introduction to research - home - nihr oxford biomedical ......introduction to research v3 may 2018...

IntroductiontoResearch

forResearchNurses,MidwivesandotherResearchProfessionals

IntroductiontoResearchV3May2018 2

CompiledbySallyBeer,OxfordBiomedicalResearchCentre–EducationandTrainingCoordinator,basedonWestYorkshire/BradfordTeachingHospitalsNHSTrustInductionPack,LeedsTeachingHospitalsNHSTrustClinicalResearchNurseInductionPack&CompetencyFrameworkandYorkshireCancerResearchNetwork’sInductionHandbook.

Theamountofinformationinthisbookletmayseemdauntingrightnow;pleasebeassuredthatitismeanttosupportyouonyourjourneyinto

researchforaslongasyouneedit,andthereisnoexpectationthatyoureaditfromcovertocoveronyourfirstdayorweek.

Referenceisfrequentlymadeto‘researchnurses’whoarecurrentlythelargestsinglestaffgroupinclinicalresearch,buttheinformationisintended

tobeusefultoallresearchpractitioners

Contents

WelcometoyourpostinResearch...................................................................................................................4

ResearchandtheNHS.......................................................................................................................................5

ResearchStructure............................................................................................................................................9

NationalInstituteforHealthResearch..........................................................................................................9

NIHROxfordBiomedicalResearchCentre..................................................................................................10

PatientsActiveinResearch(PAIR)..........................................................................................................10

ResearchEducationandTraining............................................................................................................10

ClinicalResearchNetwork–ThamesValleyandSouthMidlands(CRN)....................................................11

OxfordCLAHRC............................................................................................................................................12

OxfordAcademicHealthScienceCentre(OxAHSC)...................................................................................12

OxfordAcademicHealthScienceNetwork(AHSN).....................................................................................12

JointResearchOffice(JRO).........................................................................................................................13

ResearchGovernance(OUHR&D)andClinicalTrialsandResearchGovernanceTeams(UniversityCTRG).......................................................................................................................................................13

ResearchDrop-inSessions......................................................................................................................14

Researchbulletin.....................................................................................................................................14

UKTrialManagersNetwork(Oxford)......................................................................................................14

Section1:Yourfirstweek...............................................................................................................................15

Induction.................................................................................................................................................15

InformationGovernance.........................................................................................................................15

GoodClinicalPractice(GCP)training......................................................................................................16

InformedConsent...................................................................................................................................16

Section2:Yourfirstmonth.............................................................................................................................17

https://learn.nihr.ac.uk/.............................................................................................................................17

Networkingopportunities...........................................................................................................................17

ResearchNetwork...................................................................................................................................17

Competencies..............................................................................................................................................17

TrainingOpportunities................................................................................................................................18

LibraryServices...........................................................................................................................................18

Usefulresources..........................................................................................................................................19

GlossaryofResearchRelatedAcronyms.........................................................................................................20

DictionaryofResearchRelatedTerms............................................................................................................25

Appendix1:‘RoleTransition’whenbecomingaResearchNurse*.................................................................33

Appendix2:ThePrinciplesofGCP..................................................................................................................35

Appendix3:InformedConsent.......................................................................................................................36

Whatisinformedconsent?.....................................................................................................................36

MaintainingInformedconsent................................................................................................................36

Whoshouldreceiveinformedconsent?.................................................................................................37

GuidelinesforResearchNurses/Practitionersinobtainingconsent.......................................................37

RespectingDiversity................................................................................................................................38

Thelegalframework...................................................................................................................................39

Table1:Informedconsentforaminorasdefinedas<16yearsofage.....................................................39

Table2.Informedconsentforanincapacitatedadult................................................................................39

Appendix4:Roles&ResponsibilitiesofResearchersandOrganisations........................................................41

Appendix5:JointResearchOfficeHandbook.................................................................................................46

Appendix6:AccesstoParticipantsMedicalRecords......................................................................................50

Appendix7:Keydocumentsandregulations..................................................................................................51

TheDeclarationofHelsinki1964............................................................................................................51

TheEUDirectiveof2001.........................................................................................................................51

MedicinesforHumanUseActClinicalTrialsRegulations2004..............................................................51

MentalCapacityAct................................................................................................................................51

UKPolicyFrameworkforHealthandSocialCareResearch2017...........................................................52

DataProtectionAct1998........................................................................................................................52

TheHumanTissueAct2004....................................................................................................................53

IRMERRegulations..................................................................................................................................53

AdministrationofRadioactiveSubstancesAdvisoryCommitteeARSAC................................................53

Appendix8:HealthResearchAuthority..........................................................................................................55

EthicsandNHSApprovals...........................................................................................................................55

Ethicscommitteeapproval.....................................................................................................................55

EthicsCommittees...................................................................................................................................55

TheNationalResearchEthicsService......................................................................................................56

EthicsApplicationsthroughtheNationalResearchEthicsService(NRES)..............................................56

LocalTrustApproval................................................................................................................................56

Appendix9:PharmacovigilanceintrialsofInvestigationalMedicinalProductsandSafetyReporting.........57

Appendix10:CaseReportFormCompletionGuide.......................................................................................60

Appendix11:IntroductiontoResearchMethodology....................................................................................62

Appendix12:Whydidyoubecomearesearchnurse?..................................................................................67

WelcometoyourpostinResearchFirstly–CongratulationsonyoursuccessandwelcometotheNIHROxfordBiomedicalResearchCentre(BRC),apartnershipbetweenOxfordUniversityHospitalsNHSTrustandOxfordUniversity.

Whateveryourpreviousrolesandexperience,youwillbringwithyouavarietyofknowledgeandskills.However,comingintotheworldofclinicalresearchfromhands-oncareprovisioninvolvesthedevelopmentofnewanddifferentclinicalskills,whichisbothexcitingandchallenging.Aswellaskeepingyourexistingskills,youwilllearnmanynewones.

Wehopeyouwillfindthatyourroleinclinicalresearchisvariedandinteresting-everydayisdifferentfromtheonebefore.Researchnursestakepartinastudyfromstarttofinish(theyhearandlearnaboutacompletelynewstudy,enrolpatientsandaretheretoseetheresultsthatwillmakeadifferencetothepatientandtheirfamiliesinthefuture).

Researchnursesplayavitalroleinsupportingpatientsthroughoutthecourseoftheresearch,ensuringclinicalstudiesrunsmoothlyandthatparticipantsaresafeandfullyinformed.Theymayberesponsibleforrecruitingpatients,gainingconsentfrompatientstotakepartinastudy,collectingdata,carryingoutstudy-relatedclinicalproceduresandmuchmore.

AsaClinicalResearchNurseyouwillbeprovidingspecialistcarethatwillhaveapotentialbenefittoyourpatientsaswellasabenefittofuturepatients.TheroleofaClinicalResearchNurseisdiverse,coversmanyspecialtiesandisincreasinglybecomingrecognisedasaspecialtyinitsownright.Itcanbeachallengingrolebutisanopportunitytousetheskillsyouhavegainedinclinicalpractice,combinedwithnewresearchskillsthatyouwillacquirethatwillestablishyourcareerasaClinicalResearchNurse.

Youwillberesponsibleforensuringthatyourclinicaltrialsarecompletedaccordingtothestudyprotocol,thatyouperformanytaskswhicharedelegatedtoyouandthatyouhavesufficientexperienceandtrainingtocompletethesetasks.

Themostimportantelementsofyourrolewillbetoprovideahighstandardofcareandensurepatientsafetyandtocollectgoodqualitydata.Thesafetyofyourpatientsremainsasimportantasitwouldinanon-researchroleandpoordataqualitycanaffectthequalityoftheentirestudy.

Thisbookletisdesignedtobeapracticalandinformativeresourcetoyou.TakeeveryopportunitytoobtainadviceandsupportfromyourresearchcolleaguesandR&DDepartment.

IcangenuinelysaythatIfeelIhavethebestjobintheworld!IfeelprivilegedtobeinaprofessionwhichisfundamentaltotheprocessofensuingthatpatientcareisbasedonthebestavailableevidenceResearchNurse,MiltonKeynes

Yourmoveintoresearchwillallowyoutheopportunitytoconsideryourcareerprogression.Youwillbepresentedwithmanyopportunitiestodevelopyourself:makethemostofeveryopportunity!

ResearchandtheNHS

Whyengageinresearch

Studiessuggestthatpatientswhoreceivecareinresearch-activeinstitutionsmayhavebetterhealthoutcomesthanpatientswhoaretreatedinanon-researchenvironment.Byjoiningtheresearchcommunityyouare

activelyhelpingtodriveupthestandardofhealthcareforyourpatients.Byinvestigatingthecauseandcourseofdiseasesandhowbesttotreatthem,youarealsohelpingtoestablish‘whatworks’andbuildthebodyofevidencethatcanleadtoapositivechangeinfuturecare.

TheimportanceofResearchwithintheNHS

TheDepartmentofHealth’sstrategytoimprovethehealthofthenationcontinuestoplaceresearchattheforefrontoftheNHS.TheWhitePaperEquityandexcellence:liberatingtheNHS(DH2010)highlightsresearchintermsofquality,transparencyandvalueformoney,withtheaimofachievinghealthoutcomesasgoodasanywhereelseintheworld.Itaimstodeliverqualitycarefromevidencebasedpracticewhichisthoroughlyresearched.TheNHShasaconstantchallengetoprovideaservicethatisuptodateandefficient.Healthresearchplaysakeyroleinthisservicebyusingtheevidencefromstudiestosupporthealthstrategiesandchangesinmedicalpractice.

TheNHShasthepotentialtoprovideoneofthebesthealthresearchenvironmentsintheworld.However,priorto2000,althoughresearchwastakingplaceacrosstheUK,itwasbeingcarriedoutbyawiderangeofresearchersandorganisations:government,academia,pharmaceuticalindustries,charitiesetc.withalackofanoverallstrategyandcoordination.Henceresourceswerebeingallocatedinanadhocwaywhichdidnotreflecttheprioritiesofoptimalpatientandpublicbenefit.Therewasalsowidespreaddissatisfactionwiththelengthybureaucraticprocedureswhichdelayedtheopeningofatrial,andwiththespeedofrecruitmentandthequalityofdatacollection.

TheNHSConstitutionpublishedinJanuary2009,commitstoinnovationandtothepromotionandconductofresearchtoimprovethecurrentandfuturehealthandcareofthepopulation.Thecommitmentfeaturesinoneofsevenkeyprinciples-theprinciplethattheNHSaspirestohighstandardsofexcellenceandprofessionalism."ResearchisacorepartoftheNHS.ResearchenablestheNHStoimprovethecurrentandfuturehealthofthepeopleitserves.TheNHSwilldoallitcantoensurethatpatients,fromeverypartofEngland,aremadeawareofresearchthatisofparticularrelevancetothem.TheNHSisthereforeputtinginplaceprocedurestoensurethatpatientsarenotifiedofopportunitiestojoininrelevantethicallyapprovedresearchandwillbefreetochoosewhethertheywishtodoso."(HandbooktotheNHSConstitution,January2009).

TheHealthandSocialCareAct(2012)wentontofurtherembedresearchintheNHSandenableagreatervoiceforpatients.ThroughtheNationalInstituteforHealthResearch(NIHR)theNHSnowhasathrivingresearchculture.Asamemberofaclinicalresearchteamyouwillplayakeyroleincontributingtothisresearchculturethroughclinicaltrialsand/orhealthrelatedresearch,thereforecontinuallyimprovingthequalityandchoicesavailableforpatientsandhealthcareasawhole.

YouwillalsobesupportedandencouragedtoworkwithpatientsasequalpartnersinthisresearchendeavourthroughnumerousPatientandPublicInvolvement(PPI)activitiesthatareunderwayinOxford.PPIisnotaboutrecruitingpatientsasparticipantsintrialsandstudies(althoughgoodPPIcanmakethismucheasier)–itisaboutworkingwiththoseoutsidetheprofessionalworldofmedicine,butwhomayhaveextensiveexpertisethroughexperience,toidentifywhatresearchmatters,howbesttodoitandtocommunicateitsresultstootherpatientsandthepublic.Theoverallaimistomakesureresearchistrulyresponsivetopatients’needsandwishes.

OnthenexttwopagesoutlineresearchnationallyandmorelocallyinOxford.

IntroductiontoResearchV3May20187

ResearchandInnovationlandscape

INVENTION EVALUATION ADOPTION DIFFUSION

CharitiesandotherfundingbodiesAHSNsAHSCs

NHSPatientCare

MRCProgrammes

NIHRProgrammes

NIHRInfrastructureCLAHRCs

NIHRInfrastructureClinicalResearchNetwork

NIHRInfrastructure

BRCs,BRUs,CRFs

Research across Oxford University Hospitals NHS Foundation Trust and University of Oxford Partnership

NIHRFundersofResearch

UniversityCharitiesMRC,WellcomeTrust

Oxford Biomedical Research Centre

Themes

• Antimicrobial Resistance and Modernising Microbiology

• Cardiovascular • Clinical Informatics and Big Data • Diabetes and Metabolism • Gastroenterology and Mucosal

Immunity

• Genomic Medicine • Haematology and Stem Cells • Imaging • Molecular Diagnostics • Multi-modal Cancer Therapies • Multimorbidity and Long Term

conditions

• Musculoskeletal • Neurological conditions • Obesity, diet and lifestyle • Partnerships for Health, Wealth

and Innovation • Respiratory • Stroke and Vascular Dementia

• Surgical Innovation and Evaluation

• Technology and Digital Health • Vaccines for Emerging and

Endemic Diseases

CRN -Thames Valley and South Midlands (hosted by

Divisions 1. Cancer 2. Diabetes, stroke,

cardiovascular, metabolic and endocrine, renal

3. Children, genetics, haematology, reproductive health and childbirth

4. DENDRON, mental health and neurological disorders

5. Primary care, aging, health service and delivery, oral health and dentistry, public health, musculoskeletal disorders and dermatology

6. Anaesthetics/peri-operative medicine and pain management, critical care, injuries and emergencies, surgery, infectious diseases/microbiology, opthalmology, respiratory disorders, gastroenterology, hepatology

The Cross Divisional and Support Services team offer support with governance; study support; cost

attribution; finance; IT

Clinical Trials Units

• Diabetes Trials Unit • Primary Care and Vaccines

Collaborative • National Perinatal

Epidemiology Unit • Oxford Cognitive Health and

Neurosciences • Clinical Trials Services Unit

and Epidemiological Studies Unit

• Oxford Clinical Trials Research Unit which integrates the following trials groups

o Centre for Statistics in Medicine

o Critical Care, Trauma and Rehabilitation Trials Group

o Gastroenterology Trials Group

o Oncology Clinical Trials Office (all phases)

o Respiratory Trials Unit

o Rheumatology o Surgical

Intervention Trials Unit

Departments

• Department of Biochemistry • Nuffield Department of

Clinical Medicine • Nuffield Department of

Clinical Neurosciences • Department of Experimental

Psychology • Radcliffe Department of

Medicine • Nuffield Department of

Obstetrics and Gynaecology • Department of Oncology • Nuffield Department of

Orthopaedics, Rheumatology and Musculoskeletal Sciences

• Department of Paediatrics • Sir William Dunn School of

Pathology • Department of Physiology,

Anatomy and Genetics • Nuffield Department of

Population Health • Nuffield Department of

Primary Care Health Sciences

• Department of Psychiatry • Nuffield Department of

Surgical Sciences

Also in Oxford Oxford Health BRC for Mental Health, Oxford Academic Health Science Centre (OxAHSC), Oxford Academic Health Science Network (OxAHSN),

Oxford Collaborations for Applied Heath Research and Care (OxCLAHRC)

ResearchStructureNationalInstituteforHealthResearchhttps://www.nihr.ac.uk/

TheNationalInstituteforHealthResearch(NIHR)isfundedthroughtheDepartmentofHealthtoimprovethehealthandwealthofthenationthroughresearch.TheNIHRprovidestheframeworkthroughwhichtheDepartmentofHealthcanposition,maintainandmanagetheresearch,researchstaffandresearchinfrastructureoftheNHSinEnglandasanationalresearchfacility. The NIHR systemsrepresentthemostintegratedclinicalresearchsystemintheworld,drivingresearchfrombenchtobedsideforthebenefitofpatientsandtheeconomy.

