Transcript
Page 1: A Framework for Applying the Precautionary Principle to Transfusion Safety

TRANSFUSION

MEDICINE REVIEWS

Vol 25, No 3

July 2011

A Framework for Applying the Precautionary Principle toTransfusion Safety

Kumanan Wilson

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-tion of the precautionary principle to transfusion medi-cine has presented some challenges including clearlydefining the principle and recognizing that the applica-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-

Transfusion Medicine Reviews, Vol 25, No 3 (July), 2011: pp 177-18

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 exposurelarge? (2) Is the consequence of the exposure serious?(3) Is the consequence of the exposure irreversible? (4) Isthere minimal cost associated with the removal of theexposure? (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.

HE PRECAUTIONARY PRINCIPLE has with comparatively prohibitive cost-effectiveness

From the Department of Medicine, Ottawa Hospital ResearchInstitute, University of Ottawa, Canada Research Chair inPublic Health Policy, Ottawa, Ontario.

Address reprint requests to Kumanan Wilson, MD, MSc,FRCP(C), Associate Professor, Ottawa Hospital, Civic Campus,1053 Carling Avenue, Administrative Services Building, Room1009, Box 684, Ottawa, ON K1Y 4E9.

E-mail: [email protected]/$ - see front matter© 2011 Elsevier Inc. All rights reserved.doi:10.1016/j.tmrv.2011.01.004

T emerged 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 towardsimplementing 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 nothave an environmental dimension. The principle hasbeen largely adopted either explicitly or implicitlyby transfusion safety committees around the worldas demonstrated by their proactive approaches toaddress theoretical risks.1 However, the approach toprecaution that is being used is primarily one thatwould be defined as a strong interpretation of theprinciple with limited concern for competing issues,in particular, cost-effectiveness. The result has beena blood system with stringent safety measures butincreasing costs and the adoption of safety measures

rations. 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 theprecautionary 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,

3 177

Page 2: A Framework for Applying the Precautionary Principle to Transfusion Safety

178 KUMANAN WILSON

the 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 article

examining 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 pressure”and 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 criticizethe 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 that“the 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.12”

Problems with rigid evidence-based approachesto 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

Page 3: A Framework for Applying the Precautionary Principle to Transfusion Safety

179APPLYING THE PRECAUTIONARY PRINCIPLE TO TRANSFUSION SAFETY

in 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.17”

Although well established as a fundamental tenantof 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 do

so 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

Page 4: A Framework for Applying the Precautionary Principle to Transfusion Safety

180 KUMANAN WILSON

certainty. 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 andefforts to eliminate residual risk can be fare less cost-effective. For example, HIV antibody screening wascost-saving to $3600/QALY at the time of adoption,whereas the later HIV p24 and nucleic acidamplification testing tests had cost-effectivenessratios of greater than $2 million/QALY.37 For trulyprecautionary measures designed to address theoret-ical risk in the absence of complete evidence, thecost-effectiveness ratios are infinite since there is noscientific basis for benefit. In these cases, thepotential cost-effectiveness must be modeled basedon different scenarios. The consequence of thishighly risk averse approach to transfusion safety is asteady increase in the cost of blood products partlydue to the impact of the cost of the safety measures.38

ADAPTING PRECAUTION FORTRANSFUSION MEDICINE

The problems with precaution have resulted in aneffort by policy makers to guide decision-making.This is best reflected in the European Unions'

statement on the principle. This statement identified6 principles which should apply to the application ofthe precautionary principle: proportionality, non-discrimination, consistency, examining costs andbenefits, subject to review, and assigning responsi-bility for producing scientific evidence.39 In publichealth, the principle that precautionary measures beproportional to the risk that is presented isparticularly vital because of the potential for aprecautionary measure to cause harm. Similarly, inpublic health, precautionary decisions must besubject to periodic review given the likelihood ofscientific evidence accumulating on a matterfollowing a decision and the difficulties inherentin removing a safety measure once in place.

