Praiseldy Langi Sasongko Preparing for an Uncertain Future The Modern Blood Bank
The Modern Blood Bank Preparing for an Uncertain Future Praiseldy Langi Sasongko
Copyright 2025 © Praiseldy Langi Sasongko All rights reserved. No parts of this thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author. Provided by thesis specialist Ridderprint, ridderprint.nl Printing: Ridderprint Layout and design: Erwin Timmerman, persoonlijkproefschrift.nl Cover and chapter page illustrations: Thomas Lupu Icon Attribution Chapter 1 – Map icon by Pixel Perfect on flaticon.com Chapter 2 – Blood bag icon by SmartIcons on iconvulture.com Chapter 3 – Scales icon by VectorPortal on flaticon.com Chapter 4 – Icon by prettycons on flaticon.com Chapter 5 – Hands clasping icon by Freepik on flaticon.com Chapter 6 – Bridge icon by Freepik on flaticon.com Chapter 7 – Compass icon by Freepik on flaticon.com
The Modern Blood Bank: Preparing for an Uncertain Future ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad van doctor aan de Universiteit van Amsterdam op gezag van de Rector Magnificus prof. dr. ir. P.P.C.C. Verbeek ten overstaan van een door het College voor Promoties ingestelde commissie, in het openbaar te verdedigen in de Agnietenkapel op maandag 14 april 2025, te 14.00 uur door Praiseldy Kharistya Betsy Langi Sasongko geboren te Jogjakarta
Promotiecommissie Promotores: prof. dr. H.L. Zaaijer prof. dr. M.C. de Bruijne AMC-UvA Vrije Universiteit Amsterdam Copromotores: dr. ir. M.P. Janssen Sanquin Overige leden: prof. dr. C.E. van der Schoot prof. mr. dr. M.C. Ploem prof. dr. I.N. van Schaik prof. dr. ir. F.K. Boersma prof. dr. E.M. Merz AMC-UvA AMC-UvA AMC-UvA Vrije Universiteit Amsterdam Vrije Universiteit Amsterdam Faculteit der Geneeskunde
Table of Contents Chapter 1 General introduction 7 Part 1 Chapter 2 Past, present, and future: a qualitative study identifying historical trends, drivers, and transformational factors for the future demand of blood supply in the Netherlands 27 Chapter 3 Using a scenario approach to assess for the current and future demand of immunoglobulins 101 Chapter 4 Mapping opportunities and threats for the future demand of red blood cells in the Netherlands using a scenario approach 141 Part 2 Prelude Blood supply milestones in the Netherlands in the first weeks of COVID-19 175 Chapter 5 Something we must be proud of: an interview and document study of team improvisation in the Dutch convalescent plasma project group 183 Chapter 6 Building towards organizational resilience and complexity leadership: a case study of impacts and changes in a Dutch blood establishment during COVID-19 213 Chapter 7 Discussion and conclusion 235 Appendices Summary Samenvatting Acknowledgements PhD profile and publications Curriculum vitae 263 266 270 273 277
Chapter 1 General Introduction
9 General Introduction “The story of blood is one of metamorphosis, of a liquid that became symbolically transformed as society learned how to deconstruct and manage it.” D. Starr, Preface to “Blood: An Epic History of Medicine and Commerce”, page xv1 1.1 A Brief History of Blood Use In the 199 years since the first successful human-to-human blood transfusion (1825),2 the “story of blood” has evolved dramatically. Blood, in the beginning only perceived as a mysterious spiritual and mystical substance, has become a scientific and strategic material explored and harnessed by mankind over the centuries. The organization of blood establishments (BEs) has transformed as the donation, storage, testing, and transport of blood components have undergone significant changes from its primitive beginnings. This is most evident starting in the 20th century in which transfusion services began to lay the foundation for our modern-day services. As historian Douglas Starr writes, the 20th century saw the transformation of blood from a “scientific curiosity” (then, only recognized as a therapeutic liquid transfusible from one person to another), to a “strategic material” that scientists could master and manage and use for human enterprise.1 This began immediately at the turn of the century; in 1900-1901, a breakthrough came when the first four human blood groups were discovered (A, B, O, AB) and more would be discovered in the decades to come (e.g., Rhesus). This would allow for typing and crossmatching of blood types between donors and recipients to make sure they matched, vastly improving transfusion outcomes. In the early 1920s, no one was storing blood and donors were called upon needed (“donor on the hoof”), which proved to be unreliable and slow for finding compatible blood matching. By the 1930s, a professional donor program had begun in the United States and blood of the living (or dead) was able to be stored in collection facilities. These facilities were named “blood banks,” based on the system of deposits and withdrawals, made possible because blood, for the first time, could be stored using a citrate solution and stockpiled into inventory to be used when needed. Blood banks were begun, first in Russia, then in North America, and they spread rapidly throughout Western countries.1 In the 1940s, the process of plasma fractionation was developed. Whole blood was divided into constituents of erythrocytes (red blood cells), leukocytes (white blood cells), thrombocytes (platelets), and plasma (which can be further fractionated into various proteins, such as albumin, immunoglobulins, and clotting factors). This separation into components allowed for pharmaceutical products to be developed, and these different products became a key medical advantage for the Allies in World
