transferability of economic evaluations: approaches and factors to consider when using results from...

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Transferability of economic evaluations: approaches and factors to consider when using results from one geographic area for anotherRon Goeree a,b, Natasha Burke a,b, Daria O’Reilly a,b, Andrea Manca c, Gord Blackhouse a,b and Jean-Eric Tarride a,b

a St. Joseph’s Hospital, Hamilton, Canadab McMaster University, Hamilton, Canadac University of York, York, UK

Address for correspondence: Ron Goeree, Program for the Assessment of Technology in Health (PATH), 25 Main St. W., Suite 2000, Hamilton, ON, L8P 1H1, Canada. Tel.: +1 905 523 7284, Ext. 5266; Fax: +1 905 522 0568; email: [email protected]

Key words: Costs and cost analysis – Decision making – Economic evaluation – Economic models – Generalizability – Geographic transferability – Portability

0300-7995

doi:10.1185/030079906X167327

All rights reserved: reproduction in whole or part not permitted

CuRRENT MEDiCAl REsEARCh AND OpiNiON®

VOL. 23, NO. 4, 2007, 671–682

© 2007 liBRAphARM liMiTED

Paper 3777 671

Background: Geographic transferability of economic evaluation data from one country to another has the potential to make a more efficient use of national and international evaluation resources. However, inappropriate transferability of economic data can provide misleading results and lead to an inefficient use of scarce health care resources.

Objectives: The objective of this study was to review, summarize and categorize the literature on: (i) factors affecting the geographic transferability of economic evaluation data; and (ii) approaches which have either been proposed or used for transferability.

Methods: A systematic literature review on transferability was conducted. Electronic databases, hand searching and bibliographic searching techniques were utilized. Inclusion criteria for the review included conceptual or empirical papers with mention of factors affecting, or approaches for, transferability of economic evaluation data across geographic locations. Exclusion criteria included papers published prior to 1966, nonEnglish language papers, pure science studies and animal studies. Three databases were involved in the primary search: Ovid MEDLINE, EMBASE, and CINAHL. In addition to the primary search, the Heath Economic Evaluation Database (OHE HEED), the NHS EED database and the EconLit databases were searched.

Transferability factors were classified into major and minor categories, a classification of alternative transferability approaches was developed, and the number of empirical studies was catalogued according to this classification.

Results: There is a substantial amount of literature on factors potentially affecting transferability. Based on these papers we identified 77 factors and subsequently developed a classification system which grouped these factors into five broad categories based on characteristics of the patient, the disease, the provider, the health care system and methodological conventions. Another 40 studies were identified which attempted to transfer economic evaluation data from one country to another and these were classified according to the sources for clinical efficacy, resource utilization and unit cost data.

Conclusions: There is strong evidence indicating that transferability of economic evaluation data is a difficult and complex task. Approaches which have been used for transferability suggest that, at a minimum, there is a need for countryspecific substitution of practice pattern data as well as unit cost data. A limitation of this review relates to the lack of empirical studies which prevents stronger conclusions regarding which transferability factors are most important to consider and under which circumstances.

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672 Transferability of economic evaluation data © 2007 liBRAphARM lTD – Curr Med Res Opin 2007; 23(4)

Introduction

Thepasttwodecadeshaveseenunparalleledpressureonhealthcaredecisionmakerstomakemoreefficientuseofscarcehealthcareresources.Asaresult,publicandprivateagenciesworldwideareinhighdemandofstudiesthatprovidethemnotonlywithinformationonclinicaleffectiveness,butalsowithinformationoncost-effectiveness(i.e.,valueformoney).Theseevaluations,eitherdonebasedonatrialorobservationalstudyorseparatelyasmodelingstudies,arenotonlyincreasinginpopularity,butalsoinstatisticalsophistication,costandthetimerequiredfortheirdesign,execution,anddissemination.Asaresult,itmaynotalwaysbefeasibletofundlocalstudiesortowaitforthecompletionofanevaluationbeforeprogramfundingdecisionsneedtobemade.

Fortunately,healthcaredecisionmakersoftenhaveaccesstopreviouslypublishedeconomicevaluationsonthetopicofinterestuponwhichtohelpinformtheirdecisions.Unfortunately, it is commonly thecasethatthedecisionmakerisfromonegeographicarea (i.e., province, state, or country) while theeconomic evaluation is from another. In thesecases,decisionsneedtobemadeaboutwhetherthisinformationcanbeusedorwhetherstudiesspecifictothegeographicjurisdictionareneeded.Severaltermssuchastransferability,generalizability,portabilityandextrapolationhavebeenusedtodescribewhendatafromaneconomicevaluationdoneinonegeographicareaistransferredtoanotherlocationortransferredacrosstime.Beforeconsideringsuchanalysis,decisionmakersneedtobeawareofthefactorsaffectingthetransferabilityofdata fromonegeographicarea toanotherandthealternativeapproachesavailablefortransferringthedata.

