, proportional hazards, hazard ratio
Sample size for clinical endpoints, multiplicity adjustment
Missing data in clinical studies, multiple imputation, MCAR/MAR/MNAR
Step-by-Step Methodology
Study design assessment - Confirm study type (cohort, case-control, cross-sectional, RCT). Identify primary endpoint type (continuous, binary, time-to-event, count, ordinal). Determine if data is clustered or longitudinal.
Survival analysis - Define time origin, event definition, and censoring mechanism. Verify censoring is non-informative. Estimate survival curves with Kaplan-Meier method. Compare groups with log-rank test (or weighted variants: Wilcoxon, Tarone-Ware for non-proportional hazards).
Cox regression - Check proportional hazards assumption (Schoenfeld residuals, log-log plots). If violated, use time-varying coefficients, stratified Cox, or restricted mean survival time (RMST). Report hazard ratios with 95% CIs. Handle multiple covariates with purposeful selection or penalized regression.
Competing risks - When multiple event types exist, use cumulative incidence functions (not 1-KM). Apply Fine-Gray subdistribution hazard model or cause-specific hazard models. Report cumulative incidence at clinically relevant timepoints.
Longitudinal analysis - For repeated measures: linear or generalized mixed-effects models (random intercepts/slopes). Choose appropriate correlation structure. Handle dropout with pattern mixture models or joint models for longitudinal and survival data.
Diagnostic test evaluation - Compute sensitivity, specificity, PPV, NPV at defined cutoffs. Generate ROC curve and compute AUC with DeLong confidence intervals. For biomarker discovery, apply cross-validation to avoid overoptimism.
Missing data handling - Classify missingness mechanism (MCAR, MAR, MNAR). For MAR: multiple imputation (m >= 20 imputations, Rubin's rules for pooling). Conduct sensitivity analysis under MNAR assumptions.
Key Databases and Tools
R survival / survminer - Survival analysis packages
SAS PROC PHREG / LIFETEST - Clinical biostatistics standard
STATA stcox / stcurve - Survival modeling
R mice / Amelia - Multiple imputation
pROC / cutpointr - ROC analysis
Output Format
Kaplan-Meier curves with number-at-risk table, median survival with 95% CI.
Cox model results as a table: variable, HR, 95% CI, p-value, with PH assumption test.
Cumulative incidence curves for competing risks with event-specific estimates.
ROC curves with AUC, optimal cutpoint, and sensitivity/specificity at that point.
Missing data report: pattern, mechanism assessment, imputation method, sensitivity results.
Quality Checklist
Time origin and event definition clearly specified
Censoring mechanism described and non-informative assumption justified
Proportional hazards assumption tested and result reported
