25thJanuary2017

WHITEPAPER:DIRECT-TO-PATIENTREMOTERESEARCH

Co-AuthoredbyAbbeSteel,MSc

FounderandCEO,HealthiVibe,LLCandKarlLandert,MScPresidentandCEO,eClinicalHealthLtd

Thechallengesassociatedwithconductingandmanagingtoday’slarger,multinationalPhaseIIIclinicaltrialshaveneverbeengreater.Therehasbeenadramaticincreaseincostsandtrialcomplexityoverthelastseveralyears.Managingasinglestudysiteaveragesbetween$1,500and$2,500permonthiandthetotalnumberofproceduresperformedforaPhaseIIItrialincreasedby70%from2001-2005to2011-2015.Thishadacorrespondingincreasetothecostpervisitby34%andtothesiteworkefforttoadministerproceduresby61%iiwhichaddstotrialcosts,durationandadesignthatisnotfavorabletopatientsandcaregivers.Everydaywehearaboutbiopharmaceuticalcompaniesexploringnovelandinnovativeapproachestoconductstudiesthatwillhaveasignificantimpactoncostsavings,timelines,improveoverallpatentrecruitmentandretention,andalsocreateamoremeaningfulpatientexperience.Whilemanycompanieshaveconsideredimplementingadirect-to-patientclinicaltrialdesign(virtualtrial),mosthaveawatch-and-waitmentality,citingconcernsoverdataquality,technologicalfeasibility,drugsafetyandregulatoryhurdles.Whilenosinglestudydesignandconductstrategyshouldbetakenasthesolutiontothefinancialandoperationalburdensofclinicaldevelopment,theclinicalresearchindustryispoisedtobeginintroducingamorepatient-centeredclinicaltrialresearchmodel.Aswithanynovelapproach,therearemanyfactorsthat

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mustbeevaluated,pertinenttoscientific,operational,technological,regulatory,andotherconsiderations.Thiswhitepaperprovidesabasicoverviewofwhatisinvolvedindesigningandimplementingavirtualclinicaltrialandincludesadiscussionofimportantconsiderationsandsolutions.

What Is Direct-to-Patient Remote Research?

Thetermdirect-to-patientremoteresearchisoftenusedloosely.Weattemptedtoassessthedesignoptionsforastudythatwouldqualifyforitbeingclassifiedasdirect-to-patientremoteresearch.Inessence,thedirect-to-patientRemoteapproachrevolvesaroundtwomaindesigndimensionsforastudy:1. Theuseofremotedatacollectionandpatientengagementmethods2. Theroleofthesites

Accordingtoourdefinition,bothlowerquadrantsdoqualifyasdirect-to-patientremotetrials.

Traditional clinical trial model X

Sites maintain their roles, instead of physical visits at the site data are collected by• Conducting eVisits• Field based personnel at the patients home• By the patients themselves• In day care clinics, by primary physician at al local Lab near

the patients homePatients are engaged remotely through electronic means and home visits (if applicable)

Most/all sites do not maintain their traditional role although theymay be used to refer patients as part of recruitment, one virtualsite (per country) assumes the role of PI, date are collected• Conducting eVisits• Field based personnel at the patients home• By the patients themselves• In day care clinics, by primary physician at al local Lab near

the patients homePatients are engaged remotely through electronic means and home visits (if applicable), referring sites may continue to play a role in engaging with patients

One virtual site

Many Sites

Site visits and datacollection

Dat

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Eng

agem

ent M

odelOne virtual site

Many Sites

Full remote datacollection and remote

eVisits

Site visits and datacollection

Full remote datacollection and remote

eVisits

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Therearealsootherimportantconceptsandattributeswhendesigningclinicaltrialsthatneedtobepositioned:

• Patient-Centricity:Theresearchisindependentofsite,datacollectionandengagementmodelbutbecomesakeyelementofanyremoteapproachandmustbesupportedbysuchanapproach.