More controversial is the issue of examiningcosts and benefits. A strong interpretation of theprinciple, as articulated in the Wingspread State-ment, would argue against cost being a majorconsideration in precaution-based decision-making.Weaker interpretations, as articulated in the RioDeclaration on the Environment, explicitly call forthe implementation of cost-effective measures.15

To this point in time, the application of precautionin transfusion medicine has been more reflective ofa strong interpretation of the principle. Issues ofcost-effectiveness have not been highly weighted inthe use of the principle. However, this may need tobe reconsidered.

In a previous article in this journal, I described 4mechanisms by which precaution could be ap-plied.22 Strong precaution would be the introduc-tion of precaution on prima facie evidence of riskwith minimal to no consideration of the costs ofthese measures. A current example would beCanada's decision to declare bisphenol A a toxicsubstance because of concerns about its estrogenicproperties.40 On the other extreme is a strictadherence to evidence-based approaches and theneed for high-quality evidence to exist before actionis taken. A current example of this would be theUnited States Food and Drug Administration'sapproach to bisphenol A and the decision to defer aban until further evidence is available.41 In betweenare intermediate and weak measures which can callfor proportional or partial measures to be taken.This can include the partial introduction of a safetymeasure to balance the benefits of the measure withany potential harm, as was evident in the decision-making process concerning vCJD. Another optionis to delay introduction of measures until efforts to

Page 5: A Framework for Applying the Precautionary Principle to Transfusion Safety

Table 1. Mechanisms for Applying Precaution

Type of precautionStrength of evidenceneeded for action Extent of protective measure Example

Strong Low High • Canadian decision on bisphenol A• Donor deferral for individuals with Chronic Fatigue Syndrome

Intermediate/weak Low Low • vCJD donor deferral policies• Stockholm Convention on Persistent Organic Pollutants

No precaution:EBM approach

High Low to high, dependenton the evidence

• US approach to bisphenol A

Potential risk to transfusion safety

Is the consequence of the exposure serious? Is the consequence of the exposure irreversible?

Is the extent of exposure large?

If primarily affirmative:

Less evidence necessary

If primarily negative:

More evidence necessary

No precaution/ EBM approach

Extent of measure governed by evidence

Is there minimal negative health effect of removing the exposure?

Is there minimal cost associated with the removal of the exposure?

If primarily affirmative:

A more extensive precautionary measure is warranted

Strong precaution

If primarily negative:

A more limited precautionarymeasure is warranted

Intermediate/weak precaution

Fig 1. Algorithm for deciding on appropriate precautionaryaction.

181APPLYING THE PRECAUTIONARY PRINCIPLE TO TRANSFUSION SAFETY

control harm from the introduction of the measureare addressed, which was a strategy adopted toaddress DDT risks and benefits.42 I have adaptedthis approach as outlined in Table 1. In thisframework, the characterization of the level ofprecaution is more explicit and based on acombination of the strength of evidence requiredto trigger the action and the extent of the actiontaken. Strong precaution would be a situation inwhich the evidence of risk is low and the measurebrought in to control the risk is extensive. At theother end of the framework is the evidence-basedapproach where evidence of risk needs to be highbefore action is taken to protect against theexposure. The extent of the action would begoverned by the evidence that is available. Inbetween is an intermediate/weak approach wherethe strength of evidence to take an action canremain low but a proportional or partial responsecan be introduced.

So how does one determine what form ofprecaution to apply? This would depend on thecharacteristics of the problem that is beingaddressed. These characteristics relate to thefollowing 5 questions:

1. Is the extent of the exposure large?2. Is the consequence of the exposure serious?3. Is the consequence of the exposure

irreversible?4. Is there minimal cost associated with the

removal of the exposure?5. Is there a minimal negative health effect

associated with removing the exposure?

