the cost-effectiveness of introducing nucleic acid testing to test for hepatitis b, hepatitis c, and...

B L O O D D O N O R S A N D B L O O D C O L L E C T I O N

The cost-effectiveness of introducing nucleic acid testing to testfor hepatitis B, hepatitis C, and human immunodeficiency virus

among blood donors in Sweden_2877 421..429

Thomas Davidson, Bengt Ekermo, Hans Gaines, Birgitta Lesko, and Britt Åkerlind

BACKGROUND: The purpose of this study was to esti-mate the cost-effectiveness of using individual-donornucleic acid testing (ID-NAT) in addition to serologictests compared with the sole use of serologic tests forthe identification of hepatitis B virus (HBV), hepatitis Cvirus (HCV), and human immunodeficiency virus (HIV)among blood donors in Sweden.STUDY DESIGN AND METHODS: The two strategiesanalyzed were serologic tests and ID-NAT plus sero-logic tests. A health-economic model was used to esti-mate the lifetime costs and effects. The effects weremeasured as infections avoided and quality-adjustedlife-years (QALYs) gained. A societal perspective wasused.RESULTS: The largest number of viral transmissionsoccurred with serologic testing only. However, the risksfor viral transmissions were very low with both strate-gies. The total cost was mainly influenced by the costof the test carried out. The cost of using ID-NAT plusserologic tests compared to serologic tests alone wasestimated at Swedish Krona (SEK) 101 million (USD12.7 million) per avoided viral transmission. The costper QALY gained was SEK 22 million (USD 2.7 million).CONCLUSION: Using ID-NAT for testing against HBV,HCV, and HIV among blood donors leads to cost-effectiveness ratios that are far beyond what is usuallyconsidered cost-effective. The main reason for this isthat with current methods, the risks for virus transmis-sion are very low in Sweden.

Blood components are needed in relation to majorsurgery, trauma and/or accidents, burn injuries, obstetrichemorrhage, blood replacement in neonates, prematurity,and other causes of acute and chronic anemia. A recentpublication revealed that the majority of red blood cellunits are transfused with a high degree of clinical urgency,with only a minor proportion required to support electivesurgery.1 Blood transfusions given on the correct indica-tion are therefore vital for many patients. Approximately500,000 blood donations take place annually in Sweden,and the ratio of transfused components to donations isapproximately 1.5.2 For each donation, the donor mustcomplete a health form covering those factors whichwould temporarily or permanently prevent donations.

To test whether blood donors are infected with hepa-titis B virus (HBV), hepatitis C virus (HCV), or humanimmunodeficiency virus (HIV), the current practice inSweden is serologic testing (analysis for identification ofthe antibody, antigen, or antigen and antibody in combi-nation). Most laboratories in Sweden test for both HIV

ABBREVIATIONS: ID-NAT = individual-donor nucleic acid

testing; IWP = infectious window period; MP-NAT = minipool

nucleic acid testing; QALY(s) = quality-adjusted life-year(s);

SEK = Swedish Krona.

From the Center for Medical Technology Assessment (CMT), the

Department of Clinical and Experimental Medicine, and the

Department of Clinical Microbiology, Linköping University, and

the Department of Clinical Immunology & Transfusion Medi-

cine, Linköping University Hospital, Linköping, Sweden; and

the Swedish Institute for Infectious Disease Control and the

Swedish National Board of Health and Welfare, Stockholm,

Sweden.

Address reprint requests to: Thomas Davidson, Center for

Medical Technology Assessment (CMT), Department of Medical

and Health Sciences, Linköping University, SE 581 83 Linköping,

Sweden; e-mail: [email protected].

Received for publication March 21, 2010; revision received

June 20, 2010, and accepted July 16, 2010.

doi: 10.1111/j.1537-2995.2010.02877.x

TRANSFUSION 2011;51:421-429.

