Comparison of driving simulator performance with real driving after alcohol intake: A randomised, single blind, placebo-controlled, cross-over trial

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Accident Analysis and Prevention

jo u r n al hom e p a g e :w w w . e l s e v i e r . c o m / l o c a t e / a a p

Comparison of driving simulator performance with real driving after alcohol intake: A randomised, single blind, placebo-controlled, cross-over trial

Arne Helland

, Gunnar D. Jenssen

, Lone-Eirin Lervåg

, Andreas Austgulen Westin

, Terje Moen

, Kristian Sakshaug

, Stian Lydersen

, Jørg Mørland

, Lars Slørdal

aDepartmentofClinicalPharmacology,St.OlavUniversityHospital,Trondheim,Norway

bDepartmentofLaboratoryMedicine,Children’sandWomen’sHealth,NorwegianUniversityofScienceandTechnology,Trondheim,Norway

cSINTEFTechnologyandSociety,DepartmentofTransportResearch,Trondheim,Norway

dTheRegionalCentreforChildandAdolescentMentalHealth,NorwegianUniversityofScienceandTechnology,Trondheim,Norway

eNationalInstituteofPublicHealth,Oslo,NorwayandInstituteofClinicalMedicine,UniversityofOslo,Norway

a r t i c l e i n f o

Articlehistory:

Received19September2012 Receivedinrevisedform 20December2012 Accepted28December2012

Keywords:

Automobiledriving Trafficaccidents Ethanol

a b s t r a c t

Thepurposeofthisstudywastoestablishandvalidateadrivingsimulatormethodforassessingdrug effectsondriving.Toachievethis,weusedethanolasapositivecontrol,andexaminedwhetherethanol affectsdrivingperformanceinthesimulator,andwhethertheseeffectsareconsistentwithperformance duringrealdrivingonatesttrack,alsoundertheinfluenceofethanol.Twentyhealthymalevolunteers underwentatotalofsixdrivingtrialsof1hduration;threeinaninstrumentedvehicleonaclosed- circuittesttrackthatcloselyresembledruralNorwegianroadconditions,andthreeinthesimulator withadrivingscenariomodelledafterthetesttrack.Testsubjectswereeithersoberortitratedtoblood alcoholconcentration(BAC)levelsof0.5g/Land0.9g/L.Thestudywasconductedinarandomised,cross- over,single-blindfashion,usingplacebodrinksandplacebopillsasconfounders.Theprimaryoutcome measurewasstandarddeviationoflateralposition(SDLP;“weaving”).Eighteentestsubjectscompleted allsixdrivingtrials,andcompletedatawereacquiredfrom18subjectsinthesimulatorand10subjects onthetesttrack,respectively.Therewasapositivedose–responserelationshipbetweenhigherethanol concentrationsandincreasesinSDLPinboththesimulatorandonthetesttrack(p<0.001forboth).In thesimulator,thisdose–responsewasevidentalreadyafter15minofdriving.SDLPvalueswerehigher andshowedalargerinter-individualvariabilityinthesimulatorthanonthetesttrack.Mostsubjects displayedasimilarrelationshipbetweenBACandSDLPinthesimulatorandonthetesttrack;however,a fewsubjectsshowedstrikingdissimilarities,withveryhighSDLPvaluesinthesimulator.Thismayreflect thelackofperceiveddangerinthesimulator,causingrecklessdrivinginafewtestsubjects.Overall,the resultssuggestthatSDLPinthedrivingsimulatorisasensitivemeasureofethanolimpaireddriving.The comparisonwithrealdrivingimpliesrelativeexternalvalidityofthesimulator.

© 2013 Elsevier Ltd.

1. Introduction

Impaireddriving caused byethanol and/or drugsis a major causeoftrafficaccidents,andthusamajorpublichealthproblem (Blomberg etal.,2009).Therelationshipbetweenblood ethanol concentrations (BAC) and accident risk is well established in largeepidemiologicalstudies(Borkensteinetal.,1974;Blomberg etal., 2009).With theexception ofcannabis (Ramaekers etal., 2004),similarrelationshipshavenotbeendemonstratedforother

∗Correspondingauthorat:DepartmentofClinicalPharmacology,St.OlavUniver- sityHospital,Pb3250Sluppen,NO-7006Trondheim,Norway.Tel.:+4772829100;

fax:+4772829110.

E-mailaddresses:arne.helland@legemidler.no,arnehelland@yahoo.no (A.Helland).

psychoactivedrugs anddrugsof abuse.Case–controlstudieson non-alcoholdrugsrequirescreeningandquantificationofalarge numberofpotentiallyimpairingdrugs,aswellasalargenumber ofcases,aseachdrughasarelativelylowprevalenceofdetection incar crashdrivers.Such studieshaveseldombeenperformed, leavingtherelationbetweenblooddrugconcentrationsandcrash risklargelyunknown.Also,bloodsamplingfordrugtestingofcon- trols–ascomparedtosimplebreathtestsinethanolstudies–is necessary,andmakestherecruitmentofcontrolsmore difficult (Versteretal.,2009a).Furthermore,post-mortemdrugconcentra- tionchangesoccurtoalargerdegreeinnon-alcoholdrugs,making interpretationoftoxicologicaldatafromstudiesofkilleddrivers difficult.