10 Chapter 1 War II. More wartime innovations occurred, including complex logistical enterprises to send blood products across lands and seas, symbolizing the power of human industrialization to master and use what, only a few decades before, was considered a strange substance.1 After the war, blood-related innovations continued. In the 1950s, plastic bags and associated tubing were created (replacing decades of glass bottles), which became “the heart of a flexible blood processing system that made all subsequent advances in blood processing possible” (Starr, p. 181).1 Many more subsequent advances would occur. In the 1970s, Transfusion Medicine became a sub-specialty within medicine, paving the way to transfusion experts and the world of blood banking and transfusion services.3 However, the 1980s-1990s saw tragedies strike BEs in the form of transfusion-transmitted infections of HIV and hepatitis, and the implementation of various screening tests for donor blood. These events created a global societal and legal uproar that shook and shattered the public’s reputation in BEs. Hence, as the opening quote states, as blood metamorphosed symbolically and physically over time, so did the management of it and the organizations that were built around it.1 1.2 A Brief History of Sanquin In the Netherlands, blood banking services existed as separated entities until 1998 when a merge occurred between the then-22 locations and the Central Laboratory of the Netherlands Red Cross Blood Transfusion Service (CLB). This merge resulted in two main locations (Amsterdam and Nijmegen) under a new organization called “Sanquin,” from the Latin word sanguis, meaning blood. Its original logo of the Dalmatian pelican with a red drop over its breast refers to the legend of the pelican shedding her own blood to feed her young, and emphasizes the sacrificial action of blood donation to save lives.4 With this merge, the government passed the Blood Supply Act so that Sanquin would be the sole BE in the country. Currently, Sanquin has 136 donation centers, both fixed and mobile, five distribution centers, and one testing facility housed at the headquarters in Amsterdam. Sanquin employs approximately 2,000 employees. In 2023, there were 429,716 registered donors who donated 756,752 units of blood of which 51% were whole blood donations and 49% were apheresis donations (see Table 1.1).5
11 General Introduction Table 1.1: Number of donors and donations at Sanquin from 2017-2023 2017 2018 2019 2020 2021 2022 2023 Registered donors 331,472 341,509 366,712 391,288 384,352 406,549 429,716 Total number of donations 721,203 724,002 727,464 736,593 743,884 731,731 756,752 Whole blood donations 410,616 412,682 413,653 411,518 407,203 393,987 384,998 (frequency) (1.50) (1.51) (1.46) (1.40) (1.36) (1.24) (1.14) Apharesis donations 310,587 311,320 313,811 325,075 336,681 337,744 371,754 (frequency) (5.40) (5.29) (5.04) (4.06) (4.35) (3.95) (4.19) Sanquin is structurally organized under the umbrella of the Sanquin Foundation, with two distinct entities: 1) a not-for-profit part and 2) a for-profit part called Sanquin Health Solutions (see Figure 1).6 While distinct, these entities collaborate and provide services and support to one another and to the public. Figure 1.1 Sanquin’s organogram as of September 2024
12 Chapter 1 1.3 Brief History of Trends in the Demand of Red Blood Cells and Immunoglobulins Red blood cells Red blood cells (RBCs) have been blood banks’ staple product, its “bread and butter” for decades due to the historical need for large quantities for transfusions. However, in the past 25-30 years, this has shifted due to singular and cumulative advances within society, medical practices, and technologies.7 First, the HIV infections of the 1980s-1990s changed the public’s perceptions to how blood could be “bad”—very bad, in fact, due to the accidents and scandals and subsequent legal actions and governmental measures that occurred.1,7,8 In subsequent years, a focus on blood safety, costs, utilization, and management generated substantial data that supported using conservative transfusion triggers.1,9 This was also complimented by the adoption of Patient Blood Management (PBM), a multifaceted, multidisciplinary approach to limit the need and use of blood transfusions in surgical and non-surgical patients.10,11 Furthermore, the rise of medical innovations (e.g., laparoscopic surgery) and pharmaceutical products have dramatically decreased blood loss.7,11–13 Hence, many Western countries have seen the demand for RBCs steadily decrease.11,13–15 In the Netherlands, there has been a 47% decline from 1998-2023 (see Figure 1.2). Figure 1.2 Demand of red blood cells in the Netherlands from 1998-2023 200.000 300.000 400.000 500.000 600.000 700.000 800.000 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 Number of units supplied Year
13 General Introduction Immunoglobulins Immunoglobulins (Ig) are a group of proteins found within plasma. When the technique of plasma fractionation was discovered in the 1940s, immunoglobulins were one of the subgroups that was naturally separated in the process.1,16 Biologically, Ig act as antibodies to protect against and ward off infections. Thousands of Ig are available in pooled donations of plasma donors, which makes it a rich potential for medical use.16 Since the early 2000s, intravenous immunoglobulins (IVIG) became the driver in plasma demand, growing exponentially with time for its notable uses in treating primary and secondary immune diseases and being an immunomodulatory agent for many other diseases.16 Now, it is used as a treatment option for a wide range of conditions, both “on-label” (registered, proven to be efficacious) to “off-label” (non-registered, not yet proven to be efficacious).17 Because of this, worldwide demand for plasma has skyrocketed and continues to grow18 (see Figure 1.3). Current global supply is found insufficient, and shortages often occur worldwide.18 Figure 1.3: Worldwide and European trends in immunoglobulin sales from 2000-2022 (source: MRB)19 300 250 200 150 100 50 0 2000 2003 2005 2008 2010 2013 2016 2019 2022 Worldwide
14 Chapter 1 As demand for RBC and Ig products have changed, it highlights the need for organizations to cultivate awareness regarding future uncertainties and create preparedness plans. This need could be assessed using scenario planning methodology. 