Whereas there has been less concern about thetransfer of clinical efficacy data, it has long beenrecognizedthattheresultsofeconomicevaluationscanvarywidelyacrossregionsorcountriesand,therefore,economic evaluation results cannot simply betransferredfromonelocationtoanother.Eventhoughacommonreasoncitedintheliteratureforthelackoftransferabilityofeconomicdataacrosscountriesisdifferencesinunitcosts1,ithaslongbeenrecognizedthatanumberofotherfactorscanplayanimportantroleaswell1.Itisclearfromtheemergingconceptualandempiricalliteratureontransferabilitythattheissueoftransferringbothclinicalandeconomicdataacrossjurisdictionsrequirescarefulthoughtandplanning,andthatadjustmentstoreflectcharacteristicsofthetargetlocationarealmostcertainlyanecessarycondition.

If clinical effectiveness and cost-effectivenessinformationcanbesuccessfullyused,re-appliedorre-calculatedtomeetgeographicspecificrequirements,

thendecisionmakers canpotentially save a lot ofscarceevaluationresourcesandmakedecisionsinamuchmoretimelyfashion.However,thereisstillapaucityofstudiesonthefactorsaffecting,orsuggestedapproachesfor,transferabilityofeconomicevaluationdata.Inaddition,thesefactorsandapproacheshavenotpreviouslybeensummarizedorcategorizedinasystematicandcomprehensivefashion.Researchersanddecisionmakersshouldnotonlybeawareofthefactorsthatcanaffecttransferability,buttheyshouldalsobeawareofthealternativeapproachesfortransferabilityandthenumberofempiricalstudiesthathaveusedeachofthesedifferentapproaches.

The objectives of this paper were five-fold: toconduct a systematic literature review examiningfactors affecting the geographic transferability ofeconomicevaluationdata;todevelopaclassificationsystem to summarize the literature review resultson transferability factors; to conduct a systematicliterature review on approaches which have beenproposedfortransferability;todevelopaclassificationsystem to summarize the literature review resultsontransferabilityapproaches;andtodocumentthenumber of empirical studies that haveused thesedifferenttransferabilityapproaches.

MethodsOverall literature search strategy for both reviews

Asystematicreviewongeneralizabilityofeconomicevaluationswithaspecificfocusongeographictransfer-abilitywasdonetoaddressthefollowingtworesearchtopics:(1)factorscausingvariabilityincost-effectivenessbetweenlocationsand(2)approachesfortransferringeconomicevaluationdataacrosscountries.Duetotheoverlappingnatureofthesetwosearches,theoverallsearchstrategyforbothreviewswascombinedatthescreening level and then separatedduring title andabstractscreening.Threedatabaseswereinvolvedintheprimarysearch:OvidMEDLINE,EMBASE,andCINAHL.Inadditiontotheprimarysearch,theHeathEconomicEvaluationDatabase(OHEHEED),theNHSEEDdatabaseandtheEconLitdatabasesweresearched.

Titles andabstractsof all articleswere screenedforpossiblefulltextarticleretrieval.Inaddition,thereferencesofallacceptedpaperswerereviewedforpossibleinclusion.Amanualjournalsearch(i.e.,handsearch)wasalsoconductedofselectedjournalsfrom1990 onwards. The following journals were handsearched:HealthEconomics; International JournalofTechnologyAssessment inHealthCare; Journalof Health Economics; Medical Decision Making;PharmacoEconomics;andValueinHealth.

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© 2007 liBRAphARM lTD – Curr Med Res Opin 2007; 23(4) Transferability of economic evaluation data Goeree et al. 673

AllEnglish languagepublications from1966 toDecember2005were included in the review.Thereviewsincludedpapers,books,andbookchaptersthatdiscussedproblemswith,orapproachesfor,transfer-ability,andempiricaltransferabilitystudieswheretheoriginaleconomicevaluationwasconductedinanothercountry or geographic location. Empirical studieswherethecountry(geographiclocation)ofinterestwaspartofamultinationaleconomicevaluationwereincludedonlyiftherewasmentionofvariabilityfactorsortransferabilityapproachesinthesepapers.

Factors causing variability and classification of these factors

Factorscitedaspossiblyaffectingtransferabilityofeconomicevaluationdatawereabstractedfrombothconceptualandempiricalpapers.Norestrictionwasimposedonthelabelusedbyauthorstodescribethefactor.Factorsthatweredeemedtobedescribingthesameattribute(e.g.,practicepatternsandresourceutilizationorcostsandunitprices)werecombinedintoasinglecategory.

