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The Clinical and Cost Effectiveness of Inotuzumab Ozogamicin for the Treatment of Adult Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia: An Evidence Review Group Evaluation of a NICE Single Technology Appraisal

  • Edward CoxEmail author
  • Ros Wade
  • Mathilde Peron
  • Kristina Charlotte Dietz
  • Alison Eastwood
  • Stephen Palmer
  • Susan Griffin
Review Article

Abstract

The National Institute for Health and Care Excellence (NICE) invited Pfizer, the manufacturer of inotuzumab ozogamicin (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 the Centre for Health Economics, both 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 that compared inotuzumab with standard of care (SoC), where SoC was the investigator’s choice of chemotherapy. Inotuzumab demonstrated statistically significant improvements in response rates 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, except 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 3 years after receiving HSCT. In contrast with the trial results, the economic model estimated substantial improvement in survival with inotuzumab compared with 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 while receiving 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 with 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.

Notes

Acknowledgements

The authors thank Dr. Nick Morley, Consultant Haematologist at Sheffield Teaching Hospitals NHS Foundation Trust, for reviewing the manuscript and for providing the ERG with clinical advice throughout the project. They also thank Melissa Harden, Centre for Reviews and Dissemination, who critiqued the literature searches in the company’s submission.

Author Contributions

EC, RW, MP, KCD, AE, SP and SG were all members of the ERG that produced the ERG report described in this paper. SP and AE took overall responsibility for the cost- and clinical-effectiveness parts of the project. EC wrote the draft of the manuscript. All authors commented on the manuscript and approved the final version. This summary was not externally reviewed by PharmacoEconomics.

Compliance with Ethical Standards

Funding

This study was funded by National Institute for Health Research (NIHR) Health Technology Assessment (HTA) programme (project number 16/10/02). The views and opinions expressed herein are those of the authors and do not necessarily reflect those of NICE or the Department of Health.

Conflict of interest

Edward Cox, Ros Wade, Mathilde Peron, Kristina Charlotte Dietz, Alison Eastwood, Stephen Palmer and Susan Griffin have no conflicts of interest that are directly relevant to the content of this article.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Centre for Health EconomicsUniversity of YorkYorkUK
  2. 2.Centre for Reviews and Dissemination (CRD)University of YorkYorkUK

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