The National Institute for Health and Care Excellence (NICE) invited Pfizer, the manufacturer of inotuzumab ozogamacin (henceforth inotuzumab), to submit clinical and cost-effectiveness evidence for inotuzumab, as part of NICE’s Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned as the independent Evidence Review Group (ERG). The clinical effectiveness data were from a multicentre randomised controlled trial which compared inotuzumab to standard of care (SoC), where SoC was the investigator’s choice of chemotherapy. Inotuzumab demonstrated statistically significant improvements in the rates of response or in the proportion of patients progressing to haematopoietic stem cell transplant (HSCT), but failed to meet the second primary objective of longer overall survival. Treatment-emergent adverse events were more frequent in the SoC arm with the exception of veno-occlusive disease which was more frequent in the inotuzumab arm. The company’s economic model split patients into three post-hoc subgroups and used a partitioned survival approach within each group with a cure assumption three years after receipt of HSCT. In contrast to the trial results, the economic model estimated substantial improvement in survival with inotuzumab compared to SoC, providing an additional 5.2 life years and 2.2 quality-adjusted life years (QALYs) using a discount rate of 1.5% per annum. The ERG’s critique highlighted a number of concerns, including: the use of a post-hoc post-randomisation patient subset for extrapolation; the choice of a 1.5% discount rate; the complexity of the parametric modelling; the assumption of further treatment benefit post-HSCT; the nature of the cure assumption; and the length of inpatient stay during receipt of treatment. The combination of the ERG’s adjustments resulted in an incremental cost-effectiveness ratio (ICER) of £122,174 per QALY gained using Kaplan-Meier survival estimates, and £114,078 per QALY gained with parametric survival models fit to the trial data. The final determination of the appraisal followed four NICE Appraisal Committee meetings, an appeal by the company and other stakeholders, two patient access schemes and a company response to each appraisal consultation. The final ICER post-consultation was between £33,749 and £37,497 per QALY gained compared to SoC (excluding the confidential discount for blinatumomab received as subsequent therapy). The Appraisal Committee concluded that the ICER for inotuzumab was within the range usually considered cost-effective for end-of-life care, and recommended inotuzumab within its licensed indication.
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