Sinceitsestablishment,theNIHRhastransformedresearchintheNHS.Ithasincreasedthevolumeofappliedhealthresearchforthebenefitofpatientsandthepublic,drivenfastertranslationofbasicsciencediscoveriesintotangiblebenefitsforpatientsandtheeconomy,anddevelopedandsupportedthepeoplewhoconductandcontributetoappliedhealthresearch.

AtthecentreofwhattheNIHRdoesisthePortfolio–acollectionofhigh-qualityclinicalstudiesthatbenefitfromtheinfrastructureprovidedbytheClinicalResearchNetwork.

TheNIHRprovidesahealthresearchsysteminwhichtheNHSsupportsoutstandingindividualsworkinginworld-classfacilities,conductingleading-edgeresearchfocusedontheneedsofpatientsandthepublic.Itaimsto:

• EstablishtheNHSasaninternationallyrecognisedcentreofresearchexcellence.• Attract,developandretainthebestresearchprofessionalstoconductpeople-basedresearch.• Commissionresearchfocusedonimprovinghealthandsocialcare.• Increasetheopportunitiesforpatientsandthepublictoparticipatein,andbenefitfrom,research.• Promoteandprotecttheinterestsofpatientsandthepublicinhealthresearch.• Drivefastertranslationofscientificdiscoveriesintotangiblebenefitsforpatients.• MaximisetheresearchpotentialoftheNHStocontributetotheeconomicgrowthofthecountry

throughthelifesciencesindustry.• Actasasoundcustodianofpublicmoneyforthepublicgood.

TheNIHRworksinpartnershipwithmanysectorsincludingthepublicandserviceusers,theNHS,publichealth,otherGovernmentfunders,theacademicandthirdsectorsandindustry.

Structure

TheNIHRmanagesitshealthresearchactivitiesthroughfourmainworkstrands:

Infrastructure:providingthefacilitiesandpeopleforathrivingresearchenvironment.

Faculty:supportingtheindividualscarryingoutandparticipatinginresearch.

Research:commissioningandfundingresearch.

Systems:promotingfaster,easierclinicalresearchthroughunified,streamlinedandsimplesystemsformanagingethicalresearchanditsoutputs.

NIHROxfordBiomedicalResearchCentrehttp://oxfordbrc.nihr.ac.uk/about-us-intro/

TheNIHRBiomedicalResearchCentre,Oxford(OxBRC)isbasedattheOxfordUniversityHospitalsNHS

TrustandruninpartnershipwiththeUniversityofOxford.ItwasoneoffivecentresfundedbytheNational

InstituteforHealthResearch(NIHR)in2007throughacompetitivelyawardedgrantof£57moverfive

years.InApril2012,asrecognitionforitsoutstandingcontributiontohealthcareresearch,wasawarded

£95.5mto2017andinSeptember2016wasawarded£113.7mfor2017to2022tosupporttranslational

research.

PatientsActiveinResearch(PAIR)https://patientsactiveinresearch.org.uk/

ThePatientsActiveinResearchWorkingGroup(PAIR)bringsthepatientvoicetotheoverarchingPatientandPublicInvolvement(PPI)strategyoftheBiomedicalResearchCentre(BRC)andMusculoskeletalBiomedicalResearchUnit(BRU),withequalnumbersofpatientandprofessionalmembers(approx.16intotal)andlayandresearcherco-chairs.

PAIRguidesandpromotesinvolvementofpatientsinBRC/BRUresearch,thisincludes,forexample,

advisingonprioritiesfornewresearch,helpingtoplanandrunstudiessothatpatientswanttojointhem,

andcommunicatingnewresearchfindingstootherpatientsandtothepublic.

ResearchEducationandTrainingTheResearchEducationandTrainingGroup(RETG)aimstosupportthedevelopmentofresearchcapacity

intheNHSbyimprovingeducationandtrainingopportunitiesforNIHR-fundedresearchersandresearch

stafffromdiverseprofessionalgroups.TheWorkingGroupbelievesthatthiswillenhancethecapacityto

undertakeandunderstandhighqualityresearchwhichinturnwillgenerateinnovationsinpatient

treatmentandcare.

ClinicalResearchNetwork–ThamesValleyandSouthMidlands(CRN)https://www.nihr.ac.uk/nihr-in-your-area/thames-valley-and-south-midlands/

‘TheNIHRClinicalResearchNetworkistheclinicalresearchdeliveryarmoftheNHS.TheyoperatenationallyacrossEnglandthroughanationalcoordinatingcentreand15localbranchesdeliveringresearchintheNHSacrossalldiseaseareasTheNIHRClinicalResearchNetwork:ThamesValleyandSouthMidlandshelpstoincreasetheopportunitiesforpatientstotakepartinclinicalresearch,ensuresthatstudiesarecarriedoutefficiently,andsupportstheGovernment’sStrategyforUKLifeSciencesbyimprovingtheenvironmentforcommercialcontractclinicalresearchintheNHSintheThamesValleyandSouthMidlandsarea.TheCRN,ThamesValleyandSouthMidlandsvaluesthecontributionthatclinicalresearchcanmaketopatientcare,andworkscollaborativelywithotherNHSproviderstotranslatethatpassionintotheeffectivedeliveryofstudiesinthearea.Theyensurethatclinicalresearchoccupiestheplaceitdeservestointheday-to-dayworkoftheNHSacrosstheThamesValleyandSouthMidlandsarea.ThisincludesTrusts,primarycareorganisationsandanyotherqualifiedprovidersofNHSservices.’TheNIHRCRNThamesValleyandSouthMidlandsreceived£13.5millioninthe2015/16financialyear,andcurrentlyfundapproximately600postsNHSSupportFundinghttps://www.nihr.ac.uk/research-and-impact/nhs-research-performance/research-costs.htmCRNsarefundedtosupportNHSresearchdelivery.Thefocusisupondeliveringstudiestotimeandtarget.ThefundingprovidedviaCRNsisintendedtocovertheNHSSupportCostactivityasdefinedunderAcoRD(‘AttributingtheCostsofhealth&socialcareResearch&Development’,DoH).TheAcoRDpolicysetsoutthefundingmechanismthatappliestoallnon-commercialhealthcareresearchactivity.AllsuchresearchmustbecostedunderthefollowingcategorisationsasdefinedinAcoRD:

• ResearchCosts• TreatmentCosts• NHSSupportCosts

Theguidingprinciplefordeterminingcategorisationfocusesonwhyanactivitytakesplace,ratherthanwhere,orbywhom.ResearchCostsarethecostsoftheResearchandDevelopment(R&D)itselfthatendwhentheresearchends.Theyrelatetoactivitiesthatarebeingundertakentoanswertheresearchquestions.ResearchCostsaremetbygrantfundersthroughtheawardofaresearchgrantexceptforPartBcosts(seeAcoRDguidancereferenceresourcesformoreinformation)ifthefundisoftheAssociationofMedicalCharities.TheDoHwillmeetPartBcostsviatheCRNsandTrusts.TreatmentCostsarethepatientcarecostswhichwouldcontinuetobeincurredifthepatientcareserviceinquestioncontinuedtobeprovidedaftertheR&Dstudyhadstopped.NHSTreatmentCostsaremetthroughthenormalcommissioningprocess(inexceptionalcircumstancestheDoHmaymakeacontribution).NHSServiceSupportCostsaretheadditionalpatientcarecostsassociatedwiththeresearch,whichwouldendoncetheR&Dactivityinquestionhadstopped,evenifthepatientcareinvolvedcontinuedtobeprovided.NHSServiceSupportCostsaremetfromCRNbudgetbytheHealthDepartmentsoftheUnitedKingdom.Exampleactivitiesinclude:Theprocessingofthepatientrecordtoidentifypatientswhomaybesuitabletoapproachtoaskiftheywishtoparticipateinaresearchproject;obtaininginformedconsent;additionalinvestigations,assessmentsandtestswheretheresultsarerequiredbythepatient’scareteamtoensurepatientsafetyandwherearrangementsareinplacetofeedtheresultsbacktotheclinician.

MoredetailedinformationaboutthispolicyandtheattributionprocessisavailableviatheAcoRDwebsite:https://www.gov.uk/government/publications/guidance-on-attributing-the-costs-of-health-and-social-care-researchTheFAQs,whichareupdatedregularly,areespeciallyusefulforunderstandinghowtointerprettheguidance.ThenetworksAcoRDSpecialistsareavailabletoprovidetrainingand/orassistancewithcostattributionwhetheratgrantstageorwithcompletionoftheHRA’sScheduleofEvents.Pleasecontactthemforadviceviastudysupport.crnthamesvalley@nihr.ac.uk

OxfordCLAHRChttp://www.clahrc-oxford.nihr.ac.uk/TheNationalInstituteforHealthResearchCollaborationforLeadershipinAppliedHealthResearchandCare(NIHRCLAHRC)Oxfordcarriesoutgroundbreakingappliedhealthresearchthatwillhaveadirectimpactonpatienthealthandwell-being.Weareapartnershipbetweenuniversities,healthcarecommissionersandhealthcareprovidersintheregionofOxfordandtheThamesValley,hostedbyOxfordHealthNHSFoundationTrust.OxfordAcademicHealthScienceCentre(OxAHSC)http://www.oxfordahsc.org.uk/https://www.youtube.com/watch?v=rip3dEbczHwTheOxfordAcademicHealthScienceCentre(OxfordAHSC)coordinatesclinicalandacademicexcellencewithinOxfordUniversity,OxfordBrookesUniversity,OxfordHealthNHSFoundationTrustandOxfordUniversityHospitalsNHSFoundationTrust.TheOxfordAHSCisanintegratedresearchenvironment,physicallyandstrategicallyembeddingbasicandtranslationalresearchwithclinicalevaluation.Usingthis,thepartnershipseekstoaccelerateandrealisepatientbenefitfromresearch,byenablingsmoothtransitionofinnovationsthroughthestagesoftheresearchlifecyleandintoclinicalpractice.

TheOxAHSCwillcombinethefourinstitutions’individualstrengthsinworld-classbasicscience,translationalresearch,trainingandclinicalexpertisetoaddress21stcenturyhealthcarechallenges.Itwillallowscientificdiscoveriestomoverapidlyfromthelabtotheward,operatingtheatreandgeneralpractice,sopatientsbenefitfrominnovativenewtreatments.OxfordAcademicHealthScienceNetwork(AHSN)http://www.oxfordahsn.org/

TheOxfordAHSNisoneof15AHSNsacrossEngland.Theyaimtoturninnovationintomainstreamclinicalpracticequicklyandwidely,improvinghealthandcreatingwealththroughbetterconnectionsbetweentheNHS,researchandbusiness.

JointResearchOffice(JRO)Seepage48forfurtherinformation

OxfordUniversityHospitalsNHSTrustsupportshighqualityresearchwithinworldclassfacilitiesandthespecialistResearchandDevelopmentteamcanhelpprogressstudiesquicklyandefficiently.

TheJointResearchOfficebringstogetherallaspectsofresearchgovernance,finance,contractandsupportservices,spanningbothOxfordUniversityHospitalsNHSTrustandtheUniversityofOxford.

TheResearchGovernanceTeamsupportsandadvisesresearchersinmeetingtherequirementsoflocalandUKregulatoryframeworks.

TheFinanceTeamoffersadviceandsupportincostingstudiesandhasaroleinmanagingaccountsforcommercialandnon-commercialtrials.Contractsarenegotiatedwithexternalorganisationsforcommercialandnon-commercialtrials.

TheteamalsohasanongoingmonitoringresponsibilityforclinicaltrialsandotherstudiessponsoredbyOxfordUniversityHospitalsandforauditofresearchhostedbytheTrust.

Pleaseseehttp://oxfordbrc.nihr.ac.uk/wp-content/uploads/2013/11/PPI-Briefing-Notes-FINAL.pdfforPPIbriefingnotesforresearchers.

ResearchGovernance(OUHR&D)andClinicalTrialsandResearchGovernanceTeams(UniversityCTRG)

TheResearchGovernanceteam'sroleistoensurethatresearchwhichisusingOUHNHSresourcesincludingNHSpatients:

• iscompliantwiththerelevantregulations(e.g.DataProtectionAct)• followsClinicalResearchPrinciples(e.g.GoodClinicalPractice(GCP)andDHResearchGovernance

FrameworkforHealthandSocialCare)• isfeasibleandthattargetsareachievable• hasrelevantapprovalsinplace(e.g.ResearchEthicsCommitteeApproval,MedicinesandHealthcare

productsRegulatoryAuthority)• isofahighscientificstandard

TheResearchGovernanceTeamprovidessupportthroughouttheresearchjourney,fromactingassponsorforcertainstudiestoprovidingNHSPermissionandprovisionofGCPcomplianttraining.

Ongoingoversightismaintainedthroughcollectionofrecruitmentfigures,progressreportsandsafetydata,andthroughmonitoringandauditresponsibilities.

ResearchDrop-inSessions

TheJointresearchofficeoffersbi-monthlydrop-insessionsforresearchersrequiringadviceandsupportregardingtheirresearchstudyincludingguidanceon:

• Sponsorshipprocess• Ethicsapplications• Researchversusaudit/serviceevaluation• IRASsystem• Regulatoryapprovals• NHSpermission(Trustapproval)

Theycanalsoputyouintouchwiththerelevantcontactsforresearchgrants,contractsandagreements,BRC,intellectualproperty,andbusinessdevelopment.

Thesessionswillbeinformalwithnoneedtobookaspace-justturnup!RepresentativesfromtheNHSR&DandUniversityCTRGTeamswillbeonhandtohelpwithyourqueries.WewillalsohaveinputfromaChairofoneoftheOxfordResearchEthicsCommittees.

Forfurtherinformationoranyqueries,pleasecontact:

• Tel:01865572240• Email:ouhtma@nhs.net

Allsessionsstartat12.30pmforonehourandwillbeheldinthemeetingroomoftheJointResearchOfficeattheChurchillHospital.

Researchbulletin• R+Dpublisharegularbulletinofupdatesandevents.TojointhemailinglistcontactKatie Flight:

01865 572233 Email: ouh.resbull@nhs.net

UKTrialManagersNetwork(Oxford)http://www.tmn.ac.uk/

AsteeringgrouphasbeenformedtoexploresettingupanOxfordHuboftheUKTrialManagersNetwork.Forfurtherinformation,contactcushla.cooper@ndorms.ox.ac.uk

Section1:Yourfirstweek

WhetheryouarenewtotheTrustorUniversity,ormovingintoresearchforthefirsttime,youwillbemeetingmanynewpeople,goingplacesyoudidn’tevenknowexistedandencounteringawholenewworldofabbreviations,acronyms,protocols,SOPs(StandardOperatingProcedures)andlegislation.(Findalistofcommonlyusedacronymsandtermsonpage19)

Yourlinemanagerwillintroduceyoutomanyofthese,andwehaveincludedsomeimportantinformationbelowtohelpyouonyourpath.

InductionItisimportantthatyoumeetwithyourLineManagertodiscussthescopeofyourrole,yourpreviousexperienceandensureyourInductionProgrammecoversallaspectsofyourrole.

YourInductionProgrammeshouldincludethefollowing:

• Familiarisationwithworkingareasandinductionintothebuilding(s)asappropriate• Fireandevacuationprocedures(attendTrustmandatoryFireAwarenessTraining)• TrustinductionprogrammeifnewtoTrust• IDbadgeandaccessprocurement• Introductiontoandaccesstoelectronicinformationmanagementsystems• Absencepolicyandarrangingofannualleave• Clearunderstandingoflinemanagementandreporting• Informationgatheringaroundspecialtyareaofpractice,adviceonkeylearningandsourcesof

appropriateinformation/courses• Allocationofamentororbuddyforsupervisionandguidance• Datetosetobjectivestobereviewedafterthreemonths

Introductiontokeystaff:

• Relevantconsultantsandwidermedicalteam• Matron(orappropriateAHPlinemanager)• Directoratemanager/facultyorR&DleadatUniversity• R&Dleadforspecialty• BusinessManager• Nursingandotherlocalresearchcolleagues• Outpatientorotherpatientareastobeutilisedwhenconductingresearch• Administrativeteamandorwiderresearchsupportstaffasappropriate/availabletoyourarea

InformationGovernanceAsamemberofaresearchteamyouwillhaveaccesstoconfidentialdataalmostdaily.ItisarequirementforallstaffintheTrusttocompleteInformationGovernancetrainingannually.

