A Framework for Applying the Precautionary Principle to Transfusion Safety

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  • RANSFUSION

    July 2011

    thesion

    an W

    there minimal cost associated with the removal of theincreasing costs and the adoption of safety measures doi:10.1016/j.tmrv.2011.01.004

    Transfusion Medicine Reviews, Vol 25, No 3 (July), 2011: pp 177-183 177principle with limited concern for competing issues,in particular, cost-effectiveness. The result has beena blood system with stringent safety measures but

    1009, Box 684, Ottawa, ON K1Y 4E9.E-mail: kwilson@ohri.ca0887-7963/$ - see front matter 2011 Elsevier Inc. All rights reserved.precaution that is being used is primarily one thatwould be defined as a strong interpretation of the

    Address reprint requests to Kumanan Wilson, MD, MSc,FRCP(C), Associate Professor, Ottawa Hospital, Civic Campus,1053 Carling Avenue, Administrative Services Building, Roomaddress theoretical risks. However, the approach toby transfusion safety committees around the worldas demonstrated by their proactive approaches to

    1been largely adopted either explicitly or implicitlyFrom the Department of Medicine, Ottawa Hospital Research

    Institute, University of Ottawa, Canada Research Chair inPublic Health Policy, Ottawa, Ontario.have an environmental dimension. The principle hasimplementing safety policies in advance of com-plete evidence of risk. Transfusion medicine has,arguably, pioneered the use of the precautionaryprinciple in public health safety for issues that do not

    precautionary principle, will be applied to transfu-sion medicine. This article will describe, from aprimarily Canadian lens, how the principle emergedas a dominate paradigm in transfusion medicine,tion of precaution can itself create risks to health byreducing the donor supply. This article provides a guideto applying precaution to matters of transfusion safety.Types of risk-based decision-making can be classified asstrong, intermediate/weak, or no precaution by deter-

    T HE PRECAUTIONARY PRINCIPLE hasemerged as a dominant paradigm governingrisk based decision-making in transfusion medi-cine.1 Motivated by a perceived failure to appropri-ately address issues of scientific uncertainty in thetransfusion transmission of hepatitis C and HIV,national blood systems have moved towardsexposure? (5) Is there a minimal negative health effectassociated with removing the exposure? Using thisapproach can help standardize the approach to applyingprecaution in transfusion safety. 2011 Elsevier Inc. All rights reserved.

    with comparatively prohibitive cost-effectivenessrations. As blood systems distance themselves fromthe tragedy of the transfusion transmission ofhepatitis C and HIV, reestablish confidence in theblood supply, and confront the realities of a globalfinancial crisis and increasing economic pressures,there will be a need to reexamine how thedefining the principle and recognizing that the applica-tion of the precautionary principle to transfusion medi-cine has presented some challenges including clearly

    large? (2) Is the consequence of the exposure serious?(3) Is the consequence of the exposure irreversible? (4) IsTMEDICINEREVIEWS

    Vol 25, No 3

    A Framework for ApplyingTransfu

    Kuman

    The precautionary principle has become highly influentialin the formation of policies concerning transfusionsafety. The adoption of the principle to addresstheoretical risks has resulted in highly risk averse policywhich has both enhanced the safety of the blood supplybut also contributed to rising blood costs. The applica-Precautionary Principle toSafety

    ilson

    mining the strength of evidence required to apply aprotective measure and the extent of the protectivemeasure applied. The decision on what type of precau-tion to implement can then be determined based on theresponse to the following questions for a given transfu-sion safety matter: (1) Is the extent of the exposure

  • 178 KUMANAN WILSONthe advantages and disadvantages of its application,and conclude with recommendations for how theprinciple can be adapted to be utilized in futuretransfusion safety decisions.