Toassistinsummarizingthesefactors,attheendofthereviewofallarticlesthecombinedlistofuniquevariabilityfactorswasassessedforpossiblecollapsing,combining,andcategorizationintomajorandminorsub-categories.Formajorsub-categories,previouslypublishedreviewswereusedfortheinitialclassification.For minor sub-categories, factors were groupedaccordingtosimilarattributesorcharacteristics.Forexample,attributesrelatedtopatientdemographics(e.g.,age,gender, race,education)werecombinedinto a single category.Similarly, characteristicsoftheunderlyingdisease(e.g., incidence,prevalence,disease progression) were combined into a singlecategory.Thenumberofcitationsfromconceptualand empirical papers for each category was thenrecorded.

Approaches for transferring economic evaluation data, classification of these approaches and documentation of the number of empirical studies by approach

Possible approaches for transferring economicevaluationdata fromone locationtoanotherwereabstractedfrombothconceptualandempiricalpapers.Norestrictionwasimposedonthesuggestedapproachor labelusedbyauthors todescribe theapproach.Basedonthesesuggestedtransferabilityapproaches,an overall classification of possible approacheswasdevelopedbasedon themostcommonlycitedtransferabilityfactorsbelievednecessaryforadjustmentorsubstitutionwhentransferringdata.

Using this classification of approaches, thenumberofempiricalstudiesthatusedthesedifferenttransferabilityapproacheswastabulatedtoobservecommonapproachesused inpractice today.Theseempiricalstudieswerefurthersub-dividedintotrial-basedstudiesordecisionanalyticmodels.

ResultsOverall literature review

Atotalof5029titlesandabstractswerereviewed(seeFigure1).Inaddition57articleswereidentifiedthroughbibliographysearchingandanother16articleswereidentifiedthroughhandsearchingofselectedjournals.Ofthe5029titlesandabstractsreviewed,850(17%)mettheinclusioncriteriaandwereretrievedforfull-textreviewand4179(83%)wererejectedforreasonsshowninFigure1.Includingthe57articlesfrombibliographysearchingandthe16fromhandsearching,atotalof923articleswereretrievedforfull-textreview.

Ofthe923articlesreviewedinfulltext,102(11%)werecategorizedaseitherconceptualpapers,empiricalstudiesorreviewpapersaddressingoneorbothoftheresearchquestionsontransferability.Approximatelyhalfofthepublications(51%)werepublishedfrom1999onwards.Alargeproportionofpaperswererejectedfollowingfulltextreview(n=821or89%).Thesepaperswereexcludedonthebasisthattheydidnotdiscussoraddressvariabilityfactors(includingcriteria/guidelines/decisionrulesfordeterminingtransferabilitypotential),orapproachesfortransferability.Themajorityoftheseexclusionsweremulticenternationalorinternationalevaluationsinwhichthecountryofinterestwasalreadyincludedintheevaluation.

Factors potentially affecting the transferability of economic evaluation data

A total of 81 papers either discussed or formallyaddressedfactorsthatcanpotentiallyaffecttransfer-abilityofeconomicevaluationdataandwerereviewedinfulltext.Ofthese81papers,54wereconceptualpapers,25wereempiricalpapers,andtwowerereviewpaperscitingpotentialtransferabilityfactors(seeFigure1).Inaddition,fivepaperswereidentifiedthatfocusedoncriteria,guidelines,ordecisionrulesfordeterminingtransferabilitypotentialofeconomicevaluationdata.

Oneofthefirstresearcherswhohelpedmovethedebateabout transferability forwardwasO’Brien1.Largely through the use of illustrative practicalexamples, O’Brien identified six threats to thetransferabilityofeconomicdataacrosscountries(i.e.,demography and epidemiology of disease, clinicalpracticeandconventions,incentivesandregulationsfor

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healthcareproviders,relativepricelevels,consumerpreference,andopportunitycostofresources).Severalpapersinthelastdecadeelaboratedandexpandeduponthelistoffactorspotentiallyaffectingthetransferabilityofeconomicdataacrosscountries2–7.

Therehaverecentlybeensignificantcontributionsto the topic of geographic transferability throughthecompletionoftwoliteraturereviewsonfactorsaffectingtransferability.ThefirstofthesereviewswasbyWelteet al.8whoidentifiedtransferabilityfactorsthroughanon-systematicreviewoftheliteratureofvariousdatabasesandfromhandsearchingtechniques.AnevenmorecomprehensiveassessmentofconceptualfactorsaffectingvariabilityofeconomicevaluationdatawasrecentlycompletedthroughasystematicreviewbySculpheret al.9.

Based on our systematic literature review ofconceptual,empiricalandreviewpapersaddressingtransferabilityfactors,weidentifiedalistof77uniquevariables or factors that can potentially affect orinfluencethetransferabilityofeconomicevaluationdatafromonelocationtoanother.