Epidemiologicalapproaches cannotestablish causalrelation- ships,andarefraughtwithmethodologicaldifficulties,including

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behaviour)ofthethree“corelevels”ofdriving(Walshetal.,2008).

Muchoftheon-roadexperimentshavesofarbeenconductedinThe Netherlandsonflat,straightmulti-lanemotorways;adrivingsce- nariothatmaynotreflectconditionselsewhere.Also,legalissues andsafetyconsiderationsmayhinderon-roadexperiments,and thecostsofsuchexperimentsmaybeprohibitive.

Experimental studies utilising driving simulators may avoid someoftheproblemslistedabove.However,even verysophis- ticated simulatorscannot fullyreplicate realdriving conditions (Versteretal.,2004;Shechtman etal.,2009).Driving simulator studiesofeffectsofdepressantdrugsondrivingabilityfrequently yieldinconclusiveresultsdue tothelackofvalidation againsta knownpositivecontrol;inpractice,ethanol.Thepositivecontrol isnecessarytoensurethatcorrelationsbetweendrugintakeand drivingrelatedoutcomemeasuresactuallyreflectadrugrelated impairmentofdrivingability,andnotsimplyrandomlyobserved correlationswithnorelevancetoimpairment(Walshetal.,2008).

Ethanolasapositivecontrolalsoensuresthattheexperimental designissufficientlysensitivetotheimpairingeffectsofdepres- santdrugs.Anothercommonlimitationofdrivingsimulatorsisthe lackofvalidationagainstarealdrivingscenario;i.e.,theexternal validity.Thisleavesdoubtastowhethertestsubjectperformance inthesimulatedscenariomaypredictperformanceinrealdriving situations.

Wewantedtodevelopavalidandfunctionaltoolforassessing drugeffectsondrivingperformance,takingintoaccounttherec- ommendationsmadeinthe guidelinesforresearch ondrugged driving.Toachievethis,weconductedavalidationstudyoftheSIN- TEFdrivingsimulator.Thepurposeofthestudywastoestablisha drivingsimulatortestbatterythatissensitivetoethanoleffects, andtovalidatethetestbatterybycomparingperformanceinthe simulatorwithactualdrivingperformanceonaclosed-circuittest trackresemblingruraldrivingconditions.Eventhoughbothsimu- latorandclosedcircuitdrivingconstituteexperimentalconditions, whichdonotfullyreproducethereallifedrivingexperience,both arewidelyusedforassessingdrivingperformance,andrealdriv- ingisgenerallyconsideredtobethereferencemethodologyasfar asvalidityisconcerned.Inthispaperwepresentresultsfromthe primaryoutcomemeasureSDLP,measuredinthesimulatorandon thetesttrack.

2. Materialsandmethods 2.1. Testsubjects

Twentyhealthy,Caucasian,malevolunteersaged25–35years (mean28.7years)whohadbeeninpossessionofadriver’slicense foratleast5years(mean10.6years),wereincludedinthestudy.

Theywereallrecreationalusersofalcohol,andasagroupdrove slightlyless andhad a somewhathighereducationallevel than thegeneralpopulation.Womenandnon-Caucasianswereexcluded becauseoftheteratogenicriskassociatedwithethanoluseinthe

Fig.1.Outlineoftrialtestdesign.

formergroup,andthepossibilityofdeviantethanolmetabolism inthelatter.Theotherexclusioncriteriawerepreviousorpresent drugoralcoholabuseoratypicalreactionstoalcohol,previoushis- toryofdrivingundertheinfluence,significantadversereactionsto previousbloodsampling,regular(daily)intakeofanyprescribed drug,orhighlikelihoodofmotionsicknessasassessedwithamodi- fiedversionoftheApfelriskscoreforpostoperativevomiting(Apfel etal.,1998).Eachparticipantunderwentascreeningforeligibility, receivedwrittenandoralinformationaboutthestudyandprovided awrittenconsenttoparticipate.Thestudywasapprovedbythe RegionalEthicsCommittee,andwasregisteredasaclinicaltrialin theClinicalTrials.govdatabase.Allparticipantsreceivedagiftcer- tificateworthNOK1000(approx.USD150)uponcompletionofthe study.