Thisisavailablease-learningordropinsessionviatheOUHTLearningManagementSystem(LMS)

IfyouhaveaHonoraryTrustcontract,pleasecontactrecruitment.administrator@ouh.nhs.uktorequestapayroll/assignmentnumber,andthenregisterforanLMSaccountathttp://ouh.oxnet.nhs.uk/Pages/Home.aspxorNewE-LMSUsersregisterhere

GoodClinicalPractice(GCP)trainingAkeyrequirementforanyoneinvolvedintheconductofclinicalresearchisGoodClinicalPractice(GCP)training.GCPistheethicalandpracticalstandardtowhichallclinicalresearchisconducted.

Togetstarted,itisadvisabletocompleteanonlinecourse,buttothenattendaface-to-facesession,wherethereistheopportunitytoaskquestionsandlearnfromothersexperiences.

CRN:ThamesValleyandSouthMidlands

Forinformationaboutcoursedatesandavailability,contactCRNTrainingtraining.crnthamesvally@nihr.ac.ukor01865223292

LocalR+DandOxfordUniversityofferjointGCPtraining

http://www.admin.ox.ac.uk/researchsupport/training/gcpoxford/

Pleasecontactkarl.shepherd@admin.ox.ac.uk01865572221

WhyyouneedGCPtraining

Everyoneinvolvedintheconductofclinicalresearchmusthavetrainingtoensuretheyarebestpreparedtocarryouttheirduties.ThisislaiddownintheResearchGovernanceFrameworkforHealthandSocialCare2005,coveringallresearchintheNHSinEngland,andinlawforthosepeopleworkingonclinicaltrials.TheprinciplesofGCPstatethat:Eachindividualinvolvedinconductingatrialshouldbequalifiedbyeducation,trainingandexperiencetoperformhisorherrespectivetask(s).(2.8,E6GuidelineforGoodClinicalPractice)

HowoftendoyouneedtocompleteGCPtraining?

ThisisdecidedbyyourTrust/employer,astheanswerdependsontheresearchyouareinvolvedinandyourexperience.TheMedicinesforHumanUse(ClinicalTrials)(2004)regulations,andtheMHRA,requirethatallstaffaretrainedtocarryouttheirdutiesoneachstudytheyareworkingon.Thisisnottimebound.Ifyouhavejusthadsometrainingandaregulationchangesyouwillneedtobeinformedofthesechanges.AllNIHRCRNcoursesareappropriateforpeopleconductingCTIMPsandnon-CTIMPsresearch.

TheOUHTrustexpectationisthatGCPtrainingwillberenewedeverythreeyears,andstrictlyenforcedforthoseinvolvedinCTIMPS

SeeAppendix2forfurtherinformationonGCPTraining

InformedConsentIfyouwillbeconsentingparticipantsintostudies,itisadvisabletoattendaValidInformedConsentcoursebeforetakingonthisresponsibility.FurtherinformationinAppendix3

Section2:YourfirstmonthYouwillberequiredtocomplywithmandatorytrainingasrequiredbytheTrust,Universityandresearch,dependantonyourroleandclinicalarea.

Continuetoexplorethefollowing:

• Familiarisationwithdataprotectionlegislationandinstitutionalpolicies• Internalgovernanceproceduresandqualityassurance• UnderstandingtherolesofRECsandR&D,andthestatutorylegislationforresearchgovernance• Understandingofresearchmethods• PatientandPublicInvolvement(PPI)inresearch• Howtodescriberandomisationandequipoisetopotentialsubjects• Othertrialrelatedprocedures,clinicalandnon-clinical• Introductiontomulti-disciplinaryteamandattendanceatMDTmeetingswhereappropriate• Shadowingcolleaguesinclinicalareasandforpeerlearningreresearchtrialconduct• Introductiontobloodsamplinghandling,processing,shipment• Dryicehandlingandlegislation/guidance• FamiliarisationwithdepartmentalSOPs• Participateinamonitoringvisit• PathwayCo-ordinators(oncology)

DetailsofcurrentavailabletrainingcanbefoundontheNIHRLearningManagementsystem

https://learn.nihr.ac.uk/

NetworkingopportunitiesTakingeveryopportunitytomeetotherresearcherscanmakethedifferencebetweenfeelingpartofanextendedfamilyor‘beinginitalone’.

ResearchNetworkTheOxfordUniversityHospitals&UniversityofOxfordResearchNetworkisaforumforresearchnurses,coordinators,datamanagersandothersworkinginclinicalresearch.Theaimistofosteranopenandconstructiveenvironmentinwhichthoseworkinginresearchcanshareknowledge,experienceandinformationrelatingtohowweallwork.TheResearchNetworkhasquarterlymeetingsopentoallthoseworkinginresearchacrosstheTrustandUniversityandhasanorganisingcommitteeconsistingofexperiencedresearchnurses,managersandadministratorswhowillbehappytohelpwithanyqueries.

CompetenciesNotallcompetenciesmayberelevantinyourenvironmentbutareusefultoidentifylearningneeds

TheResearchNurseCompetencyFrameworkhttps://cambridge.crf.nihr.ac.uk/wp-content/uploads/2015/04/Research_Nurse_Competency_Framework_-_Version_2_-_Full_-_Oct_20111.pdfprovidesaframeworkfordevelopingcompetenciesandidentifyingtrainingneeds.

CompetencyframeworksareavailableformostResearchProfessionalsandcanbeadjustedtofulfilllocaldemand

TrialManagershttp://c.ymcdn.com/sites/www.tmn.ac.uk/resource/resmgr/Competency_Framework/Task_knowledge_Competency_Fr.pdf

2017Competenciesforresearchnurses,clinicaltrialcoordinators&clinicaltrialadministratorshttp://www.papworthhospital.nhs.uk/research/data/uploads/documents/r-and-d_competency_procedures-booklet-v1-0_19-july-2017.pdf

TrainingOpportunities• OxfordBRCEducationandTraininghttp://oxfordbrc.nihr.ac.uk/professional/education-and-

training/• NIHRLearningManagementSystemhttps://learn.nihr.ac.ukorcontactCRNTraining

training.crnthamesvally@nihr.ac.uk01865223292• OxfordBrookesoffersamoduleonPlanningandManagingclinicaltrials• UniversityofOxfordoffervariouscourses.ThesecoursesgivepreferencetoUniversityemployed

staff,butotherswillbeconsideredOxfordLearningInstituteMedicalScienceSkillsTrainingContinuingEducation

• UniversityofBirminghamResearchmethodscourse

LibraryServicesLibraryServices:Thelibrarianscanoffertrainingandhelpwithliteraturesearches,andmuchmorehttp://www.bodleian.ox.ac.uk/hcl

TheBodleianHealthCareLibrariesprovidearangeofservicestosupporttheinformationneedsofstaffandstudentsworkingfortheOxfordUniversityHospitalNHSTrust.Wecanhelpyoutofindtheevidenceyouneedtosupportyourresearchandhealthcarepractice,management,education,andcontinuingprofessionaldevelopment.

OurOutreachLibrariansprovidetheseservicesfromourlibrariesorinyourdepartmentatatimetosuityou.

HelpwithSearching&KeepingUp-to-DateYourOutreachLibrarianisanexpertsearcherandcanhelpyoudevelopyourliteraturesearchesinsupportofactivitiessuchassystematicreviews,researchbidsorprojectbids.Theycanhelpyoufindthefulltextofthearticleyouneed,helpyoutrackdownthatobscureconferencepaperandadviceonthebestwaysofkeepingup-to-dateinyoursubjectarea.

Group&One-to-OneTrainingWeofferfreetrainingsessionstohelpyoudevelopyoursearchskillsfrombeginnertoadvancedlevel.Mostsessionsincludehands-onpracticecoveringtopicssuchasEssentialandAdvancedSearchSkills,NHSOpenAthensResources,ReferenceManagement,OpenAccess,ImpactFactors,TrackingyourCitationsandImpact,andmanymore

Modern&ComfortableSpacesOurlibrariesprovideaccesstoawiderangeofITfacilitiesandsoftwarepackages(24/7attheCairnsandNOClibraries).YoucanborrowlaptopsandiPadsandmakeuseofourwell-equippedgroupstudyrooms

andtrainingrooms.Wealsoofferquietstudyspaceswitheasyaccesstolargecollectionsofbooksandjournals,WiFi,andbreakoutspaces.Allofthemhavefoodanddrinknearby.

SupportforWritingArticles&ThesesWecanhelpyoufindrelevantjournalstopublishin,helpyourunyourliteraturesearchandhelpyoumanageyourreferences(weruncoursesonEndnote,RefWorks,Mendeleyandotherpackages).Wecanalsoprovideadviceontopicssuchasimpactfactors,altmetrics,andhowbesttocomplywithfundingbodies'openaccesspolicies

Usefulresources

• TrialManagersGuide:http://c.ymcdn.com/sites/www.tmn.ac.uk/resource/resmgr/TMN_Guide/tmn-guidelines-web_[amended_.pdf

• Forradiographersinresearchhttp://www.sor.org/career-progression/researchers/research-resource-pack

GlossaryofResearchRelatedAcronymsThesearesomeofthemanyacronymsyouwillcomeacross

Acronym DescriptionABPI AssociationofBritishPharmaceuticalIndustryACFs AcademicClinicalFellowshipsADR AdverseDrugReaction(alsoknownasAR)AE AdverseeventAHPs AlliedHealthProfessionalsAMRC AssociationofMedicalResearchCharitiesAR AdversereactionARSAC AdministrationofRadioactiveSubstancesAdvisoryCommittee:Research

studieswishingtoadministerradioactivemedicinalproductstohumansubjectsneedtoobtainARSACapprovalbeforeNHSR&Dapproval

ASR AnnualSafetyReport:ForstudiesinvolvingtheuseofanInvestigationalMedicinalProduct,thisistheannualreportwhichmustbesubmittedtotheMHRAdetailingallSUSARsandSARsthathaveoccurredinsubjectsonthatstudyinthepastyear

BRC BiomedicalResearchCentreBRU BiomedicalResearchUnitCA CompetentAuthority-organisationapprovingthetestingofnew

drugs/devicesorapprovingthemarketinglicences,intheUKthisistheMHRACAG ConfidentialityAdvisoryGroup–functionoftheHRAtoreviewedapplications

foruseofidentifiabledatawhereconsentwasnotpracticableCAT ClinicalAcademicTrainingProgrammeCE ConformitéEuropéenneCI ChiefInvestigator-Theleadinvestigatorwithoverallresponsibilityforthe

research.Inamulti-sitestudy,theCIhascoordinatingresponsibilityforresearchatallsites.TheCImayalsobethePIatthesiteinwhichtheywork.Inthecaseofasingle-sitestudy,theCIandthePIwillnormallybethesamepersonandarereferredtoasPI.

CL ClinicalLectureshipsCLAHRCs CollaborationsforLeadershipinAppliedHealthResearchandCareCQC CareQualityCommissionCRA ClinicalResearchAssociate(Monitor)CRF CaseReportForm-datacollectiontoolsprovidedbyasponsoronwhichthe

clinicaldataisrecordedforeachparticipant,suchasweight,labresults,symptoms

CRFs ClinicalResearchFacilitiesforExperimentalMedicine-hospital-likefacilitywithconsultingrooms,standardpatientbeds,wardmedicalequipment,researchnursessupportingonlyresearch

CRN ClinicalResearchNetworkCRNTV+SM ClinicalResearchNetwork–ThamesValleyandSouthMidlandsCRNCC ClinicalResearchNetworkCoordinationCentreCRO ContractResearchOrganisation-Apersonoranorganisation

(commercial,academicorother)contractedbythesponsortoperformoneormoreofasponsor’strial-relateddutiesandfunctions

CSP CoordinatedSystemforgainingNHSPermissionCSAG ClinicalStudiesAdvisoryGroupCSP CoordinatedSystemforgainingNHSPermissions:Standardprocessfor

adoptionontoNIHRPortfolioofStudiesinordertoaccessNIHRCRNSupportandfunding;streamlinestheprocessforgainingNHSpermissionsbycollatingtheinformationforglobalandlocalapprovals;researchersinitiatethisinIRASbycompletingandsubmittingCSPApplication

FormCT ClinicalTrialsCTToolkit ClinicalTrialsToolkitCTA ClinicalTrialsAgreement:contractbetweenthelegalSponsorandthehosting

researchsites CTIMP ClinicalTrialofanInvestigationalMedicinalProductCTRG ClinicalTrialsandResearchGovernanceCTUs ClinicalTrialsUnits-DesignandmanageCTIMPs,sometimesinspecialist

clinicalareas,suchasCancer,ortypesoftrial,suchasRCTsCUREC CentralUniversityResearchEthicsCommitteeCV CurriculumVitaeDementiaTRC DementiaTranslationalResearchCollaborationDeNDRoN DementiasandNeurodegenerativeDiseasesResearchNetworkDH DepartmentofHealthDIPEx DatabaseofIndividualPatientExperience–theDIPExwebsitehasarangeof

opensourcevideosofrealpatientexperienceswww.healthtalkonline.orgDMC/DMSC DataMonitoringCommittee/DataMonitoringandSafetyCommitteeDPA DataProtectionActDRFs DoctoralResearchFellowshipsDSUR DevelopmentSafetyUpdateReportECMCs ExperimentalCancerMedicineCentresEMA TheEuropeanMedicinesAgency:AbodyoftheEuropeanUnionwhichhas

responsibilityfortheprotectionandpromotionofpublichealththroughtheevaluationandsupervisionofmedicinesforhumanuseEUEuropeanUnion

ENRICH EnablingResearchinCareHomesEQUATOR EnhancingtheQualityandTransparencyofHealthResearchNetworkEUCTD EuropeanUnionClinicalTrialsDirectiveEUDRACT EuropeanUnionDrugRegulatingAuthoritiesClinicalTrials-Adatabaseofall

clinicaltrialsinEurope,heldsince1994inaccordancewithEUdirective2001/20/EC

FAQs FrequentlyAskedQuestionsFDA FoodandDrugAdministration:theCompetentAuthorityintheUnitedStates,

givingauthorisationtoconductclinicaltrialsandissuingmarketinglicencesGCP GoodClinicalPracticeGLP GoodLaboratoryPractice-standardforlaboratoriesinvolvedinpre-clinical

analyses(e.g.animal,invitro);doesnotapplytoLaboratoriesanalysingsamplesfromclinicaltrialsinvolvinghumans

GMP GoodManufacturingPractice-qualityassurancestandardforproducingIMP,medicinalproducts

GP GeneralPractitionerGTAC GeneTherapyAdvisoryCommittee:theethicscommitteeforclinicalstudies

usinggeneticallymodifiedproducts;usuallynoRECapprovalrequiredHEE HealthEducationEnglandHETV HealthEducationThamesValleyHEI HigherEducationInstitutionHFEA HumanFertilisationandEmbryologicalAuthorityHRA HealthResearchAuthorityHS&DR HealthServicesandDeliveryResearchProgrammeHTA HealthTechnologyAssessmentProgrammeHTA HumanTissueAct/AuthorityHTCs HealthcareTechnologyCo-operativesIAT IntegratedAcademicTrainingProgramme

IB InvestigatorsBrochure-:Acompilationofclinicalandpre-clinical

pharmacological/biologicaldatarelevanttotheuseofthatIMP(s)inhuman

subjects(onesingleIBforalltrialsusingthesameIMP)ICF InformedConsentFormICH InternationalConferenceonHarmonisation(Europe,USA,Japan):Defined

standardsfortheterminology,design,conduct,monitoring,recording,analysisandreportingofastudy.Thesestandardsgiveassurancethatthereportedresultsareaccurateandcredibleandthattherights,integrityandconfidentialityofallstudyparticipantshavebeenprotectedthroughoutthestudy.

ICMJE InternationalCommitteeofMedicalJournalEditorsIDMC IndependentDataMonitoringCommitteeIEC IndependentEthicsCommitteeIMP InvestigationalMedicinalProduct-anunlicensednewdrug,oranexisting

drugtestedoutsideitslicence,orexistingdrugstestedagainsteachotherfortheirefficacy/safety.

INVOLVE INVOLVEnationaladvisorygroupIRAS IntegratedResearchApplicationSystemIRB IndependentReviewBoard-USequivalentofauthorisedRECIRMER IonisingRadiationMedicalExposureRegulationsIS InformationSystemsProgrammeISF InvestigatorSiteFile-Afiledesignedforuseinorganisingandcollatingall

essentialdocumentationrequiredtoconductastudyinaccordancewiththeprinciplesofGCPandtheapplicableregulatoryrequirements(e.g.RECapprovalletter/correspondence,MHRAapproval,blankCRF,staffCVs,delegationofdutieslogetc.)