Classification of variability factors

Theresultsofcollapsingandcombiningtheuniquelistoffactorsintomajorandminorsub-categoriesarepresentedinTable1.ThemaincategorieswerebasedonanexpansionofthecategoriesidentifiedbyWelteet al.8.Forclassificationpurposes,weidentifiedfivebroadcategoriesofcharacteristicsfromtheliteraturebasedoncharacteristicsof:(a)thepatient;(b)thedisease;

Initial search of electronic databases, n = 5029

1%24Animal study

6%266Pure science/laboratory study

10%401Non-English

83%3488No mention of variability factors or transferability

Title and abstract rejected, n = 4179 (82%) Title and abstract accepted, n = 850

(17%)

Bibliography and hand search, n = 73

Full-text review,n = 923

Included in systematic review, n = 102 (11%)

Not included in systematic review, n = 821 (89%)

102Total number of papers

72005

42004

52003

22002

92001

102000

151999

111998

91997

91996

51995

161981–1994

Breakdown of papers included in systematic review by year

and publication

40Transferability approaches from empirical papers

5

Criteria/ guidelines/decision rules for determining the transferability of economic evaluation data

2Reviews

25Empirical

54Conceptual

Variability factors

Breakdown of papers included in systematic review by type of research question

Figure 1. Summary flow chart of articles included in systematic reviews

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(c)theprovider;(d)thehealthcaresystem;and(e)methodologyusedintheanalysis(seeTable1).

Patient characteristics, attitude, and behavior

Patient characteristics vary within and acrossjurisdictionsandcanhavean important impacton

theability to transferoranalyzecost-effectivenessresultsacrossgeographicareas.Patientcharacteristicsincludefactorssuchasdifferencesinage,gender,race,education,socio-economicstatus,populationdensity,immigrationandemigrationpatterns,riskfactors,co-morbidities,lifestyle,geneticfactors,environmentalfactors,andallcausemortality(lifeexpectancy).These

Conceptual papers Empirical papers

Patient characteristics

Demographics (age, gender, race), education, socio-economic status 241,3–9,14–29 530–34

Risk factors, medical history, genetic factors 73,7–9,14,16,24 330,31,34

Lifestyle, environmental facto rs 63,4,7–9,24

Mortality rates, life expectancy 71,5,8,9,15,35,36 131

Attitudes toward treatment, culture, religion, hygiene, nutrition 104,6,8,9,14,15,19,37–39

Compliance and adherence rates, ethical standards 118,9,14,15,19,21,38,40–43

Population values (utilities) 101,7–9,14,22,44–47

Population density, immigration, emigration, traveling patterns 28,15

Income, employment rates, productivity, work loss time, friction time 28,29

Type of insurance coverage, user fees, co-payments, deductibles 18

Incentives for patients 36,8,48

Disease characteristics

Epidemiology (incidence/prevalence, disease progression, spread) 181–9,14,15,17,20,24,35,42,43,48 549–53

Disease severity, case mix 75,8,9,14,19,41,46

Disease interaction, co-morbidity, concurrent medications 71,8,9,14,19,20,41

Mortality due to disease 249,50

Provider characteristics

Clinical practice, conventions, guidelines, norms 421,3,5–9,14–17,19,21,22,24–

29,36,37,39,41,43,46–48,54–57,57–67 2230–33,49,51,52,68–82

Experience, education, training, skills, learning curve position 175,6,8,9,14,19–21,26,38,41,44,56,57,83–85 149

Quality of care provided 28,14

Method of remuneration (supplier-induced demand) 28,84

Patient identification 114

Cultural attitudes 26,16 182

Incentives for providers, liability 121,3,5–9,14,17,24,48,66 350,80,82

Health care system characteristics

Absolute or relative prices 381–3,5-9,14,15,17,19,22,24,27,28,36–38,41–

44,46–48,54,55,57–60,62,63,65–67,84 2130–33,49–51,68,70–75,76–82

Available resources (staff, facilities, equipment), programs, services 233,6,7,9,14–17,24,36–38,41–43,45,46,48,55–

57,59,66 253,68

Organization of delivery system, structure, level of competition 204–6,8,9,14,17,19–21,38,40,42,45,48,57,58,

63,67,84 349,50,74

Level of technological advancement, innovation and availability 58,9,26,42,62

Available treatment options (comparators) 131–3,7–9,14,24,25,46,48,54,67 178

Capacity utilization, economies of scale, technical efficiency 95,8,9,19,21,22,36,57,62 132

Input mix (personnel, equip.), specialization of labor, joint production 69,19,20,40,45,62

Access to programs and services, gatekeepers, historical differences 29,40

Waiting lists, referral patterns 18

Regulatory and organizational infrastructure, licensing of products 31,15,36 152

Availability of generics or substitutes 37,8,24

Market form of suppliers, payment of suppliers, supplier incentives 18

Incentives for institutions 101,3,5–7,14,17,24,48,66

Table 1. Classification and results of the literature review on factors cited in conceptual and empirical papers as potentially affecting transferability

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patientcharacteristicscanaffectthebaselineriskofdiseaseandultimatelyimpactonclinicaleffectiveness.