2.2. Trialdesign

The experiment was designed as a randomised, placebo- controlled, single blind, crossover study. Only the necessary personnelwereinformedaboutwhichinterventionsweregiven.An outlineofthedesignispresentedinFig.1.Eachparticipantunder- wentthreedrivingtestsof1hduration,bothonaclosed-circuittest trackandinanadvanceddrivingsimulator,onsixdifferenttestdays withwashoutperiodsofminimumtwodaysbetweentestdaysto allowthedissipationofanylearningorfatigueeffects.Thedriving scenariointhesimulatorwasmodelledtomimicthetesttrack,as illustratedinFig.2,toensurethatthedrivingexperiencewould beassimilaraspossibleinthetwotestconditions.Beforetest- ingcommenced,thestudysubjectsundertookatrainingsession, bothonthetesttrackandinthesimulator,inordertofamiliarise themselveswiththetestingscenarioandminimisetheimpactof possiblelearningeffects.Ontestdays,theparticipantswereobliged todeliveraurinesampleonarrivalatthetestsitetoexcludethe presenceofdrugs.Thesubjects’weightwasregisteredeachtest day,afterwhichtheywereadministeredaweight-adjusteddoseof ethanol(0,0.7and1.05gperkgbodyweight),calculatedtoobtain anintendedbloodalcoholconcentration(BAC)duringtestingof 0,0.5and0.9g/Lonthethreedifferenttestdaysbothinthesim- ulatorandonthetesttrack,respectively.TheWidmarkequation (AndréassonandJones,1995),wasusedtoestimatetheethanol doses,assumingatotalbodywatertototalbodymassratioof0.68, abioavailabilityof75%,andametabolicrateforethanolof0.15g/L perhour.Weusedvodkamixedwithfruitextracts,orangeandlime juicetomakethedrinkspalatable.Theplacebodrinkswerespiked withnon-alcoholicvodkaflavourinwatertomimicthevodkataste.

Thedrinkswereservedinclosedplastic containers,fromwhich theparticipantswereinstructedtosipthedrinkthroughastraw.

Toavoidanobviousethanoltaste,nodrinkswerestrongerthan 10%(v/v)ethanol,andtheywerekeptcoldbytheadditionofice.

Fig.2.Exampleofthedriver’svisualimpressionontheclosed-circuittesttrack(left)andinthedrivingsimulator(right).

Theparticipantswereallowed1htofinishtheirdrinks,afterwhich theywaitedanother30minbeforethedrivingteststarted,toallow forabsorptionoftheadministeredethanol.Theorderinwhichthe participantsweretestedatdifferentBAClevelswasrandomisedby useofacounterbalanced,multi-conditiondesign.Thesameorder ofBAClevelswasusedforeachparticipantbothonthetesttrack andinthesimulator.Asanadditionalconfoundertoenhanceblind- ing,thestudysubjectswereadministereda placebopill,which theyweretoldmayormaynotcontainasedativedrug,withthe drink.Venousbloodsamplesweredrawnimmediatelybeforeand aftereachdrivingsession,andthemeanvaluewasusedasthebest estimateofthemeanBACduringtesting.

2.3. Realdrivingontesttrack

Thetesttrackdrivingwasundertakenduringafrost-freeperiod ofsixweeksintheautumn.Allstudysessionsweredoneafternight- fall,between20:00and01:00h.Thetesttrackcircuitwas1.37km long,closedtoordinarytraffic,andlaidoutinhillyterrain,withboth gentleandsharpercurves.Thetrackwashard-surfaced,withtwo laneseachapprox.2.75mwide,andhadmidlineandsidemarkings similartostandardNorwegianroadmarkings.Thus,thetesttrack closelyresembledroadstypicalofruralNorway.Surpriseobstacles (1m³foamrubbercubes)wereplacedintwolocationsontwoocca- sions,oneatthebeginningandonetowardstheendofeachdriving trip,andweretobeavoidedbythetestsubjects.Stoplightspresent intwolocationsturnedredononeoccasionduringeachtrip.The participantsdroveaninstrumentedcar(VolvoV702.4s)withauto- matictransmission,fittedwithadoublesetofpedals.Theywere instructedtodriveastheywouldnormallydoonaregularroad.A professionaldrivinginstructorwaspresentinthefrontpassenger seatduringallsessionsoftesttrackdriving,inordertointervene ifnecessary.Aphysicianwaspresentonthesiteatalltimesdur- ingtestdrives.Permissiontocarryoutthetesttrackdrivingwas grantedfromthelocalpolice.Toenablecontinuousrecordingof lateralpositionintheroadlane,thetestcarwasequippedwithan infraredwide-anglecamerafixedtotheroofofthecar,andpointing atadownwardangletotherearofthecar.Thedatawerestoredina databaseandanalysedinaprogramforphotoanalysis(OpenSource ComputerVisionLibrary).Afilteringalgorithm(Houghtransforma- tion)wasusedtoidentifyroadsidemarkings.Thecaralsofeatured otherequipmentforrecordingthelocationofthecaronthetestcir- cuit(globalpositioningsystem;GPS),speed,pedaluseandsteering wheelmovements.