ISRCTN InternationalStandardRandomisedControlledTrialNumberRegister-Asimplenumericsystemfortheidentificationofrandomisedcontrolledclinicaltrialsworldwide.Allowstheidentificationoftrialsandprovidesauniquenumberthatcanbeusedtotrackallpublicationsandreportsresultingfromeachtrial;canbeobtainedfromwww.isrctn.org

JLA JamesLindAllianceJLAPSPs JamesLindAlliancePrioritySettingPartnershipsJRO JointResearchOfficeKMFs KnowledgeMobilisationFellowships-NIHRMCA MentalCapacityActmCIA modelClinicalInvestigationAgreementmCTA modelClinicalTrialAgreement-forIMPstudieswithcommercial

sponsor/CROconductedMHRA MedicinesandHealthcareproductsRegulatoryAgency-TheUKCompetent

Authority(CA)andlicensingauthorityformedicinesandmedicaldevices.ItreplacedboththeMedicalDevicesAgency(MDA)andtheMedicinesControlAgency(MCA)inApril2003

MfHU(CT) MedicinesforHumanUse(ClinicalTrials)Regulations:SI2004:1031andsubsequentamendments2006:1928,2006:2984,2008:941,2009:1164and2010:1882aretheUKStatutoryInstrumentstranslatingEUdirectives2001/20/ECand2005/28/ECintoUKlaw,layingdownthelegalrequirementsforconductingCTIMPsintheUK

mNCA modelNon-CommercialAgreementMRC MedicalResearchCouncilMRC-NIHRNPC MRC-NIHRNationalPhenomeCentreMRP MethodologyResearchProgrammeND NotdoneNETSCC NIHREvaluation,TrialsandStudiesCoordinatingCentreNHS NationalHealthServiceNHSEED NHSEconomicEvaluationDatabaseNICE NationalInstituteofHealthCareExcellenceNIHR NationalInstituteforHealthResearch

NK NotknownNOCRI NIHROfficeforClinicalResearchInfrastructureNRES NationalResearchEthicsService-umbrellaorganisationresponsibleforall

RECacrosstheUKOHSRC OxfordshireHealthServicesResearchCommitteeOSCHR OfficeforStrategicCo-ordinationofHealthResearchOUHT OxfordUniversityHospitalsNHSTrustOXTREC OxfordTropicalResearchEthicsCommitteePCPIE Patient,Carer,PublicInvolvementandEngagementPDAs ProductDevelopmentAwardsPDGs ProgrammeDevelopmentGrantsPGfAR ProgrammeGrantsforAppliedResearchProgrammePHR PublicHealthResearchProgrammePI PrincipalInvestigatorPIC ParticipantIdentificationCentre:NHSorotherorganisationwhichonly

identifiesparticipantsfromadatabaseetc,butrecruitment/receivingconsentandstudyconductaremanagedelsewhere

PIS ParticipantorPatientInformationSheet:Aninformationleafletgiventothosewhohavebeeninvitedtoparticipateinaresearchstudy.Thesheetisdesignedtoprovidethepotentialparticipantwithsufficientinformationtoallowthatpersontomakeaninformeddecisiononwhetherornottheywanttotakepart

PIL Participant/PatientInformationLeafletPIS Participant/PatientInformationSheetPPI PatientandPublicInvolvementPROSPERO DatabaseofProspectivelyRegisteredSystematicReviewsPSTRC PatientSafetyTranslationalResearchCentreQA QualityAssuranceQC QualityControlQOL QualityofLifeQuestionnaireR&D ResearchandDevelopment-oftennameofDepartmentwithinNHShospitals

givingpermissiontoconductprojectsonthosefacilitieswithpatients/staffR&G RegulationandGovernanceRAE ResearchAssessmentExerciseRCF ResearchCapabilityFundingRCGP RoyalCollegeofGeneralPractitionersRCTs RandomisedControlledTrials-ARCTisaclinicalstudyinwhichtwo(ormore)

formsofcarearecompared;theparticipantsareallocatedtooneoftheformsofcareinthestudy,inanunbiasedway

RDS ResearchDesignServices-organisationwithanumberofexpertswhocanhelpwritetheprotocol/documentsforNIHRgrantapplications

REC ResearchEthicsCommittee-authorisedbyNREStoreviewstudydocumentsforresearchtakingplaceintheNHS,orsocialservices.SomeRECspecialiseinClinicalTrials,ortopicssuchasresearchinchildren,MCA.

RETG ResearchEducationandTrainingGroup,OxfordBiomedicalResearchCentreRfPB ResearchforPatientBenefitProgrammeRGF ResearchGovernanceFrameworkRM&G ResearchManagementandGovernanceRP ResearchPassportRSS ResearchSupportServicesSAE SeriousAdverseEventSAR SeriousAdverseReactionSDV SourceDataVerification-checkingtheoriginaldatarecord,suchaslab

reports,patientmedicalnotesagainstwhatwastransferredontotheCRF/intoadatabase

Serious-ADR Adversedrugreactionwhichfallsintooneoftheseriouscriteriaandthereforewarrantsexpeditedreporting(serious=resultinginhospitalisation,prolongedhospitalisation,death,life-threatening,congenitalanomaly/birthdefectorpersistentorsignificantdisability/incapacity)

SLA ServiceLevelAgreementSmPC SummaryofMedicinalProductCharacteristics-:smallerversionof

InvestigatorBrochurewithdetailsonpharmacologicaleffects,sideeffects,butissuedforaproductthatalreadyholdsamarketinglicence

SOP StandardOperatingProcedure-detailedwritteninstructionsdesignedtoachieveuniformityoftheperformanceofaspecificfunction

SSI SiteSpecificInformation-localdetailtoinformSSAincludingqualifications/expertiseofthePIandwiderresearchteam,studyprocedures,departmentalcapacitytoabsorbproject(includesPharmacy,Pathology,Radiology)anddepartmentalleadssignatures;TheSSIformiscompletedinIRAS

SUSAR SuspectedUnexpectedSeriousAdverseReactions-ASeriousAdverseReaction(SAR)whichisUnexpected(i.e.itsnatureandseverityisnotconsistentwiththeknowninformationaboutthatproductfromtheInvestigator’sBrochureortheSmPC)andsuspected,asitisnotpossibletobecertainofcausalrelationshipwiththeIMP

TCC NIHRTraineesCoordinatingCentreTMF TrialMasterFile-filewithessentialdocumentsheldbytheChief

Investigator/SponsororganisationTSG OxfordUniversityHospitalsTrust/UniversityofOxfordTrialsSafetyGroupUKCRC UKClinicalResearchCollaborationUKCRN UKClinicalResearchNetworkUKCTG UKClinicalTrialsGateway

DictionaryofResearchRelatedTerms

Amendment Awrittendescriptionofachangeorformalclarification.Substantialamendments(Seebelowunder‘SubstantialAmendment’)toprotocol,participantinformation/consentrequireREC,R&D,MHRAapproval,Non-substantialamendmentsshouldbe‘notified’toREC,R&D,MHRA

Allocationconcealment

Atechniqueusedtopreventselectionbiasbyconcealingtheallocationsequencefromthoseassigningparticipantstointerventiongroups,untilthemomentofassignment.Allocationconcealmentpreventsresearchersfrom(unconsciouslyorotherwise)influencingwhichparticipantsareassignedtoagiveninterventiongroup.

Agrouporsubgroupofparticipantsinaclinicaltrialthatreceivesspecificinterventions,ornointervention,accordingtothestudyprotocol.Thisisdecidedbeforethetrialbegins.

Bias Alossofbalanceandaccuracyintheuseofresearchmethods.Itcanappearinresearchviathesamplingframe,randomsampling,ornon-response.Itcanalsooccuratotherstagesinresearch,suchaswhileinterviewing,inthedesignofquestions,orinthewaydataareanalysedandpresented.Biasmeansthattheresearchfindingswillnotberepresentativeof,orgeneralisableto,awiderpopulation.

Blinding Aclinicaltrialdesignstrategyinwhichoneormorepartiesinvolvedwiththetrial,suchastheinvestigatororparticipant,donotknowwhichparticipantshavebeenassignedwhichinterventions.TypesofMaskingincludeNone,OpenLabel,SingleBlindMasking,andDoubleBlindMasking.

Collaborator Anorganizationotherthanthesponsorthatprovidessupportforaclinicalstudy.Thismayincludefunding,design,implementation,dataanalysis,orreporting

Comparisonarm Agroupingofparticipantsinaclinicalstudythatisusedinsummarizingthedatacollectedduringthestudy.Thisgroupingmaybethesameasordifferentfromastudyarm.

Datamonitoringcommittee

Agroupofindependentscientistswhomonitorthesafetyandscientificintegrityofaclinicaltrial.Thegroupcanrecommendtothestudysponsorthatthestudybestoppedifitisnoteffective,ifitiscausingharmtoparticipants,orifitisnotlikelytoserveitsscientificpurpose.Committeemembersarechosenbasedonthescientificskillsandknowledgeneededtomonitortheparticularstudy.Alsoreferredtoasadatasafetyandmonitoringboard(DSMB)

Delegationlog Alistofappropriatelyqualifiedpersonstowhomtheinvestigatorhasdelegatedsignificanttrialrelatedduties

Doubleblind Atrialwheretheinvestigatorsandthesubjectsincludedinthetrial(healthyvolunteersorpatients)donotknowwhichinterventions/treatmentshavebeenassigned.

Efficacy Ameasureofwhetherthemedicinalproducthasitsintendedeffect

Eligibilitycriteria Thekeystandardsthatpeoplewhowanttoparticipateinaclinicalstudymustmeetorthecharacteristicstheymusthave.Theseincludeinclusioncriteriaandexclusioncriteria.Forexample,astudymightonlyacceptparticipantswhoareaboveorbelowcertainages.

Enrollment Theactofadmittingaparticipantintoatrial.Participantsshouldbeenrolledonlyafterstudypersonnelhaveconfirmedthatalltheeligibilitycriteriahavebeenmet.Formalenrolmentmustoccurbeforerandomisedassignment.

Exclusioncriteria Thefactors(orreasons)thatpreventapersonfromparticipatinginaclinicalstudy.

ExperimentalArm

Agroupofparticipantsthatreceivestheinterventionthatisthefocusofthestudy–sometimescalled‘treatmentarm’

Followup Aprocessofperiodiccontactwithparticipantsenrolledinthetrialforthepurposeofadministeringtheassignedintervention(s),modifyingthecourseofintervention(s),observingtheeffectsoftheintervention(s),orfordatacollection.

Generalisability

Theextenttowhichthefindingsofaclinicaltrialcanbereliablyextrapolatedfromthesubjectswhoparticipatedinthetrialtoabroaderpatientpopulationandabroaderrangeofclinicalsettings.

Hypothesis

Inatrial,astatementrelatingtothepossibledifferenteffectoftheinterventionsonanoutcome.Thenullhypothesisofnosucheffectisamenabletoexplicitstatisticalevaluationbyahypothesistest,whichgeneratesaPvalue.

IncapacitatedAdult

Anadultunablebyvirtueofphysicalormentalincapacitytogiveinformedconsent.

Inclusioncriteria Thefactors(orreasons)thatallowapersontoparticipateinaclinicalstudy.

Indemnity Compensationfordamage,lossorinjury

IntellectualProperty(IP)

IPcanbedescribedasthenovelorpreviouslyun-describedtangibleoutputofanyintellectualactivity.Ithasanownerandcanbebought,soldorlicensedandmustbeadequatelyprotected.Itcanincludeinventions,industrialprocesses,software,data,writtenworks,designsandimages.

InterimAnalysis

Ananalysiscomparinginterventiongroupsundertakenatanytimebeforetheformalcompletionofthetrial,usuallybeforerecruitmentiscomplete.Oftenusedwith"stoppingrules"sothatatrialcanbestoppedifparticipantsarebeingputatriskunnecessarily.Timingandfrequencyofinterimanalysesshouldbespecifiedintheprotocol.

Interventionalstudy

Aclinicalstudyinwhichparticipantsareassignedtoreceiveoneormoreinterventions(ornointervention)sothatresearcherscanevaluatetheeffectsoftheinterventionsonbiomedicalorhealth-relatedoutcomes.Theassignmentsaredeterminedbythestudyprotocol.Participantsmayreceivediagnostic,therapeutic,orothertypesofinterventions.

Investigator Aresearcherinvolvedinaclinicalstudy.RelatedtermsincludeSitePrincipalInvestigator,SiteSub-Investigator,StudyChair,StudyDirector,andStudyPrincipalInvestigator

LegalRepresentative

ApersonwhogiveswritteninformedconsentonbehalfofavulnerablesubjectinaCTIMPasdefinedinSchedule1,Part1(2)ofTheMedicinesforHumanUse(ClinicalTrials)Regulations,asamended.

Minor InrelationtoaCTIMP,definedin‘TheMedicinesforHumanUse(ClinicalTrials)Regulations’asapersonundertheageof16.

Monitor Thepersondesignatedbythesponsortoperformsitevisitsandconductthemonitoringprocess;egcheckwhetherthereareanydeviationsfromtheprotocolandthatallsourcedatawastransferredintotheCaseReportFormscorrectly

Monitoring Theactofoverseeingtheprogressofaclinicaltrial,andofensuringthatitisconductedandrecordedinaccordancewiththeprotocol,StandardOperatingGuidelines(SOP’s),GoodClinicalPractice(GCP)andtheapplicableregulatoryrequirement(s).

MultiCentreStudy

Astudyconductedaccordingtoasingleprotocolbutcarriedoutatmorethanonesiteandbymorethanoneinvestigator;oneCIoverseesseverallocalPIs

NonInterventionalTrial

Astudyofoneormoremedicinalproductswhichhaveamarketingauthorisation,wherethefollowingconditionsaremet:a)Theproductsareprescribedintheusualmannerinaccordancewiththetermsofthatauthorisationb)Theassignmentofanypatientinvolvedinthestudytoaparticulartherapeuticstrategyisnotdecidedinadvancebyaprotocolbutfallswithincurrentpracticec)Thedecisiontoprescribeaparticularmedicinalproductisclearlyseparatedfromthedecisiontoincludethepatientinthestudyd)Nodiagnosticormonitoringproceduresareappliedtothepatientsincludedinthestudy,otherthanthosewhichareordinarilyappliedinthecourseoftheparticulartherapeuticstrategyinquestion,ande)Epidemiologicalmethodsaretobeusedfortheanalysisofthedataarisingfromthestudy.

Nonsubstantial

amendments

Changestothedetailsofastudythathavenosignificantimplicationsforthesubjects,theconduct,themanagementorthescientificvalueofthestudy(sometimesreferredtoasadministrativeamendments).Examplesmaybeasfollows:• Correctionoftypographicalerrorsintheprotocolorotherstudy

documentation• Amendedcontactdetailsforthesponsororprojectstaff• Changesinfundingarrangements• Appointmentofnewsupportstaff• Changesinthedocumentationusedtorecordstudydata• Changesinthelogisticalarrangementsfortransportingorstoring

samples

Observationalstudy

Aclinicalstudyinwhichparticipantsidentifiedasbelongingtostudygroupsareassessedforbiomedicalorhealthoutcomes.Participantsmayreceivediagnostic,therapeutic,orothertypesofinterventions,buttheinvestigatordoesnotassignparticipantstospecificinterventions

Openlabel Describesaclinicaltrialinwhichmaskingisnotused.Thismeansthatallpartiesinvolvedwiththetrialknowwhichparticipantshavebeenassignedwhichinterventions.

Outcomemeasure

Aplannedmeasurementdescribedintheprotocolthatisusedtodeterminetheeffectofinterventionsonparticipantsinaclinicaltrial.Forobservationalstudies,ameasurementorobservationthatisusedtodescribepatternsofdiseasesortraits,orassociationswithexposures,riskfactors,ortreatment.TypesofoutcomemeasuresincludePrimaryOutcomeMeasureandSecondaryOutcomeMeasure.

PatientandPublicInvolvement(PPI;mayalsobecalled,butisdistinctfrom.PCPIE-Patient,Carer&PublicInvolvement&Engagement)

PPIisanactivepartnershipbetweenpatientsandthepublicandresearchersintheresearchprocess,ratherthantheuseofpeopleas'subjects'ofresearch.PPIinresearchisoftendefinedasdoingresearch‘with’or‘by’peoplewhouseservicesratherthan‘to’,‘about’or‘for’them.Thiswouldinclude,forexample,involvementinthechoiceofresearchtopics,assistinginthedesign,advisingontheresearchprojectorincarryingouttheresearch.