Patientcharacteristicsalsoincludeattitudetowardhealthcareandtreatment,complianceandadherencerates,utilityvaluationofhealthstates,andpatientincentivessuchastheimpactofuserfees,co-paymentsanddeductiblesontheuseofhealthcare.Theresultsofcost-effectivenessanalyseswilldependcriticallyonpatientacceptance, attitude, andbehavior.Forexample,highuserfees,co-payments,ordeductiblescanhaveaninfluenceontreatmentdecisionsandthesefactorsareknowntovaryacrossjurisdictions.Similarlycost-utilityresultswilldependonthevaluationsforhealthstatesandmostresearchersagreethatthesevaluationsdifferacrosscountriesandmayberelatedtoculture10.

Disease characteristics

Thesecondbroadcategoryoffactorsthatcanaffectvariabilityacrossjurisdictionsrelatestocharacteristicsofthedisease.Thereareanumberofcountry-specificfactorsthatcanaffecttheincidenceandprevalenceofdisease,diseaseseverity,andprogression/prognosisof disease. For example, differences in patientcharacteristicsorcultural/environmentaldifferencesmayaffectdiseaseseverityorcasemixinonecountrycomparedtoanother.Similarly,diseaseprogressionand the spreadofdisease in thecaseof infectiousdiseasesmayvaryacrossjurisdictionsdependingonenvironmentalfactors,populationdensity,life-style,treatmentacceptance,andnotificationprograms.Andfinally,disease-specificmortalitycanbeverydifferentfromoneregioncomparedtoanother.

Provider characteristics

Thethirdbroadcategoryofvariabilityfactorsrelatestocharacteristicsofproviders.Therecansometimes

bemarkeddifferencesinclinicalpractice,conventions,guidelines, or norms across countries. Rates ofhospitalizations,ratesofdiagnostictesting,lengthsofstayinhospital,thefrequencyofphysicianfollow-up,anddrugdosingregimensareallfactorsknowntovary,sometimessignificantly,across jurisdictions.Otherprovidercharacteristicsrelatetoexperience,education,training, skills, efficiency, andwhereprofessionalsareon the learningcurveofanew interventionortechnology.All thesefactorscanhaveasignificantimpactontheeffectivenessandcost-effectivenessofaprogramorservice.

Incentivesforproviderssuchasliabilityandmethodofremunerationalsovaryconsiderablyacrosslocationsandcanhaveasignificantimpactonhowpatientsaremanaged.Physiciansincountriesthatarereimbursedunderafee-for-servicesystemasopposedtosalaryorcapitationmaybemore likely togenerateextrademand for their services (i.e., supplier induceddemand).Similarly,dependingon thedisease andevidencearoundtreatmenteffectiveness,patientsmaybetreatedmoreorlessaggressivelyinsomecountriescomparedtocountrieswherethethreatoflitigationisless.Incentivessuchasremunerationandliabilitywillnotonlyaffecthowpatientsaremanaged,butalsoaffectcostsandpatientoutcomesaswell.

Health care system characteristics

Thefourthbroadcategoryofvariabilityfactorsrelatestocharacteristicsofthehealthcaresystem.Itiswellestablished that there are sometimes substantialdifferences inunitpricesacross jurisdictions.Mostresearchersadvocatethatataminimumunitpricesneedtobereplacedwhentransferringcost-effectivenessdataacross regions.But it isnot justabsoluteunitpricesthatareimportant.Relativepricescanalsohaveanimportantimpactoncost-effectivenessortreatmentdecisions.

Table 1. (Continued)

Conceptual papers Empirical papers

Methodological characteristics

Costing methodology, estimation procedures (e.g. productivity cost) 86,8,14,27,28,45,48,62 234,50

Study perspective 105,8,9,14,26–29,46,48 170

Study factors (artificial trial conditions, industry-related bias) 189,15,16,18,19,21,22,25,27,28,39,40,44,59,

64,83,85,86 231,69

Timing of the economic evaluation 49,67,83,86 169

Clinical endpoints/outcome measures 348,54,86

Discount rates 61,8,26–28,58

Exchange rates, purchasing power parities 59,14,29,61,66 168

Opportunity cost (foregone benefits) 61,7,9,24,45,61

Affordability (CE thresholds) 236,45

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Inadditiontoabsoluteandrelativeunitcosts,thereareanumberofotherimportanthealthcaresystemcharacteristicsthatcanaffecttransferability.Countrieswilldifferwithrespecttothetypesandmagnitudeofresources,programs,orservicesthatareavailable.Therearealsodifferencesinhowdiseasesaremanagedorhowinterventionsareadministered.Thetreatmentsavailableorwhatmightbeconsidered‘usualcare’inonecountrymaynotbeavailableornotconsidered‘usualcare’ inanothercountry.Countrieswillalsodifferintermsofthemixofinputsusedinhealthcaredelivery,theorganizationandstructureofthehealthcaresystem,theleveloftechnologicalinnovationusedinthecountry,andtheleveloftechnicalefficiencyinproduction(e.g.,capacityutilizationandeconomiesofscale).Andfinally,healthcaresystemscandifferintermsofregulatoryandorganizationalinfrastructure,licensingofproducts, theavailabilityofgenericoralternativemedicine,andincentivesforinstitutions.