The more affirmative the responses to each of thefirst 3 questions, the less evidence that is necessaryto trigger a precautionary measure. The moreaffirmative the response to the last 2 questions, themore extensive the need for a precautionaryresponse. Figure 1 describes how a transfusionsafety issue could be assessed using an algorithm

that incorporates the elements of this framework.Looking at the scale of precautionary measures,primarily affirmative responses would triggeractions towards the top and primarily negativeresponses would trigger action near the bottom.

What would this approach look like in trans-fusion medicine? Going back to the transfusion-transmitted viruses study and the other accumulat-ing evidence at this time, the responses to the first2 questions would have been primarily affir-mative. The exposure was wide but not populationwide. The consequences of the exposure were notclearly known but, given the model of previouschronic hepatitis, could be expected to be seriousand irreversible. Thus, a moderate degree ofevidence is necessary to trigger a precautionarymeasure, and this was provided in the observationalstudy. However, the costs of the precautionarymeasure were significant from both an economicperspective and potential impact on supply.

Page 6: A Framework for Applying the Precautionary Principle to Transfusion Safety

182 KUMANAN WILSON

Therefore, a measured response could be justified.Based on this, an intermediate approach toprecaution could be implemented—one whichwould allow for some measure of protection to beintroduced until more definitive evidence becomesavailable. Another intermediate approach would beto have focused on improving the donor base andthen introducing the policy while waiting for theresults of additional studies. A similar conclusioncould be arrived at with vCJD and donor deferral. Infact, most measures in transfusion medicine wouldrequire intermediate approaches—exposures areextensive but not population wide, and conse-quences are often serious; however, costs andimpact on supply are important considerations. Anexample of a recent policy decision that would notbe supported by this framework is the decision bythe Canadian blood system to defer donations fromindividuals who have a history of chronic fatiguesyndrome because of a potential link with aretrovirus.43,44 Chronic fatigue syndrome is adebilitating condition for those who are afflicted,but it is not life threatening and remission ispossible. Therefore, a higher level of evidence isneeded to trigger a precautionary action. However,the action was triggered by biological evidence, andsome of this evidence is conflicting.45 Thus, a morestrict evidence-based approach, waiting for higher-quality evidence, would have been warranted in thisscenario. Pathogen inactivation technologies pres-ent an interesting dilemma. They potentially canprotect against many known and unknown patho-gens, some of which could have serious and

irreversible consequences.46 However, the costsof the technology are considerable. The technology,however, would have no impact on the bloodsupply. Thus, the introduction of the measures onreduced evidence is warranted, but the prohibitivecosts would suggest a partial introduction of thetechnology if this is feasible.46

The approach outlined above is consistent withthe European Union's guidance and implicitlyincorporates the principal in a manner which iseasier to operationalize. An explicit frameworkshould encourage consistency of application and anondiscriminatory approach. The concepts of pro-portionality and examining costs and benefits areexplicitly included in the framework. Any measurearrived through the use of such a framework shouldbe subject to periodic review as a necessary andcritical part of the entire process and should beparticularly important for implementation of inter-mediate measures. All affected parties would beresponsible for identifying evidence that informs theuse of this framework.

CONCLUSIONS

The move from a conservative evidence-basedmedicine approach to risk to a more liberalprecautionary approach was necessary and success-ful. In a new era of transfusion medicine, it is worthreconsidering the balance between safety and cost.The framework provided here may be a useful startin determining how to best adapt precaution totransfusion medicine.

REFERENCES

1. Wilson K, Ricketts MN: The success of precaution?Managing the risk of transfusion transmission of variantCreutzfeldt-Jakob disease. Transfusion 44:1475-1478, 2004

2. Kriebel D, Tickner J: Reenergizing public health throughprecaution. Am J Public Health 91:1351-1355, 2001

3. Vamvakas EC: Evidence-based practice of transfusionmedicine: Is it possible and what do the words mean? TransfusMed Rev 18:267-278, 2004