Peerreview Anappropriateprocessofindependentexpertreviewhasdemonstratedthattheresearchproposalisworthwhile,ofhighscientificqualityandrepresentsgoodvalueformoney

Phase • Phase0:Exploratorystudyinvolvingverylimitedhumanexposuretothedrug,withnotherapeuticordiagnosticgoals(forexample,screeningstudies,microdosestudies)

• Phase1:Studiesthatareusuallyconductedwithhealthyvolunteersandthatemphasisesafety.Thegoalistofindoutwhatthedrug'smostfrequentandseriousadverseeventsareand,often,howthedrugismetabolizedandexcreted.

• Phase2:Studiesthatgatherpreliminarydataoneffectiveness(whetherthedrugworksinpeoplewhohaveacertaindiseaseorcondition).Forexample,participantsreceivingthedrugmaybecomparedwithsimilarparticipantsreceivingadifferenttreatment,usuallyaninactivesubstance(calledaplacebo)oradifferentdrug.Safetycontinuestobeevaluated,andshort-termadverseeventsarestudied.

• Phase3:Studiesthatgathermoreinformationaboutsafetyandeffectivenessbystudyingdifferentpopulationsanddifferentdosagesandbyusingthedrugincombinationwithotherdrugs.

• Phase4:StudiesoccurringafterFDAhasapprovedadrugformarketing.Theseincludingpostmarketrequirementandcommitmentstudiesthatarerequiredoforagreedtobythesponsor.Thesestudiesgatheradditionalinformationaboutadrug'ssafety,efficacy,oroptimaluse.

Placebo Asubstancethatdoesnotcontainactiveingredientsandismadetobephysicallyindistinguishable(thatis,itlooksandtastesidentical)fromtheactualdrugbeingstudied.

Protocol Thewrittendescriptionofaclinicalstudy.Itincludesthestudy'sobjectives,design,andmethods.Itmayalsoincluderelevantscientificbackgroundandstatisticalinformation.

QualifiedPerson AllmanufacturingactivitieswillneedtobeconductedinaunitwhichhasanIMPmanufacturingauthorisationwithanamedQualifiedPerson(QP).Thispersonensuresthataninvestigationmedicinalproduct(IMP)batchisonlyreleasedifthereisdocumentationtoconfirmcompliancewithGoodmanufacturingPractice(orequivalent).

QualityAssurance

Allthoseplannedandsystematicactionsthatareestablishedtoensurethatthetrialisperformedandthedataisgenerated,documented(recorded),andreportedincompliancewithGoodClinicalPractice(GCP)andtheapplicableregulatoryrequirement(s).

Qualitycontrol Theoperationaltechniquesandactivitiesundertakenwithinthequalityassurancesystemtoverifythattherequirementsforqualityofthetrial-relatedactivitieshavebeenfulfilled.

Randomisation Theprocessofassigningtrialsubjectstotreatmentorcontrolgroupsusinganelementofchancetodeterminetheassignmentsinordertoreducebias

ResearchDesignService(RDS)

TheNIHRhasestablishedanetworkofResearchDesignServiceinEnglandtohelpresearchersdevelopanddesignhighqualityresearchproposalsforsubmissiontonational,peer-reviewedfundingcompetitionsforappliedhealthorsocialcareresearch.

ResearchEthicsCommittee(REC)

Committeeestablishedtoprovideparticipants,researchers,funders,sponsors,employers,careorganisationsandprofessionalswithanindependentopinionontheextenttowhichproposalsforastudycomplywithrecognisedethicalstandards.ForCTIMPs,theethicscommitteemustbeonerecognisedbytheUnitedKingdomEthicsCommitteeAuthority.TheRECundertakingtheethicalreviewofanapplicationisalsoknownastheMainREC.

ResearchPassport

AsystemforHEIemployedresearchers/postgraduatestudentswhoneedtoundertaketheirresearchwithinNHSorganisations,whichprovidesevidenceofthepre-engagementchecksundertakenonthatpersoninlinewithNHSEmploymentCheckStandards(amongthemCRBandoccupationalhealthchecks)

SampleSize

Thenumberofparticipantsinthetrial.Theintendedsamplesizeisthenumberofparticipantsplannedtobeincludedinthetrial,usuallydeterminedusingastatisticalpowercalculation.Thesamplesizeshouldbeadequatetoprovideahighprobabilityofdetectingassignificantaneffectsizeofagivenmagnitudeifsuchaneffectactuallyexists.Theachievedsamplesizeisthenumberofparticipantsenrolled,treatedoranalysedinthestudy.

ServiceLevelAgreement(SLA)

Acommunicationdocumentthatmakesclearwhatthesupplierwilldeliverandwhattheorganisationwillensure.Itisbasedontheconditionsofcontractandspecificationanddoesnotinanywayreplacethem.

Site TheNHSorganisationinwhichstudyactivitiesandassessmentareperformedorthelocation(s)wheretrial-relatedactivitiesareactuallyconducted.Eachsite/TrustneedstogiveR&Dapproval

SourceData Allinformationinoriginalrecordsandcertifiedcopiesoforiginalrecordsofclinicalfindings,observations,orotheractivitiesinaclinicaltrialnecessaryforthereconstructionandevaluationofthetrial.Sourcedataarecontainedinsourcedocuments(originalrecordsorcertifiedcopies).Sourcedatamaybeinhardcopyorelectronicformat.

Sourcedocuments

Originaldocuments,data,andrecords(e.g.,hospitalrecords,clinicalandofficecharts,laboratorynotes,memoranda,subjects'diariesorevaluationchecklists,pharmacydispensingrecords,recordeddatafromautomatedinstruments,copiesortranscriptionscertifiedafterverificationasbeingaccuratecopies,microfiches,photographicnegatives,microfilmormagneticmedia,x-rays,subjectfiles,andrecordskeptatthepharmacy,atthelaboratoriesandatmedico-technicaldepartmentsinvolvedintheclinicaltrial).

Substantial

Amendment

Asubstantialamendmentcanbedefinedasanamendmenttotheprotocoloranyotherstudyspecificdocumentation,thetermsoftheRECapplicationorthetermsoftheCTAapplication(asapplicable)thatislikelytoaffecttoasignificantdegreethe:

• Thesafetyorphysicalormentalintegrityofthesubjectsofthetrial;• Thescientificvalueofthetrial;• ClinicalResearchNetwork• Theconductormanagementofthetrial;or• Thequalityorsafetyofanyinvestigationalmedicinalproductusedin

thetrial.• Otherchangestotheparticularsofastudythatqualifyassubstantial

amendmentsinclude:• Achangeofsponsor(s)• AppointmentofanewChiefInvestigatorand• Extensionoftheresearchbeyondtheplannedclosingdatefor

recruitment

AsubstantialamendmentmaynotbemadetoaresearchstudywithoutthefavourableopinionfromtheRECthatgaveafavourableopinionforthestudy(themainREC)andasapplicabletheMHRA.Theonlyexceptionstothisruleare:

• TheInclusionofanewresearchsiteor• TheAppointmentofanewPIatanindividualsite

BothofthesequalifyassubstantialamendmentsbutastheyrequirefurtherSSAandapprovalfromtheRECthereisnorequirementfornoticeofamendmenttotheREC.ThesechangesdostillhoweverneedtobenotifiedtotheMHRA(asapplicable)

TrialManagementGroup(TMG)

TheTrialManagementGroupnormallyincludesthoseindividualsresponsiblefortheday-to-daymanagementofthetrial,suchastheChiefInvestigator,statistician,trialmanager,researchnurse,datamanager.Theroleofthegroupistomonitorallaspectsoftheconductandprogressofthetrial,ensurethattheprotocolisadheredtoandtakeappropriateactiontosafeguardparticipantsandthequalityofthetrialitself.

TrialSteeringCommittee

TheroleoftheTrialSteeringCommittee(TSC)istoprovidetheoverallsupervisionofthetrial.Ideally,theTSCshouldincludememberswhoareindependentoftheinvestigators,theiremployingorganisations,fundersandsponsors.TheTSCshouldmonitortrialprogressandconductandadviseonscientificcredibility.TheTSCwillconsiderandact,asappropriate,upontherecommendationsoftheDataMonitoringCommittee(DMC)orequivalentandultimatelycarriestheresponsibilityfordecidingwhetheratrialneedstobestoppedongroundsofsafetyorefficacy.

Pleaseseewww.ct-toolkit.ac.ukforaninteractiveversion,withlinkstoextensivefurtherinformation

Appendix1:‘RoleTransition’whenbecomingaResearchNurse*

http://clinfield.com/2011/01/role-transition-when-becoming-a-research-nurse/

BlogpostonJan10,2011byKellyGleason,SeniorResearchNurse,ImperialCollegeHealthcareNHSTrust,London

Althoughthisblogiswrittenaboutresearchnurses,itisequallyapplicabletoanyoneenteringaresearchpostforthefirsttime.

Followingthedecisiontobecomearesearchnurse,thefirstfewmonthscanbequitedifficultandcanreallymakeyouwonderwhetherornotyouhavemadetherightdecision.Youmisstheroutineoftheward,thecamaraderieofyourpeersandfeelinglikeyouactuallyknowwhatyouaredoing!

Youarriveinclinicalresearchequippedwithyouryearsofclinicalexperience,feelinglikeacompetenthealthcareprofessionalabletoansweryourpatients’questions,makedecisionsregardingtheircare,andenjoythewell-establishedandtrustingrelationshipsyouhavedevelopedwithyourmedicalcolleagues.Suddenlyyouareinaseaofunfamiliaracronyms,beingaskedtosteerseveralshipstodock–andallthiswithoutalifejacketandtheusualsupport,guidanceandknowledgeuponwhichyouhadcometorely.Whilenavigatingthisnewseawehaveallalsofounditdifficulttoaskforhelpinfearthatwewilllookincompetentandthatournewemployersmightquestiontheirdecisiontorecruitusinthefirstplace!

Iwouldliketotakethisopportunitytosay:‘it’sokayanditsnormal’…weALLgothroughthesameprocess…anditdoesend…andyoudo,onceagain,findyourselffeelingliketheprofessionalyouoncewere.

Spilburyetal2007,describethisperiodas‘roletransition’:atimewhenaresearchnurseexperiencesalossofroleconfidencewhileacquiringnewskills,knowledgeandcompetence–inordertofunctioninanewroleandtoadapttoworkingmoreautonomouslythanonedidonthewards.

Itismucheasier,Ithink–onceyouacceptthatthisisgoingtobeaperiodoftransitionandthatyourroleduringthistimeistolearn–nottohavealltheanswers.AsEarlGrayStevensoncesaid,“Confidence,likeart,nevercomesfromhavingalltheanswers,itcomesfrombeingopentoallthequestions.”

Ialsothinkitisimportanttoacceptthatnoteverythingcanbelearnedstraightaway,andratherthatthefirst6monthsisagoodtimetolearnthesystemsandprocessesofyourparticularplaceofemployment,andbecomefamiliarwiththeregulationsthatgovernclinicalresearch,yourassignedtrialportfolio,yourpatientpathwaytooptimiserecruitment,andgettoknowthemultidisciplinaryteamyouwillbeworkingwith.

Inmyexperienceittakesmostpeople6monthstostartfeelingmore‘athome’inthisnewchosenfield.Thisofcoursewilldependonwhatyouareexposedtointhisfirst6months,andwhoyouhavesupportingyou.Supportintheroleoftheresearchnurseisalsoessentialforsurvival,somakelinkswhereyoucan–evenifitiswithresearchnursesinotherdiseaseareas.The‘peergroup’forresearchnursesisgrowingandthereisnowgreaterawarenessoftherole–soifyouhavenotcomeintoateambutinsteadworkmoreinisolation,thentrytospeakto

managementoryournursingdirectorate,astheywilllikelyknowotherresearchnursesinyourorganisationwhocanprovideyouwithsupportandunderstandingwhenyouneedit.

Ibelievethatformostofus,persistencethroughthisinitialtransitionperiodiswellworthit.Thefieldofclinicalresearchisgrowingandbeginningtooffernurseswonderfulopportunitiestodevelopthemselvesprofessionally.TheanticipatedchangesintheNHSovertheforeseeablefuturewillundoubtedlyaffecthowwedelivercareandhowwesupportresearch.Let’sbereadytooffersolutions.Solutionsthatwillbenefitthehealthcaresystem,andsolutionsthatwillsupportresearchnursesindevelopingthemselvesasadvancedpractitioners,committingthemselvestoinnovationandthehigheststandardsofcare–allofwhichcanonlybeachievedifresearchfullyintegratesitselfintheservicewedeliver.

Soifyouliketobechallenged,haveapassionforleadershipandformakingthingsbetter,mayberesearchnursingreallyisforyou…theinitialchangecanbealittleuncomfortable–butwithalittleunderstandingthatthisislikelyonlytobetemporaryandthatyouareallowedthistimetolearn,youwillhopefullycomeout‘theotherside’toseemanyopportunitiesthatthisnewandgrowingfieldhastooffer.

SpilburyK,PetherickE,CullumN,NelsonA,NixonH&MasonS,(2007)‘Theroleandpotentialcontributionofclinicalresearchnursestoclinicaltrials’JournalofClinicalNursing17(4),549-57.

Appendix2:ThePrinciplesofGCPInordertostandardiseGCP,representativesfromthepharmaceuticalindustriesinthethreemajorregions(USA,Japan,andEurope)createdtheInternationalConferenceonHarmonisation(ICH)andsetuptheICHGCPguidelines.SincetheEUDirectivein1997,allstudiesintheUnitedKingdomhavetobeconductedincompliancewithICHGCP.

Goodclinicalpracticeisthequalitystandardbywhichclinicaltrialsmustbeperformed,bydetailingtheprocessesrequiredintheconductofclinicaltrials.Ifnotfollowed,clinicaltrialdatacanberejectedandfoundtobeunreliable,thereforeitisvitalthatallinvolvedinclinicaltrialshaveathoroughworkingknowledgeofGCPrequirementsandadheretothem.

1. ClinicaltrialsshallbeconductedinaccordancewiththeethicalprinciplesthathavetheiroriginintheDeclarationofHelsinki,andthatareconsistentwithgoodclinicalpracticeandtherequirementsoftheUKRegulationsofMedicinesforHumanUse(ClinicalTrials).

2. Beforethetrialisinitiated,foreseeablerisksandinconvenienceshavebeenweighedagainsttheanticipatedbenefitfortheindividualtrialparticipantandotherpresentandfuturepatients.Atrialshouldbeinitiatedandcontinuedonlyiftheanticipatedbenefitsjustifytherisks.

3. Therights,safety,andwellbeingofthetrialsubjectsarethemostimportantconsiderationsandshallprevailoverinterestsofscienceandsociety.

4. Theavailablenon-clinicalandclinicalinformationonaninvestigationalmedicinalproductshallbeadequatetosupporttheclinicaltrial.

5. Clinicaltrialsshallbescientificallysound,anddescribedinaclear,detailedprotocol.6. Atrialshallbeconductedincompliancewiththeprotocolthathasafavourableopinionfromanethics

committee.7. Themedicalcaregivento,andmedicaldecisionsmadeonbehalfof,subjectsshallalwaysbethe

responsibilityofanappropriatelyqualifieddoctoror,whenappropriate,ofaqualifieddentist.8. Eachindividualinvolvedinconductingatrialshallbequalifiedbyeducation,training,andexperienceto

performhisorherrespectivetask(s).9. Subjecttotheotherprovisionsrelatingtoconsent,freelygiveninformedconsentshallbeobtainedfrom

everysubjectpriortoclinicaltrialparticipation.NBInformedconsentisdiscussedindetailinchapter6.10. Allclinicaltrialinformationshallberecorded,handled,andstoredinawaythatallowsitsaccurate

reporting,interpretationandverification.11. Theconfidentialityofrecordsthatcouldidentifysubjectsshallbeprotected,respectingtheprivacyand

confidentialityrulesinaccordancewiththerequirementsoftheDataProtectionAct1998andthelawrelatingtoconfidentiality.

12. Investigationalmedicinalproductsusedinthetrialshallbe:a. manufacturedorimported,andhandledandstored,inaccordancewiththeprinciplesandguidelinesof

goodmanufacturingpracticeb. usedinaccordancewiththeapprovedprotocol.13. Systemswithproceduresthatassurethequalityofeveryaspectofthetrialshallbeimplemented14. Atrialshallbeinitiatedonlyifanethicscommitteeandthecompetentauthoritycomestothe

conclusionthattheanticipatedtherapeuticandpublichealthbenefitsjustifytherisksandmaybecontinuedonlyifcompliancewiththisrequirementispermanentlymonitored.

