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

cost-effectiveness analysis
systematic review
Authors

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.

Published

Feb 2016

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 >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

BibTeX 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.}
}
For attribution, please cite this work as:
Crathorne, L., Huxley, N., Haasova, M., Snowsill, T., Jones-Hughes, T., Hoyle, M., Briscoe, S., et al. 2016. “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.” Health Technology Assessment 20 (13). https://doi.org/10.3310/hta20130.