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Ruth Sanger Oration 2009

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Oration given on the occasion of the award of the Ruth Sanger Medal to Albert Farrugia by the Australia and New Zealand Society for Blood Transfusion, October 2009

Oration given on the occasion of the award of the Ruth Sanger Medal to Albert Farrugia by the Australia and New Zealand Society for Blood Transfusion, October 2009

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  • 1. Karl Popper, Thomas Kuhn and the common sense of transfusion medicine
    Albert Farrugia
    Ruth Sanger Oration
    Adelaide 20 October 2009
  • 2. Disclosures and Disclaimers
    Compensated services to the blood industry internationally
    None of the views expressed in this oration reflect those of my past or current affiliations
  • 3. 19 October 2009
  • 4. Summary
    Some philosophy
    Some epistemology
    Some sociology
    Some transfusion medicine
    Some regulation
    Acknowledgments
    Final reflections
  • 5. Scientific certainty
    “It is certainly no small advantage that we enjoy living at the present day with the medical arts already brought to such a perfection.”
    Galen106 A.D. – 211 A.D.
  • 6. Scientific certainty
    The fact of global warming is "unequivocal." The certainty of the human role is now somewhere over 90 percent. Which is about as certain as scientists ever get.
    I would like to say we're at a point where global warming is impossible to deny. Let's just say that global warming deniers are now on a par with Holocaust deniers, though one denies the past and the other denies the present and future.
    Ms Ellen Goodman
  • 7. Two Titans
    In so far as the statements of mathematics speak about reality, they are not certain, and in so far as they are certain, they do not speak about reality
    There is nothing new to be discovered in physics now. All that remains is more and more precise measurement
    Five years after William Thomson Lord Kelvin made this statement in 1900, Albert Einstein published his papers on special relativity, the quantum theory of light and others
  • 8. Popper’s Falsifiability
    Scientific theories make predictions that can be proved wrong
    At this point the scientific theory is abandoned
    Science makes testable predictions, and then does the experiments
    Most of science consists of trying to prove itself wrong
    “I generally have a lot of respect for common sense……..But it is not always reliable…..And in matters of scientific [] theory, it is extremely important to have a really critical attitude to it”
  • 9. Falsificationism and progress of science
    Science starts with problems.
    Falsifiable hypotheses are proposed by scientists as solutions to the problems.
    The conjectured hypotheses are then criticized and tested.
    Some will be quickly eliminated.
    Others might prove more successful.
    These must be subject to even more stringent criticism and testing.
    • When a hypothesis is eventually falsified, a new problem has emerged.
    • 10. This new problem calls for the invention of new hypotheses, followed by renewed criticism and testing.
    • 11. It can never be said of a theory that it is true, however well it has withstood the rigorous tests
    • 12. Hopefully it can be said that a current theory is superior to its predecessors - in the sense that it is able to withstand tests that falsified those predecessors.
  • Benjamin Rush(Founding Father of USA, and famous physician)
    He believed the best treatment for Yellow Fever was vigorous bloodletting
    If patient got better it was because of treatment
    If patient died then it was because the patient had been too ill for any treatment to work.
    This error in thinking illustrates one of the most important principles in scientific thinking.
    Rush violated the most important rule regarding the construction and testing of theories in science: He made it impossible to falsify his theory.
  • 13. Thomas Kuhn’s The Structureof Scientific Revolutions
    First published in 1962
    Translated into 20 languages
    Has sold over a million copies
    Has affected just about every field and discipline
    Remains a point of controversy
  • 14. Paradigms.
    Framework that affects world view.
    Synonyms :Theory, Model, Protocols, Patterns, Methodologies, Routines, Habit, Common Sense, Customs, Rituals
    We may not even be aware of our paradigms as we have always had them, or we acquire them gradually through our experience.