4. Sackett DL, Rosenberg WM, Gray JA, et al: Evidencebased medicine: What it is and what it isn't. BMJ 312:71-72, 1996

5. Upshur RE: Are all evidence-based practices alike?Problems in the ranking of evidence. CMAJ 169:672-673, 2003

6. National Forum on Health: Canada Health Action:Building on the Legacy—Volume I—The final report. Ottawa,Canada, Health Canada; 1997. http://www.hc-sc.gc.ca/hcs-sss/pubs/renewal-renouv/1997-nfoh-fnss-v1/index-eng.php#a3

7. Aach RD, Szmuness W, Mosley JW, et al: Serum alanineaminotransferase of donors in relation to the risk of non-A,non-B

hepatitis in recipients: The transfusion-transmitted viruses study.N Engl J Med 304:989-994, 1981

8. Alter HJ, Purcell RH, Holland PV, et al: Donortransaminase and recipient hepatitis. Impact on blood transfusionservices. JAMA 246:630-634, 1981

9. Krever H: Canada's rejection of surrogate testing.Commission of Inquiry on the Blood System in Canada. FinalReport. Vol. Chapter 24. Ottawa, Canadian GovernmentPublishing, 1997, pp 649-686

10. Blajchman MA, Bull SB, Feinman SV: Post-transfusionhepatitis: Impact of non-A, non-B hepatitis surrogate tests.Canadian Post-Transfusion Hepatitis Prevention Study Group.Lancet 345:21-25, 1995

11. Wilson K, Graham I, Ricketts M, et al: VariantCreutzfeldt-Jakob disease and the Canadian blood system afterthe tainted blood tragedy. Soc Sci Med 64:174-185, 2007

12. Wilson K, Hebert PC, Laupacis A, et al: A policy analysisof major decisions relating to Creutzfeldt-Jakob disease and theblood supply. CMAJ 165:59-65, 2001

Page 7: A Framework for Applying the Precautionary Principle to Transfusion Safety

183APPLYING THE PRECAUTIONARY PRINCIPLE TO TRANSFUSION SAFETY

13. Wilson K: Risk, causation and precaution. In: Bailey T,Caulfield T, Ries N, (editors): Public health law &policy in Canada,Vol. 3. Markham, ON, LexisNexis Butterworths, 2005, pp 59-87

14. Foster KR, Vecchia P, Repacholi MH: Risk management.Science and the precautionary principle. Science 288:979-981, 2000

15. United Nations. (United Nations): Report of the UnitedNations Conference on Environment and Development, RioDeclaration on Environment and Development, 1992

16. European Community. Treaty Establishing the EuropeanCommunity, Feb 7, 1992, reprinted in 31 ILM 247 art 130r(2)(1992)

17. Wingspread conference participants: Wingspread state-ment on the Precautionary Principle. Wingspread Conference.Racine, Wisconsin, 1998

18. VanderZwaag D: The precautionary principle inenvironmental law and policy: Elusive rhetoric and firstembraces. J Environ Law Pract 8:355-375, 1999

19. Goldstein BD, Carruth RS: Implications of the precau-tionary principle: Is it a threat to science? Int J Occup MedEnviron Health 17:153-161, 2004

20. Morris J: Defining the precautionary principle. In:Morris J,editor. Rethinking risk and the Precautionary Principle. Oxford,Butterworth-Heinemann, 2000, pp 1-21

21. Goklany IM: From precautionary principle to risk-riskanalysis. Nat Biotechnol 20:1075, 2002

22. Wilson K, Wilson M, Hebert PC, et al: The application ofthe precautionary principle to the blood system: The Canadianblood system's vCJD donor deferral policy. Transfus Med Rev17:89-94, 2003

23. Attaran A, Maharaj R: Ethical debate: Doctoring malaria,badly: The global campaign to ban DDT. BMJ 321:1403-1405,2000

24. BBC News: Famine-hit Zambia rejects GM food aid. 29October, 2002. http://news.bbc.co.uk/2/hi/africa/2371675.stm

25. Krever H: Commission of Inquiry on the Blood System inCanada. Final Report. Ottawa, Canada, Canadian GovernmentPublishing; 1997