Methodological characteristics (issues, conventions)

Finally,thefifthbroadcategoryofvariabilityfactorsrelatestomethodologicalcharacteristics.Perhapsthemostobviousfactorhereisdifferencesingeographicsettingsanddifferencesinrequirementsorconventionsfor economic evaluations. The study perspectiveadoptedcanbeaproblemfor transferability if thestudyperspectiveusedintheanalysisisdifferentthanthedesiredperspectiveofthetargetcountry.Althoughthisproblemcanusuallybeovercomebydisaggregatedreportingofstudyresults,notallstudiesadoptabroadenoughperspectiveandnotallstudiesprovideresultsinadisaggregatedfashion.Otherstudyconcernsthatcanaffecttransferabilityrelatetoartificialtrialconditions,industrysponsoredbias,thetimingoftheeconomicevaluationitself,andclinicalendpointsoroutcomemeasuresusedinthestudy.

Approaches for transferring economic evaluation data

AsshowninFigure1,theresultsoftheliteraturereviewidentified40empiricaltransferabilitypaperswhichutilizedvariousapproachesfortransferringeconomicevaluationdatafromonecountryor jurisdictiontoanother. Inbroad terms, the approachesused canbe categorized into non-modeling and modelingapproaches.

Non-modelingapproachesessentiallyinvolvetrans-formingcost-effectivenessresultsfromonecountrytoanotherusingexchangeratesorPurchasingPowerParities(PPPs).Theseattemptstotransfereconomicdatahavebeencommonlyused,especiallytoobtain

rough estimates for the country of interest. Withexchangerates,thestudiedcountry’scost-effectivenessresultsaretransferredovertothetargetcountryusingthecurrencyexchangeratebetweenthetwocountries.Sinceexchangeratesreflectdifferencesinthesupplyanddemandofcurrencies, thisapproach isagrossadjustmentandnotareflectionofdifferencesinunitprices,practicepatterns,orpatientcasemixbetweenthetwocountries.Inresponsetosomeoftheconcernsand criticisms of using exchange rates, PPPshavecommonlybeenadvocated11.Someresearchershavearguedthattheuseofgrossdomesticproduct(GDP)PPPsmaybetooglobalandthathealthormedicalcarespecificPPPsshouldbeusedinstead11–13.

Asidefromtheglobalstudy-widecostadjustmentsthatresultfromtheuseofexchangeratesorPPPs,anyattempttotransfereconomicdatafromonecountrytoanotherbysubstitutingincountry-specificdatacanbeconsideredaformofmodeling.Bymodeling,wemeanmodelinginageneralsenseandnotnecessarilythroughtheuseofdecisionanalyticmodelingtechniques.Evensubstitutingdrugprices for the targetcountrycanbeconsideredasimpleformofmodeling.Modelingapproachescanrangefromtheverysimplesubstitutionofselectedunitpricesthatareknowntovaryacrosscountries(e.g.,drugordevicecosts)tomoreelaboratedecisionanalyticmodelswherevariouscountry-specificinformationissubstitutedintoaglobalmodel.

Classification of transferability approaches used in empirical papers

Basedonthereviewoftransferabilityfactors,itwasapparentthatitwasnotpossibletoidentifyageneralframeworkthatclassifiesallpossibleapproachesfortransferringeconomicevaluationdata.Adoptingamorepragmaticapproach,thereviewofconceptualpapersontransferabilityapproachessuggestedtherearethreemainfactorsthatarecommonlyadvocatedwhentransferringdataacrosscountries:unitcosts;resourceutilization(practicepatterns);andclinicalefficacy.Using these factors, we developed a classificationsystem of alternative transferability approaches.PresentedinTable2arefivemodelingapproachesthatarepossiblebasedondatasourcesforrelativeclinicalefficacy,resourceutilization,andunitcostdata.

Modelingbysubstitutingcountry-specificcharacter-isticsintoaggregatesummaryresultsfromthestudiedcountrytendtobeusedmorefrequentlyinthefirstfewmodeling approaches,while decision analyticmodelstendtobeusedacrossallmodelingapproachesandareessentialforthefifthmodelingapproach.Thefirstmodeling approach,whereonly selectedunitcostsaresubstitutedintotheanalysis,representstheleastcountry-specifictypeofanalysis,whilethefifth

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modelingapproach,whererelativeclinicalefficacy,resourceutilization,andunitcosts fromthetargetcountryaresubstitutedintoaglobalmodel,representsthemostcountry-specifictypeoftransferabilityanalysispossible.