    • Many times those around us also share our paradigms making us less aware of them as we do not encounter any different paradigms
  • Kuhn’s viewsScience, like all other types of human activities, is a fundamentally social and community-based process
    Science
    Science is based above all on shared paradigms, not methods or sets of facts
    Progress in science has been discontinuous and revolutionary, not incremental and evolutionary – and certainly not consensual
    Scientific Revolutions
    • Involve the replacement of one paradigm by another
    • 15. Involve the rethinking of everything that had been “known” before
    • 16. Are driven by communities of scientists who act to some degree on “faith”
  • When a paradigm is good/bad?
    • A paradigm is good when the problem to be solved is within the boundary that the paradigm is effective /efficient to solve.
    • 17. A paradigm is bad when it is no longer effective /efficient to solve your problem and yet, you are blinded by the paradigm without notice - Paradigm Paralysis.
    • 18. When:
    • 19. the current paradigm failed to solve problem effectively or efficiently.
    • 20. you found a better way.
    • 21. Then it’s time for a paradigm shift
  • Stages of Paradigm Shift
    A paradigm shift is a REVOLUTIONARY way of thinking about an old problem - a dramatic change in our perception.
    • An existing paradigm is in place
    Kuhn begins from the premise that a person or even an entire society have one or more existing paradigms in place that are passed on from generation to generation.
    • Investments made in existing paradigm
    By investments, Kuhn means many different things. For some people it might mean their career or standing in their profession
    • Resistance to anomalies and preservation of existing paradigm
    • 22. Adoption of new paradigm
  • Kuhn’s Basic Model
    Paradigm Shifters
    GallileoGalilleiMarie Curie Albert Einstein Neils Bohr Barry Marshall and Robin Warren
  • 23. EARLY MENTORS
    MALTA 1981 PRAGUE 2006
    EDINBURGH 1983 CAPE TOWN 2006
  • 24. The (current) paradigm of transfusion medicine (?)
    Blood component therapy
    Blood donation is safe and needs to be increased
    Voluntary non – remunerated donation
    National self sufficiency
    Sheltered from EBM, efficacy assumed historically
    Australia (and Germany, Yemen, Monaco, the Galapagos Islands…) has the safest blood in the world
    Hospital practice unquestioned
  • 25. The position of WHO “The Melbourne declaration”
    “evidence shows that regular voluntary, non-remunerated blood donors are the cornerstone of safe and sustainable national supplies of blood and blood products”
    “national blood services based on 100% voluntary non-remunerated blood donations ...... will increase the safety of the blood supply by reducing the transmission of transfusion-transmissible infections”
    “Urge all governments to appreciate and protect all voluntary non-remunerated blood donors, develop a strategy for a stepwise progression from whole blood to the preparation of labile components and ensure that all recovered plasma is used for fractionation, thereby fully utilizing every donation”
    ( http://www.who.int/entity/worldblooddonorday/MelbourneDeclaration2009.doc)
  • 26. Blood Component Therapy
  • 27. CT bad for kidneys
    More ARDS with FWB
  • 28. Whole Blood in the Management ofHypovolemia Due to Obstetric HemorrhageAlexander et al ObstetGynecol 2009;113:1320–6)
  • 29. Duration of red blood cell storage is associated with increased incidence of deep vein thrombosis and in-hospital mortality in patients with traumatic injuries Critical Care 2009, 13:R151 doi:10.1186/cc8050 P Spinella,CCarroll,I Staff, R Gross,J Mc Quay,LKeibel, C Wade, and J Holcomb
  • 30. Patel et al Bristol UK
    BLOOD KILLS !
    TRANSFUSION OF STORED LEUCODEPLETED RED BLOOD CELLS CAUSES CARDIAC, PULMONARY AND RENAL DYSFUNCTION AND INJURY.