1.4 Brief History of Scenario Planning or Scenario Development Modern-day scenario planning (also known as scenario development) has origins in two schools of thought from the United States and France in the 1950s-1960s.20 Herman Kahn created scenarios for the U.S. military while his French counterpart, Gaston Berger, created prospective thinking (La Prospective) which was later carried on by Pierre Masse and Bertrand de Jouvenel.20 Scenario planning came to the limelight in the 1970s when Pierre Wack and Ted Newland of the Royal Dutch/Shell Company employed and redefined scenario planning methodology to find scenarios that were plausible (i.e., valid, likely, or acceptable) instead of probable (i.e., likely to happen).21 Wack criticized how forecasting techniques were merely extensions of the past or present and emphasized that one needed to embrace uncertainty, try to understand it, and incorporate it into reasoning. Under his direction, his team created multiple memorable storylines (i.e., scenarios) that invited disruptions and uncertainties while remaining relevant to management. These scenarios were not predictions of what could happen but an invitation into a future world for participants to imagine themselves as actors in and a reflect upon their human assumptions of how that world would work.21,22 Hence, what was important was not the specific details of the future, but the plausibility of the storylines and how it could open the mind up to new dynamics.21–23 Using scenario planning, Shell survived the oil and price crises in the 1970s. As Shell’s corporate fame in using this technique spread, many other organizations and fields adopted it. Over the years, it has been used in many private and public sectors, including corporate businesses, the military, public policy, transportation, energy, education, and academia.20,24 While there are different schools of scenario planning, it is generally agreed that scenario planning is a “structured and analytical process to create characterization of multiple futures to enable stakeholders to rethink strategic decisions and policies” (Bouhalleb and Smida, p. 2).25,26 The core steps of scenario planning are:25 1. The preparatory phase, where the focal issue is defined, and the trends and principal drivers of change are identified;
15 General Introduction 2. The developmental phase, where storylines are created and key scenarios are chosen; 3. The use phase, which uses the scenarios from the former step to create strategies. Dean describes these steps in more detail, summarized below:24 1. Scoping (the foundation): The scenario planning team decides on the scope of the exercise, the issue, the timeframe, and the stakeholders who will be involved. 2. Information search: With the foundation in mind, basic data and information on all the factors that potentially influence future developments are obtained. This includes searching through (gray) literature and interviews with experts and relevant stakeholders. 3. Trend and uncertainty analysis: With a thorough list of factors from Step 2, the most relevant factors are chosen and placed in an importance/uncertainty grid. This ranking exercise can be done with the participation of relevant experts and stakeholders. 4. Scenario building: The identified trends and critical uncertainties from Step 3 are made into plausible scenarios that describe future possible states; 2x2 or 2x2x2 matrices can be used. 5. Strategy definition: With the selected scenarios in mind, strategic options can be tested against the future conditions using various tools and techniques to find the most flexible and robust strategy. 6. Monitoring: The critical uncertainties and trends need to be continuously monitored by a set of key indicators that are defined to help monitor the environment. Doing so helps the users see if the scenario from previous steps remain valid and/or if the strategy employed needs to be altered. As individuals undergo these steps, it is a learning process at the individual and collective level. At the individual level, scenario planning challenges individuals’ mental models of assumptions of how the world works by alerting them to elements of novelty that may be uncomfortable and surprising and engages them to think of innovating strategies. At the collective level, this is a tool that encourages strategic conversation between stakeholders, confronting different perspectives and mental models with the external environment.20,21,24,25 Overall, by having strategic foresight into how the current strategy would fare under different scenarios or by discovering new strategic options within multiple scenarios.25 Hence, as Transfusion Medicine and blood banking management have changed dramatically, as past and current trends show decreasing demand of RBCs, and as
16 Chapter 1 medical innovations and new research occur, the future demand of blood products is likely to change. Therefore, applying scenario planning to a new field such as Transfusion Medicine was considered useful to aid BE management in developing strategic thinking and becoming more proactive to the uncertainties of the future. This would, ultimately, enable BEs to become (more) resilient. 1.5 Brief Introduction to Organizational Resilience “To survive in uncertain environments and to foster future success, organizations must be able to handle all of these manifestations of the unexpected” (Duchek, p. 2).27 Resilience is a common concept in fields like psychology, which has focused on the individual and familial contexts.28 While the terminology shares commonalities with similar words such as flexibility, agility, or robustness, the emphasis of resilience is on unexpected threats and crises. Resilience is relatively new in business and management research and it has only been in the early 21st century that research focusing on organizational resilience has grown.27,29 This relative new emergence is reflected in in the diversity of definitions, conceptualizations, and measures of resilience across literature.27,30 Duchek synthesizes how three broad groups of definitions have emerged:27 1. Organizational resilience is the ability to resist adverse events and/or the ability to recover after disturbances and return to a normal state; 2. Organizational resilience is the ability to look beyond the maintenance and restoration of an organization’s functionality and focus instead on the advancement of its processes and capabilities so it may come out of a crisis stronger than before; 3. Organizational resilience is the ability to anticipate adverse events so that it can identify potential risks and take proactive steps to prevent dangers before they occur. Furthermore, four groups of conceptualizations have been found in literature:27,31 1. Organizational resilience is an outcome (linked to definition #1 above) comprised of specific behavioral, resource, or processual factors that may contribute towards a resilient outcome (or not); 2. Organizational resilience is a process made of distinct stages such as anticipation and learning; 3. Organizational resilience is a set of capabilities comprised of an organization’s resources, routines, practices, and processes.