2.4. Drivingsimulator

Testinginthedrivingsimulatortookplaceinlateautumnafter thetest trackdrivingtests werecompleted.Testsessionswere

doneatthesametimesduringtheeveningandnightasonthe test track, using a virtualmodel of the test track and a night- timescenario(Fig.2),toensurecomparableresultsandeliminate differences in circadianinfluences. In addition toobstaclesand stoplights,thesimulatorscenarioalsoincludedtwoincidents(a carabruptlyenteringtheroadandapedestriancrossingtheroadin frontofthedriver)thateachoccurredonceattheendofthedriving session.Thesimulatorhadtheappearanceofaregularcar(Renault Scenic)withautomatictransmissionandoriginalcontrols(Fig.3).

Informationfromtheuseofsteeringwheel,pedals,transmission etc.wasfedintoadedicateddrivingscenariographicscomputer.

Thedrivingscenariowasdepictedonscreenscovering180^◦ofthe driver’sforwardfieldofvisionand90^◦ oftherearfieldofvision, andsynchronouslyininternalandexternalmirrors.Thevertical fieldofviewwas47^◦bothtothefrontandtotherear.Thesimu- latorreproducedrealisticmotion,vibrationandsoundthrougha three-axismovingplatform,avibrationsysteminthechassisand afour-channelsoundsystem.Dataonlateralposition,speed,pedal useandsteeringwheelmovementsovertheentiredurationofthe testsessionswereextracteddirectlyfromthesimulatorcomputer andlogged20timespersecond.AdetaileddescriptionoftheSINTEF simulatorcanbefoundinEngen(2008).

2.5. Measurements

The predefinedprimary outcome measurewas thestandard deviation of lateralposition (SDLP),which is a measure of the degreeofweavingofthecarontheroad.SDLPhasbeenshown tocorrelatewithBAClevelsinadosedependentmanner,andis athoroughlyvalidatedmeasureofthedegreeofdrivingimpair- ment (Verster etal., 2004).Secondary outcomemeasures were numberofbrakepedalpressuresperlap,numberofaccelerator

Fig.3. Setupofthedrivingsimulator.Vehicleandsurroundingfrontalscreens.

icationanddrivingperformance.

Bloodethanolconcentrationswerequantifiedusingaheadspace gas chromatography–mass spectrometry (GC–MS) method. In brief,200␮Lbloodwasmixedwith50␮Linternalstandard(d6- ethanol). Samples were left for 30min to achieve equilibrium beforethegasfractionwasaspiratedintoanAgilentHP6890-5973 GC–MSsystem(Agilent,PaloAlto,CA).Separationwasperformed ona J&W Scientific123-9134 DB-ALC1(30m×1.2mm)column withaheliummobilephaseandaruntimeof0.90min.Ethanolwas monitoredatm/z31andtheinternalstandardatm/z33.Thelevelof quantification(LOQ)was2mmol/L(approx.0.09g/L).Between-day coefficientofvariation(CV)calculatedfromqualitycontrolsamples was4.5%at5mmol/L(0.22g/L)and1.8%at50mmol/L(2.2g/L).

2.6. Statisticalanalyses

Anapriorisamplesizeestimationperformedwithone-tailed, pairedt-testsindicatedthatatotalsamplesizeofn=11wouldbe sufficienttodetectsignificantdifferencesinBAClevelinfluence onSDLPwithsignificancelevel (˛)of 0.05and power(1−ˇ)of 0.95.Althoughtheoretically11subjectswouldsuffice,wechoseto include20subjectsinthestudy,toallowfortheuncertaintyinthe underlyingassumptionsofthesamplesizeestimation,aswellas thepossibilityofdropouts,forinstanceduetosimulatorsickness.

Intheresultsanalyses,weusedalinearmixedmodelwithSDLP asdependentvariable, measuredBACas covariate,and partici- pantasrandomeffect.Separateanalyseswereperformedfortest trackandsimulator.Reportedresultsarefromrestrictedmaximum likelihoodestimation.Themaximumlikelihoodestimationdidnot alwaysconverge.Theindependentvariablestestedforsignificance wereBAClevel,curved/straightsectionandpartoftripdriven(each tripwasdividedinfourequalpartsof15min).Toidentifypossi- blelearningeffectsthatcouldinterferewiththeresults,theimpact ofthenumberoftripsdrivenbeforetheactualonewasalsoana- lysed.Two-sidedp-values<0.05wereconsideredsignificant.The analyseswereperformedinSPSS18andStata12.

3. Results

Ofthe20participantsenrolledinthestudy,allcompletedthree drivingsessionsonthetesttrack,while18outof20completed allthreesessionsinthedrivingsimulator.Twosubjectsdidnot completethesimulatortesting;one becauseofintolerablenau- sea,andtheotherbecauseofasurgicalprocedureunrelatedtothe study.Onthetesttrack,10outofthe60drivingsessionsdidnot yieldsufficientSDLPdatatobeincludedintheanalyses.Thecar- mountedcamerawasoutofpositionineightsessions,thecamera wasnotswitchedoninoneinstance,and oneparticipantinhis firstsessionmisinterpretedtheinstructionstodriveinlane.Thus, acompletesetofoutcomedatawasobtainedfrom10participants onthetesttrackand18participantsinthesimulator.Datafromthe validdrivingsessionsofallsubjectswereincludedintheanalyses.

