Calibration of quality-adjusted life years (QALYs) for oncology clinical trials (OCT).

Abstract

6108 Background: Quality-adjusted life year (QALY) estimation is a well-known but little-used technique to compare survival adjusted for complications in OCT. Lack of calibration and interpretation guidance hinder implementation of QALY analyses. Methods: We conducted simulation studies to assess the impact of differences in survival, toxicity rates and utility value on QALY results. Survival comparisons used both log-rank and Wilcoxon testing. We examined power considerations for an NCCTG phase III lung cancer clinical trial (89-20-52). Results: Sample sizes of 100 events evaluable for survival per treatment have low power to generate a statistically significant difference in QALYs unless the toxicity rate is 65% higher in one arm. For sample sizes of 200/arm and equal survival time, toxicity would have to be at least 50% more in one treatment arm for the result to be statistically significant, using a utility of 0.5 for days with toxicity (see Table). Sample sizes of 300 (500)/arm provided 80% power if there is a 40% (33%) toxicity difference. If the overall survival hazard ratio between the two treatment arms is 1.25, then samples of at least 150 pts and 20% increased toxicity are necessary to have 80% power to detect QALY differences. In 89-20-52 there was only 56% power to detect the observed QALY differences, clarifying the enigmatic conclusion of no statistically significant difference in QALY despite an observed 14.5% increase in toxicity between treatments. Conclusions: This calibration analysis allows researchers to interpret the clinical significance of QALY analyses and will facilitate QALY inclusion in OCTs through improved study design. Funded by NCI grant CA25224. Power for QALY test of equality for utility = 0.5 with varying hazard ratios and differences in toxicity rates N HR = 1.00 HR = 1.25 Difference in percent of days with toxicity 20% 40% 60% 10% 20% 30% 50 9 21 46 27 37 50 100 12 38 75 48 65 78 150 16 52 90 68 83 92 200 20 65 97 79 91 98 300 27 81 100 92 98 100 500 41 96 100 99 100 100 1,000 70 100 100 100 100 100 No significant financial relationships to disclose.