    PROBLEMS WITH EVIDENCE-BASEDDECISION-MAKING IN TRANSFUSION SAFETY

    The precautionary principle represents a para-digm in risk decision-making, providing a mecha-nism to guide policymakers in areas of scientificuncertainty.2 At the time when HIV and hepatitis Cwere being transmitted to thousands of recipientsthrough blood transfusion, decision-making intransfusion safety was being largely governed bya different paradigm, evidence-based medicine.3

    Evidence-based medicine was primarily intendedfor the care of individual patient and was aconsolidation of principles that had long existedin medicine and science. The movement reflected aconcerted effort to standardize the approach toexamining evidence and applying it to patients.4

    Evidence-based medicine is largely governed by ahierarchy of evidence where randomized controlledtrials are the gold standard and lower levels ofevidence are believed to be more susceptible to biasor systematic error.5

    In the 1980s and 90's there was a concerted effortto take the evidence-based medicine approach,which was designed for individual patient care, anduse it to guide decision making in the health systemin general.6 The call for an evidence based healthcare system influenced decision making in all areasof health care including transfusion medicine.However, the evidence-based medicine approachwas designed for individual patient care, and therewere potential problems with applying it to largepopulations. This was particularly true in publichealth and for matters of safety. An example of thiscould be seen in the decision on whether to adoptsurrogate testing for hepatitis C.The interpretation of the transfusion-transmitted

    viruses study published in the New EnglandJournal of Medicine in 1981 illustrated theproblems with rigid evidence-based approachesand adherence to a hierarchy of evidence.7 Thestudy demonstrated the potential usefulness ofalanine transaminase (ALT) as a surrogate markerfor what would later be identified as hepatitis C.While demonstrating some utility to the test, thestudy also demonstrated the potential for draw-backs. This was articulated in a separate articleexamining the questionwhere the authors concluded,...approximately 30% of PTH might be prevented,.70%will not be prevented, and that the preventionof 30% is in some doubt unless confirmed by arandomized clinical trial; the estimated additional$20 million in the annual cost of blood in the US andthe potential national loss of 45 000 donors and90 000 blood units. It is a difficult equation.8"Those concerns were reflected in testimony beforethe Canadian Blood Committee which stated thatthose countries which were implementing surrogatetesting were responding to nonscientific pressureand that Canada had an opportunity to assess thereasonableness of surrogate testing before facingthe considerable financial consequences.9 Theresult, in Canada, was a decision to forgo surrogatetesting until the results of a randomized controlledtrial were available, which would ultimately rein-force the value of the tests.10 Unfortunately, thedelay in implementing testing potentially contributedto thousands of individuals being infected withhepatitis C through blood products.Although in retrospect it may be easy to criticize

    the surrogate testing decision-making process, thedecisions need to be analyzed in the context inwhich they were being made.11 An evidence-basedhealth system requires high-quality data beforeadopting new measures. This often meant waitingfor the results of controlled trials and not acting onobservational data. Such a strategy is appropriatefor individual patient care. However, the manage-ment of transfusion transmission of hepatitis Cdemonstrated the limitations of this approach at thepopulation level and for matters of public healthsafety. This was clearly articulated by JusticeHorace Krever when he stated, the decision ofthe Red Cross not to implement anti-HBc and ALTtesting of blood donations in Canada as surrogatesfor non-A, non-B hepatitis was not an acceptableone.9 In his final report, Justice Krever argued thatthe safety of the blood supply is an aspect of publichealth, and, therefore, the blood supply systemmust be governed by the public health philosophy,which rejects the view that complete knowledge ofa public health hazard is a prerequisite for action.12Problems with rigid evidence-based approaches

    to establish risk are not limited to the delay inacquiring controlled trial data and the risk this delaymay pose to populations. In most instances, it is notethical or moral to conduct randomized controlledtrials to establish risk where doing so would result

  • 179APPLYING THE PRECAUTIONARY PRINCIPLE TO TRANSFUSION SAFETYin one arm of the trial being knowingly exposed tosomething which could cause harm. Furthermore,trials are best at ruling in an association and are notnecessarily intended to rule out risk. A negativestudy does not necessarily mean that an associationdoes not exist but simply that it did not meetstatistical significance.13

    THE PRECAUTIONARY PRINCIPLE

    Because of these limitations, an alternate para-digm for managing risk was sought. The precau-tionary principle emerged out of the Europeanenvironmental movement of the 1970s and reflecteda recognition of the limitations of scientific modelsto accurately describe complex issues pertaining toenvironmental harm.14 Since the time of its intro-duction, the precautionary principle has had asubstantial impact on environmental policy. It hasbeen incorporated into the 1992 Rio Declaration onEnvironment and Development and the MaastrichtTreaty Establishing the European Community.15,16