3.1. Safetyandadverseevents

Nosafetyviolationsorseriousorunexpectedadverse events occurredduringthestudy.Themostcommonadverseeventinthe simulatorwasnausea,whichisaknowndisadvantageofdriving simulators.Six subjects(fouratBAC0and twoatBAC0.5)had toterminatetheirfirstsimulatorsessionearlybecauseofthis,but fiveofthemwereeventuallyabletocompleteallthreesessions.

Thus, onlyone subjecthad towithdrawfromthe studydueto nausea.Priorexperiencesuggeststhatethanolmayprotectagainst simulatorsickness,andrepeatedexposurestothesimulatortend toattenuatethenausea.Therefore,inordertopreventdropouts, allparticipantswhoterminatedtheirsessionsearlyduetonausea weretestedatthehighestBAClevelinthesubsequentsession.The randomorderwasalsomodifiedinanadditionalthreesubjectsdue tootherpracticalcauses.Thesemodificationstotherandomisation didnotaffectconcealmentoftheinterventions,anddidnotappear tointroducesystematicbias,sincetherewasnostatisticallysig- nificantcorrelationbetweenBAClevelandthenumberofprevious testsessions(Pearsoncorrelation0.241(p=0.080)insimulatorand 0.094(p=0.477)ontesttrack).

3.2. Bloodalcoholconcentrations

TheethanolconcentrationsarepresentedinTable1.Ethanol concentrationswereslightlylowerthanintendedbothinthesim- ulatorandonthetesttrack,withconcentrationscloserto0.4g/L attheintendedlevelof0.5g/L.TheBACalsotendedtobeslightly lowerinthesimulatorthanonthetesttrack.Pairedsamplet-test showedastatisticallysignificantdifferencebetweentheBAClevels insimulatorandontesttrackforthedesignatedBAClevelof0.5g/L (p=0.041);however,themeandifferencewasonly0.039g/L.For thedesignatedBAClevelof0.9g/L,therewasnostatisticallysig- nificantdifferencebetweenBAC levelsinsimulatorand ontest track(p=0.21).Inthefollowing,ethanollevelsarereferredtoas theintendedlevels(BAC0,BAC0.5andBAC0.9,respectively).

3.3. Questionnaires

Aftereachdrivingsession,theparticipantswereaskedwhether theythoughtthedrinkandthepillhadcontainedalcoholanda sedativedrug,respectively.Mostsubjectscorrectlyidentifiedthe drinkascontaining/notcontainingethanol(in32of38placebotri- als,35of38BAC0.5trialsand37of38BAC0.9trials,respectively).

However,afewmisidentifiedtheirdrinks,andquiteafewwrongly identifiedthepillascontainingasedativedrug(in15of38placebo trials,3of38BAC0.5trialsand7of38BAC0.9trials,respectively).

ThereweresignificantcorrelationsbetweenhigherBAClevels and subjective (self reported) ratings of poorer driving perfor- mancebothinthesimulator(R=0.35,p=0.013)andonthetest track (R=0.63, p<0.001). Likewise,there wasa strongcorrela- tionbetweenhigherBAClevelsandobjective(drivinginstructor

Fig.4. Regressionanalysisoftherelationshipbetweenbloodalcoholconcentration(BAC)andstandarddeviationoflateralposition(SDLP)insimulator(left;filledcircles) andontesttrack(right;opencircles).ThecirclesrepresentindividualBACandthecorrespondingSDLPvalue.Theregressionlinesandtheir95%confidenceintervalsare shownascontinuouslinesandbrokenlines,respectively.

reported)ratingsofpoorerdrivingperformanceonthetesttrack (R=0.52,p<0.001).

3.4. SDLP

Fig.4showstheindividualSDLPvaluesatthecorresponding BAC,withtheestimated regressionlineand its95% confidence interval.Bothinthesimulatorandonthetesttrack,therewere significantpositivecorrelationsbetweenBACandSDLP(positive regressionslopewithp<0.001).Theestimatedregressionlinesfor thesimulator(Eq.(1))andthetesttrack(Eq.(2))areasfollows, withstandarderrorsfortheestimatesinparentheses:

(simulator):SDLP(cm)=29.43(±2.57)+13.20(±3.61)×BAC (1) (testtrack):SDLP(cm)=22.30(±1.89)+7.61(±1.91)×BAC (2) SDLPvalueswerehigherinthesimulatorthanonthetesttrack atbaseline(placebo)conditions(29.4cmvs.22.3cm,respectively), andshowedasteeperincreasewithincreasingBAC,asseenfrom Eqs.(1)and(2),aswellasFig.4.AsevidentfromFig.4,SDLPvariance wasalsolargerinsimulatordrivingthanintesttrackdriving.

TherelationshipbetweenBAClevelsandSDLPresultsshowa dose–responseeffect,asquantifiedbytheslopes13.20and7.61in Eq.(1)and(2).Furthermore,avisualcomparisonofSDLPresults inthesimulatorandonthetesttrackineachofthe20individual subjectsshowssimilar,positiveslopesinmostsubjects(Fig.5).

