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A pharmacoepidemiological study of the multi-level determinants, predictors, and clinical outcomes of biosimilar epoetin alfa for renal anaemia in haemodialysis patients: background and methodology of the MONITOR-CKD5 study

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Abstract

Prior longitudinal observational studies have examined the practice patterns and outcomes of anaemia management, including the use of erythropoiesis-stimulating agents (ESAs). Several dimensions of effectiveness remain unaddressed; especially considering the revised ESA label (target Hb levels between 10 and 12 g/dL), the recently published TREAT study, and the European approval of the first ESA biosimilar (HX575). Anecdotal evidence suggests that patient outcomes are influenced by physician-related variables and whether anaemia management is congruent with practice guidelines, but this has not been studied systematically. MONITOR-CKD5 is an international, prospective, observational, pharmacoepidemiological study evaluating the multi-level factors and outcomes of treatment with HX575 for renal anaemia in haemodialysis patients. Driven by a novel, integrated, multi-focal framework for post-approval observational studies, it examines determinants of response at both the patient and the physician level; integrates an advocated statistical methodology here to fore used mainly in the social and behavioural sciences; assesses factors potentially predictive of a poor treatment response; and evaluates the extent to which treatment is congruent with evidence-based guidelines, good practice evidence, and the revised ESA label. This pan-European study will recruit at least 1,000 patients from a minimum of 75 centres, and follow them for up to 24 months following initiation of anaemia management with biosimilar epoetin alfa. MONITOR-CKD5 will not only study the core issues addressed by prior observational studies but also aims to take knowledge discovery a step further by assessing outcomes across varying cohorts of patients, and examining the impact of evidence-based practice on clinical outcomes, differentiating, in the process, between physician-level and patient-level determinants.

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Abbreviations

ANOVA:

Analysis of variance

CKD:

Chronic kidney disease

CKD5:

Chronic kidney disease stage 5

CRF:

Case report form

DOPPS:

Dialysis Outcomes and Practice Patterns Study

eCRF:

Electronic case report form

ESA:

Erythropoiesis-stimulating agent

ESAM:

European Survey on Anaemia Management

GFR:

Glomerular filtration rate

Hb:

Haemoglobin

HR:

Hazard ratio

MANOVA:

Multivariate analysis of variance

RCT:

Randomized controlled trial

RRT:

Renal replacement therapy

χ 2 :

Chi-squared

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Acknowledgments

The study is sponsored by research grants from Sandoz Biopharmaceuticals, a Novartis company, Holzkirchen, Germany. The authors thank Liam Smith for editorial, proofreading, and administrative assistance. Data will be analysed independently from the Sponsor, although the Sponsor will have the right of review and comment.

Conflict of interest

L. Gesualdo, G. London, D. Goldsmith, A. Covic, P. Zaoui, C. Combe, J. Mann, and F. Dellanna serve as consulting investigators to the MONITOR-CKD5 study. M. Turner and M. Muenzberg are employees of Sandoz Biopharmaceuticals. C. Lee, K. MacDonald, and I. Abraham are employees of Matrix45. By company policy, they are prohibited from owning equity in client organizations (except through mutual funds or other independently administered collective investment instruments) or contracting independently with client organizations. Matrix45 provides similar services for other biopharmaceutical companies.

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Authors and Affiliations

  1. Department of Nephrology, Università degli Studi di Bari, Bari, Italy

    Loreto Gesualdo

  2. Department of Nephrology and Hemodialysis, Centre Hospitalier F. H. Manhès, Fleury-Mérogis, France

    Gérard London

  3. Sandoz Biopharmaceuticals, Holzkirchen, Germany

    Matthew Turner & Michael Muenzberg

  4. Matrix45, 620 Frays Ridge Road, Earlysville, VA, 22936, USA

    Christopher Lee, Karen MacDonald & Ivo Abraham

  5. Center for Health Outcomes and Pharmaco-economic Research, College of Pharmacy, The University of Arizona, Tucson, AZ, USA

    Christopher Lee & Ivo Abraham

  6. King’s Health Partners, Guy’s and St Thomas’ NHS Foundation Hospital, London, UK

    David Goldsmith

  7. Dialysis and Transplantation Center, G. I. Popa University Hospital of Medicine and Pharmacy, Iasi, Romania

    Adrian Covic

  8. Centre Hospitalier Universitaire de Grenoble and Université de Grenoble, Grenoble, France

    Philippe Zaoui

  9. Department of Nephrology and INSERM U889, Centre Hospitalier de Bordeaux and Université de Bordeaux 2–Victor Segalen, Bordeaux, France

    Christian Combe

  10. Schwabing Klinikum and Friedrich Alexander Universität Erlangen-Nurnburg, Munich, Germany

    Johannes Mann

  11. Dialysezentrum, Duesseldorf, Germany

    Frank Dellanna

Authors
  1. Loreto Gesualdo
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  2. Gérard London
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  3. Matthew Turner
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  4. Christopher Lee
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  5. Karen MacDonald
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  6. David Goldsmith
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  7. Adrian Covic
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  8. Philippe Zaoui
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  9. Christian Combe
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  10. Johannes Mann
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  11. Frank Dellanna
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  12. Michael Muenzberg
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  13. Ivo Abraham
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Corresponding author

Correspondence to Ivo Abraham.

Additional information

Trial Registration:clinicaltrials.gov NCT01121237

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Gesualdo, L., London, G., Turner, M. et al. A pharmacoepidemiological study of the multi-level determinants, predictors, and clinical outcomes of biosimilar epoetin alfa for renal anaemia in haemodialysis patients: background and methodology of the MONITOR-CKD5 study. Intern Emerg Med 8, 389–399 (2013). https://doi.org/10.1007/s11739-011-0622-7

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  • DOI: https://doi.org/10.1007/s11739-011-0622-7

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