    The precautionary principle essentially states thatcomplete evidence of risk does not have to exist toprotect individuals and society from the risk. TheWingspread Statement defines it as follows: Whenan activity raises threats of harm to human health orthe environment, precautionary measures should betaken even if some cause and effect relationships arenot fully established scientifically. In this context,the proponent of an activity, rather than the public,should bear the burden of proof.17Although well established as a fundamental tenant

    of environmental policy, the principle has beencontroversial. Of most significance is the difficulty inobtaining a consensus on how the principle should bedefined.18 Other criticisms of the use of theprecautionary principle include the problem withdetermining how much evidence is needed tointroduce a precautionary measure, over-regulation,and the loss of beneficial new technologies that mayresult from precautionary measures and the potentialto create unnecessary fear about theoretical risks.19,20

    However, in public health, there are otherconcerns with the use of the principle. Theseprimarily relate to the use of precaution resulting inthe decision to not adopt a measure whose absencecan cause harm in and of itself.21,22 Examples ofthis include concerns about dichlorodiphenyltri-chloroethane (DDT) and bioaccumulation, whichresulted in a ban on the substance in the UnitedStates and pressure on developing countries to doso as well. South Africa, which had been usingDDT for malaria control, introduced a ban based onthe theoretical concerns, which was followed by aresurgence of malaria deaths.23 Another exampleincludes the decision by Zambia to reject donationof genetically modified food in the presence offamine and quoting the precautionary principle as aprimary reason for this decision.24 In transfusionmedicine, the analogy would be the impact onblood supply of safety measures that restrict donors.

    THE PRECAUTIONARY PRINCIPLE INTRANSFUSION MEDICINE

    In Canada, as described, a judicial inquiryexamining the management of transfusion transmis-sion of hepatitis C and HIV effectively called for theuse of the precautionary principle.25 The recreatedblood system was guided by the precautionaryprinciple and the fundamental tenant that safety isparamount. Early evidence of the principle's influ-ence was apparent in the decision-making process toprotect the blood supply from potential contamina-tion with variant Creutzfeldt-Jakob disease. Thisthreat manifested itself immediately upon creation ofthe new blood system. The decision to introduce adonor deferral policy excluding individuals who hadlived for 6 months in the United Kingdom during thepeak of the Bovine Spongiform Encephalopathyoutbreak reflected an effort to balance protection ofthe blood supply against the impact on reduction ofdonors.12 Importantly, this decision was made purelyon a biological model of potential harm and in theabsence of any case reports or even animal data.26

    The emergence of subsequent evidence on thetransfusion transmissibility of vCJD supported theintroduction of the policy.27-30 The influence of theprecautionary principle continued in subsequentpolicy decisions. The blood system introduced adonor deferral policy during the SARS outbreak inthe absence of any evidence of risk, and immediatelyupon evidence of the possibility of West Nile virustransmission through blood products, the Canadianblood system instituted a product recall.31-34

    The introductions of precautionary measures inthe blood system, however, have created somechallenges. The first is the problem with a reductionin donors and potential impact on supply. Eachdonor deferral policy for a theoretical risk whittlesaway at the donor base and potentially restricts theblood systems' ability to introduce donor deferralpolicies in the future for risks with higher levels of

  • 180 KUMANAN WILSONcertainty. Another increasing concern is the impactof precautionary style decision-making on costs.The precautionary principle reflects an effort toachieve a zero risk blood supply. A parallel andclosely related policy process is the reducedtolerance for known but minimal risks. Part of thisis borne out of theoretical concerns about the riskbeing larger than expected or the possibility that theresidual risk could be amplified through continuedtransmission. Although distinct, the 2 approachesare attempting to achieve the same objective and areproducing similar consequences. One of these hasbeen a system that has not endured a serious safetycontroversy since HIV and hepatitis C. The secondis a system which is facing rising costs.How cost-effective is transfusion medicine?

    Although there is no established acceptable cost-effectiveness threshold for a medical technology,many accepted technologies in widespread use havecost-effectiveness estimates that range between$20 000-$100 000/quality-adjusted life year(QALY).35 However, the cost-effectiveness ratiosfor many safety measures in the blood system farexceed these levels.36 The cost-effectiveness ratiosof p24 antigen and nucleic acid amplificationtesting for HIV and hepatitis C virus are approx-imately $2 million/QALY.37 These prohibitivecost-effectiveness ratios are partly a consequence ofthe law of diminishing marginal returns. The firstdollar usually provides the greatest benefits a...

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