• Telemedicine:“Closelyassociatedwithtelemedicineistheterm"telehealth,"which isoftenusedtoencompassabroaderdefinitionofremotehealthcarethat does not always involve clinical services. Videoconferencing,transmission of still images, e-health including patient portals, remotemonitoring of vital signs, continuing medical education and nursing callcenters are all considered part of telemedicine and telehealth”(http://thesource.americantelemed.org/resources/telemedicine-glossary)

• Remote Patient Monitoring: “Remote patient monitoring (RPM) usesdigital technologies to collectmedical and other forms of health data fromindividuals in one location and electronically transmit that informationsecurely to health care providers in a different location for assessment andrecommendations”(http://www.cchpca.org/remote-patient-monitoring)

WewillintroducetheconceptofeVisitswhichdoencompassalloftheabove,butcanbetailoredtothespecificneedofatrial.• eSource data (FDA, “Guidance for Industry: Electronic Source Data inClinicalInvestigations”,2013):datainitiallyrecordedinelectronicformat.They can include information of clinical findings, observations or otheractivities captured prior to or during a clinical investigation used forreconstructingandevaluatingthe investigation.LikeSourcedata,eSourcedata should also be attributable, legible, contemporaneous, original, andaccurate (ALCOA). Reconstruction of the course of modification (such asadditions,deletionsoralteration)relatingtothisdata is facilitatedbytheuseofanaudittrail.

Inessence,usingthedefinitionsandclassificationsintroducedabove,clinicaltrialsmaybecategorizedalongthefollowingdimensionsinto‘Traditional’,‘Hybrid’andfully‘Virtual’trials.

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Fullyvirtualtrialsarenotlimitedbytheneedtohaveanestablishednetworkofqualifiedsitesthatcanbephysicallyaccessiblebythepatient.Instead,acentralsitemaybeusedforpatientenrollmentandmanagement,actingasavirtualsite.Inthisscenario,theroleandtheburdenofthesiteisgreatlyreduced,leadingtosignificantlybetterquality,morecost-effectiveandpatient-centrictrials,andavastlyimprovedbottomlineforsponsors.BetterqualityandimprovedservicetopatientsisachievedbyhavingonesitehandlinghighervolumesallowingformoreflexibleandefficientresourcingofprofessionalstaffingandbettertrainingandalsointroducingtheuseofeSourcesandelectronictoolsthatmaybecomemoreaffordableinthisscenario,minimisinghumanerroreitherduringdatacollection(directlyviadevices)orduringdataentry(e.g.,validationofdataduringdataentry).

Forces Driving Towards Direct-to-Patient Remote Research Focus onmore patient-centered trial designs: Remote clinical trials offer apatient-focused approach to pharmaceutical research. Many of the barriers toparticipationinsite-centeredstudiesarenolongeranissueinaremotetrial.Thestudy isconducted in thepatient’shome,so travel isno longeraconsideration,allowing those who have mobility issues, or who live in rural areas, theopportunitytoparticipate.

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Insite-centeredstudies,lackofconvenientaccesstostudysites,combinedwiththenumberofstudyvisitsrequired,oftenleadstolowerrecruitmentandhigherdropoutratesamongparticipants.Ina2015surveyofclinicaltrialparticipantspolledabouttheirstudyexperienceiii,nearlyathirdofallrespondentssaidthevisitschedulewasnotatall,slightly,oronlymoderatelyflexible.Only27%saidgettingtothestudysitewasnotatall,slightly,ormoderatelyeasy.Twenty-sixpercentfoundparkingatthestudysitewasnotatall,slightly,oronlymoderatelyconvenient.Alloftheseconsiderationsarepotentialhurdlestoretentionthatdonotexistinaremotestudy,wheredatacollectionandmonitoringisdoneinthepatient’shome.EmpoweredPatients:Peoplelivingwithchronic,acute,orterminalillnessesareturning to the Internet for information in ever-increasing numbers, andempowering themselves to make better healthcare decisions. According to a2015 survey, 62% of smartphone owners used their phone to seek outinformationregardingahealthcondition,withthatnumberexpectedtogrowastheglobalmobilehealthcaremarketcontinuestogrowiv.Aspatientstakechargeoftheirhealthandgrowmoretech-savvy,theyareengaginginmorepatient-drivenresearchinitiatives.Withorganizationssuchaspatient-centeredOutcomesResearchInstitute(PCORI)educatingpatientsandprovidingavehicletolearnaboutresearchspecifictotheircondition,thesepatientsareleveragingtechnologytostayinformedandengaged.FindingandRetainingPatients:Recruitingandenrollingparticipants isoftenthemostdifficult aspectof a clinical trial,withnearly80%of studies failing tomeet initial targetsv. Enrollment for traditional site-centric studies is limited topatientswholivewithinareasonableradiusofthestudysite.Recruitmentreliesmainlyonphysicianreferralsof,andadvertisingto,localpatients.Asthedistancefromthesitegrows,sodothehurdlestoparticipation.Inaremotestudy,participantsarenotlimitedbytheirproximitytothestudysite.Advocacygroups,trialfinderwebsites,andsocialmediacampaignscanallbeharnessedtofindpatientswithinanygeographicalregion—oracrossthecountryortheentireworld.