To identify possible differential effects of test duration and curved/straightsectionsonSDLP,theSDLPresultswereanalysed withrespecttotimeintervals(fourequalintervalsof15mineach), andperformanceoncurvedandstraightsectionsofthedrivingsce- nario.Inthesimulator,meanSDLPvaluesweresignificantlyhigher incurved sectionsthanin straightsections(p=0.047), whereas therewerenosuchdifferencesonthetesttrack(p=0.17).Inthe simulator,statisticallysignificantdifferencesinSDLPbetweenBAC levelswereseeninallfourtimeintervals.Onthetesttrack,the differencesinSDLPweresimilarbutlesspronounced,andmostly didnotreachsignificanceduringthefirsthalfhourofthetest.In thesimulator,therewasatrendtowardshigherSDLPvalueswith longertestduration,especiallyatthehighestBAClevel.Nosuch tendencywasevidentonthetesttrack.

Toidentifypossible learningeffects that would beexpected toreduceSDLPwiththenumberofpriortestsessions,thenum- beroftripsdrivenbeforetheactualonewasalsoanalysedasan

independentvariable.However,thishadnostatisticallysignificant correlationwithSDLPresultseitherinthesimulator(p=0.70)or onthetesttrack(p=0.66).

4. Discussion 4.1. SDLP

Ourresultsshowapositivedose–responsecorrelationbetween BAC and SDLPin the simulator and onthetest track, both for individualandmeandata.Ahighdegreeofintra-individualsim- ilarity in the BAC-correlated increase in SDLPin the simulator and on the test track, suggests that SDLP is a valid and sen- sitive measure of ethanol-induced driving impairment in the simulator.

AbsolutevaluesofSDLPwerehigherinthesimulatorthanon thetesttrack,withmeanSDLPatBAC0(soberstate)of29cmand 22cm,respectively.SDLPvaluesduringplaceboconditionsinthe simulatorwerealsoconsiderablyhigherthanthoseseeninDutch on-roaddrivingtests,wheremeanbaselineSDLPisapprox.19cm (range9–30cm)(VersterandRoth,2011).Therelativelydemand- ingdrivingscenariothatwasusedinourexperimentmayaccount fortheslightlyhigherSDLPvaluesonthetesttrackthanthoseseen duringpreviouson-roadtests.HigherabsoluteSDLPvaluesinthe simulator compared toreal drivingmay beexplained by unfa- miliarity withthedrivingexperienceinthesimulator,alackof perceiveddanger,andlackofgravitationalcuesandfeedbackthat willnormallyadjuststeering.Thisnotionisalsosupportedbythe observationthatSDLPvalueswerehigherincurvedsectionsthan instraightsectionsinthesimulator,whereassuchadifferencewas notobservedonthetesttrack.Togetherwiththemoredemand- ingdrivingscenarioinourexperiment,thismayaccountforthe considerablyhigherSDLPvaluesthanthoseseenforinstancein theDutchSTISIMsimulatoremployingamonotonoushighwaysce- nario(Metsetal.,2011b).

MosttestsubjectsshowedsimilarSDLPincreasesinthesim- ulatorandonthetesttrack.However,fromtheindividualSDLP datashowninFig.5,afewsubjectsbehavedifferently,evidenced byexcessiveSDLPvaluesinthesimulator.Forinstance,testsubject no.15hadameanSDLPexceeding1matthehighestBAClevel.This wouldcorrespondtothecarbeinglocatedmostlyoutoflaneduring thetrip,whichisinaccordancewiththeactualobservationsmade

Fig.5. IndividualSDLPdataatactualBAClevelsinsimulator(filledcircles)andontesttrack(opencircles).Fortestsubject15,theBACandSDLPvaluesatthehighestBAC levelinthesimulatorwere0.79g/Land102cm,respectively.

duringthisindividual’ssimulatordriving.Itisourexperiencefrom thepresentandearliersimulatorexperimentsthatsomepartici- pantsregardthesimulatorasakindofgameandbehavemorelike virtualrallydriversinsteadoffollowingtheinstructionstodrive appropriatelyaccordingtoconditions.Thiscanexplainthelarge discrepanciesinSDLPbetweentesttrackandsimulatorseenina fewofthesubjects.Subjectno.14attainedanunexpectedlyhigh BACathishighestBAClevelinthesimulator(1.25g/L),whichmay explainthehighSDLPobservedinthatdrivingsession.Also,we cannotexcludethepossibilitythatsomeparticipants’SDLPscores wereinfluencedbysimulatorsickness.

4.2. BAC

Meansubjectiveandobjectiveratingsofintoxicationanddriv- ingperformancecorrelatedwithBAClevelintheexpectedmanner.