17 General Introduction 4. Organizational resilience is a multi-level approach composed of attributes and processes at different levels occurring simultaneously and interactively. Newer studies are shifting from singular to combination perspectives as there is realization that the aforementioned groups are all aspects of resilience.30,31 Therefore, this thesis uses Duchek’s comprehensive definition of organizational resilience as a meta-capability consisting of a set of organizational capabilities that allow for the successful completion of the three successive stages of anticipation (responding before the unexpected event), coping (responding during the event), and adaptation (responding after and learning from the event).27 Her framework provides a comprehensive understanding of the unique stages of resilience, characterizing the underlying capabilities within each stage, and explaining the interrelationships between the stages, its antecedents and its drivers (see Figure 1.4).27 Figure 1.4 Duchek’s framework of organizational resilience27 In the first stage, an organization anticipates by observing and detecting critical developments in their environment and reacting proactively to prepare the organization without specifically knowing, if when, or where the unexpected will occur. This stage is driven particularly by the availability of resources the organization has. The second stage of coping calls for the organization to accept the reality of the unexpected occurring and finding immediate/short-term solutions. This requires
18 Chapter 1 collective sensemaking and coordination at the group-level, entailing vital traits as improvisation, communication, and quick implementation. Thus, an organization’s social resources are an important driver at this phase. The third stage of adaptation entails reflecting from the crisis, learning from it, and using it to catalyse change (and overcoming the resistance to it). However, an organization’s power dynamics and chains of responsibility directly influence whether change does occur. With every stage, the organization learns “from” and “through” the experience so that it feeds into its knowledge base feedback loop.27 1.6 Outline and contents of this thesis As the story of blood is one of metamorphosis, so has the journey of the research presented in this thesis been. It was originally intended to be a traditional scenario exercise in identifying the historical trends and transformational factors that would impact blood demand, to create specific scenarios for the medium and long-term future. As interesting as that would have been, it gradually morphed as the flow of circumstances changed. After much time spent on the identification of important drivers that would affect the future demand of RBCs (which, in retrospect, was Duchek’s first step of “anticipation” in the resilience framework), we found ourselves, at the end of the day, turning the focus inwards, into the organization. “If blood demand is going to change in this or that direction in 20- or 50-years’ time, what would Sanquin need to do to respond to that change?” I asked as one of the last questions in my interviews during the first two years of conducting this research. And this is where respondents, especially Sanquin employees, would become very attentive and articulate. Suddenly, the question was no longer on a theoretical level but on personal level regarding their daily experiences at work. As I compiled and compared the answers to this question, the overarching themes concerned organizational change, organizational innovation, and organizational resilience. Hence, it made sense to me to explore these themes further, still using scenario principles, so that the scope shifted from creating a set of specific scenarios to understanding and describing the many opportunities and threats of these transformational factors and the organizational implications for Sanquin instead. It shifted our lens from looking externally to looking internally. While conducting our internal analysis of the organization, the COVID-19 pandemic occurred. This again changed the course of our plans, but it enabled us to see one of our results, the possibility of a disruptive event bringing opportunities and threats, and observe and assess how the organization developed accordingly.
19 General Introduction (Hence, we could see Duchek’s second and third stages, “coping” and “adaptation” in “real time.”) Ultimately, we decided to forgo creating specific scenarios for the value of understanding our results from an organizational resilience perspective. Therefore, the overarching research question is: How can Sanquin respond to future changes in blood demand of RBCs and Ig? To answer this question, the thesis is divided into two parts: I. To identify external opportunities and threats regarding the future demand of RBCs and Ig products for Sanquin (Chapters 2-4), II. To identify organizational elements of resilience in response to a disruptive event (Chapters 5-6). Part I reflects the beginning of our journey in which we set out to find the historical drivers, transformational factors in society, technology, ecology, economics, and politics/legislature that are considered most important in affecting future RBC and Ig demand (Chapters 2 and 3). Drawing from the results of the transformational factors in Chapter 2, Chapter 4 highlights 10 main themes of transformational factors, ranked by respondents in terms of importance and uncertainty to affect future RBC demand. It lists the organizational implications for Sanquin by describing specific opportunities and threats within those themes. In doing so, Chapter 4 shifts the thesis from the external (Part I) to the internal perspective (Part II) as the remaining chapters will illustrate Sanquin’s actions at the beginning of the COVID-19 pandemic (prelude to Chapters 5 and 6) and specific organizational initiatives during the pandemic. Chapter 5 assesses which elements of improvisation in the early-group convalescent plasma project contributed towards successful teamwork and organizational resilience, while Chapter 6 provides a broad overview of the various organizational initiatives and reflects on whether elements of complexity leadership occurred. Finally, the Discussion and Conclusion in Chapter 7 answers the research questions, reflecting upon the two overarching objectives and lessons learned for organizational resilience for BEs. It ends with organizational recommendations and further research questions. Table 1.2 lists the specific research questions per chapter.