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Asmanyas40%ofparticipantsintraditionalPhaseIIItrialsloseinterestanddropoutofthestudyvi,sokeepingpatientsengagediscritical.Remotestudiescanleveragepatientportals,datacollectiondevices,andinteractivesmartphoneappstopromoteengagementandenhancethepatientexperience.Participantstransmitdataviawirelessdevices,completequestionnairesintheprivacyoftheirhome,andmeetvirtuallywithstudystaff.Thedirect-to-patientclinicaltrialreducessitevisitsandlessenstheoverallburdenonpatientsandtheirfamilies.Aclinicaltrialthatminimizestheimpactonapatient’slifestylehasthepotentialtoincreaserecruitmentby60%ormore,whileover95%ofparticipantstypicallycompletethestudy.vii

RealWorldEvidencestudies:Ascompaniesare looking todemonstratevaluefortheirproducts“beyondthepill,”thereisapushandinterestindesigningandrunning more post-approval studies that provide real world evidence (RWE),with patients in a more naturalistic setting. RWE studies often use manystakeholderscontributingtodatacollectionandpatientengagementtactics(e.g.,caregivers,personaltrainers,GPs,nutritionists).Suchstudiesoftentargetbroadpopulationsofpatientsandhavealongduration,posingcost,retentionanddataqualitychallenges, lendingthemselves tousemanyof theconceptsofdirect-to-patientremoteresearch.IncreasedCostsandComplexityofTraditionalResearch:Clinical trialshavemoreeligibilitycriteria,protocolamendments,patient-recorded-outcomes(PRO)assessments,procedures,andendpointstodaythantheydidjustadecadeago.Allof these factors combine to increaseboth the cost andcomplexityof the study.Addinthecostsassociatedwithsupportinganetworkofstudysitestoprovidemonitoring,guidanceandinsuringthequalityofdatacollectionandtheeconomicburdenoftraditionalstudiesbecomesordersofmagnitudegreater.Direct-to-patientremotestudiesaddnewcostsandsupportingservices.Whilethenumberofstudysitesisgreatlyreduced,sponsorsmustinvestintechnology,platforms,andequipmenttheyotherwisewouldnothavetopurchase.

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TechnologicalAdvances:Internetandmobilenetworkaccessaroundtheworldhasgrownexponentially inthepast fiveyears.Bytheendof2015over80%ofhouseholdsindevelopingcountrieshadinternetaccessand78%ofinhabitantsinEuropeandtheAmericashadmobilebroadbandaccessviii.Thisconnectivityhascreated a cultural shift in the mind-set of consumers and raised levels ofexpectation regarding how they prefer to engage in everything from onlineshoppingtointeractingwiththeirhealthcareproviders.ThisInternetandmobilenetworkaccesshascreatedalevelplayingfieldforpatientslivinginremotelocations,andthosewithmobilityissues,allowingthemtoparticipantinremoteresearchwiththesameconvenienceandaccessibilityaspatientswholivenearstudysites.

Considerations

Notallstudieslendthemselveseasilytothedirect-to-patientremotestudymodel,however.Therearemanyfactorstoconsiderdesigningasuccessfulvirtualstudy.ScientificThePatientPopulation–Carefulconsiderationtothepatientpopulationmayprovideinsightastowhetherornotremoteresearchwouldbeasuccessfulalternativetoatraditionalstudy.Inagingpopulations,forexample,proficiencywithtechnologymayprovetoogreatahurdletoparticipationormaycompromisetheintegrityofthedatabeingcollected.TechnologyAdoption&Training–Adoptingnewtechnologycomeswithalearningcurve.Devicetrainingforfieldnurses,sitestaffandparticipantsiscriticaltoproperdatacollectionanddevicemanagement.TheStudyDesign–Doestheprotocollenditselftoremoteresearch?Willthestudyrelyonpatient-reporteddataoristhereagreaterneedforinvestigatorassessments?Reviewtheprotocoltodetermineifremotetechnologiescanbeusedinplaceofcertainstudyvisits.Aretherewaystoleveragetechnologytoincreasepatientengagementandadherence?