Number of empirical studies by type of transferability approach

Table3presentsasummaryofthenumberofempiricalpapersthathaveusedthesedifferenttransferabilityapproaches.Thevastmajorityofpublishedstudies(40/41= 98%) used modeling approaches fortransferability and justunder ahalf of theseuseddecision analytic modeling techniques (18/40=45%).Almostathirdofthestudies(13/40=33%)used efficacy and resource utilization data fromthe studied country and substituted only targetcountry unit costs into the analysis (modelingapproaches1and2).Anothercommontransferabilityapproach (9/40= 23%) was where a mixture ofresourceutilizationdatafromboththestudiedandtargetcountrieswasusedintheanalysis(modelingapproach 3). Approximately half of these studiesweretrial-basedanalyses(55%)andhalfweredecisionanalyticmodels(45%).

The most common transferability approach(16/40= 40%) was where the studied country’srelativeclinicalefficacywasusedbuttargetcountry-specific resource utilization and unit costs weresubstituted into the analysis (modeling approach4). Three quarters of these studies used decisionanalyticmodeling techniques (12/16=75%).Andfinally, a less common transferability approach(2/40=5%)waswhere a decision analyticmodelstructure fromanother studywasused,butwhererelativeclinicalefficacy,resourceutilization,andunitcostsforthetargetcountrywereallsubstitutedintotheanalysis(modelingapproach5).Decisionanalyticmodeling techniques were used in both of thesestudies.

Discussion

Theincreasingpressureonhealthcaredecisionmakersto make more efficient use of scarce health careresourceshasresultedinanincreaseddemandforcost-effectivenessevidence,eitherintheformofprospectivetrials or from decision analytic modeling studies.However,conductingapropereconomicassessmentofeachhealthcareprogram,service,productordevicefor each jurisdiction is not only infeasible, but islikelytoresultinasignificantinefficientuseofglobalevaluationresources.Evenifresourceswereavailabletoevaluateeveryhealthcare technology, the timedelayforproperassessmentsofcost-effectivenessmaybeconsiderablylongerthanthetimeavailablebeforefundingrecommendationsfornewprograms,services,orproductsarerequired.

Asaresult,decisionmakingbodieswillincreasinglybelookingattheapplicabilityofusingcost-effectivenessevidencegeneratedfromanotherjurisdictionfortheirownlocalinterest.Geographictransferabilitycanbeapromisingwayofmakingmoreefficientuseofevaluationresourcesandmaybetheonlyalternative forsomejurisdictionswithlimitedresources.However,inordertoconsidertransferringdata,decisionmakersneedtobeawareofthefactorsaffectingthetransferabilityofdatafromonegeographicareatoanotherandthealternativeapproachesavailablefortransferringthedata.

Theresultsfromthisreviewexpanduponpreviouslyavailablereviews.Ourreviewidentified86conceptualpapersandempiricalstudiesontransferabilityfactors,comparedtoWelteet al.8whoidentified44conceptualpapersandempiricalstudiesandSculpheret al.9whoidentified36 articleswhich considered sources ofvariabilityinconceptualtermsand33empiricalpaperswhichreportedtransferabilityfactors.Inaddition,oursystematicresultsonapproachesidentified40empiricalpapersthatusedoneormorealternativetransferabilityapproach.Wecannotcomparethesefindingstootherreviewsasthisinformationhasnotpreviouslybeenreportedorpublished.

Table 2. Modeling approaches based on the three most commonly advocated transferability factors

Source of data by transferability factor Modeling approach

Relative clinical efficacy data Resource utilization data Unit cost data

1 Studied country only Studied country only Mixture of studied and target country

2 Studied country only Studied country only Target country only

3 Studied country only Mixture of studied and target country

Target country only

4 Studied country only Target country only Target country only

Least to most country-specific analysis

5 Target country only Target country only Target country only

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Althoughanumberofarticleshavebeenpublishedthatdiscussthefactorswhichcanaffecttransferabilityoralternativeapproachesfortransferability,alimitationofthisreviewrelatestothelackofempiricalstudies.Thislackofempiricalstudiespreventsus,atthistime,fromdrawingstrongerconclusionsonwhichfactorsaremostimportanttoconsiderwhentransferringeconomicdataandunderwhichcircumstancesthesefactorsaremostimportant.Anotherlimitationofthisreviewisthatthetopicoftransferabilityisevolvingandgrowingandthisreview,whichcoversarticlespublisheduptoDecember31,2005,reflectstheavailableliteratureuptothatpointintimeonly.