ThesomewhatlowerBAClevelsinsimulatorthanontesttrackmay beduetoapossibleconditionednausearesponseinthesimulator thatcouldhavecausedretentionofstomachcontentwithdelayed ethanolabsorption.Oneparticipant(subjectno.6)wasunableto

finishhisdrinkattheintendedBAC0.9levelinthesimulator,and consequentlyacquiredalowBAC.

Mostparticipantscorrectlyidentified theirdrinkascontain- ing/notcontainingethanolandthepillascontaining/notcontaining asedativedrug,althoughquiteafewoftheparticipantsmisiden- tifiedtheplacebopill,especiallyintheBAC0trials.Thisprobably reflectsanexpectation biasin somesubjects,and indicatesthat the use of placebo pills to enhance blinding of the interven- tion in experimental trials with ethanol may be worthwhile.

Previousexperiencesuggeststhatconcealmentofethanolisdif- ficultinblindedstudiesduetothedistinctivetasteandsmelland thecharacteristicandfamiliareffectsofethanol.

4.3. Comparisonwithotherdrivingsimulatorstudiesand on-roadtests

To date, there are few other studies validating the use of drivingsimulatorsfordrugand/orethanolimpairmentresearch.

Asimulator validation studypublishedin 2009useddatafrom two separate previous studies (on-road and in simulator). The

descriptionofthesimulatortheyusedsuggeststhatitwassimi- lartotheSINTEFsimulator,butthedrivingscenarioandoutcome measureweredifferent(urbantrafficandnumberofdrivingerrors atintersectionsasassessedbyadrivinginstructor,respectively).No ethanolorotherdrugswereused.Resultsindicatedrelativevalid- ityforthesimulator,andsuggestedabsolutevalidityforthetype oferrorspertaininglanemaintenance,adjustmenttostimuliand visualscanning(Shechtmanetal.,2009).

Thereare fewprevioussimulatorstudiesusingSDLPasout- comemeasure.OnlyonestudyhasvalidatedSDLPasanindicatorof unsafedrivinginthesimulatorthatwasused.Metsetal.published avalidationstudyin2011showingtheabilityoftheSTISIMdriving simulatortodifferentiatebetweendifferentBAClevelsbasedon SDLPresults.Inthisstudy,27healthyvolunteersunderwentasim- ulatoradaptationofthestandardisedDutchon-roadtestscenario (multi-lanehighwaydrivingfor 1h).BAClevelsof0g/L, 0.5g/L, 0.8g/Land1.1g/LyieldedmeanSDLPvaluesof28.0cm,29.7cm, 33.8cmand36.3cm,respectively.Thisstudydidnotvalidatethe simulatorresultsagainstarealdrivingtest(Metsetal.,2011b).

Apartfromthis,onlytwosimulatorstudiesconcerningdrivingper- formanceafterdrugintakehavebeenpublishedusingSDLPasan outcomemeasure.Metsetal.haveinvestigatedtheeffectsofcaf- feine(givenintheformoftheenergydrinkRedBull^®andcoffee, respectively)ondrivingperformanceinhealthyvolunteersintwo studiesintheDutchSTISIMsimulator,andfoundsmallbutsignifi- cantreductionsinSDLPaftercaffeineadministrationinbothstudies (Metsetal.,2011a,2012).

In2009,avalidationstudywithethanolinadivided-attention steeringsimulator(DASS)waspublished. Asthenamesuggests, thesimulatorisdesignedtomeasureabilityofdividedattention.

Accordingly,itemploysaratherartificialtestscenario,wheresub- jects must keepthe car inlane and simultaneouslyrespondto peripheralvisualstimuli.Also,thesimulatoruseddidnotresemble anormalcar.Dose-dependentimpairmentwasfoundwithhigher ethanollevels(Versteretal.,2009b).

Thestandardisedon-roaddrivingtestwithSDLPastheoutcome measuredevelopedinTheNetherlandsremainsthemethodofref- erencetoexaminedrivingimpairmentfromdrugs.Insuchtesting, BAClevelsof0.5g/Land 0.8g/LonaverageincreasesSDLPfrom placeboconditionswith2.4cmand 4.3cm,respectively(Verster andRoth,2011).Ourresultsfromthetesttrackshowslightlylarger increasesinSDLP,whereastheBAC-relatedincreasesinthesim- ulatorwereconsiderablylarger.Again,thediscrepancy between ourresultsand theDutchon-roadresultsmaybeexplainedby themoredemandingdrivingscenarioemployedinourvalidation study.

4.4. Implicationsforthevalidityandfurtheruseofthesimulator

Externalvalidityofadrivingsimulatorreferstothetestsce- nario’sabilitytoinvokesimilarreactionsinthedriversasareal drivingscenario.Validityisspecificfortheparticulartypeofsce- narioandsimulator,test, andpopulationusedinthevalidation experiments,andwillnotnecessarilybetransferabletootherdriv- ingscenarios,simulators,tests,orpopulations.Externalvalidityis absoluteifthesameeffectisinvokedtothesameextentbothin thesimulatorandintherealdrivingenvironment.Relativeexter- nalvalidityimpliesthatthereexistsatrendofchangeinthesame directionbothinthesimulatorand intherealdrivingenviron- ment,butthemagnitudeofchangeisdifferent(Shechtmanetal., 2009).