Volume 51, February 2011 TRANSFUSION 421

antigen and HIV antibody (HIV combined test). However,despite these tests for infection, there is always an infec-tious window period (IWP) during which the infectioncannot be detected. If the serologic tests are combinedwith nucleic acid testing (NAT), the IWP can be shortened,thus decreasing the risk of viral transmission. NAT can beused to test for the three infections separately or in com-bination. Furthermore, NAT can be used either on indi-vidual donors (ID-NAT) or on minipools (MP-NAT).ID-NAT provides the highest safety but is more expensivethan MP-NAT. In this study we focus on ID-NAT, becausethis is the method discussed to be potentially introducedin Sweden (as it was in Denmark and Finland) due to thelow viral load in the preseroconversion window phaseamong blood donors.3

Introducing ID-NAT as an additional test for blooddonors in Sweden would increase the direct costs. It isthus important to study its cost-effectiveness, to ensurethat optimal use is made of scarce health care resources. Acost-effectiveness analysis compares the additional costsand effects of one treatment strategy with a comparativestrategy, to generate an incremental cost-effectivenessratio. The effects can be estimated in any relevantoutcome measure; one of the most common is quality-adjusted life-years (QALYs). A QALY is a measure that com-bines the value of a health state with the number of yearslived in that state of health.

Some previous studies have examined the cost-effectiveness of NAT as a method for identification of HBV,HCV, and HIV among blood donors,4-6 and a number ofother researchers have also considered the question inhealth-economic terms.7-10 All of these studies found thatNAT leads to lower viral transmissions but also to highercosts, with cost-effectiveness ratios much higher thanwhat is normally considered cost-effective in Sweden aswell as in other countries. However, the above-mentionedstudies are some years old and notbased on Swedish data. Therefore, acost-effectiveness analysis based on thecurrent decision problem for Sweden,and using Swedish data, is of impor-tance for decision-makers.

The purpose of this study was toestimate the cost-effectiveness of usingID-NAT in addition to serologic testscompared with the sole use of serologictests for the identification of infection

with HBV, HCV, and HIV among blood donors inSweden.

MATERIALS AND METHODS

The two strategies analyzed were serologic tests andID-NAT plus serologic tests (see Table 1). Since the conse-quences of virus infection give rise to costs and effectsover a long period, a health-economic model was used toestimate the lifetime consequences. An additional advan-tage of using this model was that data from differentsources could form the basis of the weighted result. QALYswere used as the main outcome measure, and cost peravoided viral transmission was also calculated. The modelwas programmed and analyzed using computer software(Microsoft Office Excel, Microsoft Corp., Redmond, WA).

The model was constructed as a decision tree (seeFig. 1). The tree starts with a blood donor and then one ofthe two strategies for testing for HBV, HCV, and HIV isselected. Only two possible outcomes per branch exist;either the blood recipient becomes infected or not. Eachstrategy involves a certain cost and a certain effect calcu-lated for a lifetime.

In accordance with Swedish guidelines,11 a societalperspective was chosen for the analysis. In this perspec-tive, all the costs and effects that occur in society are takeninto consideration in the analysis, regardless of where,when, or to whom they occur. Future costs and QALYswere discounted by 3% annually. All costs were calculatedin Swedish Krona (SEK) and US dollar and updated to 2009year price level.

Characteristics of the blood recipientsThree scenarios were analyzed. The base case used themedian age of blood recipients (73 years).12 Since the

Blood recipient infected

Serologic tests

Blood recipient not infected

Blood donor

Blood recipient infected

ID-NAT + serologic tests

Blood recipient not infected

Fig. 1. The structure of the decision tree.

TABLE 1. Test methods divided by virus for each strategy*Strategy HBV HCV HIV

Serologic tests HBsAg Anti-HCV Anti-HIV or HIV combinedID-NAT + serologic tests HBV ID-NAT + HBsAg HCV ID-NAT + anti-HCV HIV ID-NAT + anti-HIV or HIV ID-NAT + HIV combined

* HIV combined = antigen and antibody test.