15. Therightsofeachsubjecttophysicalandmentalintegrity,toprivacyandtotheprotectionofthedataconcerninghimorherinaccordancewiththeDataProtectionAct1998aresafeguarded.

16. Provisionhasbeenmadeforinsuranceorindemnitytocovertheliabilityoftheinvestigatorandsponsorthatmayariseinrelationtotheclinicaltrial.

Appendix3:InformedConsentFreelygiveninformedconsentiscentraltoethicalresearchinvolvinghumanparticipantsortheuseofhumantissuesorgeneticmaterial.Thissectiondiscussestheconceptofinformedconsentandtheinformationpotentialparticipantsneedtoreceiveandunderstandinordertogiveinformedconsent.Itconcludeswithasummaryoftheprocedureswhichneedtobefollowedinordertocomplywiththestrictlegalandregulatoryrequirementsinrelationtothiscrucialissueinresearch.

Itisessentialtoensurethatthosewhoparticipateinresearchunderstandexactlywhatitwillinvolveforthem.Itismorallyandprofessionallyunacceptabletoperformanyresearchrelatedprocedureonsomeonewithoutfirstobtainingtheirfullyinformedconsent.Itisalsoimportanttorememberthatafteraconsentformhasbeensigned,aparticipantcanstillwithdrawfromthetrialatanytimewithoutgivingareason.Itisthedutyoftheinvestigatortoreiteratethisandtoreassureparticipantsthattheywillnotcompromisetheirfuturemedicalcareiftheydecidetowithdraw.

Whatisinformedconsent?Informedconsentisanongoingagreementbyapersontoparticipateinresearch,afterrisks,benefitsandalternativeshavebeenadequatelyexplainedtothem.Ithelpstoensurethatpeoplearenotdeceivedorcoercedintoparticipatinginresearch.Inordertogivefullyinformedconsent,potentialparticipantsneedtounderstandthefollowing:

• thepurposeoftheresearch• thepracticalitiesandproceduresinvolvedinparticipating• thebenefitsandrisksofparticipationand,ifappropriate,thealternativetherapies• howdataaboutthemwillbemanagedandused• theconsentform• theirroleiftheyagreetoparticipateintheresearch• howinformationwillbeprovidedtothemthroughoutthestudy• thattheirparticipationisvoluntary• thattheycanwithdrawfromthestudyatanytime,withoutgivinganyreasonandwithout

compromisingtheirfuturetreatment• theinsuranceindemnityarrangementsfortheconductoftheresearchwhereappropriate• thattheresearchhasbeenapprovedbyaresearchethicscommittee.

Inaddition,theyshouldbegiventhecontactdetailsofthePrincipalInvestigatorandresearchnurse/practitioner,shouldtheyhavefurtherquestionsorshouldtheywishtowithdrawfromthestudy

MaintainingInformedconsentInformedconsentisnotaone-offprocess,itisanongoingrequirement.Theparticipant’sconditionmaychange;therecouldbedifficultieswithcompliance,orsideeffectsfromtrialtreatments.Newinformationmayemergewhichcouldberelevanttothetrial.

• Researchersmustensurethatparticipants:• Arekeptfullyinformedaboutanychangestotheinformationthattheyhavebeengiven• Understandtheinformationandanychangesinthatinformation• Continuetoconsenttoparticipatethroughoutthestudy.

Whoshouldreceiveinformedconsent?Theissueofwhoshouldtakeinformedconsenthasbeendebatedatlength.

TheoriginalDeclarationofHelsinki(1964)statedthat:

‘…thePhysicianshouldthenobtainthesubjectsfreelygiveninformedconsent,preferablyinwriting…’

However,ithasrecentlybeenwidelyacknowledgedthatresearchnurses/practitionersinthestudyteamfrequentlyplayamajorroleinobtainingandmaintaininginformedconsent.Theymayhaveexcellentcommunicationskillsandpatientsoftenconsiderthemtobemoreapproachablethantheinvestigator.ICHGCPguidelines(1996}statethat:

‘…TheInvestigator,orapersondesignatedbytheInvestigator,shouldfullyinformthesubject…theconsentformshouldbesignedbythepersonwhoconductedtheinformedconsentdiscussion…‟(19964.85)

HencetheRevisedDeclarationofHelsinki2008statesthat:

‘…Specialattentionshouldbegiventothespecificinformationneedsoftheindividual.Afterensuringthatthepotentialsubjecthasfullyunderstoodtheinformation,thephysicianoranotherappropriatelyqualifiedindividualmustthenseekthepotentialsubject’sfreelygiveninformedconsent…’

Atlocallevel,therewillbeaStandardOperatingProcedure(SOP)whichallresearchstaffshouldadhereto.Althoughothersmayplayamajorroleintheconsentprocessexplainingprocedures,answeringquestionsetc,forstudiesinvolvingmedicalintervention,ultimateresponsibilityforenrollingthesubjectusuallylieswiththeinvestigator.(Innon-interventionstudiestheinvestigatormaynotnecessarilybeaphysician)Theinvestigatorshouldensurethatsubjectshavefullyunderstoodwhattheyareconsentingtoandsignanddatetheconsentformaccordingly.Anyotherresearchpersonnelinvolvedingivinginformationduringtheinformedconsentprocedureshouldalsosigntheinformedconsentform.

Hence,overallresponsibilityforallelementsofresearchactivity,includinggaininginformedconsent,restswiththeleadresearcher.S/hemaydelegatethetaskofobtaininginformedconsenttoanotherappropriatelyqualifiedandexperiencedmemberoftheresearchteam,butthisdelegationmustbeclearlydocumented,andthepersongaininginformedconsentmustsignanddatetheconsentform.Individualmembersoftheresearchteamremainresponsiblefortheirownspecificactions.

Thisapproachmeetsthecriteriaofthekeydocuments,andadherestotheDeclarationofHelsinki

GuidelinesforResearchNurses/PractitionersinobtainingconsentGuidelinesstate:“Theinformationtothepatientshouldbegiveninoralandwrittenformwhereverpossible’…and…’Subjectsmustbeallowedsufficienttimetodecidewhetherornottheywishtoparticipate’.(ICHGCP1996)

Whendiscussingaresearchstudywithpotentialparticipants,itisimportantthatyouasaresearcherunderstandtheprotocolsufficientlytoexplainitandtoanswerquestionsthatthepotentialparticipantmayhave.Ifyoucannotansweraquestion,youmustallowtimetoseektheanswerfromacolleaguebeforetakingconsent.

Itisveryimportanttounderstandandtoexplaininsimpleterms,theconceptofequilibriumbetweenthedifferentresearcharms.Thisexists,despiteanypromiseshowninearlytrials,oranyexpectationbiasonthepartofresearchersortrialpromoters.Accordingtocurrentevidence,standardtreatment(whichmaymeansupportivecareonly)remainsthegoldstandard,untilanynewtreatmentorprocedurehasbeenproventohavebenefitswhichoutweighitsdisadvantages.

Henceyoushouldensurethatanypersonalviewsyoumayhavedonotinfluencewhetherornotanindividualconsentstotakepart.Youneedtoassesssuitabilityandeligibilityaccordingtotheprotocol,andtogiveadequateinformationandthenallowthemtodecideforthemselves.Ifapatientwantssomeonetohelpthemmaketheirdecision,recommendthattheydiscussitwitharelativeorfriend,orahealthcareprofessionalwhoisnotinvolvedintheresearch,suchasaGP.However,youshouldemphasisethatultimately,theyshouldonlyconsenttoparticipateiftheyarecertainthattheywishtodoso.Forvariousreasonsapatientmightfinditdifficulttodeclineparticipation.Inthiscaseitisyourroletoenableandempowerthemtosay„no.‟

Potentialparticipantsshouldalsounderstandthat,iftheyagreetotakepartinresearch,theyhaveadutytotheresearchers.Ingivinginformedconsenttheyareagreeingtocomplywiththerequirementsoftheresearch.Ifatanytimetheyareunableorunwillingtodothistheyshouldconsiderwithdrawingfromthestudy.Itisimportanttoemphasisethatwithdrawalfromaclinicalstudywillnotcompromisethequalityofcaretheyreceive,althoughtheirtreatmentmaychange.

Forthepurposesofauditandinspections,thewholeprocessofobtainingconsentshouldbedocumentedinthepatient’scasenotes.Thisshouldincludewhospoketothepatient,whatwasdiscussedandwhen.

RefertoyourlocalSOPforinformedconsentandadheretoanyadditionallocalpolicies.

RespectingDiversityThecoreethicalprincipleinresearchisrespectforeveryindividual(RoyalCollegeofNursing2004)Researchersmustthereforerespectdiversitywhengaininginformedconsent(DepartmentofHealth,2001&2005);ScottishExecutiveHealthDepartment,2001;WalesOfficeofResearchandDevelopment,2001).

Researchersmusttakeintoaccountfactorssuchas:

• age• ethnicity• gender• disability• religiousbeliefs• culture• language• levelofunderstanding.

Researchersneedtobesensitiveastohowanyorallofthesefactorsmightaffectapotentialparticipant,takingcaretoavoidmakingstereotypicalassumptions.Specialrulesapplyinresearchinvolvingminorsandincapacitatedadults.Inassessingaperson’scapacitytounderstand,itisimportanttobeawareofanyreading,writing,orlanguagedifficulties,andthatthesemightbehidden.Theycouldhavevisualorhearingimpairments,oremotionaldifficulties.Alsoapersonmayhavecapacityattheinitialstageofconsent,butloseitastreatmentprogresses.Thismayhavebeenexpected,forexampleifthepatientisterminallyill,soitdoesnotnecessarilyinvalidatetheconsent.

ThelegalframeworkGaininginformedconsentinresearchwhichinvolvesinvasiveproceduresisalegalrequirement.Ifaresearchactivityproceedswithoutanindividual’sinformedconsentlegalactioncouldbetakenagainstthechiefinvestigatororresearcher.

CaselawonconsentintheUKhasestablishedthreerequirementstobesatisfiedbeforeapotentialresearchparticipantcangiveinformedconsent:

• theconsentshouldbegivenbysomeonewiththementalcapacitytodoso• sufficientinformationshouldbegiventoandunderstoodbytheparticipant• theconsentmustbefreelygiven

Table1:Informedconsentforaminorasdefinedas<16yearsofagePersonwhomaygiveconsent Definition Commentary1. Parent Aparentorpersonwithparental

responsibility.Shouldalwaysbeapproachedifavailable.

2. Personallegalrepresentative Apersonnotconnectedwiththeconductofthetrialwhois:(a)suitabletoactasthelegalrepresentativebyvirtueoftheirrelationshipwiththeminor,and(b)availableandwillingtodoso.

Maybeapproachedifnopersonwithparentalresponsibilitycanbecontactedpriortotheproposedinclusionoftheminor,byreasonoftheemergencynatureoftheinterventionprovidedaspartofthetrial.

3. Professionallegalrepresentative Apersonnominatedbytherelevanthealthcareprovider(e.g.anacuteNHSTrustorHealthBoard)whoisnotconnectedwiththeconductofthetrial.

Maybeapproachedifnopersonsuitabletoactasapersonallegalrepresentativeisavailable.

Table2.InformedconsentforanincapacitatedadultEngland,WalesandNorthernIreland Scotland1.PersonallegalrepresentativeApersonnotconnectedwiththeconductofthetrialwhois:

a. suitabletoactasthelegalrepresentativebyvirtueoftheirrelationshipwiththeadult,

andb. availableandwillingtodoso.

1.Personallegalrepresentativea. Anyguardianorwelfareattorneywhohaspower(in

law)toconsenttotheadult’sparticipationinresearch.

b. (b)Ifthereisnosuchperson,theadult’snearestrelativeasdefinedinsection87(1)oftheAdultswithIncapacity(Scotland)Act2000.

2.ProfessionallegalrepresentativeApersonnotconnectedwiththeconductofthetrialwhois:(a)thedoctorprimarilyresponsiblefortheadult’smedicalcare,or(b)apersonnominatedbytherelevanthealthcareprovider(e.g.anacuteNHSTrust)Aprofessionallegalrepresentativemaybeapproachedifnosuitablepersonallegalrepresentativeisavailable.

2.ProfessionallegalrepresentativeApersonnotconnectedwiththeconductofthetrialwhois:(a)thedoctorprimarilyresponsiblefortheadult’smedicalcare,or(b)apersonnominatedbytherelevanthealthcareprovider.Aprofessionallegalrepresentativemaybeapproachedifitisnotreasonablypracticabletocontacteither1Aor1Bbeforethedecisiontoentertheadultintothetrialismade.

Appendix4:Roles&ResponsibilitiesofResearchersandOrganisations

Reviewofresearch

• Anindependentexpertreviewofprotocolsisrequired.• Aseparateethicalreviewofthestudyisrequired.• Alldatamustbeavailabletoinspectionandauditingbodiesfrombothinternalandexternal

organisations.• Theprotocolmustnotchangewithoutformalagreementfromthosewhogaveappropriate

permissionforthestudy.• Funderofresearch• Ensuresqualityandvalueformoney,basedonresearchcostsandanycareortreatmentcosts

andmakesarrangementsforindependentexpertreview.• Ensuresfundingisconditionalonidentifyingasponsor(usuallyauniversityorNHSTrust).• Providesassistancetoanyenquiry,auditorinvestigationofthefundedwork.

Sponsor

Allclinicaltrialsandstudies:• Responsibleforensuringexpertscientificandethicsreviewsarecarriedout.• PutsinplacearrangementstoadheretoGCP(ifnootherpersonisspecified)andensures

arrangementsareinplacetobealertedtosignificantdevelopments.• Takesappropriateurgentsafetymeasures(withinvestigator).• Ensuresarrangementsareinplaceforcompensation(indemnity/insurancearrangements).• Keepsrecordsofalladverseeventsreportedbyinvestigators.• EnsurestheResearchEthicsCommitteeisnotifiedwhenthetrialhasended.

ClinicalTrialsinvolvinginvestigationalmedicinalproducts(CTIMP):

• EnsurestheEudraCT(EuropeanClinicalTrialsDatabase)Numberisobtained.• CompetentAuthorityAuthorisationisobtained(ChiefInvestigator).• Pharmacovigilancereportingandtimeframesareadheredto.• EudraCTandtheCompetentAuthorityarenotifiedwhentrialhasended.

ChiefInvestigator

• Isresponsibleforthedesign,managementandreportingofthestudyforallsites.• Isresponsibleforensuringthateachinvestigatorisawareoftheirlegaldutiesandobligations.• Isresponsibleforensuringtheprotocolisapprovedbyrelevantbodies,anypre-conditionsare

actedupon,andthatresearchfollowstheagreedprotocolexceptinthecaseofurgentsafetymeasures.

• Undertakesdutiesdelegatedbythesponsor(usuallyworkinginconjunctionwithaclinicalresearchorganisationCROifitisapharmaceuticallyfundedtrial).

• Publishestheclinicalstudyresultsassoonaspossiblefollowingstudycompletion.Inamulti-centrestudy,thechiefinvestigatormustensurethatthedatafromonecentreisnotpublishedbeforethepublicationofthewholestudywithouthis/herconsent,andmustobtainSponsorapprovalpriortopublication.

PrincipalInvestigator

ItistheresponsibilityofthePItoconductthestudyaccordingtotheprotocolandtoensurethathe/shehasthenecessarypatientpopulationavailabletoconductthestudywithintheperioddefinedinthestudyprotocol.Theinvestigatoralsoholdsadditionalresponsibilities:

• ToensurethatthestudyisperformedinaccordancewiththeInternationalGoodClinicalPracticestandards(ICH-GCP)andconformswiththeprinciplesoftheDeclarationofHelsinki(revisedversion1996),alllocallawsandregulationsconcerningclinicalstudies.

• Tosubmittheprotocol,patientinformationsheetandconsentformforlocalResearchManagement&Governanceapproval(R&Dapproval).

• Toensurethatallstaffinvolvedinthestudyhaveafullunderstandingoftheprotocolanditsrequirements,andthattheirrolesaredocumentedonastudydelegationlog.