    20 pigs randomized to four units of 42 DO SAG-M RCCs or sham
    RCCs similar to human at D42, s/n toxins, RBCchanges etc
    Relative to sham group, Txd pigs showed:
    Acute Kidney Injury – 14% reduction in creatinine clearance, 46% reduction in free water clearance and 69% increase in urinary protein/creatinine ratio
    At autopsy – marked changes in renal tubular morphology with dilation and vacuolation
    Lung Injury – 10% reduction in lung compliance, 20% increase in inspiratory airway resistance
    Cardiac injury – nine fold increase in serum troponin
    Endothelial injury – reduced excretion of urinary nitric oxide
  • 31. 2008 Report
    Compared to the risks suggested by emerging evidence on stored red cells, these risks are insignificant
  • 32. Safety of Blood Donation
  • 33. Iron deficiency in Oz donors at start of fresh blood regulationDoherty et al ARCBS 2000
    [Iron deficiency defined as serum ferritin<12 µg/l]
  • 34. Australian Longitudinal Study on Women's HealthPatterson et al Quality of Life Research 9: 491±497, 2000.
    Associations between self-reported `low iron‘ and general health and well-being in women.
    Women who had `low iron' reported significantly lower mean scores, and greater prevalence of `constant tiredness' at baseline.
    Mean scores at follow-up were significantly lower for women who reported recent iron deficiency.
    The results suggested that iron deficiency is associated with decreased general health and well-being and increased fatigue.
  • 35.
  • 36. TRANSFUSION 2006;46:1667-1681.
    “Short-term iron replacement is effective and safe therapy for blood donors who are iron-deficient and is not harmful to those who have adequate iron…..iron should be recommended to all menstruating women to prevent harm”
  • 37. Gordeuk et al Trans 1990;30:239-245
    Randomised double blind trial of low dose carbonyl iron in female donors post donation
    Iron replaced 85% carbonyl group vs 29% control (p<0.001)
    Deferral for low Hb 8% in carbonyl group vs 36% control
    SO – what are we waiting for?
    (Is regulator cooperating?)
    March 2009
    BUT
  • 38. Safety and Ethics
  • 39. Paid or unpaid?
    Germany University Hospital Marburg
    Transfus Med Hemother 2004;31:301–307
    Look-back Procedures Because
    of Sero-converted Donors
    RCBSMarburgp value*
    Compensation No Yes
    Blood units 86,331 179,426
    Total 16 2 <0.0001
    HIV 3 1 n.t.
    HBV 3 0 n.t.
    HCV 9 1 n.t.
    *Chi-square test.
    Whole blood safety in LithuaniaVoxSanguinis(2008) 94 , 209–215
    • In both first time and regular non-remunerated donors, anti-HCV and (1st time) HBsAg were much higher than in source (compensated) US donors
    • 40. No difference in risk ratio existed when comparing the regular donations who were remunerated and non-remunerated.
  • Volunteerism?
     “What is true volunteerism? ........ I was also struck, even recently, in 2003 by the photographs published in a newspaper: parades of medals - silver medals, star-studded and gilded silver medal – with perfectly identifiable persons. With this, maybe excessive visibility, aren’t there grounds to question the links between voluntarism and anonymity?”
    Professor Didier Sicard, President of the CCNE National Ethics Advisory Committee, Trans ClinBiol 2008
    Donation in Italy
    • Offering a day off work increases average donation rate by one/year
    • 41. Donors cluster their donation days around Friday – long w/e’s
    • 42. Awards in the form of medals increase donations
    • 43. Public recognition of such award increases them most of all
    “individuals are responsive to economic considerations in their blood donation decisions in a way that is largely consistent with standard economic intuition”
    Lactera and Macis Bonn Institute of Labour 2008
  • 44. Blood Donation is an Act of Benevolence Rather Than Altruism
    • The sociology literature now abounds with studies showing that “altruistic” acts also benefit the givers
    • 45. This is also the case for “voluntary” blood donation - Fergusson et al University of Nottingham UK, Health Psychology 2008, Vol. 27, No. 3, 327–336
    • 46. Test two hypothesis for blood donation
    • 47. Benevolence - both the donor and recipient benefit
    • 48. Altruism - only the recipient gains
    • 49. Three United Kingdom–based studies
    • 50. Committed blood donors were more willing to donate blood when exposed to a benevolent message rather than an altruistic one.