DAVIDSON ET AL.

422 TRANSFUSION Volume 51, February 2011

consequences of a viral transmission were expected to begreater in younger age groups, the analysis was alsoundertaken for a group of 30-year-old female bloodrecipients (representing blood transfusion in relation tochildbirth) and a group of newborn babies. Annualexpected mortality was included in the model using datafrom Statistics Sweden.13 An increased mortality of 20% inthe first year was assumed in the base case only. An annualabsolute increase in mortality risk of 0.1, 0.2, and 0.5 per-centage units for HBV, HCV, and HIV, respectively, was alsoincluded in the model, on the basis of expert estimateswithin the project group.

RisksThe estimated risk of viral transmission by blood transfu-sion in Sweden with the current testing strategy (serologictests) is fewer than 0.5 per million transfusions for each ofHBV and HCV and fewer than 0.2 per million transfusionsfor HIV.14 Actual reported cases of transmission of thesethree viruses via transfusion in Sweden during the past 15years support these estimates. There have been no knowncases of HIV transmission by blood transfusion in Swedensince the introduction of anti-HIV tests at each blood col-lection in 1985. The shortened IWP that would follow fromthe introduction of ID-NAT would further reduce theserisks.

Table 2 shows the IWPs for HBV, HCV, and HIV usedin our modeling. The IWP for HBV using serologic testshas been estimated at approximately 45 days.5,14,15 Byusing ID-NAT, a reduction of 25 days can be assumed.14,16

For HCV, the use of ID-NAT is assumed to decrease theIWP from approximately 60 days to only 3 days.5,6,14

However, we believe that in the case of HIV it is importantto be more specific, due to controversies in this area. Amean IWP of approximately 6 weeks was reported for thefirst-generation HIV antibody tests (employing cell-lysateantigens) available from 1985, but this was shortened toapproximately 3 weeks by the second-generation tests(with recombinant antigens) available from the end ofthe 1980s.17 The third-generation sandwich tests (alsodetecting immunoglobulin M antibodies) presentedduring the 1990s further closed the IWP to approximately1 to 2 weeks for the assays most sensitive to the early-

appearing HIV antibody response.18 During the earliestpart of the IWP, no antibody test can detect infectionsince an antibody response to HIV has not yet beendeveloped by the infected person, but viremia can bedemonstrated by tests that detect the virus, such as HIVantigen testing or NAT. The determination of IWPs hasbeen a moving target over the years, as new andimproved technologies have repeatedly been introducedand many different tests with different sensitivities for theearly-appearing HIV markers have been supplied bymany manufacturers.

In Sweden, a particular interest in patients presentingwith primary HIV infection was established early duringthe epidemic. The Karolinska Institutet Primary HIVInfection Study Group has been able to identify a largenumber of patients presenting with primary HIV infec-tion and thus obtain collections of sequential serumsamples—often obtained daily during early infection—from several patients infected early not only by HIVsubtype B but also by other clades of HIV. These materialshave been employed to evaluate different tests and tech-niques for the diagnosis of early HIV infection, and overthe years the group has presented the first well-performedstudies comparing first-,19 second-,17 and third-generation18 HIV antibody tests, as well as demonstratingthe viral kinetics as shown by HIV antigen tests17 and HIVRNA tests.20 With increasing experience with patientsseeking medical attention in the first days after onset ofprimary HIV infection illness, it was found that the incu-bation period from exposure to onset of symptoms is gen-erally 14 days (13-15 days), and that during the first daysof illness, these patients present extremely high levels ofviremia (peaking during the first week of illness) withmore than 106 HIV RNA copies/mL and HIV antigen testsdisplaying maximum levels. Clearly, patients presenting14 days after infection with such high levels of viremiahave already been viremic for many days and hencewould have been detectable by both HIV antigen and HIVRNA tests for many days; this was confirmed in a fewcases when samples were obtained during the incubationperiod.20 By combining our knowledge with informationprovided by other articles in the medical literature, weestimated the duration of the IWP for ID-NAT at approxi-mately 3 days, the IWP for sensitive HIV antigen tests at 3to 4 days longer (i.e., 6-7 days IWP in total for HIV antigentests), and the total IWP for sensitive HIV antibody tests at14 days.

