Effects of cohort selection on the results of cost-effectiveness analysis of disease-modifying drugs for relapsing-remitting multiple sclerosis.

BACKGROUND Decision-analytic cost-effectiveness models are used to determine the most cost-effective treatment option on the basis of the best available data. Guidelines for pharmacoeconomic model development indicate that models should be updated as new evidence becomes available. OBJECTIVE To evaluate the appropriateness of the clinical data that were selected for Goldberg et al.'s 2009 model of cost-effectiveness in multiple sclerosis and calculate results based on a revised cohort selection method for intramuscular (IM) interferon (IFN) beta-1a. METHODS The original model compared cost per relapse avoided for IM IFN beta-1a, subcutaneous (SC) IFN beta-1a, IFN beta-1b, and glatiramer acetate (GA) based on intent-to-treat (ITT) results from clinical trials. However, due to lower-than-expected subject dropout rates, the IM IFN beta-1a trial had sufficient statistical power to be terminated early and was subsequently found to have met its primary endpoint, time to sustained 1.0-point Expanded Disability Status Scale progression. Within the "all-patient"(ITT) cohort (n=301), approximately 43% of patients were followed for less than 2 years; 172 patients were followed for 2 years or more. In contrast, the proportions of patients followed for at least 2 years in the clinical trials of IFN beta-1b, SC IFN beta-1a, and GA were 92%, 90%, and 86%, respectively. To test the impact of data selection on the cost-effectiveness model results, we recreated the original model using both the all-patient and 2-year cohorts from the IM IFN beta-1a pivotal trial. We then compared our results with those of the original model. RESULTS In the original model, costs per relapse avoided were $141,721 for IM IFN beta-1a, $80,589 for SC IFN beta-1a, $87,061 for SC IFN beta-1b, and $88,310 for GA. In the reanalysis using the 2-year completer data for IM IFN beta-1a, costs per relapse avoided were $77,980 for IM IFN beta-1a, $80,121 for SC IFN beta-1a, $86,572 for IFN beta-1b, and $87,767 for GA. The cost per relapse avoided for IM IFN beta-1a was approximately 45% lower than in the original analysis, whereas the recreated results for the other 3 therapies differed from the original results by less than 1%. Sensitivity analyses showed that the recreated model was robust and that the rank order of cost-effectiveness results was unaffected by changes to any univariate parameter. CONCLUSIONS The current study highlights the importance of data selection in cost-effectiveness analyses. After limiting the pivotal trial data for IM IFN beta-1a to patients followed for at least 2 years, we found that IM IFN beta-1a was more cost-effective than in the original analysis, while results for the other first-line disease-modifying drugs remained stable.