Some reflections on the Code of Ethics of the International Society of Blood Transfusion

Introduction

Following its then President’s reflections¹, the International Society of Blood Transfusion (ISBT) is reviewing its Code of Ethics² (“the Code”), which was developed over the 1970s and first published in 1980, to “define the ethical principles and rules to be observed in the field of transfusion medicine”³. Dr Flanagan drew particular attention to the tension between the Code and commercial plasmapheresis as a route to the manufacture of plasma products. It may well be expected that a document reflecting practice in the transfusion industry, mainly embedded in the Not-for-Profit (NFP) sector and specifying blood as a public resource, could grate with the predominantly commercial plasma product sector, particularly over the issue of paying plasma donors. This issue has long drawn controversy from different perspectives, which are unavoidable given that the transfusion sector itself is connected to the plasma product sector through the sale of its plasma for manufacture into commercial products. This article attempts to synthesise these perspectives into a practical framework for the delivery of these therapies today. One perspective, in agreement with the principles asserted in numerous documents, including that the human body and its parts should not be commercialised, is that the donation of blood should be a freely made and unpaid voluntary gesture. According to this perspective, any “reimbursement” should not be such as to distort the nature of the act, which should remain a donation and a gesture of altruism. Recent contributions^4–6 suggest that there are certain contradictions between the principle of non-commercialisation, the enormous movements of money inevitably involved in centralised blood systems, and the need to make the most of the system. As will be discussed in this article, from the ethical point of view these contradictions could be at least partially mitigated. We reflect on areas which have stimulated controversy and debate and offer a synthesis of views which may assist in the development of guidance for members of the ISBT in approaching a less absolutist, but more realistic, set of aspirational ethical principles in their practice. We consider that such a synthesis is preferable to an attempt at consensus, believing that such attempts, as discussed by Farjaudon and Morales⁷, could reflect the imposition of one set of dominant interests over another. We will exemplify where we feel that this has happened in the particular landscape covered by this work.

The individual Clauses of the Code are addressed in turn.

Clause 1

This Clause currently states: “Blood donation including haematopoietic tissues for transplantation shall, in all circumstances, be voluntary and non-remunerated; no coercion should be brought to bear upon the donor. A donation is considered voluntary and non-remunerated if the person gives blood, plasma or cellular components of his/her own free will and receives no payment for it, either in the form of cash, or in kind which could be considered a substitute for money. This would include time off work other than that reasonably needed for the donation and travel. Small tokens, refreshments and reimbursements of direct travel costs are compatible with voluntary, non-remunerated donation...”.

The issues underpinning this Clause are the foremost drivers in the ISBT’s current reflections on its Code. The emotive issue of donor motivation and compensation has been reviewed from different perspectives^8,9. Clause 1 reflects statements from the World Health Organisation (WHO) and the Council of Europe (COE)¹⁰ underpinning the Code which appear, more often than not, to be observed in the breach. It is difficult to reconcile many of the benefits used to reward blood donors in landscapes claiming to adhere to this definition⁴. The word “reward” is used intentionally in concordance with the recent considerations of the Nuffield Council on Bioethics¹¹ which have been the subject of extensive comment⁴, outlining the ethical concerns which may ensue, and which are among the sources used by the ISBT in its review of the Code³. The gradualist basis of the Nuffield concept, recognising the need to assess ethical issues as a spectrum of complexity, is especially useful. For example, the characterisation of paid plasma donation, clearly positioned on Rung 6 of the Nuffield “ladder” (Table I) as “ethically vindicated” (page 196 in the Nuffield report)¹² on the basis of clinical need and regulated safety measures, would be a preferable designation to an absolutist, “unethical”, label. These safety measures have also ensured that, despite the unfavourable epidemiology of some paid donors¹³, the recipients of therapies manufactured from paid donor plasma have been free from infection for the past 25 years¹⁴. Close examination of the Nuffield framework may also allow recognition of the motives of donors which can lend themselves to inclusion in the Code. In this context, language, as proposed in a recent review¹⁵, requires alignment with reality. Given that donation is, ipso facto, gratis, appropriate language should be developed to include the individuals who contribute to the world’s supply of essential blood-derived therapies, receiving benefit in return. Hence, the word “providers” may be considered to describe all the individuals contributing to the blood supply, irrespective of motive. For the purposes of the Nuffield ladder of donor incentives (Table I), in the “altruistic” and “non-altruistic” rungs the designations “donor” and “supplier” may be further considered.

Table I.

Proposed classification of the contributors to the blood supply chain relative to the Nuffield framework¹².