• Toconfirmsubjecteligibilityaccordingtotheinclusion/exclusioncriteriastatedintheprotocol.• Toobtainandrecordsubjectconsent.• Towithdrawasubjectfromtheclinicaltrialforanyreasonshouldthisbethoughttobeintheir

bestinterests.• Toperformprotocoldirectedmedicalcareincludingassessment,examinationandprescriptionof

studyandsupportmedication.• Toensuresubjectanonymityismaintained.• Toensurethecompletenessandaccuracyofcasereportforms.• Toagreetoallowthemonitor/auditor/inspectortohaveaccesstoanyorallofthestudy

materialsneededforsourcedataverificationandproperreviewofstudyprogress.• Toreportallsafetyevents:SAEs,SARs,SUSARsasoutlinedintheprotocol,includingprompt

reportingtoSponsortoensurefurthercommunicationwithMHRA/RECifapplicablewithinthestatutorytimelines.

• ToretainallessentialdocumentsasperNHSandTrustguidelines(usuallyaminimumoffiveyearsfollowingtheendofastudy,atleasttwoyearsaftertheapprovalofamarketingapplication,foranewdrug,orlongerifrequiredbytheregulatorrequirements).

• Tocomplywiththestudysponsorandregulatoryauthorityrequirementsregardingtheauditingofthestudy.

Co-investigator(Medical)

Theco-investigatorisresponsibleformedicalcareofpatientsparticipatinginresearchstudies,workingunderthesupervisionoftheprincipleinvestigator.Theco-investigatorisusuallydelegatedthefollowingresponsibilities:

• ToensurethatthestudyisperformedinaccordancewithICH-GCPandconformswiththeprinciplesoftheDeclarationofHelsinki(revisedversion1996),alllocallawsandregulationsconcerningclinicalstudies.

• Toconfirmsubjecteligibilityaccordingtotheinclusion/exclusioncriteriastatedintheprotocol.• Toobtainandrecordpatientconsent.• Towithdrawasubjectfromtheclinicaltrialforanyreasonshouldthisbethoughttobeintheir

bestinterest.• Toperformprotocoldirectedmedicalcareincludingassessment,examinationandprescriptionof

studyandsupportmedication.• Toensuresubjectanonymityismaintained.• Toensurethecompletenessandaccuracyofcasereportforms.

• Toagreetoallowthemonitor/auditor/inspectortohaveaccesstoanyorallofthestudymaterialsneededforsourcedataverificationandreviewofstudyprogress.

• ToretainallessentialdocumentsasperNHSandTrustguidelines(usuallyaminimumoffiveyearsfollowingtheendofastudy,atleasttwoyearsaftertheapprovalofamarketingapplication,foranewdrug,orlongerifrequiredbytheregulatorrequirements).

• Tocomplywiththestudysponsorandregulatoryauthorityrequirementsregardingtheauditingofthestudy.

TrialCoordinator/Manager

• Tohavealeadingroleinplanning,co-ordinatingandcompletingclinicaltrials,bringingprojectmanagementandadministrativeexpertisetothetrialteam.

• Provideadministrativesupportfortheallocatedclinicaltrials,takingresponsibilityforthepreparationandsubmissionofrelevantapprovalsandregistrationandorganisationofTSC,DMECandothermeetings.Thismayinvolvesupervisionofclericalandsupportstaff.

• EnsurethatclinicaltrialsadheretotheStandardOperatingProceduresdevelopedbytheClinicalTrialsUnitandTrustandUniversitypoliciesandprocedures.

• Design,produceandregularlyupdatetrialmaterials,includingclinicalresearchformsanddatabases.

• Assistwithtrialsetupandactivationandestablishproceduresthatensurecompliancewiththeprotocol.Thismayinvolvetraveltositesandprovidingtraining.

• Takeoverallresponsibilityfordatamanagementandqualityassuranceaccordingtoregulatoryguidelinesandrequirementsofindividualtrials(ICHGCPandDataProtectionAct1998).Thismayinvolvesupervisionofdataentryclerks.

• Traveltocentresinvolvedintrialsandundertaketrialrelateddutiesasrequired.• Establishgoodworkingrelationshipswithlocal,nationalandinternationalclinicalnetworksas

appropriate.• Identifywhenprotocolamendmentsbecomenecessaryandtakeactionasappropriate.• Maintainregularcontactwiththechiefinvestigatorandactasthemaincommunicationsource

betweenfunding,regulatoryagencies,clinicalteamsandinvestigators.• Ensurethattrialsrecruitatanacceptablelevelateachcentre.Suggestandimplementstrategies

forimprovingrecruitment.• Maintainup-to-dateelectronicandpaperfilesforallparticipatingcentres/investigators,including

comprehensiveethicsandresearchgovernancedocumentation.• Produceprogressreportsontrialsasnecessary,underthedirectionofChiefInvestigator,Clinical

TrialsUnitManager,TSCorDMEC.

ResearchNurse/AHP/Midwife/ClinicalTrialsOfficer/Practitioner

Theresearchnurse/AHP/Midwife/CTOisdelegatedresponsibilitiesbythePI,thesemayinclude:

• Preparingandsubmittinglocalregulatoryapprovalapplications.• Ensuringthattheyhaveattendedaninitiationmeetingandreceivedanyappropriatetraining

priortothetrialcommencement.• Co-ordinatingtheclinicaltrialintermsofpatientscreening,recruitment,entryintothetrialvia

randomisationifapplicableandsubsequentpatientvisits.• Checkingpatienteligibilityaccordingtotheinclusion/exclusioncriteriastatedintheprotocolin

collaborationwithmedicalstaff.

• Collaboratingwithclinicianstoassesspatientsandmakingtreatmentdecisionsaccordingprotocol.

• Deliveryofinvestigationalagents/treatmentsandprotocoldirectedcare.• Handling,spinning,labelling,storageandshippingofbloodandurinepharmacokineticsamples.• Ensuringthatsourcedocumentationisatruereflectionofdecisionsandactionstakenforeach

individualpatient.• Completionofcasereportformsandensuringrelevantfollowupdataiscollected(egQoLdata).• Monitoringandreportingallsafetyevents:SAEs,SARs,SUSARsasoutlinedintheprotocol,

includingpromptreportingtoSponsortoensurefurthercommunicationwithMHRA/RECifapplicablewithinthestatutorytimelines.

• Liaisingwiththestudysponsorregardingtheconductofthetrial.• Educatingpatients/subjectsanddisseminationoftrialrelatedinformationtostaff.

DataManagers/ResearchAssistants

NonClinicalresearchsupportstaffworkcloselywiththeresearchnursesandothermembersoftheclinicalteamtoensureaccurateandappropriatedatacollection.Theirdelegatedresponsibilitiesmayinclude:

• Ensuringthattheyhaveattendedasiteinitiationmeetingandreceivedanyappropriatetrainingnecessaryinordertoconductthetrialsafelyandefficiently.

• Enteringsubjectsintoclinicaltrials,utilisingappropriaterandomisationprocedureswhennecessary.

• Completingcasereportformsandotherresearchrecords.• Ensuringthatalldataisavailableformonitoringvisits.• AssistingwithorcompletingsubmissionstoEthics/ResearchandDevelopment.• Archivingallclinicaltrialrelateddocumentsaccordingtoregulatoryrequirements.• Shippingbloodandurinepharmacokineticsamples.• Enteringdataandupdatingfields/informationwithindatabases.

ClinicalTrialsPharmacist

Asthenumberandvarietyoftrialscontinuestoincreaseitisvitalthatthereisagoodcommunicationbetweenthesponsor,theresearchteamandthetrialspharmacist.Thiswillensureissuesareraisedandresolvedatanearlystage,allowingthetrialtorunsmoothlyandeffectively.Earlyinputfrompharmacyintheplanningofaclinicaltrialenablesearlyrecognitionofpotentialpharmaceuticalissues;pharmacyshouldbegivenacopyoftheprotocolattheearliestopportunity.

TheClinicalTrialsPharmacistwillreview:

• Thedesignofprescriptionssothecorrecttrialsuppliesareensured.• Howtheblindingoftrialmedicationistobeachievedandmaintained.• Therequirementfordocumentationandrecordkeeping.• Labellingrequirements.• Drugreceipt,delivery,reorderingandstockchecks.• Themechanismforcontinuationofsupplies,ifappropriate,oncethetrialperiodhasfinished.• Storageconditionsforthetrialmedication.• Sizeofpackaging,whichhasimplicationsforstoragespace.• Forparenterallyadministeredproductstheremaybearequirementforasepticpreparation.

Organisationsprovidingcare

• Mustensurethesponsorhasassumedresponsibility,researchhasbeenreviewedbyappropriatebodies,andthatanauthorisedpersonhasgivenwrittenpermissiononbehalfofthecareorganisationfortheresearchtobegin.

• MustarrangeforresearchersnotemployedbyanyNHSorganisationtoholdanNHShonorarycontract.

• Mustensureadverseincidentsarereported.

Appendix5:JointResearchOfficeHandbookTheOxfordJointResearchOfficeprovidesanintegratedspecialistsupportservicetoworld-leadingmedicalresearchteamsattheUniversityofOxfordandOxfordUniversityHospitalsNHSFoundationTrust.

HeadsoftheOxfordJointResearchOfficeDrRichardLiwickiDrChrisBrayDeputyDirectorHeadofResearch&DevelopmentResearchServicesOperationsUniversityofOxfordOxfordUniversityHospitalsNHSrichard.liwicki@admin.ox.ac.ukFoundationTrustchristopher.bray@ouh.nhs.ukTheOxfordJointResearchOffice(JRO)isanintegratedspecialistsupportserviceforworld-leadingmedicalresearchattheUniversityofOxford(OU)andOxfordUniversityHospitalsNHSFoundationTrust(OUH).CombiningexpertteamsofUniversityofOxfordandNHSstaff,itprovidescomprehensivesupportthroughouttheresearchprocess,frompre-setupthroughtocontractandcommercialisationexpertiseandcommunicationsadvice.Specialistsinresearchgovernance,ethicalapproval,finance,grants,contracts,businessdevelopment,intellectualpropertyandcommunications,ensureprojectsandclinicaltrialsaresetupeffectivelyandefficiently,adheringtolegal,NHSanduniversityrequirements.Theoffice,currentlybasedattheChurchillHospitalsiteinOxford,supportsmorethan1800studiesandclinicaltrialsandaresearchinvestmentofmorethan£200m.World-classmedicalandhealthcare-relatedresearchatOxfordUniversityHospitalsNHSFoundationTrustandtheUniversityofOxfordcombinesclinicalandacademicexpertise,state-of-the-artfacilitiesandintegratedsupportservicestoacceleratediscoveryintopatientbenefit

BusinessDevelopment(OU/OUH)TheprincipalroleoftheBusinessDevelopmentteamistopromotejointworkingbetweenexternalcompaniesandtheUniversity/OUHpartnership.Wefacilitatecollaborationsviaavarietyofmodels,fromclinicaltrialstofundamentalresearchandwitharangeofpartners,frommulti-nationalpharmaceuticalcompaniestosmallerbiotechandmedicaldeviceindustries.Aswellasworkingtoidentifyandpromotenewopportunitiesweareabletoofferongoingalliancemanagementinparticulartosupportourlargerstrategicalliances.WeworkcloselywiththeotherJROteamsinordertobeabletoofferindustrialpartnersasinglepointofcontacttoidentify,executeandmanagecollaborativepartnerships.TeamContactDrMaxineAllenHeadofBusinessDevelopmentandPartneringmaxine.allen@medsci.ox.ac.uk01865572217https://www.medsci.ox.ac.uk/support-services/teams/innovation-industry/business-development/introduction-to-business-development

ContractsandGrantsTeam(OU)ResearchServicesMedicalSciencesDivisionalteamprovidescomprehensivesupporttoresearchersintheUniversity’sclinicaldepartments.Ourservicesinclude(a)assistancewiththesubmissionofresearchgrantsbyprovidinginformationandadviceoncostingandpricing,reviewingandapprovingcompleteapplicationsandfacilitatingtheirsubmission(b)negotiationofresearch-relatedcontractswithotherUniversities,governmentalagenciesandindustrytoensuretermsareconsistentwithUniversitypolicesandacademicmissionand(c)undertakingthefirststepsintheestablishmentofresearchexpenditurebudgets.ResearchServicesMedicalScienceshasacloseworkingrelationshipwithotherdepartmentsintheJROtoensureresponsibleconductofresearchandcompliancewithregulatoryandsponsorspecificrequirements.WearepartofalargerResearchServicesteamwhichservesthewholeoftheUniversityandisbasedinOxfordcitycentre.

TeamContactGillRoweHeadofResearchServices,MedicalSciencesgill.rowe@admin.ox.ac.uk01865572200https://www.admin.ox.ac.uk/researchsupport/

ClinicalTrialsResearchGovernance(CTRG)(OU)CTRGtakesontheroleofSponsoronbehalfoftheUniversitywhererelevanttoclinicalresearchstudies.Thisincludesensuringthatthestudyisfunded,reviewedandmanagedappropriatelyandthattheyarecompliantwiththerelevantlegislation,bothpriortoregulatoryandethicssubmissionandthroughoutitsconduct.Allstudiesaresubjecttopre-submissionchecksandprogressismonitoredaccordingtoarisk-basedapproach.ClinicalTrialsofInvestigationalMedicinalProducts(CTIMP)anddevicetrialshaveadditionalregulatoryrequirementsandneedmoreintensiveoversight,throughmonitoringofdata.CTRGalsoprovidetrainingcoursesinGoodClinicalPracticeandotherrelevantareasforresearchteamsworkingwithintheUniversityandOUH.TeamContactKarlShepherdOfficeAdministratorkarl.shepherd@admin.ox.ac.uk01865572221http://www.admin.ox.ac.uk/researchsupport/ctrg/

IPandResearchContracts(OUH)TheOUH’sIPandResearchContractsTeamprovidesdedicatedsupporttodraft,review,negotiateandfinaliseresearchandintellectualpropertyrelatedcontractsonbehalfofOUHandinaccordancewithOUHpolicies.Italsoprovidesassistancewiththesubmissionofresearchgrants.TheteamworksinconjunctionwithOUHInvestigators,Researchteams,theR&DGovernanceteam,R&DFinanceTeam,BusinessDevelopmentandLegalServices.TheteamalsoworkscloselywiththeUniversityofOxford’sMedicalSciencesContractsandGrantsteam,ResearchServices’IPRightsteamandOxfordUniversityInnovationLtd.TheteamalsoassistsOxfordHealthNHSFoundationTrustandtheOxfordAHSN.TeamContactCharlesALescottHeadofIPandResearchContractscharles.lescott@ouh.nhs.uk01865572202http://orh.oxnet.nhs.uk/IPResearchContracts/

NIHROxfordBiomedicalResearchCentre(OUH)TheNationalInstituteforHealthResearch(NIHR)OxfordBiomedicalResearchCentre(BRC)isapartnershipbetweentheUniversityofOxfordandOxfordUniversityHospitals.ItbringstogethertheclinicalexcellenceofOUHandtheacademicexpertiseoftheUniversityofOxfordtosupportpatient-centredresearch.BiomedicalResearchCentresarepartoftheGovernment’sinitiativetoimprovethetranslationofbasicscientificdevelopmentsintoclinicalbenefits.ItwasoneoffiveBRC’sfundedbytheNationalInstituteforHealthResearch(NIHR)in2007throughacompetitivelyawardedgrantof£57moverfiveyears.InApril2012,inrecognitionofitsoutstandingcontributiontohealthcareresearchitwasawarded£95.5m.InSeptember2016itwasawarded£113.7mfrom2017to2022tosupporttranslationalresearchacrosstwentyResearchThemes:https://oxfordbrc.nihr.ac.uk/.TheBRCManagementteamofficeformspartoftheJointResearchOffice.Inadditiontoprojectandresearchstafffunding,theBRCprovidesadministrativesupportfortheJRO,itsstaffanditsresearchportfolio.Thisincludes:

• Researchco-ordinationandfunding• Businessdevelopment• Legal,IPandcontractservices

• Systemsandinformaticssupport• Patientandpublicinvolvementadvice• Media,eventsandcommunication• NIHRresearchperformancemetrics• TrainingandEducation

TeamContactDrLornaHendersonClinicalResearchManagerLorna.henderson@ouh.nhs.uk01865572551http://oxfordbrc.nihr.ac.uk/