20 Chapter 1 Table 1.2 Overview of the chapters and specific research questions per chapter. Part Chapter Publication Research Question(s) I 2 Past, present, and future: a qualitative and literature study identifying historical trends, drivers, and transformational factors for the future demand of blood supply in the Netherlands Which transformational factors in society, technology, ecology, economics, and politics / legislature are considered most important in affecting future RBC demand? 3 Using a scenario approach to assess for the current and future demand of immunoglobulins: an interview and literature study from the Netherlands Which transformational factors in society, technology, ecology, economics, and politics / legislature are considered most important in affecting future Ig demand? 4 Not a crystal ball: Mapping opportunities and threats for the future demand of red blood cells in the Netherlands using a scenario approach What are organizational practices to mitigate the threats or embrace the opportunities of the transformational factors regarding future RBC demand? II Prelude Letter to the Editor: Blood Supply Milestones in the Netherlands in the First Weeks of COVID-19 5 “Something we must be proud of” Team improvisation of the early-stage COVID-19 convalescent plasma project group in the Netherlands: a case study What elements of organisational resilience are employed in response to a disruptive event? What are organizational elements that Sanquin needs to improve its organizational resilience? 6 Building towards organizational resilience and complexity leadership: a case study of impacts and changes in a Dutch blood establishment during COVID-19
21 General Introduction References 1. Starr, D. Blood: An Epic History of Medicine and Commerce. (Perennial, New York, 2002). 2. Tanchanco, R. The Surprising Story of the First Blood Transfusion. History News Network https://www.historynewsnetwork.org/article/the-surprising-story-of-the-first- blood-transfusio (2015). 3. Farrugia, A. & Starr, D. Where now for transfusion: the evolution of a paradigm and its logical progression: WHERE NOW FOR TRANSFUSION. Transfusion (Paris) 56, S224–S232 (2016). 4. Sanquin. Sanquin History. Sanquin https://www.sanquin.org/about-sanquin/sanquins- activities/history. 5. Sanquin Health Solutions BV. Sanquin Health Solutions Group BV, Annual Report 2021. https://www.sanquin.org/about-sanquin/publications/annual-reports. 6. Sanquin. About Sanquin https://www.sanquin.org/about-sanquin. 7. McCullough, J. Innovation in transfusion medicine and blood banking: documenting the record in 50 years of TRANSFUSION. Transfusion (Paris) 50, 2542–2546 (2010). 8. Alter, H. J. & Klein, H. G. The hazards of blood transfusion in historical perspective. Blood 112, 2617–2626 (2008). 9. Hébert, P. C. et al. A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care. N. Engl. J. Med. 340, 409–417 (1999). 10. Meybohm, P. et al. Patient Blood Management Bundles to Facilitate Implementation. Transfus. Med. Rev. 31, 62–71 (2017). 11. Van Hoeven, L., Koopman, R., Koffijberg, H., Roes, K. & Janssen, M. Historical time trends in red blood cell usage in the Netherlands. Int. J. Clin. Transfus. Med. Volume 4, 67–77 (2016). 12. Gombotz, H., Rehak, P. H., Shander, A. & Hofmann, A. The second A ustrian benchmark study for blood use in elective surgery: results and practice change. Transfusion (Paris) 54, 2646–2657 (2014). 13. Tinegate, H. et al. Ten-year pattern of red blood cell use in the North of England. Transfusion (Paris) 53, 483–489 (2013). 14. Ellingson, K. D. et al. Continued decline in blood collection and transfusion in the U nited S tates–2015. Transfusion (Paris) 57, 1588–1598 (2017). 15. Schönborn, L. et al. Longitudinal Changes in the Blood Supply and Demand in North- East-Germany 2005-2015. Transfus. Med. Hemotherapy 44, 224–231 (2017). 16. Farrugia, A. & Scaramuccia, D. The dynamics of contract plasma fractionation.Biologicals 46, 159–167 (2017).
22 Chapter 1 17. Brand, A. et al. Review of indications for immunoglobulin (IG) use: Narrowing the gap between supply and demand. Transfus. Clin. Biol. 28, 96–122 (2021). 18. Marketing Research Bureau. DATA & ANALYSIS OF IMMUNOGLOBULIN SUPPLY AND PLASMA REQUIREMENTS IN EUROPE 2010-2021. Revised May 19 2023. https:// marketingresearchbureau.com/wp- content/uploads/2023/05/MRB_EU_SOHO_Figures-2023.pdf. 19. Marketing Research Bureau. Marketing Research Bureau (MRB) Data for Syeldy on Worldwide and European Ig sales from 2000-2022. (2024). 20. Bradfield, R., Wright, G., Burt, G., Cairns, G. & Van Der Heijden, K. The origins and evolution of scenario techniques in long range business planning. Futures 37, 795–812 (2005). 21. Wack, P. Scenarios: Uncharted Waters Ahead. Harvard Business Review (1985). 22. Wack, P. Scenarios: Shooting the Rapids. (1985). 23. Wilkinson, A. & Kupers, R. Living in the Futures. Harvard Business Review (2013). 24. Dean, M. Scenario Planning: A Literature Review. https://www.researchgate.net/ publication/343722823_Scenario_Planning_A_Literature _Review. 25. Bouhalleb, A. & Smida, A. Scenario planning: An investigation of the construct and its measurement. J. Forecast. 37, 489–505 (2018). 26. Bowman, G. The Practice of Scenario Planning: An Analysis of Inter- and Intra- organizational Strategizing. Br. J. Manag. 27, 77–96 (2016). 27. Duchek, S. Organizational resilience: a capability-based conceptualization. Bus. Res. 13, 215–246 (2020). 28. Martin-Breen, P. & Anderies, J. M. Background Paper. Resilience: A Literature Review. (2011). 29. Rieckert, A. et al. How can we build and maintain the resilience of our health care professionals during COVID-19? Recommendations based on a scoping review. BMJ Open 11, e043718 (2021). 30. Linnenluecke, M. K. Resilience in Business and Management Research: A Review of Influential Publications and a Research Agenda: Resilience in Business and Management Research. Int. J. Manag. Rev. 19, 4–30 (2017). 31. Kim, J. Y. et al. Quality assessment of conventional and traditional oriental medicine clinical practice guidelines for knee osteoarthritis using AGREE II instrument. Med. U.S. 100(51), 1–12 (2021).