Conclusions

Our systematic review of the published literatureidentifiedanextensivelistoffactorsthatcancontributetovariabilityincost-effectivenessresultsacrosscountries,andtherefore,canbeseenasthreatstotransferability.Asaresultofthefindingsfromourreviewonvariabilityfactors,we subsequentlydevelopeda classificationsystemforthesefactorsintofivebroadcategoriesrelatedtocharacteristicsofthepatient,thedisease,theprovider,thehealthcaresystem,andmethodologicalcharacter-istics,suchasdifferencesincostingmethodologiesorlocalconventions.Thislistof77variabilityfactorswillassistresearcheranddecisionmakerawarenessofthefactorsthatcanpotentiallyaffectthetransferabilityofdatafromonegeographicareatoanother.

Onceithasbeendeterminedthatcost-effectivenessresultsfromonecountrycanandshouldbetransferredovertoatargetcountry,thenthenextobstacleistodeterminehowthiscanbestbeaccomplished.Our

secondsystematicreviewwasaroundapproachesfortransferringeconomicdataacrosscountriesthathaveeitherbeenproposedorusedinthepublishedliterature.Basedonthisreview,wedevelopedaclassificationsystemthatgroupedtheapproachesintotwobroadcategories:modelingandnon-modelingapproaches.Non-modelingapproachesaremoreglobalinnature,wheremodelingapproachessubstitutefactorssuchasrelativeclinicalefficacydata,resourceutilizationdata,orunitcostdatafromthestudiedcountrytothetargetcountryofinterest.Modelingapproacheswerefoundtobethemostcommonapproachesusedinthepublishedliterature.Therehasalsobeenatrendinthemorerecentliteratureontransferabilitytoformallyincorporatedifferencesinpracticepatternsandevendifferencesinrelativeclinicalefficacyacrosscountries.

Thereviewsconductedhereclearlysuggestthereisenoughconceptualandempiricalevidencethatcost-effectivenessresultscanvaryacrosscountriesandthatthereareanumberoffactorsthatposeasthreatstotransferability. It is also clear from the small, butemerging,literatureoncriteria,guidelines,ordecisionrules fordeterminingtransferabilitypotential, thatadditionalworkindevelopingtheseapproachesandsystems isneeded.Additionalempiricalresearch isneededtodeterminetherelativeimpactofdifferentfactorswhentransferringeconomicevaluationdata,andwhetherthisimpactvariesbytypeofdisease,inter-vention,orgeographiclocation.

Acknowledgment

Declaration of interest: Fundingforthisprojectwasprovidedby a researchgrant from the2004HTA

Table 3. Results of the systematic literature review from empirical studies of the different transferability approaches

Number of empirical studies Transferability approach

Trials Decision analytic models

Total

Non-modeling approaches

Exchange rates32 1 0 1

PPPs 0 0 0

Modeling approaches

No. 1. Studied country relative clinical efficacy and resource utilization, mixture of studied and target country unit costs49

1

0

1

No. 2. Studied country relative clinical efficacy and resource utilization, target country unit costs33,33,69,74,76,87–93

12

0

12

No. 3. Studied country relative clinical efficacy, mixture of studied and target country resource utilization, target country unit costs30,72,75,80,94–98

5

4

9

No. 4. Studied country relative clinical efficacy, target country resource utilization and unit costs31,50,51,71,73,77–79,81,82,99–104

4

12

16

No. 5. Target country relative clinical efficacy, resource utilization and unit costs 52,68 0 2 2

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CapacityBuildingGrantsProgram(No.67)of theCanadian Agency for Drugs and Technologies inHealth(CADTH),formallytheCanadianCoordinatingOfficeofHealthTechnologyAssessment(CCOHTA).RonGoeree,GordBlackhouse,andDariaO’ReillyweresupportedbyaresearchgrantfromtheOntarioMinistryofHealthandLongTermCare(MOHLTCgrantNo.06129).NatashaBurkewassupportedbytheHTACapacityBuildingResearchGrant.AndreaMancaistherecipientofaWellcomeTrustTrainingFellowship inHealthServicesResearch. Jean-EricTarridewassupportedbySt.Joseph’sHealthcareofHamilton,Ontario.TheauthorsexpresstheirdeepappreciationtoChristineHendersonandJanWatsonfortheirpatienceandvaluableresearchassistanceonthisproject.Theviewsandopinionsexpressedinthisreportarethoseoftheauthorsanddonotnecessarilyreflectthoseofthefundingagenciesorinstitutions.

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CrossReflinksareavailableintheonlinepublishedversionofthispaper:http://www.cmrojournal.com

PaperCMRO-3777_4,Accepted for publication:23January2007Published Online:21February2007doi:10.1185/030079906X167327

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transferability of economic evaluations: approaches and factors to consider when using results from...

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