Rung of altruism	Type of encouragement	Example in the blood industry	Proposed classification (this paper)
1	Information about the need for the donation of bodily material for others’ treatment or for medical research		Donor
2	Recognition of, and gratitude for, altruistic donation, through whatever methods are appropriate both to the form of donation and the donor concerned	Awards, medals, etc. to unpaid donors	Donor
3	Interventions to remove barriers and disincentives to donation experienced by those disposed to donate	Reimbursement for travel expenses to donate	Donor
4	Interventions as an extra prompt or encouragement for those already disposed to donate for altruistic reasons	Small gifts, refreshments, etc. to unpaid donors	Donor
5	Interventions offering associated benefits in kind to encourage those who would not otherwise have contemplated donating to consider doing so	Paid time off over and above what would be reasonably associated with donation	Supplier
6	Financial incentives that leave the donor in a better financial position as a result of donating	Direct cash payment and access to improved services, e.g. health as a result of donation	Supplier

The exact position of various groups of donors in the current broad landscape does, however, merit further scrutiny. An important differentiation should be whether the incentive offered affects the decision to donate. For example, individuals offered the incentives in Rung 2 may well have doubts cast on their altruistic status if one considers that public recognition affects their willingness to donate, and the more public the recognition, the greater the willingness¹⁶. This kind of outcome led Didier Sicard, the President of the French National Institutional Review Board, to question the social valorisation of blood donation: “What is true voluntarism? I was very surprised when working with the Assistance Publique for 10 years by the confusion between voluntarism and the recuperation of half a day off work, always the same, over the Whitsun or Ascension Day bank holiday, and sometimes full days. I always asked myself how you could reconcile voluntarism with this reimbursement in the form of working days. 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 medals - with perfectly identifiable people. With this, maybe excessive visibility, aren’t there grounds to question the links between voluntarism and anonymity. In this kind of voluntarism, doesn’t the counter donation seem to have undermined the real interest of the other and consequently, the safety requirements?”¹⁷.

To which Bourdieu’s contention may be added: “There is no society that does not render homage to those who render homage to it in seeming to refuse the law of selfish interest”¹⁸.

Sicard’s point regarding another well-known incentive in the form of day’s off work is also well-taken. This inducement is well established in countries such as Italy¹⁹ and Greece²⁰. The Nuffield report suggests that such an intervention would be positioned on Rung 3 (page 189 of the report)¹². We would pose the question as to whether this type of inducement is sufficient to propel donors to Rung 5, given that the Nuffield report suggests that donors who are employees ensure maximisation of this benefit to levels exceeding the losses in time incurred through donation¹⁹. Similarly, plasma and platelet donors in Austria and Germany are paid a carefully calibrated amount, legally specified to not exceed a day’s wage^21,22, intended to prevent more financial gain than might otherwise have been the case. This may well position some individuals in Rung 3 rather than Rung 6.

The plethora of substantial material benefits includes the system of calibrated medical benefits in Malaysia²³, giving donors increasingly greater access to free private health care depending on how many donations are given. The latter is possibly an example of what the Nuffield Council specifies as a benefit closely associated with the donated material, but a “Rung 6” benefit nevertheless. The USA Food and Drug Administration’s definition of allowable benefits specifies that they cannot be converted into cash²⁴, an issue with benefits such as blood credits for possible transfusion, which have become a tradable commodity in South Korea²⁵. It may be perceived that the role of such benefits in economically pressured situations is resonant with coercion. Such benefits will also move many donors currently in the altruistic landscape into “non-altruistic” rungs of the Nuffield scheme. It is very difficult to assess what individuals accessing these benefits are really feeling, but “Rummaging in our souls, we often dig up something that ought to have lain there unnoticed”²⁶.

In a world in which demographics are remorselessly eroding the traditional donor base²⁷, the blood delivery system, in whatever form it takes, needs to grapple with the reality that the exclusion of groups of donors and suppliers because of considerations other than patients’ welfare will undermine the basis for the existence of blood transfusion. Irrespective of the motivation of individuals who contribute to the delivery of blood therapies, all such individuals are entitled to basic and immutable human rights and dignity. Among these rights one of the primary should be the absence of coercion in all its forms, including that found in systems which, while claiming adherence to the WHO principles, have instituted processes such as blood quotas, compulsory collection from students and compulsory replacement of transfused blood^28,29. All organisations involved in blood procurement have a duty of care to ensure the preservation of the welfare of all providers, as detailed in the Nuffield document. The issues of the effect of frequent blood³⁰ and plasma³¹ harvesting on the health of the individuals concerned is especially pertinent.

