Ivo Abraham, PhD, RN

Professor of Pharmacy and Medicine
Director, Center for Health Outcomes and PharmacoEconomic Research
Member, Arizona Cancer Center
Affiliate Member, Center for Biomedical Informatics and Biostatistics
Member, Arizona Center on Aging

UACC Information

UACC Organizational Unit: 
Professional Bio: 

Dr. Abraham received the BS (Psychiatric Nursing; 1975-1979) from Leuven University College (Leuven, Belgium), followed by the MS (Psychiatric-Mental Health Nursing; 1979-1982) and the PhD (Clinical Research; 1980-1984) from the University of Michigan (Ann Arbor, MI). He also completed execuctive education programs in Pharmaceutical Medicine (2001-2003) at the University of Basel (Basel, Switzerland), and in Entrepreneurship and Innovation in the Life Sciences (2011-2012) at the Vlerick Business School (Leuven/Gent, Belgium).

Dr. Abraham has served on the faculty of Case Western Reserve University (Cleveland, OH), University of Virginia (Charlottesville, VA), and (part-time) Katholieke Universiteit Leuven (Leuven, Belgium); and as visiting professor at Universiteit Maastricht (Maastricht, The Netherlands), University of Florida (Gainesville, FL), Rijksuniversiteit Groningen (Groningen, The Netherlands), University of Pennsylvania (Philadelphia, PA), and Chang Gung University (Kwei-Shan Tao-Yuan, Taiwan). He came to the University of Arizona on a part-time basis in 2007, joining the faculty on a full-time basis in late 2012.

Dr. Abraham's research and innovation work has been funded continuously since 1984 by governmental agencies, foundations, and corporations worldwide. He has served in the US as appointed and ad hoc reviewer for the NIH, the NIMH, and the AHRQ; in Europe for EU health research funding programs; and in Japan, The Netherlands, and Catalunya (Spain) for national health research funding agencies. He currently serves as expert adviser to the Innovative Medicines Initiative, a joint undertaking of the European Union and the biopharmaceutical industry to stimulate innovation in human therapeutics.

As a clinically trained research methodologist specialized in clinical and economic outcomes and effectiveness research, Dr. Abraham's work over the past 30+ years has focused on interventions across the full spectrum from singular molecules to models of care (m2m) at both the patient and population levels (p2p) and moving from empirics into evidence (e2e). More generally, his work has focused on the three areas of (1) models, systems, processes, patterns, and outcomes of care, (2) chronic illness, and (3) the development and adaptation of research methods and analytics from the social, behavioral, and life sciences for health research. In this work, He has focused on complementing conventional methods and analytics in the health sciences with those from the social, behavioral, and life sciences.

Dr. Abraham has been funded continuously for the past 31 years by US agencies (NIH, NIMH, NIA, HRSA), European and Asian governmental funding agencies, US foundations, and global corporations; and has served as appointed or ad hoc reviewer for US, EU, and Japanese funding agencies, among others. While, as a methodologist, his studies have ranged across disease, populations, and therapeutic domains, he has served as PI/CoPI on 30+ cancer-related (tumor control and supportive care) studies that have incorporated clinical, economic, and/or patient-centered outcomes.

Dr. Abraham has (co)sponsored several predocs, postdocs, and junior and mid-career faculty for career development awards; and current support directly 4 predoctoral and 10 postdoctoral fellows in his programs on Clinical Research in Human Therapeutics and Outcomes and Comparative Effectiveness. He has (co)founded two academic research centers and four private research enterprises; and currently lead the Center for Health Outcomes and PharmacoEconomic Research, Arizona Board of Regents Center of Excellence.

Research Information

Research Program: 
Cancer Prevention and Control
Member Status: 
Associate Research Member
Year of Membership Acceptance: 
2014
Summary of Research Activity: 

Ivo Abraham, PhD, RN, a nurse by profession and an outcomes and effectiveness researcher by trade, is a clinician-methodologist interested in of how variations in treatments, from molecules to models of care, are associated with variations in clinical, patient-centric, and economic outcomes at the patient and population levels. As a methodologist, his work spans several therapeutic domains, however all tied together by common methodological and analytical threads – often drawing upon those from disciplines other than the health sciences. A large part of his work has been in supportive and curative cancer care, spanning both solid and hematological malignancies.

