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Azacitidine for treating acute myeloid leukaemia with more than 30 % bone marrow blasts: an Evidence Review Group perspective of a National Institute for Health and Care Excellence single technology appraisal

Azacitidine for treating acute myeloid leukaemia with more than 30 % bone marrow blasts: an Evidence Review Group perspective of a National Institute for Health and Care Excellence single technology appraisal
Azacitidine for treating acute myeloid leukaemia with more than 30 % bone marrow blasts: an Evidence Review Group perspective of a National Institute for Health and Care Excellence single technology appraisal

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE’s Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company’s submission to NICE. The clinical effectiveness data used in the company’s economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: “Remission”, “Non-remission”, “Relapse/Progressive disease” and “Death”. The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine compared with the CCR was £20,648 per quality-adjusted life-year (QALY) gained. In the probabilistic sensitivity analysis, the mean ICER was £17,423 per QALY. At the willingness-to-pay of £20,000, £30,000 and £50,000 per QALY, the probability of azacitidine being cost effective was 0.699, 0.908 and 0.996, respectively. The ERG identified a number of errors in Celgene’s model and concluded that the results of the company’s economic evaluation could not be considered robust. After amendments to Celgene’s model, the base-case ICER was £273,308 per QALY gained. In the probabilistic sensitivity analysis, the mean ICER was £277,123 per QALY. At a willingness-to-pay of £100,000 per QALY, the probability of azacitidine being cost effective was less than 5 %. In all exploratory analyses conducted by the ERG, the ICER exceeded the NICE’s cost-effectiveness threshold range of £20,000–30,000 per QALY. Given the evidence provided in the submission, azacitidine did not fulfil NICE’s end-of-life criteria. After considering the analyses performed by the ERG and submissions from clinician and patient experts, the NICE Appraisal Committee did not recommend azacitidine for this indication.

1170-7690
363-373
Tikhonova, Irina A.
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Hoyle, Martin W.
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Snowsill, Tristan M.
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Cooper, Chris
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Varley-Campbell, Joanna L.
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Rudin, Claudius E.
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Mujica Mota, Ruben E.
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Tikhonova, Irina A.
577ccbcc-6643-4190-bb6d-19e13b44bcd1
Hoyle, Martin W.
c45bff8b-b34d-4622-a09a-61d4af518969
Snowsill, Tristan M.
33dbf192-8a97-43ed-9317-538d41cf498f
Cooper, Chris
0d982dd3-1fab-40c3-95c9-2cdb0229d27e
Varley-Campbell, Joanna L.
0952839e-b1f4-4e45-b538-6dfc7936f259
Rudin, Claudius E.
e3d4c19f-6e52-457f-8a34-9ad85c5c1322
Mujica Mota, Ruben E.
f9f4bb4c-5245-45fc-ae9e-2cd2672a0fef

Tikhonova, Irina A., Hoyle, Martin W., Snowsill, Tristan M., Cooper, Chris, Varley-Campbell, Joanna L., Rudin, Claudius E. and Mujica Mota, Ruben E. (2017) Azacitidine for treating acute myeloid leukaemia with more than 30 % bone marrow blasts: an Evidence Review Group perspective of a National Institute for Health and Care Excellence single technology appraisal. PharmacoEconomics, 35 (3), 363-373. (doi:10.1007/s40273-016-0453-5).

Record type: Review

Abstract

The National Institute for Health and Care Excellence (NICE) invited the manufacturer of azacitidine (Celgene) to submit evidence for the clinical and cost effectiveness of this drug for the treatment of acute myeloid leukaemia with more than 30 % bone marrow blasts in adults who are not eligible for haematopoietic stem cell transplantation, as part of the NICE’s Single Technology Appraisal process. The Peninsula Technology Assessment Group was commissioned to act as the Evidence Review Group (ERG). The ERG produced a critical review of the evidence contained within the company’s submission to NICE. The clinical effectiveness data used in the company’s economic analysis were derived from a single randomised controlled trial, AZA-AML-001. It was an international, multicentre, controlled, phase III study with an open-label, parallel-group design conducted to determine the efficacy and safety of azacitidine against a conventional care regimen (CCR). The CCR was a composite comparator of acute myeloid leukaemia treatments currently available in the National Health Service: intensive chemotherapy followed by best supportive care (BSC) upon disease relapse or progression, non-intensive chemotherapy followed by BSC and BSC only. In AZA-AML-001, the primary endpoint was overall survival. Azacitidine appeared to be superior to the CCR, with median overall survival of 10.4 and 6.5 months, respectively. However, in the intention-to-treat analysis, the survival advantage associated with azacitidine was not statistically significant. The company submitted a de novo economic evaluation based on a partitioned survival model with four health states: “Remission”, “Non-remission”, “Relapse/Progressive disease” and “Death”. The model time horizon was 10 years. The perspective was the National Health Service and Personal Social Services. Costs and health effects were discounted at the rate of 3.5 % per year. The base-case incremental cost-effectiveness ratio (ICER) of azacitidine compared with the CCR was £20,648 per quality-adjusted life-year (QALY) gained. In the probabilistic sensitivity analysis, the mean ICER was £17,423 per QALY. At the willingness-to-pay of £20,000, £30,000 and £50,000 per QALY, the probability of azacitidine being cost effective was 0.699, 0.908 and 0.996, respectively. The ERG identified a number of errors in Celgene’s model and concluded that the results of the company’s economic evaluation could not be considered robust. After amendments to Celgene’s model, the base-case ICER was £273,308 per QALY gained. In the probabilistic sensitivity analysis, the mean ICER was £277,123 per QALY. At a willingness-to-pay of £100,000 per QALY, the probability of azacitidine being cost effective was less than 5 %. In all exploratory analyses conducted by the ERG, the ICER exceeded the NICE’s cost-effectiveness threshold range of £20,000–30,000 per QALY. Given the evidence provided in the submission, azacitidine did not fulfil NICE’s end-of-life criteria. After considering the analyses performed by the ERG and submissions from clinician and patient experts, the NICE Appraisal Committee did not recommend azacitidine for this indication.

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e-pub ahead of print date: 17 October 2016
Published date: March 2017

Identifiers

Local EPrints ID: 438197
URI: http://eprints.soton.ac.uk/id/eprint/438197
ISSN: 1170-7690
PURE UUID: ea5a1409-1b2c-4ce8-aaf8-934f5bbc13a4
ORCID for Irina A. Tikhonova: ORCID iD orcid.org/0000-0003-2723-0802

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Date deposited: 04 Mar 2020 17:30
Last modified: 17 Mar 2024 12:37

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Contributors

Author: Irina A. Tikhonova ORCID iD
Author: Martin W. Hoyle
Author: Tristan M. Snowsill
Author: Chris Cooper
Author: Joanna L. Varley-Campbell
Author: Claudius E. Rudin
Author: Ruben E. Mujica Mota

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