There was a large degree of similarity in the relationship betweenSDLPand BAC levelsin thesimulator and onthetest track.However,theabsolutevaluesofSDLPinthesimulatorwere consistentlyhigherthanonthetesttrack.Thus,therelative(but not theabsolute) external validity of theSINTEF simulator has

beenestablished whenvalidated againsttest track drivingin a driving scenario that is representative of the demanding rural drivingconditionsinNorway,usingethanolasapositivecontrol.

Webelievethatthis validationmaybeextendedtorealdriving undersimilarconditions;however,thisassumptionhasnotbeen proven.

In the simulator, we found consistent and significant BAC- related increases in SDLP in all time intervals when the hour-long test was divided into four 15-min time inter- vals. This suggests that the duration of the simulator test in order to reach significant results may be shortened in future studies.

4.5. Limitationsofthestudy

In ourstudy,alltest subjectswerehealthyyoungmale vol- unteers, who are not representative for the general driving population. Ourresultsmaythereforegivea somewhatinaccu- rate estimation of the impact of BAC on SDLP in the general population.

Therearethreelevelsofbehaviourrelevanttotrafficsafety:

automatic, control and executive planning behaviour (Michon, 1985;Walshetal.,2008).SDLPastheprimaryoutcomemeasure inthisstudyismainlyrepresentativefortheeffectofethanolon automatedactionsatabehaviouralcontrollevel.Outcomemeas- uresofdrivingbehaviouratmanoeuvringandstrategiclevelswill bereportedinaseparatepublication.Drivingsimulatorsmaybe especially suitable totest higher behaviourallevels likehazard avoidance, dualattention, risk taking and impulsivity, both for ethical(riskofinjury)andpractical(easeandreliabilityofmea- surements)reasons.

Weemployedasingleblinddesign,keepingtheintervention concealedfromthetestsubjectsbutnotfromthestudypersonnel orthoseresponsibleforanalysingtheoutcomedata.

Unlike some of the most advanced simulators in use, the SINTEFsimulatorallowsonlylimitedtilting(threedegreesoffree- dom).Motion-basedsimulatorswithfulltiltingtechnologymight increasetherealismofthedrivingexperience,andthusheighten theexternalvalidityofthesimulator.

Severalofthetestsubjectsexperiencednauseainthesimula- tor,whichcaused onesubjecttowithdrawfromthestudy,and mayhaveaffecteddrivingbehaviourinothers.Thisis ageneral drawback of driving simulators,which may to someextent be unavoidable,evenwhenusingscreeningproceduresincludingtest drivesbeforeenrolment.Wealsoemployedaratherchallenging drivingscenario,withmanycurvesandlongduration,whichmay haveexacerbatedtheproblemsrelatedtonausea.

Thevalidationagainstrealdrivingwasdoneonaclosedtest track.Thelength(approx.1.4km)andlayout(curvy,hard-toproad approx.5.5mwidewithmidlineandsidemarkings)ofthetesttrack ensuredthatthedrivingexperienceresembledrealdrivingonrural Norwegianroads.However,itmaybeimpossibletofullyeliminate thefeelingofanartificialsituationwhendrivingonaclosedtest track.Forsafetyreasons,adrivinginstructorwaspresentinthe passengerseatatalltimesonthetesttrack,aswellasapoliceofficer onthetesttracksite.Thismayhaveconstitutedarestrainingeffect aswellasheightenedtheattentionoftestsubjects,causingthem todrivemorecarefullyandattentivelythantheywouldotherwise havedone.

Finally,ourstudyhadalimitedsamplesize,whichgenerally increasestheriskoftypeIIerrors(i.e.,failingtodetectrealdiffer- ences).Also,missingdatafrom10of60drivingsessionsonthetest trackmayhavelimitedthestatisticalsignificanceofourfindings.

Themissingdataoccurredduetorandomincidents,andwehave noreasontobelievethisintroducedsystematicbias.

depressantdrugs.

Acknowledgements

TheresearchprojectwasfundedbyagrantfromtheResearch CouncilofNorway.

Theauthorswouldliketothankthefollowing employeesat SINTEFTechnology and Society and the Department of Clinical PharmacologyatSt.OlavUniversityHospitalwhomadevaluable contributionstotheresearchproject:ThomasEngen,DagfinnMoe, KennethSørensen,TerjeGiæver,CatoMausethagen,NinaHusby, Marianne Nordtømme, Odd Hjelkrem, Guro Haltbrekken,Anita Skogholt,TrudeKristineVaagGjerde.

WewouldalsoliketothankProf.Dr.JanRamaekersatMaas- trichtUniversity,TheNetherlands,forvaluableadviceandhelpful discussionsduringthepreparationsofthestudy.

Finally,we wouldlike toexpressourgratitudetothestudy subjectswhouncomplaininglyunderwenttheratherdemanding trials.

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