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IntegrityoftheData–Selectingthebesttechnologytosupportaremotestudyisimperative.Withoutcheckpointstoinsurecleanandqualitydataatthesource,dataverificationbecomesasignificantburdenonsitestaff.RemoteMonitoring–Whenselectingtechnologytosupportthestudy,theabilitytomonitordataremotelyoffersadditionaloptimalefficiencyandcostsavings.AdverseEvents–Evenintraditionalstudies,adverseeventreportingbeginswiththepatientsharinginformation.Reportsareoftenmadebyphone,email,orinpersonatstudyvisits.Withremotestudies,thetechnologymustbeabletocaptureadverseeventreportsandrelaytheminatimelymannerforfollowupbysitestaff.DeviceDeliveryorBYOD(bringyourowndevice)–Carefulconsiderationmustbegiventodisbursementofdevicesorusingthepatient’sowndevices.Formaximumutilizationandreach,thebestmodelisusingaplatformthatcanworkonmultipledevices(smartphone,laptop,tablet,etc.).GlobalStudies–Whenconductingglobalstudies,allrelevantlanguagesandlocalculturesmustbesupported.Country-specificprivacyregulationsmustbeobserved.OperationalOnlinesystemscanbeutilizedtosupportclinicaloperations.Inaremotestudy,participantssharetheirdataviatheInternetfromtheirhomeusingastudyportalorwebsiteontheircomputerormobiledevice.Multiplestakeholders,includingsponsors,sites,andhealthcareprofessionalscanprovidereal-timesupportthroughsolutionssuchasonlinechats,call-centers,oremail.Importantoperationalconsiderationsinclude:

• Isspecialequipment(i.e.,MRI,CTscan,etc.)needed?• Whatarethedrugdistributionregulations(atthestatelevelintheUSoratcountrylevel)?

• Aretherespecialphysician/raterassessmentsthatonlyatrainedcliniciancanperform?

• Is the physician the best method of recruitment (i.e., newly diagnosedpatients)?

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• Canphysicalexamsorlabworkbeperformedbyanurseorisaphysicianrequired?

PatientCareandDataCollection– If theprotocolrequiresspecialoversiteorequipment for testing patients, a remote studymay not be the best choice forstudy design. Careful consideration should be given to the logistics involved inmanagingparticipantneedsandstudyrequirements.Notalldatacollectioncanbe passively transmitted back to the study site. However, one solution to thisdilemmamightbetoutilizetheservicesofhomehealthnurses.Oftentheycanbetheconduitbetweenstudysiteand thepatient’shome,performingsomeof theactivities traditionally conducted at sites such as specimen collection, physicalexams, and administration of study drug. This patient-centric approach candecrease the need for site visits and monitoring while increasing patientretention.PatientRecruitment–Similartoatraditionalclinicaltrial,virtualtrialsmusthaveaproactive,wellplannedpatientrecruitmentstrategy.Thereareavarietyofcost-effectivetechniquesthatcanbeemployed,includingphysicianreferrals,communityefforts,patientadvocacygroups,aswellasonlinetactics,suchassocialmediaandvariousinternetsites.Onlineoutreachisanidealwaytoreachpatients,astheywilllikelybeseekingmedicalinformationonline,relatedtotheirconditionorasetofsymptoms.Additionally,onlinetacticsareveryeasytoturnonandoff,soitiseasytocloselymonitorsourcesofreferralsandmaximizefundsspentwithoutwastingbudget.Nomatterwhichtacticisemployed,itisessentialtosourcetheeffortsbycreatinguniquelinks,eliminatingtheneedforaseparatepre-screeningwebsiteoraskingthepatientshowtheyheardabouttheprogram.Thegoalistoeliminate/reduceasmanyclicksaspossibleforthepatient.

Technological

Softwaresystemssupportingdirect-to-patientremotetrialsmustbeeasytouseandcosteffective,whileprovidingahighlevelofsecurityduringprocessingofhealthdata.Theyshouldactasasinglesourceofinformationforallparticipants,givingthemeasyaccesstotheinformationtheyneedinacompliantwaybasedontheneedtoknow/use/seethisinformation.

