A note on the estimation of confidence intervals for cost-effectiveness when costs and effects are censored

<i>Background</i>. 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. <i>Methods</i>. 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 (p) 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. <i>Results</i>. 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 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). <i>Conclusions</i>. 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

Thinking outside the box: recent advances in the analysis and presentation of uncertainty in cost-effectiveness studies

As many more clinical trials collect economic information within their study design, so health economics analysts are increasingly working with patient-level data on both costs and effects. In this paper, we review recent advances in the use of statistical methods for economic analysis of information collected alongside clinical trials. In particular, we focus on the handling and presentation of uncertainty, including the importance of estimation rather than hypothesis testing, the use of the net-benefit statistic, and the presentation of cost-effectiveness acceptability curves. We also discuss the appropriate sample size calculations for cost-effectiveness analysis at the design stage of a study. Finally, we outline some of the challenges for future research in this area—particularly in relation to the appropriate use of Bayesian methods and methods for analyzing costs that are typically skewed and often incomplete

Probabilistic analysis of cost-effectiveness models: choosing between treatment strategies for gastroesophageal reflux disease

When choosing between mutually exclusive treatment options, it is common to construct a cost-effectiveness frontier on the cost-effectiveness plane that represents efficient points from among the treatment choices. Treatment options internal to the frontier are considered inefficient and are excluded either by strict dominance or by appealing to the principle of extended dominance. However, when uncertainty is considered, options excluded under the baseline analysis may form part of the cost-effectiveness frontier. By adopting a Bayesian approach, where distributions for model parameters are specified, uncertainty in the decision concerning which treatment option should be implemented is addressed directly. The approach is illustrated using an example from a recently published cost-effectiveness analysis of different possible treatment strategies for gastroesophageal reflux disease.It is argued that probabilistic analyses should be encouraged because they have potential to quantify the strength of evidence in favor of particular treatment choices

Clinical and economic comparison of an individualised immunoglobulin protocol vs. standard dosing for chronic inflammatory demyelinating polyneuropathy

Background The clinical and economic implications of an individualised intravenous immunoglobulin (IVIg) protocol for chronic inflammatory demyelinating polyneuropathy (CIDP) are unknown. Comparison with standard dosing regimens has not been performed. Methods We retrospectively studied 47 IVIg-treated subjects with CIDP over 4 years with an individualised, outcome-measured, dose-modifying protocol. We evaluated responder and remission rates, clinical improvement levels and dose requirements. We compared clinical benefits and costs with those reported with standard dosing at 1 g/kg every 3 weeks. Results The IVIg-responder rate was 83% and the 4-year remission rate was 25.6%. Mean IVIg dose requirements were 22.06 g/week (SD:15.29) in patients on ongoing therapy. Dose range was wide (5.83–80 g/week). Mean infusion frequency was every 4.34 weeks (SD:1.70) and infusion duration of 2.79 days (SD:1.15). Mean Overall Neuropathy Limitation Scale improvement was 2.54 (SD:1.89) and mean MRC sum score improvement of 12.23 (SD:7.17) in IVIg-responders. Mean modified-INCAT (Inflammatory Neuropathy Cause and Treatment) score improvement was similar (p = 0.47) and mean MRC sum score improvement greater (p < 0.001) in our cohort, compared to the IVIg-treated arm of the ICE Study. Mean drug costs were GBP 37,660/patient/year (€ 43,309) and mean infusion-related costs of GBP 17,115/patient/year (€ 19,682), totalling GBP 54,775/patient/year (€ 62,991). Compared to standard dosing using recorded weight, mean savings were of GBP 13,506/patient/year (€ 15,532). Compared to standard dosing using dosing weight, savings were of GBP 6,506/patient/year (€ 7,482). Conclusion Our results indicate that an individualised IVIg treatment protocol is clinically non-inferior and 10–25% more cost-effective than standard dosing regimens in CIDP