    • 51. Conclusions: The benevolence hypothesis is supported, suggesting that blood donor motivation is partly selfish.
    • 52. Blood donation campaigns should focus on benevolent rather than purely altruistic messages.
  • Replacement Donors and WHO’s Blood Policy in South Saharan Africa
    Policy
    Blood should only be sourced from voluntary non-remunerated donors
    Replacement donor system not mentioned in policies or recommendations
    Claims
    <40%, 58% and 73% of blood in Africa in 2002, 2006 and 2007 was from voluntary donors – target by 2012 is 80%
    12/46 countries have 100% VNRD (including Ghana and Malawi)
    Reality
    • Average annual blood collection rate is 5.14/103
    • 53. 77.9% VD, 21.9% family/ replacement donors, 0.2% paid donors
    • 54. 50% were from repeat voluntary donors.
    • 55. 17/41 countries had <50% VNRD
  • Blood as a Therapeutic Good
  • 56. Getting therapeutic goods on the market.......and how blood is different
    Regulators’ brief
    …...AND COST
    EFFECTIVENESS!!!
    SAFETY
    QUALITY….
    EFFICACY….
    GMP
    PRECAUTIONISM
    ASSUMED
    IGNORED
    (UNLESS POLITICS SAYS OTHERWISE)
  • 57. Blood components – Do they work?
    RCCs
    “To increase oxygen delivery to the tissues”…but
    Do tx red cells increase VO2 ?
    Yes, around the critical [Hb]ie about 50g/l, but
    At 80 g/l, no obvious effect (Walsh et al 2004)
    Platelets
    PLADO study – Low vs Medium vs High dose platelets
    Same clinical outcome irrespective of dose
    FFP
    Two higher quality trials - Both evaluated prophylaxis
    No benefit reported in either trial
    The move to component therapy was driven by need for plasma derivatives for a few, not to improve care for the majority of recipients
  • 58. What role can regulation have in a new blood safety paradigm?
    Regulation has contributed primarily to product quality through the pharmaceutical model
    However, regulators also assess and approve efficacy and therapeutic claims
    With the increasing cost and complexity of the blood system, consideration of such claims is becoming an urgent need
    Regulation also includes post-approval assessment and monitoring of therapeutic goods on the market
    Increasingly, blood systems have implemented systems for such assessment
  • 59. Proposed regulation of blood 2005-
    Tiered system geared to risk
    Risk seen as a function of
    Manufacturing complexity
    Source
    Historical use
    Established components exempt from efficacy assessment
    THIS PRINCIPLE DEMANDS REVISION
    “……the light of history will shine from their helmets……..”
    W.S.Churchill 1945
  • 60. “Safe…never as safe……safer than its ever been….safest in the world”
  • 61. Dr Janet Heinrich
    US GAO
    Congressional testimony 1999
    Australia is, indeed, in a very envious position. We have one of the world’s safest and best managed blood supplies…….
    Sen J McLucas,
    Minister for the TGA
    2007-09
    We are fortunate to live in a nation that has the safest blood supply in the world
    Tell ‘em Mo
    Blood Kills!
  • 62. Arboviruses in OzARCBS 08 (Communicable Diseases Australia) Aust N Z Public Health. 2008; 32:354-60
  • 63. The Dengue Story
    TGA concern early 2003 – request ARCBS to not use blood from Dengue areas
    ARCBS skepticism “…there is only minimal evidence for transfusion transmission, and no other country in the world has introduced severe restrictions…..”
    Interaction led to policy – 14 April 2003– use plasma for fractionation, discard transfusable components – during period of outbreak
    • TGA showed considerable courage – no other authority used this policy
    • 64. There was nothing “consensual” about this – synthesis of two views, still strongly held
    • 65. TGA – Dengue is a blood risk
    • 66. ARCBS – risk minimal and secondary to supply maintenance
  • Blood in Hospitals
  • 67.
