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.
Citation
@article{i.a.2017,
author = {Tikhonova, I. A. and Hoyle, M. W. and Snowsill, T. M. and
Cooper, C. and Varley-Campbell, J. L. and Rudin, C. E. and Mujica
Mota, R. E.},
title = {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}},
journal = {PharmacoEconomics},
volume = {35},
number = {3},
pages = {363-373},
date = {2017},
url = {https://tristansnowsill.co.uk/azacitidine-for-treating-acute-myeloid-leukaemia-with.html},
doi = {10.1007/s40273-016-0453-5},
langid = {en},
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.}
}