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Essential Requirements

PatientAccessingtheSystem• Thesystemmustprovideaneasymechanismtoonboardpatients.• The systemshouldbeable to informpatients about theirprogress in thestudy and patients should be guided by the system on which task toperformnext.

• Thesystemshouldactasaconduittokeeppatientsengagedandinformed,e.g.,byprovidingthemadditional informationsuchasstudynews,overallprogressofthestudy,andeducationalvideos.

• Ideally, electronic informed consent should be supported by the samesystem,givingthepatientsareducednumberofsystemstouseand loginto.(Ifthisisnotfeasible,asinglesign-onsolutionshouldbedeployed.)

• Thesystemmustsupportthepatient’spreferencesonhowtoaccessitandshouldbebeintuitive,toaccommodatevaryingdemographics.

DataIntegrityandSupportofeSource• Thesystemmustallowforpatientsandothercontributorstoenterdata.• Checkpointsandconfirmationsmustbebuiltintothetechnologytoenableclinicianstoreduceoverheadattributedtodataverification.

• Thesystemmustbeabletoensurecleanandqualitydataatthesourceofinputwithuser-friendlyverification.

• MultipleRoles,EnteringData,Co-operatingandReviewingData

• Thesystemmustsupportmultiplerolesbeingabletoenterdata,view,andcommunicate via the system, e.g., site staff reviewing data entered bypatients,aswellasalertsforadverseevents.

• Thesoftwaresystemshouldbeadaptiveandsupportmultipledevicetypesand/orallowforadeploymentmodelusingmobileapps.

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Desired / Required Depending on Trial Design:

High-ToucheVisit,InteractiveModel

• ThesystemshouldsupporteVisitswhichcanbeconductedbytelephoneorvideoconferencing. Data entry forms should allow capturing eSourceinformationduring theeVisit,both fromthesitesaswellasdirectly fromthepatients(questionnaires,eDiaryentries,medicationcompliance,etc).

• Ideally,thevideoconferencingtoolisanintegratedpartofthesystem.Moreloosely coupled systemsmay provide an alternative (e.g., via Quicklinks)andinsomesettingsusingtoolslikeSkype(orsimilar).

• Acall/communicationslogforallcommunicationswiththepatientshouldbe captured automatically by the system or support a manual inputaccordingtooperatingprocedures.

• The system should provide sites, a call center and/or supporting teammembers with the ability to communicate with patients securely via aregulatory-compliantmessagingplatform.

• Duringin-homevisitsbyavistingnurse(oranyotherrole),datashouldbecaptured within the system as well along with visit reports. Allappointmentsandvisitsshouldbeeasilyscheduledthroughthesystemandreminders should be sent out to ensure adherence to protocolrequirements.

• Buildingon thepatient communication capabilities, the interactivemodelshould be extensible, allowing the monitors and sites easy access to avideoconferencingservice.

ReminderSystems(Medication,VisitScheduling)forStudyParticipants

• Thesystemshouldhaveataskmanagementandschedulingsystemwhichuses reminders that use different channels to alert participants (inapplicationmessaging,pushmessages,e-mail,SMS).

RewardSystem

• Ideally, a reward mechanism is provided as part of the system. This isespecially beneficial for long-term studies to help keep the patientsengaged. Specific rewards shouldbegrantedbasedonaction carriedout,

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for example, the completion of an electronic patient-reported outcomes(ePRO)questionnaire,compliancewithmedicationintake,orcompletionofstudyeVisits.

CapabilitytoCollectDatafromSmartDevices(BloodGlucoseMeter,Spirometer,Scales,Wearables)

• Thesystemshouldprovideawaytocollectdatafromarangeofdifferentbluetoothorcloud-connecteddevices.

DrugSupplyManagement

• Thesystemshouldsupportthedrugdispensing,trackingandmanagementprocessandcomplywithlocalandcountry-levelregulations.

RemoteMonitoring• Monitoring data remotely, visit reports, summary, and progress reportsshouldbesupportedbythesamesystemallowingforefficientmanagementandnear-realtimeprogressoverview.