Given the current epidemiologic situation in Sweden,and the procedures and recommendations surroundingblood donation, the risk of infection with HBV, HCV, orHIV in blood transfusion in Sweden is very low. Supple-mentation of the serologic test methods using ID-NAT ofevery blood donation would mean a reduction of the IWPby approximately 25 days for HBV, on the order of 57 daysfor HCV, and 3.5 days for HIV. The infection risks used in

TABLE 2. IWP (days)*Test method HBV HCV HIV

Antibody test 60 14Antigen test 45 6.5HIV combined test 6.5MP-NAT 35 5.5 5.5ID-NAT 20 3 3

* ID-NAT = test of single samples; MP-NAT = test of 10-20pooled samples; HIV combined test = antigen and antibodytest.

COST-EFFECTIVENESS OF NAT


the model are presented in Table 3 together with othervariables used in the model.

CostsNo costs for the blood donors were included in this analy-sis, because the various test strategies are similar in termsof time use and procedure and therefore would not affectthe cost-effectiveness ratio. The cost of the serologic test iscurrently around SEK 100 (USD 12.5), which includes thecost of tests and analysis. The combined test (antibodyplus antigen) does not increase the cost. There is currentlyno price for ID-NAT in Sweden, but the use of ID-NAT totest for HIV, HBV, and HCV in Denmark (introduced inJanuary 2009) is estimated to increase the cost by approxi-mately SEK 50 million (USD 6.25 million) annually.Assuming that Sweden would have a similar cost toDenmark for testing with ID-NAT, the extra cost per testwould be SEK 136 (USD 17). The cost of using ID-NAT plusserologic tests is therefore estimated to cost SEK 236 (USD29.5) per blood donation in Sweden. Due to the lack ofinformation about the price of ID-NAT, we chose to testdifferent price levels in a sensitivity analysis.

The costs caused by infection depend on whether theinfection becomes chronic or not. We assumed that 5% of

adults and 90% of newborns infected with HBV wouldcontract a chronic infection, while in the other cases wecalculated only a one-time cost of acute infection. We alsoassumed that HCV infection would become chronic in50% of all infections. HIV infection is always chronic.

A German study conducted in year 2000 estimatedthe cost of HBV as DM 7702 for an acute infection and DM4247 per year of chronic infection.21 Updated to 2009 pricelevel this is similar to SEK 46,000 (USD 5750) for an HBVacute infection and SEK 25,000 (USD 3125) per year ofchronic infection. The expected annual cost of HCV infec-tion in Canada in 2007 was estimated at USD 473 (SEK3780), but this is a mean of all patients infected by HCV.22

The Swedish council on health technology assessment(SBU) has calculated the cost of a treatment as betweenSEK 41,300 and 120,800 (USD 5000-15,000) depending onthe drugs and treatment duration,23 but this cost is onlyrelevant for those who fall ill and need treatment. In ourmodel, we used an annual cost of SEK 10,000 (USD 1250)per year for all infected with HCV. An American study con-ducted from the perspective of a health care providerestimated the annual cost of HIV infection at USD 20,114(SEK 160,000) per patient in 2006.24 A study in Sweden25

estimated the annual cost of treating HIV as SEK 122,100(USD 15,262); however, as in the American study, this

TABLE 3. Data in the modelParameter Value Reference

Blood recipientsBase case (median age) 73 years Tynell et al.12

Women (childbirth) 30 years, womenNewborn 0 years

Serologic testsRisk for HBV 0.0000005 Based on Jackson et al.,5 Coste et al.,14 and Biswas et al.15

Risk for HCV 0.0000005 Based on Jackson et al.,5 Marshall et al.,6 and Coste et al.14