  • 68. Moment of “Faine”Jon Faine Morning Program ABC Melbourne 27/8/07
    ………the Therapeutic Goods Administration is thinking only of blood and blood products, which they also licence, as a medicine and not as a gift from a donor………. Albert Farrugia, who's the - oh, a very senior person in the Office of Devices in the TGA. Well, my comment - my colleagues said that he was extremely upset at one of the presentations where they showed that one Melbourne hospital had been able to reduce the wastage of SFP - that's thawed but not transfused - down to about two per cent, which was really fantastic……..
  • 69. The Protective Effects of FFP on the Endothelium after Shock
    Holcomb IABS Cambridge 209
    Central hypothesis that FFP has the capacity to “normalize” injured endothelium by inhibiting and repairing the damage from a number of detrimental processes induced by Haemorrhagic Shock.
    49
  • 70. Holcomb IABS Cambridge 209
    50
  • 71. Acknowledgments
  • 72. Thanks to…….Innumerable colleagues from the Transfusion Family
    TWO RUTH SANGER RECIPIENTS !
    Manchester UK 1985
  • 73.
  • 74. Take care of all your memories, said Nick
    If you cannot relive them,
    And remember, when you come to heal the sick,
    That you must first of all forgive them
    Bob Dylan
  • 75. Final Thoughts of a TransfusionistHistory and Beliefs
    Whole blood transfusion for haemorrhage saved lives that would previously have been lost. Belief started there
    Blood became interdependent with the expanding medical industry: businesses and empires were built.
    We market the “gift of life” to encourage donors and we believe our own advertising
  • 76. Final Thoughts of a transfusionistHistory and beliefs
    Having failed to appreciate pathogen related risks for a long time, we now focus on marginal issues while major problems are ignored.
    Component therapy has been preached to the world by “experts” without regard to local needs
    We still damn whole blood without seeking evidence about when it might be a good treatment
  • 77. Consensual statements
    People who fail to tackle climate change are acting like an Austrian man who locked his daughter in a cellar for 24 years, an Anglican bishop has said.
    The Bishop of Stafford, Gordon Mursell, wrote in a parish letter that not confronting global warming meant people were "as guilty as" Josef Fritzl.
    BBC 2008
    British Foreign Secretary Compares Global Warming Theory Skeptics to Islamic Terrorists
    “...let us deny the terrorists the historical importance they claim to themselves………In practical terms that means avoiding the temptation to artificallypolarise debate. …..I've seen it so often in the long-running debate on climate change: wheel out the resident sceptic, however unrepresentative or discredited, to generate tension and voice provocative views …. it is not the way to build a common consensus on the ground we share...”
    Margaret Beckett
  • 78. John LockeEnglish Philosopher(1632-1704)
    Aaron Wildavsky
    American Political
    Scientist
    (1930-1993)
    “There must be more than one alternative policy ; they must come from more than a single source; and there must be sufficient dispersion of power in society so that competing sources of advice have a chance of being heard and acted upon”
    “New opinions are always suspected, and usually opposed, without any other reason but because they are not already common.”
    The best option is the one which persuades and can be justified
    The best process is the one which encourages argument
  • 79. Toads
  • 80. Towards a new paradigm…..and its already happening
    Whole blood needs to become a product again
    Supply to patients should not be impeded by non-clinical interests
    The blow torch of EBM needs to be applied to TM
    Plasma for fractionation should be collected for that purpose by the fractionating agency
    Safety concerns need to focus on real issues
    Vein to Vein means oversight over the whole transfusion chain
  • 81. And, remember, in defiance of “common sense”………..
    BECAUSE
    “If it ain’t broke, break it”
    Marvin Lee Aday
    (aka Meat Loaf)
    “there is a crack, a crack in everything,that’s how the light gets in” Leonard Cohen

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