Part I Chapters 2 – 4
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Chapter 2 Past, present, and future: a qualitative and literature study identifying historical trends, drivers, and transformational factors for the future demand of blood supply in the Netherlands This chapter is published as: Langi Sasongko, P., Rolink, M., Hurk, K., Kraaij, M. & Janssen, M. Past, present, and future: a qualitative and literature study identifying historical trends, drivers, and transformational factors for the future demand of blood supply in the Netherlands. Transfusion (Paris) 59, 3413–3423 (2019). MJ conceived the initial idea of the study, and designed the methodology. PLS conducted the literature review and interviews. PLS and MR conducted analyses. PLS wrote the manuscript and all authors critically reviewed and revised the manuscript.
28 Chapter 2 Abstract BACKGROUND: As blood transfusion has evolved, there is a need to understand its historical trends and underlying drivers. Furthermore, for blood bank management to make decisions about the future, they need to consider what transformational factors (defined as developments in science, society, and technology) could significantly impact blood demand and to what effect. This study has a two-fold aim: to explore transfusion experts’ perspectives regarding 1) historical trends and drivers of red blood cells (RBCs) in the past 20 years and 2) transformational factors that would impact the future demand of RBCs and to what effect. STUDY DESIGN AND METHODS: Forty-two semi-structured interviews were held with transfusion experts from the Netherlands and abroad, supplemented with a literature review of Pubmed, Google Scholar, and gray literature. RESULTS: With regard to historical trends and drivers, experts shared two main trends: decreased or increased demands for RBCs. Various drivers were reported for each trend, coupled with evidence from literature. With regard to the future, experts anticipated that RBC demands will either increase (17%), decrease (45%), decrease but stabilize (12%), or stabilize as is (7%). Various transformational factors were found to support each trend (e.g., gene therapy will reduce RBC demand), although there were factors for which experts were unsure about its effects (e.g., cultured RBCs). Seven groups of transformation factors were identified in the literature review. CONCLUSION: While the future of blood transfusion is uncertain, there are actions that blood banks may take now to prepare for potential future developments.
29 Past, present, and future of red blood cells 2.1 Introduction “Study the past if you would define the future.” Confucius Studying the past of blood transfusion in the past 25 years alone is a fascinating look into the expected and unexpected. In high-income countries, there have been many general changes, such as greater emphasis on safety and the implementation of various technologies.1–4 Simultaneously, there have been substantial specific changes in blood demand, such as the decline of red blood cells (RBCs). Literature documents this across the United States,5,6 Australia and New Zealand,7–9 and Western Europe.10–12 This decline is attributed to the singular and cumulative effects of patient blood management (PBM), blood-conserving surgical techniques, and alternative treatments for blood transfusion, to name a few.5–7,10,11,13 In the Netherlands, this decline has been especially prominent. Sanquin’s Blood Bank, the sole provider of blood products on a not-for-profit basis, has seen a 43% decrease of RBC demand from 1995 to 2017 (Figure 2.1). Van Hoeven et al.14 studied this decline from 1995 to 2005 and found various trends and suggested underlying reasons. While this study provided a glimpse of the changing blood transfusion landscape in the Netherlands, additional insights are needed to understand the trends and underlying drivers of RBC use in the Netherlands and in comparison to other high-income countries. This is the first step, as the opening quote suggests. Figure 2.1 RBC demand in the Netherlands from 1998 to 2017 showing a 43% decrease 200.000 300.000 400.000 500.000 600.000 700.000 800.000 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Number of units supplied Year
30 Chapter 2 Furthermore, to “define the future,” it is beneficial for blood bank management to consider what transformational factors (broadly defined as any development in science, society, or technology) may have a significant impact on blood demand and to what effect. For example, the aging population may increase blood demand, with subsequent shortage,15–18 but it may also be mitigated by the effects of gene or immune therapy, even leading to a continual decline.14,19 However, predicting the effects of these transformational factors is difficult for its uncertainty. Current forecasting literature solely focuses on quantitative methods to predict the future demand of blood products,10,13,19–21 but because blood transfusion is a complex environment with uncontrollable factors and various stakeholders, quantitative predictions have limited reliability. Therefore, it may be beneficial to also include qualitative input, such as expert perspectives, to integrate knowledge, imagination, and even intuition, into forecasting literature.22,23 To the best of our knowledge, there is no current literature that assesses transfusion experts’ perspectives on the historical trends and drivers and the transformational factors that may impact the future demand for high-income countries. Therefore, as the first step of a larger project to predict the future demand of blood products in the Netherlands, we sought to explore and compare perspectives of various transfusion experts from the Netherlands and abroad to answer two research questions: 1. What were historical trends of RBCs in the past 20 years and underlying drivers to these trends? 2. What are transformational factors that would impact the future demand of RBCs for the medium term (10-20 years) and to what specific effect? 2.2 MATERIALS AND METHODS Semi-structured interviews From November 2017 to July 2018, 42 semi-structured interviews were held with Dutch experts (including Sanquin employees, clinicians, and other national experts) and abroad. Experts were purposefully selected for their specific role and experience in blood transfusion. If they agreed to participate, each interview lasted approximately 30 to 60 minutes and was recorded with consent. Further respondents were “snowballed,” a method in which prior respondents were asked to refer other individuals they thought would be appropriate for this study.