For the past 15+ years, Dr. Abraham’s research has focused mainly on “real-world evidence” on how variability in (drug-centric) treatment regimens is associated with variability in clinical and patient-centric outcomes – including how this translates into economic outcomes. Instead of merely evaluating effectiveness (“does the treatment work?”), the work of his research group addresses the equally important questions of “when does the treatment work, when not, and why?”, “what influences whether the treatment works, what not, and why?”, “why does the treatment work in some patients but not in others, and why?”, “why does the treatment work with some clinicians but not with others, and why?”, “why is the treatment tolerated by some patients but not by others?”, “how much of patient outcomes is related to patient vs. clinician or treatment center, and why” – and, eventually, “is this economically worth it and sustainable, and why or why not?”  In this process, his group uses a comprehensive framework of treatment patterns and outcomes assessment, vulnerability profiling, hierarchical modeling, (non-)responder analysis, pharmacovigilance, and economic evaluation. By integrating methods and analytics from other disciplines, his group also tries to establish alternate pathways of inferring causality.

Taking a scientific rather than polemic tack, he has been the scientific lead on several international real-world studies on the clinical and economic outcomes of supportive cancer care with growth factors (erythropoiesis-stimulating agents and granulocyte-colony stimulating factors). Working initially in Europe but now also in the US, this work has since extended into the clinical effectiveness and safety of biosimilar versions of originator growth factors, as patents for these products are expiring. His group was the first to demonstrate the economic benefits that can achieved by using quality biosimilars; and, importantly, how the cost savings associated with biosimilar use can be reallocated to purchase more curative cancer care (e.g., with targeted agents) in a budget-neutral fashion.

Another area of impact research concerns patient adherence to oral anticancer agents. Non-adherence to these agents in general, this group demonstrated that, despite the high efficacy of imatinib in the management of chronic myeloid leukemia, (a perhaps surprising) one-third of patients admitted to occasional non-adherence. Importantly, this group was able to associate non-adherence, as measured by pill count, with incomplete cytogenetic response and (composite) suboptimal response. The group is now looking into mathematically modeling gradients of medication adherence and the probability of achieving hematological, cytogenetic, and molecular response. In an effort to support clinical practice, the group is also examining whether a single-item query or rating of adherence might predict treatment response.

On the economic side, and in addition to its work on biosimilar savings, his group is examining new concepts and methods for the economic evaluation of increasingly more costly cancer treatments. They aim to abandon the limitations of absolute or quality-adjusted gains survival benefits and the use of non-empirical value thresholds for treatment and reimbursement decisions. 

Frustrated by the abundance of evidence-based guidelines but clinicians’ limited adoption of these guidelines, his group has started examining how practicing in accordance with evidence-based guidelines is directly associated with patient outcomes. This line of work involves the development of methods for quantifying patient-level guideline-congruent care and ways of associating these with clinical outcomes. Relatedly, though an early advocate of meta-analytic methods, Dr. Abraham has become concerned about imputed biases that cannot be detected by currently available methods, especially as they relate to scope specification, interpretation, and (polemic or economic rather than scientific) positions.