Whateversystemisselectedfordirect-to-patientremotetrials,itshouldbeeasytointegratewithothersystemsselectedandbecomeanintegratedtoolforday-to-dayoperations.Thenumberofsystemsshouldbeminimizedtoeliminatecomplexityandtheintegrationandinterfacinghasslethatinmanycasesmakesuchdeploymentsimpossiblewithinthetighttimeframes.Fromanend-userperspective,thereductionoftheamountofsystemstheyusewillincreaseengagementsignificantly.Aflexible,adaptablemanagementofrolesthatcontributetothetrial’ssuccessisbestorchestratedwithinone‘master’systemthatmanagestheirtasksandprovidesreal-timeoverviewofprogressandbottlenecksreducingreportingandmonitoringburdensignificantly.Finally,reducingthenumberofsystemsandhavinga‘single’scaleablesystemprovidingmanyofthefeaturesdescribedabovemakesthedirect-to-patientremotetrialmodeleconomicallyaffordable,evenwithverylarge,multi-nationalstudies.

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Regulatory:The regulatoryhurdles to conducting a global, remote studyoftencenter around the informed consent process, drug shipment rules andregulations,andprotectionofpersonaldata.Itisimportanttoengageregulatorsearly and often throughout the protocol development process. Some EuropeanEthicsCommittees,forexample,requirethepatientandInvestigatortomeetfaceto face to complete the informed consent form (ICF), and to retain an original,papercopysignedbybothpartiesonfile.Itmaybedifficulttoobtainapprovalforan electronic versionof the ICF.Also, inmany countries shipment of the studydrugdirectly topatients’homeswouldnotbeapproved.These factorsmustbeconsideredandoften“negotiated”at theonset toensure thedesign isacceptedandapproved.CommercializationofApprovedDrug:Often,physicianswhoareincludedinaPhaseIIIorPhaseIVclinicalstudybecomeearlyprescribers/adoptersofthedruguponapproval.Ifapatient-centricstudyisemployedwherephysiciansarenotused,thesponsormaynothavethoseearly-adoptingphysicianstocountonforinitialsales.Physicianexperienceandsupportisanimportantpartofanylaunchstrategy.Itisimportanttoconsiderwhetherthedrugbeingstudiedisanovel,firstgenerationtherapeuticandpossibleproductlaunchmodel.Creatingaroleforsites,evenifnotfullinvestigators,whichprovideexposuretothenewcompound,maybebeneficialasacompanypreparesfordrugapprovalandlaunch.(Forexample,referringsites(ifused)mayhaveaccesstostudyprogressandviewtheprogressofpatientstheyreferred).Clinical(exams,labs,drugshipment/administration):Fromaclinicalstandpoint,direct-to-patientresearchcanrepresentnewchallenges.SuperficialphysicalexaminationscanbeperformedusingvideoconferencingtoolslikeSkype,butunlessothervitalsignsarerecordedviathetechnologyusedaspartofthestudy(smartphoneapp,electronicdevice)sitevisitsorhomehealthnursesmayneedtobeemployed.Forspecimencollection,workingwithnationallaboratoriessuchasQuestDiagnosticsorLabCorpmaybeaviablesolution,allowingparticipantstovisitalabnearthemwithanordertheycandownloadfromthestudyportal.