Pondering on the intent of Clause 1, the emphasis is on the principle that the human body should not give rise to financial gain. This issue has been reviewed³² relative to the Oviedo Convention³³. While the principle cited underpins biolaw, a recognition of a right of property by an individual over that individual’s body or parts thereof may, paradoxically, reinforce the principle as such a recognition requires that explicit consent must be sought for a specific use of that body or part. The principle of explicit and informed consent is inseparable from the intent of Clause 1 and will be discussed further below.

Coercive pressures may underpin blood donation even in unpaid donor systems. In China, despite their formal abolishment³⁴, a number of measures still play a role in eliciting blood donation, including enforced quotas at the community and workplace level²⁸. We are concerned that socio-economic coercion can play a role in paid donation, which we have proposed is associated mainly with the lower levels of Maslow’s Hierarchy of Needs³⁵, and may affect donors’ health. We suggest that the protection of the health of donors, whether paid or unpaid, linked as it is to the frequency of donation which is a regulated activity, needs to be formally recognised in the Code. To summarise, to the extent possible, the issues around this clause, providers of blood are recognised as being motivated by a number of factors. Donors who contribute altruistically and other suppliers who receive material rewards in money or in kind are all important in ensuring adequate and safe supplies of blood and blood products.

A pragmatic synthesis of these considerations could underpin a revised Clause 1: “All provision of blood and related tissues should be freely undertaken with full consent, without coercion, and respecting human rights and the dignity of the providers. The health of the donor must be the primary factor in shaping donation practices”.

It is hoped that the synthesis offered permits the ISBT to maintain its commitment to its historical value base while recognising the realities which permeate its own landscape.

Clause 1 continues: “The donor should provide informed consent to the donation of blood or blood components and to the subsequent (legitimate) use of the blood by the transfusion service”.

We discuss this component further in our review of Clause 3.

Clause 2

Clause 2 currently states: “A profit motive should not be the basis for the establishment and running of a blood service”.

The issue of commercialisation also underpins Clause 2. The intent, and its link to the ethos of Clause 1, is clear. In the real world of globalised commerce, with governments rapidly divesting themselves of their historical enterprises in social capital, no area of enterprise can operate outside the reality of the market. The blood sector’s historical adherence to Titmuss’ welfarist resistance to the concept of health’s inclusion in the market economy³⁶ is a source of anguish to many, compounded by the enthusiasm with which social market economies including the United Kingdom have dismantled much of the national health fabric. Segregating, as far as possible, the issue of donor payment, these developments may be observed in the traditional NFP landscape.

1. In countries in which no segment of the NFP blood sector is granted a monopoly, competition for the consumer (hospital) market occurs in a manner indistinguishable from normal free market commerce. This is most particularly visible in the USA where the organisations under the umbrella of America’s Blood Centres compete ferociously with each other and with the American Red Cross^37,38. This reality appears to be recognised as well by the NFP European Blood Alliance (EBA) which states: “EBA recognises that there is a place for competing blood services, provided that the competition is fair, i.e. is between serious long-term players who are meeting their full obligations under the Blood Directive and State law and operate under similar regulatory and inspection regimes” ³⁹.

2. The NFP plasma fractionation sector, under the umbrella of the International Plasma Fractionators Association (IPFA), includes companies such as the French LFB and the Dutch Sanquin which are statutorily required to ensure a margin for their products from their main stakeholders i.e. the respective national governments. The UK government has sold 80% of the former national fractionator BPL to Bain capital.

3. The corporate ethos permeating even the NFP sector is evident when one scrutinises the compensation and related conditions of the senior executives of the major blood agencies.

All these realities cause us to ponder on the basic nature of these NFP agencies within the blood sector and their differentiation from businesses. We reflect on the purpose of businesses as suggested by Sternberg “The defining purpose of business is maximizing owner value over the long term by selling goods or services”⁴⁰ (our italics). It is clear that no organisation involved in the procurement and delivery of blood can afford to run at a loss, as may be observed in the ongoing crisis in the traditional blood sector as it grapples with the revenue losses imposed by the changing clinical landscape⁴¹. What, therefore, is the characteristic differentiating large blood providers such as the various Red Cross organisations, the self-designated NFP plasma product sector grouped under the IPFA and similar agencies, and the clearly commercial plasma product industry composed of large multinational corporations? It may be argued that generating a return for shareholders constitutes the imperative for such corporations, but how does this sit with the undeniable need for the “NFP” agencies such as those specified, to generate a return for the respective governments, parent organisations etc. which own these agencies? The British government’s decision to sell its fractionator after many years of losses offset by public subsidy shows the reality in which such agencies operate. We reflect on the anomalies and lack of transparency evident in such agencies, exemplified by the apparent cross-subsidisation across product types⁴², the use of taxes unrelated to the blood system to subsidise plasma prices⁴³ and their use of plasma from paid donors for activities which are clearly for profit⁴⁴. The anomalies regarding the NFP sector have been extensively analysed^45–48. Surveying the landscape of NFP blood agencies, their commitment to continuous improvement, research and other activities is clear. These activities demand frequent investment. The need to make a return on investment, or, in common parlance “make a profit”, whether it is through social or financial capital, is imperative for all blood organisations, whether they are NFP or for profit.