31 Past, present, and future of red blood cells An interview guide was created in accordance with the research questions and composed of three sections: 1) historical trends and drivers in blood demand, 2) transformational factors (broadly defined as changes or innovations within society, science, or biomedical technology), and 3) medium-term scenarios in relation to future trends in blood demand (see Appendix A). Experts from the Netherlands answered from the Dutch context, while international experts answered from the perspective of their home country or high-income countries at large. A semi-structured approach was adopted so that the interview guide was followed with additional probing and follow-up questions when appropriate to the response. This allowed for the interviews to be more conversational in nature, which is essential for such an exploratory topic.24 Analysis of semi-structured interviews Of the 42 interviews done, 41 were recorded with consent and one was not recorded due to the difficulties of the (noisy) setting. Interview notes were kept for all. Recorded interviews were transcribed verbatim and then coded using qualitative software (MAXQDA 2018, VERBI Software GmbH). First-cycle coding followed a provisional (predetermined) coding scheme based on the research aims.25 Authors PLS and MR first assessed three transcripts individually and came together to discuss coding differences. Coding differences were settled through consensus, and adjustments were made to the framework. This was repeated in the process of coding the remaining transcripts separately to ensure continual agreement. After all transcripts were coded, the authors applied second-cycle coding, where categories were combined under emergent themes. A codebook was developed with the final themes and categories (see Appendix B). MAXQDA 2018 was also used to calculate simple descriptives for the final themes and categories. Literature review A literature review was conducted as a secondary data source to triangulate findings from the semi-structured interviews. This helped to ensure more comprehensiveness than one method alone.26 From January to February 2018, the literature review was conducted with a twoaim focus on 1) historical trends and drivers and 2) innovations that would impact blood demand. This literature review was not systematic but applied systematic principles. Key words related to and including blood transfusion, history/trends, and innovation were created and inserted in Pubmed, Google Scholar, and gray literature. For Pubmed, search strategies were created in which Mesh terms were first exploded to check if its subdivisions were relevant (see Appendix C). These
32 Chapter 2 search strategies were also applied for gray literature (AABB, ISBT, World Health Organization, Centers for Disease Control and Prevention, and European Centre for Disease Control and Prevention). Finally, it was also applied for Google Scholar. For all searches, inclusion criteria included articles from 1998 to 2018, humans, and the English language. Due to the premise of this study, exclusion criteria included studies from low- to middle-income countries and studies primarily describing a time period prior to the 21st century. For the first aim, 1268 articles were found in total and after title and abstract screening, 107 were read full text. For the second aim, 81 articles were obtained and after title and abstract screening, 69 were specifically about RBCs, and read thoroughly. Twenty-seven relevant articles were selected from gray literature with regard to historical trends. 2.3 RESULTS Of the 42 experts that were interviewed, many (n = 17, 40%) held dual roles as a researcher-clinician, working both in their respective blood banks and the clinic or using their clinical background accordingly with their research. The majority of experts (n = 23, 55%) had 21+ years of experience in their roles. Experts represented nine countries, seven medical specialties, and were grouped according to if they worked in the Netherlands or abroad, with the former subdivided into whether they worked for Sanquin or not. A summary of their characteristics can be found in Table 2.1. I. Historical trends and drivers Two main trends emerged from the interviews regarding the historical trends of RBCs: RBC decrease and RBC increase. For each trend, various drivers were given. The literature review paralleled these interview findings, with a few differences described below (see Appendix D for the full listing of literature classified for its trends and drivers). Drivers of the decreased RBC demand Nearly all experts (n = 38; 90%), equivalent among those from the Netherlands (Sanquin and non-Sanquin experts) and abroad, spoke of the decline in RBC demand. Many emphasized that this decline began due to and part of significantly changed perceptions regarding RBC transfusions, which were attributable to the HIV scandals and/or evidence-based medicine, leading to great emphasis on safety and cost
33 Past, present, and future of red blood cells (effectiveness). Ultimately, this resulted in shifting public and medical perspectives, as reflected in experts’ phrases, from “blood is always lifesaving” so that it is “given like lemonade” to “blood is bad!” Forty-one articles (41/107; 38%) mentioned or thoroughly described this historical decline and its subsequent effects. Within these 41 articles, safety and cost were common drivers, with 27 articles mentioning safety, 18 mentioning cost, and 15 articles mentioning both cost and safety. Experts further outlined other drivers, which were grouped under three categories: 1) lowered transfusion thresholds, 2) surgical techniques and pharmacologic agents, and 3) organizational changes. These categories were often interlinked. Table 2.1 Characteristics of interviewed experts Respondent characteristics From the Netherlands International (%) Total (% of total) Sanquin (%) Non-Sanquin (%) Total number (% of total) 20 (48) 8 (19) 14 (33) 42 (100) Female (% within subgroup) 11 (55) 3 (38) 5 (36) 19 (45) Functions Researcher only 1 0 0 1 (2) Researcher-clinician/clinical background 5 2 2 9 (21) Management only 4 0 0 4 (10) Researcher-management 8 0 3 11 (26) Researcher-clinician-management 3 5 9 17 (40) Years of experience 0-10 4 2 0 6 (14) 11-20 7 4 2 13 (31) 21-30 7 0 6 13 (31) 30+ 3 1 6 10 (24) Clinical specialties represented Anesthesiology, cardiothoracic surgery, hematology, intensive care, obstetrics and gynecology, neonatology, pediatric hematology Countries Australia, Canada, Denmark, France, Germany, Netherlands, Singapore, United Kingdom, United States In the first category, the majority of experts stated that the decline was due to the lowered transfusion thresholds, linked to evidence and awareness of transfusion’s adverse reactions. Overall, 74% of experts with up to 20 years of experience in blood transfusion, compared to 52% who had 21+ years of experience, attested to the lowered transfusion thresholds. More specifically, nearly all (90%) Dutch experts stated the Dutch national guidelines on transfusion thresholds (4:5:6 mmol/L as measured