26. Cashman NR: New variant Creutzfeldt-Jakob disease andthe Canadian blood supply: Scientific basis of risk. Report forLaboratory Centre for Disease Control, January 15, 1999

27. Wroe SJ, Pal S, Siddique D, et al: Clinical presentationand pre-mortem diagnosis of variant Creutzfeldt-Jakob diseaseassociated with blood transfusion: A case report. Lancet368:2061-2067, 2006

28. Llewelyn CA, Hewitt PE, Knight RS, et al: Possibletransmission of variant Creutzfeldt-Jakob disease by bloodtransfusion. Lancet 363:417-421, 2004

29. Hewitt PE, Llewelyn CA, Mackenzie J, et al: Creutzfeldt-Jakob disease and blood transfusion: Results of the UKTransfusion Medicine Epidemiological Review study. VoxSang 91:221-230, 2006

30. Wilson K, Ricketts MN: Transfusion transmission ofvCJD: A crisis avoided? Lancet 364:477-479, 2004

31. News CBC. Blood agency takes precautions againstSARS. 2003 Apr 11.

32. Pealer LN, Marfin AA, Petersen LR, et al: Transmissionof West Nile virus through blood transfusion in the United Statesin 2002. N Engl J Med 349:1236-1245, 2003

33. Vamvakas EC, Kleinman S, Hume H, et al: Thedevelopment of West Nile virus safety policies by Canadianblood services: Guiding principles and a comparison betweenCanada and the United States. TransfusMed Rev 20:97-109, 2006

34. Wilson K: The Krever Commission—10 years later.CMAJ 177:1387-1389, 2007

35. Laupacis A, Feeny D, Detsky AS, et al: How attractivedoes a new technology have to be to warrant adoption andutilization? Tentative guidelines for using clinical and economicevaluations. CMAJ 146:473-481, 1992

36. AuBuchon J, Petz L: Making decisions to improvetransfusion safety. In: AuBuchon J, Petz L, Fink A, (editors):Policy alternatives in transfusion medicine. Bethesda (Md),AABB Press, 2001, pp 184-226

37. van Hulst M, de Wolf JT, Staginnus U, et al: Pharmaco-economics of blood transfusion safety: review of the availableevidence. Vox Sang 83:146-155, 2002

38. Custer B, Hoch JS: Cost-effectiveness analysis: What itreally means for transfusion medicine decision making. TransfusMed Rev 23:1-12, 2009

39. Commission of the European Communities: Communi-cation from the commission on the Precautionary Principle.COM(2000) 1 (Brussels: 2 February 2000). http://ec.europa.eu/dgs/health_consumer/library/pub/pub07_en.pdf.2000

40. Canada Gazette Part II –Order Adding a Toxic Substanceto Schedule 1 to the Canadian Environmental Protection Act,1999 – SOR/2010-194. Vol. 144 No. 21. October 13 2010 (at1806-1818). Available: http://www.gazette.gc.ca/rp-pr/p2/2010/2010-10-13/pdf/g2-14421.pdf

41. vom Saal FS, Myers JP: Bisphenol A and risk ofmetabolic disorders. JAMA 300:1353-1355, 2008

42. United Nations Environment Programme. StockholmConvention of persistent organic pollutants. http://www.pops.int/documents/convtext/convtext_en.pdf. 2004

43. Lombardi VC, Ruscetti FW, Das Gupta J, et al: Detectionof an infectious retrovirus, XMRV, in blood cells of patients withchronic fatigue syndrome. Science 326:585-589, 2009

44. Kermode-Scott B:Canada bans blood donations frompeoplewith history of chronic fatigue syndrome. BMJ 340:c1974, 2010

45. Groom HC, Boucherit VC, Makinson K, et al: Absence ofxenotropic murine leukaemia virus-related virus in UK patientswith chronic fatigue syndrome. Retrovirology 7:1-10, 2010

46. Alter HJ: Pathogen reduction: A precautionary principleparadigm. Transfus Med Rev 22:97-102, 2008


Recommended