Risk for HIV, combination 0.0000002 Based on Coste et al.14

ID-NAT + serologic testsRisk for HBV 0.0000002 Based on Jackson et al.,5 Coste et al.,14 and Biswas et al.15

Risk for HCV 0.000000025 Based on Coste et al.14

Risk for HIV 0.000000083 Based on von Sydow et al.,17 Lindback et al.,18,20 and Gaines et al.19

CostsCost for serologic tests SEK 100, USD 12.5Cost for ID-NAT plus serologic tests SEK 236, USD 29.5One-time cost, acute HBV SEK 46,000, USD 5,750 Harbath et al.21

Annual cost, chronic HBV SEK 25,000, USD 3,125 Harbath et al.21

Annual cost, HCV SEK 10,000, USD 1,250 Based on El Saadany et al.22 and SBU Alert23

Annual cost, HIV SEK 200,000, USD 25,000 Based on Roberts et al.24 and Ghatnekar et al.25

Utility (QALY) weightsUtility weight, mean Age-based mean Burström et al.29

Annual utility decrementHBV 0.1 Based on Niederau et al.26

HCV 0.15 Based on Foberg et al.27

HIV 0.2 Based on Eriksson et al.28

OtherRatio transfused/donation 1.5 Svensk Förening för Transfusionsmedicin2

Increased yearly mortalityHBV 0.001 Expert assessmentHCV 0.002 Expert assessmentHIV 0.005 Expert assessment

Discounting costs 3% Läkemedelsförmånsnämnden11

Discounting QALY 3% Läkemedelsförmånsnämnden11

DAVIDSON ET AL.


estimate did not include productivity loss. We set the totalannual cost of HIV as SEK 200,000 (USD 25,000) in ourcalculations, to also include productivity loss. All the costsused in the model are presented in Table 3.

EffectsThe effects of the different test methods depend on severalfactors such as remaining IWP, age, and survival of thosewho receive blood. The IWP is the basis for the risk that ablood recipient becomes infected with one of the viruses.

Quality of life in patients with HBV has been shown tobe lower than in healthy individuals but higher than inpatients with HCV, as measured by the SF-12 instrument.26

In a cost-effectiveness study performed by Borkent-Ravenand coworkers,4 utility decrements of 0.30 for the acutephase of HBV and specific decrements for certain infec-tions were used. A Swedish study found that quality of lifewas lower in patients with HCV than in those notaffected.27 Studies have also shown deterioration inhealth-related quality of life in patients with HIV.28

However, there are no data on patients’ utility weights,which would be needed to create QALYs. This analysisassumes that a patient without HBV, HCV, or HIV has autility weight equal to the age- and sex-relevant Swedishpopulation-based weight29 and that HBV, HCV, and HIVreduce the utility weight by 0.10, 0.15, and 0.20, respec-tively. The Swedish population-based weights areestimated by the EQ-5D instrument,30 using Britishpreference-based scores.31 The reduced utility weight wasalso applied for cases where the individual is not actuallysick as a result of infection, due to the anxiety and worriesthat come with having an infection.

RESULTS

The largest number of viral transmissions occurred withserologic testing only. However, the risks were very smallwith both strategies. The total cost was mainly influencedby the cost of the test carried out; the cost of viral trans-mission was very low, due to the low background risk.

The costs and effects for the strategies are comparedand presented in Table 4. ID-NAT plus serologic testing

led to increased costs and a slightly improved effect. Thecost per avoided viral transmission for ID-NAT plus sero-logic tests was SEK 101 million and USD 12.7 million com-pared to only serologic tests. The cost per QALY gainedwas lower, but still very high (SEK 22 million and USD 2.7million). The reason why the cost per QALY gained waslower is that each transmitted infection affects both mor-tality and quality of life of the patients for several years.