34 Chapter 2 in the Netherlands, equivalent to 6.4:8.0:9.7 g/dL) affected Dutch transfusion practice by setting a standard for physicians to avoid impulse transfusion (“if the [patient] looks pale, give blood” Dutch Expert 27) or transfusing based on their prior education or experience (“20 years ago, it was normal, even in the clinics, to give two or three units of blood!” Dutch Expert 26). In comparison, 70% of international experts specifically linked lowered thresholds to PBM, which brought “evidence to the forefront or made people aware of the need for transfusion research” (International Expert 9) and a strong “sense of stewardship” (International Expert 29) across various clinical specialties. Experts stated that PBM has led to steep declines in many countries. Fewer experts from the Netherlands (25%) explicitly mentioned PBM, probably due to terminology differences. Of those articles that discussed either lowered transfusion thresholds/guidelines (n = 38) or PBM or blood conservation programs (n = 34), 20 articles explicitly linked the lowered thresholds with PBM. Furthermore, these lowered thresholds were connected to both scientific and public-related evidence. Experts described how various clinical studies in the past decades supported that both the transfusion trigger and the dosage could be safely lowered, such as Hébert’s influential TRICC (Transfusion Requirements in Critical Care) trial. However, there was a noticeable difference between those who stated this with up to 20 years of experience (11%) compared to those with 21+ years of experience (35%). Public evidence was seen in the survival of Jehovah’s Witnesses. The combination of this evidence, challenged medical perspectives and brought awareness of transfusion’s adverse reactions, which was “an eye-opener” (Dutch Expert 6) due to the traditional only-beneficial perspective experts had. Four articles27–30 reflect on particular studies that have shaped the evolution of transfusion. One author questions whether transfusion has now become too restrictive29 and warns that the evidence is still limited with gaps in knowledge.27 Another author describes successful transfusion-free liver transplantations of Jehovah’s Witnesses with implications for all surgical patients,31 and Nollett32 highlights the rise of specialists caring for patients who refuse transfusion, exemplified in Japan. The second most common reason (n=22, 52%) was minimally invasive surgical techniques, alternatives to blood transfusion, and pharmacologic agents. Overall, 47% of experts with up to 20 years of experience in blood transfusion and 57% who had 21+ years of experience, indicated this. Experts verified that this cumulative driver had a profound impact on transfusion, as described by one expert who observed a radical reduction in surgical blood use: “I saw the evolution of cardiac surgery, orthopedic surgery, any surgery. I did a lot of liver transplantation … 20 years ago, the minimum transfusion was
35 Past, present, and future of red blood cells 20 or 25 units of blood … [now] 75% of our liver transplants do not require transfusion.” (International Expert 32) Thirty-three articles mentioned how this driver was key to the overall decline, with several examples in the fields of orthopedics, cardiothoracic surgery, and prostate cancer.33–35 Further, one of these studies highlighted how the decline of RBCs had been solely due to the decline of surgical patients.10 Conversely, one study reports increased demand across a broad range of surgical patients,36 while another showed no changes in total hip and knee arthroplasty.37 All of this contributed to different organizational and operational changes for blood banks and hospitals, which was the third driver to reducing demand. Experts overall shared how blood banks underwent cost-saving efforts, such as consolidation of the organization and improving monitoring and efficiency of the supply chain. Those with 21+ years of experience could provide multiple illustrations of how this occurred while those with less experience provided only one (the Dutch clinical chemist). More specifically, Dutch experts identified how, in the Netherlands, clinical chemists and transfusion committees created an environment of consensus practice and feedback loops for monitoring usage, which expedited RBC reduction within hospitals. (Here, the clinical chemist is head of the hospital laboratory but has direct responsibility for blood transfusion in the hospitals through ensuring adherence to guidelines, monitoring usage and providing feedback across specialties, and being active in transfusion decision making, thereby being called the “gatekeeper”). Interestingly, two international experts (with 21+ years of experience) strongly vouched that the decline of RBCs was due to clinical management focusing on using algorithms and the improved logistics of the blood bank and hospitals instead of the aforementioned scientific evidence (because of the poor to mediocre quality of those studies). Thirty articles (30/107; 28%) discuss a wide range of organizational/ operational issues; of note were the studies involving implementation of clinical decision support tools that enabled physicians to order and use less blood.38–41 Drivers of the increase of RBC demand Simultaneously, irrespective of the RBC decline seen in other specialties, non-Sanquin and international experts (4/42; 10%, all with 21+ years of experience) shared how they had seen increased demand in specialties such as oncology and hematology. These specialties already require consistent transfusion for their patients and yet have seen increased demand. This is due to the aging population who suffer the most from cancers and other noncommunicable diseases, requiring treatments.
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