A necessary corollary to this discussion is the assessment of the effect of increasing commercialisation on the traditional NFP blood sector. The sector now represents a multibillion dollar industry that delivers products in the developed countries through blood organisations which, in multi-supplier systems such as in the USA, compete vigorously for a market estimated at $9.5 billion in the USA in 2012⁴⁹. The progression of a modest technology assisting medical practice to a specialty in its own right has clearly generated a substantial nexus of interests, commercial, academic and otherwise, which have, arguably, detached from the patient interface. There is little discernible difference between the for-profit and NFP sectors in this regard.

These realties may still reflect the intent of Clause 2 when this is worded as follows: “The operation of modern blood services within a free market framework should occur in a way respectful of donors, suppliers and patients, and care should be delivered ethically and not impeded by organisational or business interests”.

Clause 3

Clause 3 currently states: “The donor should be advised of the risks connected with the procedure; the donor’s health and safety must be protected. Any procedures relating to the administration to a donor of any substance for increasing the concentration of specific blood components should be in compliance with internationally accepted standards”.

The current wording of Clause 3 seeks to imprint informed consent into the donation/supply process in relation to the health of the individuals concerned. This needs to be extended to the whole donation process. We refer to the second component of the current Clause 1: “The donor should provide informed consent to the donation of blood or blood components and to the subsequent (legitimate) use of the blood by the transfusion service”.

Donated blood which is used by both NFP and for-profit agencies has a commercial value. The clear example of agencies in the USA which sell directly to hospitals is only one manifestation of this reality. Most of the agencies recovering plasma from whole blood donations sell the portion of this valuable material which is surplus to their transfusion requirements, mostly to the for-profit fractionation industry for manufacture into products for commercial sale⁵⁰. The NFP agencies argue that through this “legitimate” use (Clause 1 current language) they are optimising the donors’ gift by ensuring that a valuable part of blood is not wasted but instead gives rise to life-saving therapies. Additionally, it is claimed that the revenue generated is not part of a profit construct but simply recovers the cost involved in generating the plasma. These statements have not been tested through rigorous economic analysis. Doubts also exist as to the extent to which donors are informed that parts of their donation will be subject to commercial trafficking, irrespective of the cause. It has been pointed out³² that if the right of property exists over the human body, then it follows that explicit consent must be sought for a specific use. Lenk and Beir⁵⁰ propose that a triad of more information, more detailed ethical analysis and clear normative statements should assist in approaching an enhanced positioning of informed consent in the donation process.

We propose a new Clause 3 synthesised from the issues involved in the informed consent required for all aspects of blood procurement: “The health of all blood providers should be protected through rigorous standards reflecting all the evidence available. They should be fully informed of the risks involved in donation, and of the uses made of their blood, through processes which are independent of the commercial interests involved, and they should give their explicit consent to these uses”.

Clauses 4 and 5

• - Clause 4. Anonymity between donor and recipient must be ensured except in special situations and the confidentiality of donor information assured.

• - Clause 5. The donor should understand the risks to others of donating infected blood and his or her ethical responsibility to the recipient.

We see no need to modify the current Clauses 4 and 5.

Clause 6

Clause 6 currently states: “Blood donation must be based on regularly reviewed medical selection criteria and not entail discrimination of any kind, including gender, race, nationality or religion. Neither donor nor potential recipient has the right to require that any such discrimination be practiced”.

Issues of donor selection relative to gender and sexuality have occupied the sector for many years. As an example, the problematic issue of males having sex with males (MSM) has been a source of contention; ongoing developments are leading to a relaxation of the measures, initially established to address the risk of transmission of human immunodeficiency virus, which are now redundant as a result of advances in donor testing. The MSM ban has had other consequences interpretable as gender-based discrimination, in that the USA Food and Drug Administration has interpreted the ban as extending to people of transgender status when born male⁵¹. The process of donor/supplier selection is, by definition, selective, but not inherently discriminatory. Discrimination occurs when selection measures are without justification or only weakly justified without evidence. We propose that selection measures require reflection concerning:

1. the position of the patient, which will be discussed further below;

2. the need for regular review, which is an essential element of any application of the precautionary principle which has underpinned much of blood transfusion policy over the past decades⁵².