When the analysis was carried out for 30-year-oldwomen the cost per QALY gained decreased, but was stillhigh (SEK 16 million and USD 2.0 million). There are tworeasons for this; the cost of a viral transmission is higherwithin a lifetime perspective for a younger person, and thenumber of lost QALYs is greater. The cost-effectivenessratio for newborns allows investigation of the most long-term consequences of the different strategies; however,since both costs and QALYs were discounted by 3% annu-ally, the costs and effects occurring far into the future hadonly a small impact on the analysis. For newborns, thecost per QALY gained decreased further with the introduc-tion of ID-NAT, but the level was still high (SEK 14 millionand USD 1.8 million).

Sensitivity analysisSeveral of the analytical variables lacked empirical evi-dence. A probabilistic analysis where all the uncertaintiesin the included variables are varied at the same time wasnot possible as this type of data does not exist. Instead, wevaried some of the most influential variables in one-waysensitivity analyses. One of the most important variableswas the risk of viral transmission given the different tests.Because the strategies including ID-NAT generated suchhigh cost-effectiveness ratios, we performed an analysiswith risks that could be more favorable toward the use ofID-NAT. Specifically, in this analysis we lowered the risk ofviral transmission with HBV, HCV, and HIV when usingID-NAT by 50%. This assumption led to a lower cost perQALY gained compared with the serologic tests (SEK 19million and USD 2.4 million), but adding ID-NAT still gen-erated a high cost per QALY gained. Another importantaspect in the analysis where evidence was missing con-cerned the costs for the tests and the cost of infection. In

TABLE 4. Incremental cost-effectiveness ratios of ID-NAT plus serologic tests versus serologic tests for 1000blood recipients, SEK and USD

Blood recipients Change in costs

Change in effects ICER

Infections avoided QALY Cost per infections avoided Cost per QALY gained

Base case, 73 years old SEK135,618 0.00134 0.00624 SEK101,397,000 SEK21,734,000USD 16,952 USD 12,675,000 USD 2,717,000

30-year-old women SEK134,943 0.00134 0.00826 SEK100,892,000 SEK16,346,000USD 16,868 USD 12,611,000 USD 2,043,000

Newborn babies SEK134,539 0.00134 0.00950 SEK100,590,000 SEK14,164,000USD 16,817 USD 12,574,000 USD 1,770,000

ICER = incremental cost-effectiveness ratio.



another analysis, the cost of ID-NAT was reduced fromSEK 136 to 75 and the cost of each viral transmission wasdoubled; however, even with these changes, the cost perQALY gained was high (SEK 12 million and USD 1.5million). Finally, if the ratio of transfused components todonations is increased from 1.5 to 2.0, the cost per QALYgained is SEK 10 million (USD 1.2 million).

Variation of other variables had no strong influenceon the cost-effectiveness ratios, and ID-NAT generated ahigh cost per QALY gained in all situations. The reason forthis is that the underlying risk of viral transmission is lowin Sweden.

DISCUSSION

The introduction of ID-NAT in addition to the serologictests to detect HBV, HCV, and HIV in blood donors leads toa reduced IWP, which slightly lowers the risks of viraltransmission. It also leads to slightly increased effects inthe model used in this study, in terms of both avoided viraltransmission and QALYs gained. However, the costsincrease sharply. The cost per avoided viral transmissionwith the addition of ID-NAT was estimated at SEK 101million and USD 12.7 million, and cost per QALY gainedwas estimated at SEK 22 million and USD 2.7 million. Forthe base case, where the median age is 73 years, the costper QALY gained was at a maximum. A slightly bettercost-effectiveness ratio was achieved in the two othercohorts, consisting of 30-year-old women and newborns,respectively.