Selected Publications: 
  1. Gharaibeh M, McBride A, Bootman L, Abraham I. Economic evaluation for the UK of nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreas cancer. British Journal of Cancer, 2015;112:1301-1305.
  2. Sun D, Andayani TM, Altyar A, MacDonald K, Abraham I. Potential cost savings from chemotherapy-induced febrile neutropenia prophylaxis with biosimilar filgrastim and expanded access to targeted antineoplastic treatment across the European G5 countries: a simulation study. Clinical Therapeutics, 2015;37:842-857.
  3. Abraham I, Han L, Sun D, MacDonald K, Aapro M. Cost savings from anemia management with biosimilar epoetin α and increased access to targeted antineoplastic treatment: simulation for the European G5 countries. Future Oncology 2014;10:1599-1609.
  4. Van Meerbeeck J, Galdermans D, Bustin F, De Vos L, Lechat I, Abraham I. Survival outcomes in patients with advanced non-small-cell lung cancer treated with erlotinib: expanded access program data from Belgium (the TRUST study). European Journal of Cancer Care 2014;23:370-379.
  5. Delforge M, Selleslag D, Triffet A, Mineur P, Theunissen K, Graux C, Trullemans F, Boulet D, Van Eygen K, Beguin Y, Noens L, Van Steenweghen S, Lemmens J, Pierre P, D’hondt R, Ferrant A, Deeren D, Van De Velde A, Wynendaele W, André M, Breems D, Deweweire A, Geldhof K, Pluymers W, Harrington A, MacDonald K, Abraham I, Ravoet C. Adequate iron chelation therapy for at least six months improves mortality in transfusion-dependent patients with lower risk myelodysplastic syndromes. Leukemia Research 2014;38:557-563.
  6. Tharmarajah S, Mohammed A, Bagalagel A, MacDonald K, Abraham I. Clinical efficacy and safety of Zarzio (EP2006), a biosimilar recombinant human granulocyte colony stimulating factor. Biosimilars 2014;4:1-9.
  7. Bagalagel A, Mohammed A, MacDonald K, Abraham I. Clinical efficacy and safety of Tevagrastim® (XM02), a biosimilar recombinant human granulocyte colony stimulating factor. Biosimilars 2013;3:55-62.
  8. Mohammed A, Bagalagel A, MacDonald K, Abraham I. Clinical efficacy and safety of XM01, a biosimilar recombinant human erythropoietin, in the management of anemia. Biosimilars 2013;3:45-53.
  9. Bagalagel A, Mohammed A, MacDonald K, Abraham I. Clinical efficacy and safety of SB309, a biosimilar recombinant human erythropoietin, in the management of anemia. Biosimilars 2013;3:35-43.
  10. Abraham I, MacDonald K, Tharmarajah S, Bokemeyer C, Ludwig H, Soubeyran P, Battistel V, Aapro M. Modeling of treatment response to erythropoiesis-stimulating agents in older (age > 70 years) and younger (age < 70 years) cancer patients with anemia: findings from the Anemia Cancer Treatment study. Journal of Geriatric Oncology 2013;4:196-201.
  11. Abraham I, Tharmarajah S, MacDonald K. Clinical safety of biosimilar recombinant human granulocyte colony stimulating factors. Expert Opinion on Drug Safety 2013;12:235-246.
  12. Kim HJ, Abraham I, Malone P. Analytical methods and issues for symptom cluster research in oncology. Current Opinion in Supportive and Palliative Care 2013;7:45-53.
  13. Abraham I, MacDonald K. Clinical safety of biosimilar recombinant human erythropoietins. Expert Opinion on Drug Safety 2012;11:819-840.
  14. Abraham I, MacDonald K. Why are patients with chronic myeloid leukaemia (non-)adherent? British Journal of Cancer 2012;107:901-903.
  15. Abraham I, MacDonald K. Clinical efficacy and safety of HX575, a biosimilar recombinant human erythropoietin, in the management of anemia. Biosimilars 2012;2:13-25.
  16. Aapro M, Cornes P, Sun D, Abraham I. Comparative cost-efficiency across the European Union G5 countries of originators and a biosimilar erythropoiesis-stimulating agent to manage chemotherapy-induced anemia in cancer patients. Therapeutic Advances in Medical Oncology, 2012;4: 95-105.
  17. Aapro M, Cornes P, Abraham I. Comparative cost-efficiency across the European G5 countries of various regimens of filgrastim, biosimilar filgrastim, and pegfilgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia. Journal of Oncology Pharmacy Practice 2012;18:171-179.
