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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
#MMPMID26907163
Crathorne L
; Huxley N
; Haasova M
; Snowsill T
; Jones-Hughes T
; Hoyle M
; Briscoe S
; Coelho H
; Long L
; Medina-Lara A
; Mujica-Mota R
; Napier M
; Hyde C
Health Technol Assess
2016[Feb]; 20
(13
): 1-588, v-vi
PMID26907163
show ga
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 £ 19,429 to
£ 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.
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