Jackson and coworkers5 studied the cost-effectivenessof using NAT compared to current serologic assays todetect HBV, HCV, and HIV among blood donors in theUnited States in 2002. They tested both ID-NAT andMP-NAT. Cost-effectiveness was investigated with aMarkov model where each blood recipient was followed inthe model until he or she died. The analysis examinedvarious options, and the cost-effectiveness ratios rangedfrom USD 4.3 million per QALY gained up to USD 9.1million per QALY gained for the MP-NAT compared withserologic tests. When ID-NAT was compared with MP-NATthe cost per QALY gained was even higher (USD 15 million).NAT generated a high cost per QALY gained in all situations.

Marshall and colleagues6 studied the cost-effectiveness of adding NAT (both ID-NAT and MP-NAT)to the serologic testing of blood donors to identify HBV,HCV, and HIV in the United States in 2003, using a modelincorporating future costs and effects. The cost-effectiveness ratio of adding MP-NAT to the serologic testswas estimated at USD 1.5 million per QALY gained.Replacing MP-NAT with ID-NAT led to a cost-effectivenessratio of USD 7.3 million per QALY gained compared withthe serologic tests.

All studies that have examined the cost-effectivenessof adding NAT to other tests have been in agreement;

there is a particular advantage of using NAT to detectHBV, HCV, and HIV among blood donors, but this benefitcomes with a large increase in cost.4-10 The cost-effectiveness ratios presented are far beyond what is nor-mally perceived as cost-effective. A recent study has evenshowed that previous cost-effectiveness studies may haveunderestimated the costs per QALY gained due to wrongsurvival assumptions.32 As NAT has been implemented inmany countries anyway, some authors conclude thatsociety seems to be accepting a higher cost per QALYgained for intervention in blood safety.9 However, thisview is not correct from a welfare economics perspective,where all resources have an alternative use.33 The wayQALY is created makes it comparable with other areas,and there is no reason to accept a higher cost per QALY inthe area of transfusion medicine compared to otherimportant areas within health care. There is no statedcost-effectiveness threshold value per QALY in Sweden,but generally a value per QALY of SEK 500,000 is oftenused (equal to USD 65,000).

There are uncertainties over some of the variables inthe model used to calculate cost-effectiveness in thisstudy. There are no exact values for the risks of contami-nation by blood transfusion in Sweden, and thereforehigher risks were analyzed in sensitivity analyses. In allcases, however, ID-NAT substantially increased the costsand only moderately improved the effects. There is alsouncertainty regarding the costs and QALY weights for thedifferent viral transmissions, but this does not affect theanalysis due to the very small risks of viral transmission.The model used was simple in its design, because the onlyoutcome measure was whether the blood recipient wasinfected or not. While it would have been possible tomodel the progression of the different infections, thiswould have required a much more comprehensive modeland would not have greatly enriched the analysis due tothe low risk of viral transmission.

Two main factors distinguish our study from theearlier cost-effectiveness studies; the underlying risk ofviral transmission is estimated to be lower in Sweden thanin the United States, and the expected precision of ID-NATwas higher in this study. These factors affect the outcomein different directions and may explain why the cost-effectiveness ratios do not differ greatly between thestudies.

The IWP for HIV using serologic tests was lower in ouranalysis than in many others, which is worth further dis-cussion. One way to obtain materials for evaluating testsand determining IWPs is to collect series of negative-positive seroconversion samples from blood donors. Thedrawback of this strategy is that samples are often col-lected many days and even weeks apart, and the incuba-tion period has only been determined for a limitednumber of donors. However, such materials are appropri-ate for the blood donor situation, and if the sample is large

DAVIDSON ET AL.


enough, it should be possible to use itfor IWP estimations.