We propose synthesising Clause 6 to: “Blood providers should be educated that their contribution to the blood supply does not constitute a right, but a responsibility to the recipients of their blood. Any measures introduced to ensure selection of safe providers should be supported by evidence of their effect on both providers and recipients, and subject to continuing review”.

Clauses 7 to 9

• - Clause 7. Blood must be collected under the overall responsibility of a suitably qualified, registered medical practitioner.

• - Clause 8. All matters related to whole blood donation and haemapheresis should be in compliance with appropriately defined and internationally accepted standards.

• - Clause 9. Donors and recipients should be informed if they have been harmed.

We see no need to modify the current Clauses 7 to 9.

Clause 10

Clause 10 currently states: “Blood is a public resource and access should not be restricted”.

The issue of access is central to the intent of the Code. This importance demands reflection through expanding the position of the patient in the blood transfusion chain. The realities of the commercial issues around blood therapies also require appreciation. If the phrase “public resource” is interpretable as resonating to the exclusion of the commercial sector, as is evident in processes such as the WHO’s constant iterations⁵³, then we would reiterate, on our part, our assertions above. We would summarise these as proposing that access would certainly be catastrophically restricted if the private sector were to be excluded from the blood system.

We propose to synthesise Clause 10 as: “Evidence-based clinical indications should be the only criteria for free and open access to blood-derived therapies”.

The position of the patient

One of us (AF) has proposed that a necessary paradigm shift in blood transfusion would place the patient at the centre of all decisions and attendant processes⁵⁴. This apparently obvious principle requires constant iteration as blood transfusion continues its apparently inexorable evolution from a modest medical technology to a complex multi-billion dollar industry, with increasing detachment from its core mission of alleviating illness.

Clauses 12 to 17

Clauses 12 to 17 of the Code address patient issues:

• - Clause 12. Patients should be informed of the known risks and benefits of blood transfusion and/or alternative therapies and have the right to accept or refuse the procedure. Any valid advance directive should be respected.

• - Clause 13. In the event that the patient is unable to give prior informed consent, the basis for treatment by transfusion must be in the best interests of the patient.

• - Clause 14. Transfusion therapy must be given under the overall responsibility of a registered medical practitioner.

• - Clause 15. Genuine clinical need should be the only basis for transfusion therapy.

• - Clause 16. There should be no financial incentive to prescribe a blood transfusion.

• - Clause 17. As far as possible the patient should receive only those particular components (cells, plasma, or plasma derivatives) that are clinically appropriate and afford optimal safety.

The position of the patient in all medical matters suggests that these and all other patient issues are positioned first in the Code. The principle would be reinforced by the following preamble: “Blood transfusion and the collection, manufacture and supply of blood and its constituents is conducted for the benefit of patients needing these therapies. All the ethical principles specified in this code should be compatible with this principle”.

This would bring the Code into conformity with other processes emphasising the role of the patient, including Patient Blood Management (PBM) and Patient-Centred Outcomes Research (PCOR) which are driving modern trends in healthcare.

Clause 18

Currently Clause 18 states: “Blood transfusion practices established by national or international health bodies and other agencies competent and authorized to do so should be in compliance with this code of ethics”.

The ISBT’s position as a peak body is acknowledged but the current wording of Clause 18 is somewhat hubristic. Matters of national sovereignty sometimes require primacy for national legislative requirements. In addition, we question the concept of legitimising a set of ethical requirements by imposing them through bodies operating under national or international law.

A possible rewording of Clause 18 which reflects this reality could be: “This Code is recommended for the consideration of all national and regional health care bodies seeking to align their decision making to an ethical framework”.

Conclusions

The blood transfusion landscape is rich in problems which evoke strong responses from the field’s participants. The issues discussed in this contribution are controversial and include areas in which consensus, even in the broad context of the ISBT, is difficult to attain. The ISBT’s initiative to start this process is commendable. A Code observed, tacitly or otherwise, in its breach has limited use and we agree that “Official documents should effectively address the reality of medicine, and not calm patients and citizens by avoiding problematic issues”⁵⁰. We propose that refocusing the issues discussed in this paper towards the ISBT’s membership through a set of aspirational principles may prove more useful than establishing an absolutist code seeking to draw legitimacy from external endorsement. While trying to avoid codifying current practice, we have attempted a synthesis between ethics and reality as the goal of the exercise undertaken by the Society. “With malice towards none, with charity for all, with firmness in the right”⁵⁵, we hope to have contributed some modest guidance to the ISBT in its worthy endeavour.