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ThePatientPerspective(mindfulnessindesign):Wehavespokentohundredsofpatientsandcaregiversfrommorethan25countriesoverthepasttwoyears,includingtrial-naïvepatientsandpatientswhohaveparticipatedinclinicalstudies,togaininsightsintowhatpatientscareabout.Whatwehaveheardisthatregardlessofwhetherthepatienthasararedisease,isanoncologypatient,orhasamorecommonconditionsuchasasthma,acommonthemeemergesacrosstheboard-thatpatientstrustandrelyheavilyontheirphysiciansandvaluethecareandsupporttheygetfromthem.Whenwetalktopatients,theyusewordslike“appreciation“,“communications“,“responsive“,“support“,“education“,“care“,“compassion“,and“trust“asthemostimportantaspectsofdecidingtoparticipateandaspartoftheiractiveparticipationinastudy.Butinthesamebreath,patientssaytransportationisamajorissue,aswellastimeawayfromschoolandwork,andthatconvenienceisacriticalfactorinfluencingpatientparticipation,retention,andoverallsatisfaction.Therearenumerousadvancementsofnew,high-touchtechnologiesthatcanhelpcreateapersonalizedenvironmentforthepatient,allowingforahigh-touchexperiencewithallthebenefitsofamoreconvenientdesign.And,becauseindividualsacrosstheglobehaveimprovedbandwidth,areusingsmartphonesandwearablesmoreandmore,andarecomfortablewithtelemedicineandvideo-conferencingsystemslikeSkype,thevirtualstudyoffersauniqueopportunity.Studiescanbedesignedtomeetthe“sweetspot,”wherethetechnologiesnowavailabletosupportvirtualclinicaltrialsis,inequalmeasure,balancedwiththepatient’sneedforhumaninteractionandamodelthatworksfor–andwithin–patients’lives,toimprovethepatientexperienceandultimatelyremovetheburdensoftraditionalparticipation.Designingthesestudiessotheycanbepatient-centricandcreateameaningfulexperienceforpatientsiscriticaltotheirsuccess.Aswebeginexploringthesetypesoftrials,withpatientsupportandcarealwayscentraltodesign,remotestudieshavethepotentialtoimprovethepatientexperiencesignificantlyifexecutedproperly.Takingthepatientperspectiveintoconsiderationwhendesigningthestudyiscrucialtosuccess.Recruitmentandretentionoftenhingeonhowmuchofanimpactthestudywillhaveonthepatient’sdailylife.Thenumberofstudyvisitsrequired,logisticsregardingtransportation,takingtimeofffromwork,andaccesstochildcarecanallinfluencethedecisiontojoinastudyortocontinueparticipating.

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Creatingapersonal–evenintimate–connectionbetweenthetrialteamandthepatientisimperative.Whiletechnologiescanhavegreat,robustfeatures,theystillmustbesuitedforthepatient.Often,combiningtechnologywithhigh-toucheffortssuchashomehealthnurses,regularphoneorvideocalls,moretwo-wayinteractionandcommunicationwillenrichthetechnology-basedmodel.

TheCaregiverRole:Intraditional,site-basedstudies,ifapatientreliedonacaregivertodrivehimorhertoaresearchsite,thecaregivermaynolongerhaveaprimaryroleinaremotetrialandmaynotfeelasneeded.Considerotherwaystosupportandinvolvecaregivers.Teachingthemaboutthetechnologybeingusedinthestudysotheycansupportthepatient,orincorporatingcaregiverremindernotificationsifapatienthasn’ttakentheirmedicationareexamplesofusefulwaystoincludecaregivers,andultimatelyincreasecompliance.Caregiverscanbeinstrumentalinrecruitmentandretention.Appealingtothosewhohavetocommit,outsideofjustthepatient,andalsoaddressingtheirneedsiscritical.Excludingcaregiversbecausetheyarenotneededtodrivethepatienttovisits,forexample,mayfeellikealienationandnotreductionofburden.Caregiversshouldbegivenaroleinavirtualtrialandshouldbeabletoaccessthesystemandcontributeindefinedwaystokeepthemengaged.

Conclusion and Recommendations

Virtualclinicaltrials,canpotentiallysolvearealproblemwehavewithaccess,especiallyamonghardtoreachpopulations,peoplewholiveinrurallocations,andverysickindividuals.Patient-centrictrialscantrulyeasetheburdenonthepatientandallowpatients,especiallyinremotelocations,tohaveaccesstoclinicalresearch.Andwhilethereareimportantoperational,scientific,andtechnologicalconsiderations,ifdesignedandexecutedsuccessfully,virtualtrialscanbesignificantlymorecost-effective,efficient,andapatient-friendlymodelforclinicalresearchprogramsglobally.

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References ihttp://xtalks.com/Virtual-Clinical-Trials-1.ashxiiGetzKA,CampoRA,“Trialwatch:Trendsinclinicaltrialdesigncomplexity,”NatureReviewsDrugDiscovery16,May2017

iiiHealthiPerspectivesvalidationreportonfilewithHealthiVibeivhttp://www.pewinternet.org/2015/04/01/us-smartphone-use-in-2015/vAppliedClinicalTrials,July122016vihttp://www.appliedclinicaltrialsonline.com/virtual-clinical-trials-future-patient-engagementviihttps://www.clinicalleader.com/doc/home-clinical-trial-visits-a-patient-centric-solution-0001 viiihttp://www.itu.int/en/ITU-D/Statistics/Documents/facts/ICTFactsFigures2015.pdf