In one study performed in 1995,34

102 seronegative samples (as per first-generation antibody test) from 81 sero-converting blood donors were tested;four of these were positive for HIVantigen and five were positive for HIVRNA (NAT). The authors calculated amedian (confidence interval) reductionof IWP in comparison with antibodytests of 26.4 (13.0-39.9) days for HIVantigen tests and 31.0 (16.7-45.3) daysfor HIV RNA tests. In comparison with the 42-day IWP forfirst-generation antibody tests presented in another study,this implied that the IWPs would be 16 days for HIVantigen tests and 11 days for HIV NATs.34,35 Clearly, thedifference between HIV antigen and NATs was not at allsignificant, and the authors concluded that their resultscould not be employed to suggest that NAT should be usedfor blood donors. However, the results of the study havegreatly influenced other studies in subsequent years, andmany researchers have surprisingly inferred that the IWPsare 16 days for HIV antigen and 11 days for HIV NAT andhence that the difference between HIV antigen and HIVNAT IWPs is 16 - 11 = 5 days.6,16,36-38

The authors of one article published in 2005 definedthe onset of IWP as the time point when one HIV copy/20 mL appeared in blood donor samples and thenemployed back-extrapolation of acute viral replicationdynamics to estimate IWPs of 5.6 days for HIV NAT and 15days for HIV antigen.39 However, we believe these periodsto be overestimates, since they are not at all consistentwith our finding of patients being regularly highly positiveby HIV antigen tests 14 days after infection. One possiblecause of these overestimations could be that the research-ers assumed that the viral load increased at a constant rateon a log scale during the time of detectability, using resultsfrom models assuming linear appearance and increase ofviral load. One explanation for the different results may bethat HIV does not enter the blood stream as a single virus,which then doubles at constant intervals, but rather as alarger amount of HIV that breaks through at one time, withlevels then stabilizing in constantly increasing levelswhich subsequently reach millions of HIV copies/mLduring the early peak 1 to 2 weeks later. Such dynamicswould be consistent with our finding of shorter IWPs.However, the differences between our estimated IWPs (3and 6.5 days, respectively) and those estimated in theabove-mentioned study (5.6 and 15 days, respectively) arenot of great importance for the calculations presented inour study. The only difference in our model from using thelonger IWPs would have been that ID-NAT would havereduced the number of transmissions compared toantigen tests by 54 and 63%, respectively, a difference that

is not very important for the general model of our study.The results of this cost-effectiveness analysis are

clear. Inclusion of ID-NAT for testing against HBV, HCV,and HIV among blood donors leads to cost-effectivenessratios that are far beyond what is usually considered cost-effective. The main reason for this is that the risks for viraltransmission via blood transfusion with the methods usedtoday are very low in Sweden.

Cost consequencesA cost-effectiveness analysis provides an estimate of whatit costs to gain an extra effect with one strategy in relationto another. It says nothing about how large the costs areexpected to be, nor how the costs are allocated. This maybe evaluated separately.

In Sweden, 497,158 instances of blood collection werecarried out in 2008 to approximately 100,000 patients.2

Testing each of these with serologic tests to identify HBV,HCV, and HIV would lead to an annual cost of around SEK50 million (USD = 6.25 million; see Table 5). The introduc-tion of ID-NAT plus serologic tests would increase the costby approximately SEK 68 million annually.

If only serologic tests are used, there is a 83% risk eachyear of transmitting a virus, while with ID-NAT plus sero-logic tests a virus is transmitted approximately everyfourth or fifth year. However, it is important to note thatmost transmitted viruses are HBV or HCV and that theseoften do not affect the patient’s estimated lifetime. Therisk of transmission of HIV with a combined test isapproximately one case every seventh year, while ID-NATplus combined test decreases the expected frequency toapproximately one event every 17 years.

CONFLICT OF INTEREST

No conflict of interest.

REFERENCES

1. Shortt J, Polizzotto M, Waters N, Borosak M, Moran M,

Comande M, Devine A, Jolley DJ, Wood EM. Assessment

TABLE 5. Annual consequences in Sweden, divided by strategyVariable Serologic tests ID-NAT + serologic tests

CostsTests SEK 49,715,800 SEK 117,329,288

USD 6,214,475 USD 14,666,161Infections SEK 156,900 SEK 59,500

USD 19,612 USD 7,437Number of viral transmissions

HBV 0.38 0.15HCV 0.38 0.02HIV 0.15 0.06Total 0.83 0.23



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