A Note on the Estimation of Confidence Intervals for Cost-Effectiveness When Costs and Effects Are Censored

BACKGROUND: The relation between methodological advances in estimation of confidence intervals (CIs) for incremental cost-effectiveness ratios (ICER) and estimation of cost effectiveness in the presence of censoring has not been explored. The authors address the joint problem of estimating ICER precision in the presence of censoring. METHODS: Using patient-level data (n = 168) on cost and survival from a published placebo-controlled trial, the authors compared 2 methods of measuring uncertainty with censored data: 1) Bootstrap with censor adjustment (BCA); 2) Fieller's method with censor adjustment (FCA). The authors estimate the FCA over all possible values for the correlation (rho) between costs and effects (range = -1 to + 1) and also examine the use of the correlation between cases without censoring adjustment (i.e., simple time-on-study) for costs and effects as an approximation for rho. RESULTS: Using time-on-study, which considers all censored observations as responders (deaths), yields 0.64 life-years gained at an additional cost of 87.9 for a cost per life-year of 137 (95% CI by bootstrap -5.9 to 392). Censoring adjustment corrects for the bias in the time-on-study approach and reduces the cost per life-year estimate to 132 (=72/0.54). Confidence intervals with censor adjustment were approximately 40% wider than the base-case without adjustment. Using the Fieller method with an approximation of rho based on the uncensored cost and effect correlation provides a 95% CI of (-48 to 529), which is very close to the BCA interval of (-52 to 504). CONCLUSIONS: Adjustment for censoring is necessary in cost-effectiveness studies to obtain unbiased estimates of ICER with appropriate uncertainty limits. In this study, BCA and FCA methods, the latter with approximated covariance, are simple to compute and give similar confidence intervals.