The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model
BACKGROUND: Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE: To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES: The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS: The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS: Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed indication (based on start dose administered) were included in the review. None of the RCTs were completely aligned with current European Union licenses. The results suggest a clinical benefit from ESAs for anaemia-related outcomes and an improvement in HRQoL scores. The impact of ESAs on AEs and survival remains highly uncertain, although point estimates are lower, confidence intervals are wide and not statistically significant. Base-case incremental cost-effectiveness ratios (ICERs) for ESA treatment compared with no ESA treatment ranged from pound 19,429 to pound 35,018 per QALY gained, but sensitivity and scenario analyses demonstrate considerable uncertainty in these ICERs, including the possibility of overall health disbenefit. All ICERs were sensitive to survival and cost. LIMITATIONS: The relative effectiveness of ESAs was not addressed; all ESAs were assumed to have equivalent efficacy. No studies were completely aligned with their European labelling beyond the starting dose evaluated. There is questionable generalisability given that the included trials were published >20 years ago and there have been many changes to chemotherapy as well as to the quality of supportive treatment. Trial quality was moderate or poor and there was considerable unexplained heterogeneity for a number of outcomes, particularly survival, and evidence of publication bias. Adjustments were not made to account for multiple testing. CONCLUSIONS: ESAs could be cost-effective when used closer to licence, but there is considerable uncertainty, mainly because of unknown impacts on overall survival. STUDY REGISTRATION: This study is registered as PROSPERO CRD42013005812. FUNDING: The National Institute for Health Research Health Technology Assessment programme.
Citation
@article{l.2016,
author = {Crathorne, L. and Huxley, N. and Haasova, M. and Snowsill,
T. and Jones-Hughes, T. and Hoyle, M. and Briscoe, S. and Coelho, H.
and Long, L. and Medina-Lara, A. and Mujica-Mota, R. and Napier, M.
and Hyde, C.},
title = {The Effectiveness and Cost-Effectiveness of
Erythropoiesis-Stimulating Agents (Epoetin and Darbepoetin) for
Treating Cancer Treatment-Induced Anaemia (Including Review of
Technology Appraisal No. 142): A Systematic Review and Economic
Model},
journal = {Health Technology Assessment},
volume = {20},
number = {13},
date = {2016-02-01},
url = {https://tristansnowsill.co.uk/the-effectiveness-and-cost-effectiveness-of-erythropoiesis.html},
doi = {10.3310/hta20130},
langid = {en},
abstract = {BACKGROUND: Anaemia is a common side effect of cancer
treatments and can lead to a reduction in quality of life.
Erythropoiesis-stimulating agents (ESAs) are licensed for use in
conjunction with red blood cell transfusions to improve cancer
treatment-induced anaemia (CIA). OBJECTIVE: To investigate the
effectiveness and cost-effectiveness of ESAs in anaemia associated
with cancer treatment (specifically chemotherapy). DATA SOURCES: The
following databases were searched from 2004 to 2013: The Cochrane
Library, MEDLINE, MEDLINE In-Process \& Other Non-Indexed Citations,
EMBASE, Web of Science, Cumulative Index to Nursing and Allied
Health Literature, British Nursing Index, Health Management
Information Consortium, Current Controlled Trials and
ClinicalTrials.gov. The US Food and Drug Administration and European
Medicines Agency websites were also searched. Bibliographies of
included papers were scrutinised for further potentially includable
studies. REVIEW METHODS: The clinical effectiveness review followed
principles published by the NHS Centre for Reviews and
Dissemination. Randomised controlled trials (RCTs), or systematic
reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating
people with CIA were eligible for inclusion in the review.
Comparators were best supportive care, placebo or other ESAs.
Anaemia- and malignancy-related outcomes, health-related quality of
life (HRQoL) and adverse events (AEs) were evaluated. When
appropriate, data were pooled using meta-analysis. An empirical
health economic model was developed comparing ESA treatment with no
ESA treatment. The model comprised two components: one evaluating
short-term costs and quality-adjusted life-years (QALYs) (while
patients are anaemic) and one evaluating long-term QALYs. Costs and
benefits were discounted at 3.5\% per annum. Probabilistic and
univariate deterministic sensitivity analyses were performed.
RESULTS: Of 1457 titles and abstracts screened, 23 studies assessing
ESAs within their licensed indication (based on start dose
administered) were included in the review. None of the RCTs were
completely aligned with current European Union licenses. The results
suggest a clinical benefit from ESAs for anaemia-related outcomes
and an improvement in HRQoL scores. The impact of ESAs on AEs and
survival remains highly uncertain, although point estimates are
lower, confidence intervals are wide and not statistically
significant. Base-case incremental cost-effectiveness ratios (ICERs)
for ESA treatment compared with no ESA treatment ranged from pound
19,429 to pound 35,018 per QALY gained, but sensitivity and scenario
analyses demonstrate considerable uncertainty in these ICERs,
including the possibility of overall health disbenefit. All ICERs
were sensitive to survival and cost. LIMITATIONS: The relative
effectiveness of ESAs was not addressed; all ESAs were assumed to
have equivalent efficacy. No studies were completely aligned with
their European labelling beyond the starting dose evaluated. There
is questionable generalisability given that the included trials were
published \textgreater20 years ago and there have been many changes
to chemotherapy as well as to the quality of supportive treatment.
Trial quality was moderate or poor and there was considerable
unexplained heterogeneity for a number of outcomes, particularly
survival, and evidence of publication bias. Adjustments were not
made to account for multiple testing. CONCLUSIONS: ESAs could be
cost-effective when used closer to licence, but there is
considerable uncertainty, mainly because of unknown impacts on
overall survival. STUDY REGISTRATION: This study is registered as
PROSPERO CRD42013005812. FUNDING: The National Institute for Health
Research Health Technology Assessment programme.}
}