  18. Delforge M, Selleslag D, Triffet A, Mineur P, Bries G, Graux C, Trullemans F, MacDonald K, Abraham I, Pluymers W, Ravoet, C. (2011). Iron status and treatment modalities in transfusion-dependent patients with myelodysplastic syndromes. Annals of Hematology 2011;90:655-666.
  19. Mazzeo F, Duck L, Joosens E, Dirix L, Focan C, Forget F, De Geest S, D’haeyer J, van Lierde MA, MacDonald K, Abraham I, De Grève J. Nonadherence to imatinib treatment in patients with gastro-intestinal stromal tumors: the ADAGIO study. Anticancer Research 2011;31:1411-1415.
  20. Gascón P, Aapro M, Ludwig H, Rosencher N, Turner M, Song M, MacDonald K, Lee C, Muenzberg M, Abraham I. Background and methodology of MONITOR-GCSF, a pharmaco-epidemiological study of the multi-level determinants, predictors, and clinical outcomes of febrile neutropenia prophylaxis with biosimilar granulocyte-colony stimulating factor filgrastim. Critical Reviews in Oncology and Hematology 2011;77:184-197.
  21. Gascón P, Aapro M, Ludwig H, Rosencher N, Boccadoro M, Turner M, MacDonald K, Muenzberg M, Abraham I. Update on the MONITOR-GCSF study of biosimilar filgrastim to reduce the incidence of chemotherapy-induced febrile neutropenia in cancer patients: Protocol amendments. Critical Reviews in Oncology and Hematology 2011;77:198-200.
  22. Van Erps J, Aapro M, MacDonald K, Soubeyran P, Turner M, Warrinnier H, Albrecht T, Abraham I. Promoting evidence-based management of anemia in cancer patients: concurrent and discriminant validity of RESPOND, a web-based clinical guidance system based on the EORTC guidelines for supportive cancer care. Supportive Care in Cancer 2010;18:842-858.
  23. Abraham I. Intravenous bisphosphonate treatment and osteonecrosis of the jaw in patients with cancer: wide CIs, Yule-Simpson and King Kong effects, and no therapeutic outcomes. Journal of Clinical Oncology 2010;28:e143-e144.
  24. Aapro M, Ludwig H, Bokemeyer C, MacDonald K, Soubeyran P, Turner M, Albrecht T, Abraham I. Modeling of outcomes and response rates to treatment with erythropoiesis stimulating agents in cancer patients with anemia: findings from the Anemia Cancer Treatment (A.C.T.) study. Annals of Oncology 2009;20:1714-1721.
  25. Ludwig H, Aapro M, Bokemeyer C, MacDonald K, Soubeyran P, Turner M, Albrecht T, Abraham I. Treatment patterns, outcomes, and response rates in the management of cancer-related anemia in Europe: findings from the Anemia Cancer Treatment (A.C.T.) study. European Journal of Cancer 2009;45:1603-1615. 
  26. Noens L, van Lierde MA, De Bock R, Verhoef G, Zachée P, Berneman Z, Martiat P, Mineur P, Van Eygen K, MacDonald K, De Geest S, Albrecht T, Abraham I. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood 2009;113:5401-5411.
  27. Aapro M, MacDonald K, Van Erps J, Soubeyran P, Turner M, Warrinnier H, Albrecht T, Abraham I. Managing cancer-related anemia in congruence with the EORTC guidelines is an independent predictor of haemoglobin outcome: Initial evidence from the RESPOND study. European Journal of Cancer 2009;45:8-11. 
  28. Aapro M, MacDonald K, Van Erps J, Soubeyran P, Turner M, Muenzberg M, Dunlop R, Abraham I. Promoting evidence-based management of anemia in cancer patients: background, development, and scientific validation of RESPOND, a web-based clinical guidance system based on the EORTC guidelines. Critical Reviews in Oncology and Hematology 2008;65:32-42.
  29. Aapro M, Abraham I, Bokemeyer C, Ludwig H, MacDonald K, Soubeyran P, Turner M. The background and methodology of the Anaemia Cancer Treatment (A.C.T.) survey: a retrospective study of practice patterns and outcomes in the management of anaemia in cancer patients and their congruence with evidence-based guidelines. Supportive Care in Cancer 2008;16:193-200.
  30. Gascón P, Aapro M, Ludwig H, Bokemeyer C, Boccadoro M, Turner M, Denhaerynck K, MacDonald K, Abraham I. Treatment patterns and outcomes in the prophylaxis of chemotherapy-induced (febrile) neutropenia with biosimilar filgrastim (MONITOR-GCSF study). Supportive Care in Cancer, in press.

Academic Information

Doctorate: 
Clinical Research, University of Michigan (Ann Arbor, MI)
Master's Degree: 
MS, Psychiatric-Mental Health Nursing, University of Michigan (Ann Arbor, MI)
Undergraduate School: 
BS, Nursing, Katholieke Hogeschool Leuven (Leuven, Belgium)