R&DFinance(OUH)TheR&DFinanceteamprovidesmanagementaccountingandbusinesssupporttothoseresearchersundertakingorapplyingtoundertakeresearchactivitywithintheOUH.Theteammanagescirca£53mofR&DFundingannuallyfortheTrust.TheFinanceteammanageandfacilitatefinancialprocessestoensurethattheNHSresourcesusedinresearcharefullyidentified,fundedappropriatelyandalsoensurethatcostsarerecoveredfromthefundingbodies.Inundertakingtherole,theteamengagewithalargenumberofstakeholders.TheteamsupportandprovidefinancialinformationtosupportR&Ddevelopments.Thereare3Teams:TheCostingteamareresponsiblefortheaccurateandtimelycostingofallresearchgrantsandstudies,ensuringthatthecoststotheNHSareidentifiedandfunded.TheStudyFinanceteamprovidescomprehensivesupporttoresearcherstomanagefundingflowsrelatingtoallresearchprojects,inlinewithcontractagreements.TheManagementAccountsteamprovideon-goingfinancialsupportinthemanagementoffundingstreamsfromtheNIHR.TheteamworkswithresearchteamstoensurethemoniesgrantedtosupportResearchinfrastructurearemanagedeffectively.TheteamsalsoworkcloselywiththeOUHTrustClinicaldeliverystaffandengagewiththemconcerningresearchrelatedspend.TeamContactstudy.finance@nhs.net01865572244http://www.ouh.nhs.uk/researchers/

R&DGovernance(OUH)TheResearchGovernanceteam’sroleistoensurethatresearchwhichisusingOUHNHSresourcesincludingNHSpatientsiscompliantwiththerelevantregulations(e.g.DataProtectionAct);ClinicalResearchPrinciples(e.g.GoodClinicalPractice(GCP)andDHResearchGovernanceFrameworkforHealthandSocialCare);hasrelevantapprovalsinplace(e.g.ResearchEthicsCommitteeApproval,MedicinesandHealthcareproductsRegulatoryAuthorityandHealthResearchAuthority);andisofahighscientificstandard.TheResearchGovernanceTeamprovidessupportthroughouttheresearchjourneyfromactingasSponsoronbehalfofOUHforcertainstudies;providingpharmacovigilancefunctionforsponsoredandhostedstudies;providingconfirmationofcapabilityandcapacity/localTMAapprovalandprovidingGCPandothertraining.On-goingoversightismaintainedthroughcollectionofrecruitmentfigures,progressreportsandsafetydata,andthroughmonitoringandauditactivities.TeamContactouhtma@ouh.nhs.ukouh.sponsorship@ouh.nhs.ukhttp://www.ouh.nhs.uk/researchers/

RiskandInsurance(Research)(OU)EmbeddedwithinResearchServices,withadotted-linereportintotheInsuranceTeaminFinancesectionoftheUniversity,GrahamisresponsibleforassessingprojectsfromariskandinsuranceanglearisingfromtheUniversity’sresearchactivities.Insomeareasthisishighlyregulated–clinicaltrialsinparticular-whileinothersthereisaneedtounderstandtheanticipatedrequirementsarisingfromnovelresearchendeavours:autonomousroadvehiclesbeingarecentandon-goingexample.GrahamliaiseswithotherdepartmentsintheJRO,particularlysocolleaguesinResearchServices[MedicalSciences],andClinicalTrialsandResearchGovernance,concerningtheinsuranceandrelatedneedsofcontractsandotherresearch-centredagreements.Increasingly,theserequireanunderstandingoftheevolvinglegal,andfinancial-servicesregulationsofresearchconductedbeyondtheUK,andanappreciationofmajorrisk-transfermechanismswhicharedistinctfromcommercialpoliciesofinsurance,particularlythosecomprisingthesuiteofschemesadministeredbytheNHSLitigationAuthority.TeamContactGrahamWaiteRiskandInsurance(Research)Managergraham.waite@admin.ox.ac.uk01865572209https://www.admin.ox.ac.uk/researchsupport/

Appendix6:AccesstoParticipantsMedicalRecords

IfaresearcherispartofaResearchParticipantsClinicalCareTeamandwouldnormallyandappropriatelyhaveaccesstothoserecords,thennoadditionalauthorisationisrequired.

Ifhowever,asamemberofaresearchteamyouwouldnotnormallyhavesuchaccessyouneedtogetpermissiontoaccessthoserecords,anddependingonyouremployerfollowoneoftworoutes:

Either:

1. Employedbyanotherorganisation–OxfordUniversity/OtherUniversity/OtherNHSTrust–contactR&DOUHTMA@nhs.nettodiscusswhetheryourequireanHonoraryResearchContractoraLetterofAccess.

2. InadditioncompleteaResearchAccesstoNotesRegistrationForm(RANRform)andsendtoR&Dforverification,ifthisisrequired,foreachproject.

3. Onceapproved–taketheRANRwithyoueverytimeyouwishtorequestresearchparticipant’smedicalrecords.

1. EmployedbytheOUHTrust–completeaResearchAccesstoNotesRegistrationFormandsendtoR&Dforverification.

2. Onceapproved–takewithyoueverytimeyouwishtorequestresearchparticipant’smedicalrecords.

TheResearchAccesstoNotesRegistration(RANR)formcanbedownloadedfromtheR&DWebsiteorwillbesenttoyouonrequestbytheR&DteamatOUHTMA@nhs.net.

TheMedicalRecordsLibrarystaffwillrequesttoseetheRANRformbeforeretrievingnotesforresearchersorallowstafftoretrievenotesthemselvesoneachoccasiontheresearchattendstheMedicalRecordsLibrary.

WherenewstaffjointheresearchteamtheRANRformshouldbeupdatedwiththeirnamesthroughcontactwithR&D.[Ifstaffareconductingastudyandtheydonothavearesearchnumberasignedletterfromtheheadofthestudyandalistofpatientsshouldbegiventothelibrarystaff.]

AllstaffusingthelibraryarerequiredtoattendLibrary&HIMTrackertraining.Thisistoensurethatstaffareableto‘track’medicalnotesandhowtolookfornoteswithinthelibraries.ResearcherscancontacttheMedicalRecordsTrainingTeamviaemailmedrecstraining@ouh.nhs.uk

Appendix7:KeydocumentsandregulationsTheDeclarationofHelsinki1964TheDeclarationofHelsinkiistheoriginalkeydocumentthatprotectstherightsofindividualparticipantsinthefieldofbio-medicalresearchthroughouttheworld.Itwasproducedin1964,andhasbeenrevisedon6separateoccasions;themostrecentofthesewasin2008.Acopyofthe2008revisedversionoftheDeclarationofHelsinkiisattachedasanappendixtothismanual.Theunderlyingprincipleshavenotchanged,butrevisionshavebeenmadetoreflectchangingperspectives.Forexample,thewordingofthephysician’sdutyto“obtain”consenthasbeenchangedto“seek”consentwhichreflectstheincreasingcomplexityofthistask.

Otherrecentmodificationsincludeclarificationon:theethicaluseofplacebos,issuessurroundingvulnerablegroups,andarequirementthatresearchparticipantsshouldbeinformedabouttheoutcomesoftheresearchthattheyhaveparticipatedin.Theyshouldalsohavepoststudyaccesstonewinterventionswhichhaveprovedtobebeneficialandprotocolsmustincludearrangementsforhowthiswillbeachieved.Similarly,researchersareundergreaterpressuretopublishanydisbenefitsastheyaccrueandprotocolsshouldclearlystateinadvanceanyexpectedunwantedsideeffects,andwhatarrangementstherearetocompensateparticipantsforanyharmthatmayoccurasaresultoftheirresearch

Thedeclarationwaspreviouslynotlegallybinding,buttheprincipleshavenowbeenincorporatedintotheEUDirective(2001)andintoUKlaw(2004)asdescribedbelow.

TheEUDirectiveof2001TheEUDirectiveaimstoharmoniseandstreamlineclinicaltrialsproceduresthroughoutthememberstates,andrelatestoalltrials,exceptnon-interventionstudies.Itcoversalltrialsinvolvingmedicinalproducts,andencompassesallpersonnelinvolvedwiththeclinicaltrialprocedures.TheEUDirectiveisapplicabletoallcentresperforminginterventionalresearchtrials.Theseincludeacademicinstitutionsandthosetrialunitssupportedbycharities.

MedicinesforHumanUseActClinicalTrialsRegulations2004ThisActensuredthattheICHGCPguidelineswereenshrinedintoUKLawandcompelsallpartiespracticingresearchtoadheretothem.

MentalCapacityActTheMentalCapacityAct2005(MCA)providesastatutoryframeworkforpeoplewhomaynotbeabletomaketheirowndecisions,forexamplebecauseoflearningdifficulties,braininjuryormentalhealthproblems.Itsetsoutwhocantakedecisions,inwhichsituations,andhowtheyshouldgoaboutthis.TheActappliestoEnglandandWalesonly.

Forfurtherinformationsee:http://www.legislation.gov.uk/ukpga/2005/9/contents

Apatientfacingwebsitesimplifiesthelegislationhttp://www.nhs.uk/Conditions/social-care-and-support-guide/Pages/mental-capacity.aspx

UKPolicyFrameworkforHealthandSocialCareResearch2017PreviouslytheResearchGovernanceFramework2005,updated2008

https://www.hra.nhs.uk/planning-and-improving-research/policies-standards-legislation/uk-policy-framework-health-social-care-research/

Thepolicyframeworkappliestohealthandsocialcareresearchinvolvingpatients,serviceusersortheirrelativesorcarers.Thisincludesresearchinvolvingthemindirectly,forexampleusinginformationthattheNHSorsocialcareserviceshavecollectedaboutthem.

TheHealthResearchAuthorityandthehealthdepartmentsinNorthernIreland,ScotlandandWaleshavedevelopedthepolicyframeworkfollowingpublicconsultation.ItreplacestheseparateResearchGovernanceFrameworksineachUKcountrywithasingle,modernsetofprinciplesforthewholeUK.

ThispolicyframeworksetsoutprinciplesofgoodpracticeinthemanagementandconductofhealthandsocialcareresearchintheUK.

Theseprinciplesprotectandpromotetheinterestsofpatients,serviceusersandthepublicinhealthandsocialcareresearch,bydescribingethicalconductandproportionate,assurance-basedmanagementofhealthandsocialcareresearch,soastosupportandfacilitatehigh-qualityresearchintheUKthathastheconfidenceofpatients,serviceusersandthepublic.

Itisfororganisationsandindividualsthathaveresponsibilitiesforhealthandsocialcareresearch.Thisincludesfunders,sponsors,researchersandtheiremployers,researchsitesandcareproviders.

DataProtectionAct1998TheDataProtectionAct(DPA)wasintroducedinresponsetotheEuropeanCommunityDataProtectionDirective1995.Itappliestopersonalinformation,whichmustbeprocessedinaccordancewitheightmainprinciples.

Datashouldbe:

• Fairlyandlawfullyprocessed• Processedforlimitedpurposes• Sufficientandrelevant• Accurate• Notstoredforlongerthanisnecessary• Processedinlinewithdatasubjects‟rights• Secure• Transferredonlytocountrieswithadequatesecurity• Thenatureofresearchmeansthatthereisalargeamountofpaperandelectronicdataheld

aboutresearchsubjects.Researchstaffhavearesponsibilitytotheirresearchsubjectsandtheiremployerregardingdataprotection.

• Allsubjectdatashouldbestoredinasecureroom.• Allsubjectdatamustbelockedawayifunattended.• Nooneshouldaccesssubjectdataunlessauthorisedtodosobyresearchpersonneland/ordata

protectionofficer.• Subjectconfidentialityshouldbemaintainedbyuseofinitials/numbersonresearchmaterial

whereappropriate.

• Electronicdatamustbepasswordprotected.InaccordancewiththeComputerSecurityPolicy.• Personaldatathathasthepotentialtoidentifyresearchsubjectsshouldbekeptinasecureplace.

Allstaffshouldbefamiliarwiththeirinstitutionsdataprotectionpolicies.Allmembersofstaffdealingwithdata,whichisregardedasbeingsensitive,mustsignadataprotectionstatementtosaythattheyhavereadandunderstandthisdocument.Thestatementalsorequiresstaffnottodiscussconfidentialdataunlessrequiredaspartoftheirjob.Anyconcernsrelatingtodataprotectionissuesmustbediscussedwithyourlinemanager.

Formoreinformationvisit:www.dataprotection.gov.uk

TheHumanTissueAct2004Thiswasintroducedtoregulatetheremoval,storageanduseofHumanOrgansandTissue.

TheAct:

• streamlinesandupdatescurrentlawonorgansandtissuesothatcurrentgapsandanomaliesareputrightandthesystemismadefitforthe21stcentury

• providessafeguardsandpenaltiestopreventarecurrenceofthedistresscausedbyretentionoftissueandorganswithoutproperconsent.TissueororganscannotbetakenorkeptwithoutconsentotherthanforaCoronertoestablishthecauseofdeath

• setsupanoverarchingauthoritywhichwillrationaliseexistingregulationandwillintroduceregulationofpostmortemsandtheretentionoftissueforpurposeslikeeducationandresearch

• providesfortheHumanTissueAuthoritytoissueCodesofpracticegivingpracticalguidanceontheconductofactivitieswithinitsremit

• willhelpimprovepublicconfidencesothatpeoplewillbemorewillingtoagreetovaluableusesoftissueandorganslikeresearchandtransplantation

• willimproveprofessionalconfidencesothatproperlyauthorisedsuppliesoftissueforresearch,educationandtransplantationcanbemaintainedorimproved.

FurtherinformationcanbefoundontheHumanTissueAuthoritywebsite.

https://www.hta.gov.uk/

IRMERRegulations:TheIonisingRadiation(MedicalExposure)(Amendment)Regulations(2000,2006)

Trialpatientsareoftenexposedtohigherlevelsofradiationthannontrialpatientsastheyundergomoretestsandimagingtomonitorprogressandresponsetotrialtreatments.ThisAct(amendedin2006)requiresstaffinvolvedinundertakingmedicalexposurestoestablishdiagnosticreferencelevels(DRLs)andtoundertakeappropriatereviewsiftheseareconsistentlyexceeded.DHhasissuedguidanceonnationalDRLswhichisavailablefromthelinkbelow:-https://www.gov.uk/government/publications/the-ionising-radiation-medical-exposure-regulations-2000

AdministrationofRadioactiveSubstancesAdvisoryCommitteeARSACTrialpatientsareoftenexposedtohigherlevelsofradiationexposurethanisnecessaryforroutinediagnosisandtreatment.ThisisallowedbutanARSACresearchcertificatemustfirstbeobtainedforeachresearchprojectwhichexposespatientstothesehigherlevels.ARSACassesseseachapplicationonitsownmeritsandwhileitisimportanttokeepdosesaslowasreasonablypracticable,theactivityadministered

(andtheresultingdose)shouldbethatnecessarytoprovidetheinformationrequired.AllARSACcertificatesaresite-specific,thereforeinthecaseofmulticentrestudies;eachstudysiterequiresitsowncertificate.

https://www.gov.uk/government/organisations/administration-of-radioactive-substances-advisory-committee

Appendix8:HealthResearchAuthorityhttps://www.hra.nhs.uk

HRAApprovalisthenewprocessfortheNHSinEnglandthatbringstogethertheassessmentofgovernanceandlegalcompliance,undertakenbydedicatedHRAstaff,withtheindependentRECopinionprovidedthroughtheUKHealthDepartments’ResearchEthicsService

Avideoisavailablewithinformation‘ApplyingforHRAApproval’https://www.crn.nihr.ac.uk/can-help/life-sciences-industry/brighttalk-channel/?commid=197623

EthicsandNHSApprovalsAllstudiescarriedoutinNHSorganisationsrequirepriorapprovalby:

• anethicscommittee• HealthResearchAuthority(replacestheneedforlocalchecksoflegalcomplianceandrelated

mattersbyeachparticipatingorganisationinEngland)• localtrustR&D(assess,arrangeandconfirmtheircapacityandcapabilitytodeliverthestudy)

EthicscommitteeapprovalAnyhealth-relatedresearchprojectwhichinvolveshumans,theirtissueand/ordatamustbereviewedbyaResearchEthicsCommittee(REC)priortoitcommencing.Thisapplieswhethertheprojectistobeexternallyorinternallyfunded,and/orwhethertheprojectistobeconductedintheUKoroverseas.Theresearchermustsubmitaprotocolandsupportinginformationtothecommitteeforreview,inaccordancewiththeethicalprinciplesdevelopedbytheWorldMedicalAssociationinitsDeclarationofHelsinki(1964,latestrevision2008)Thisstates:

Thedesignandperformanceofeachresearchstudyinvolvinghumansubjectsmustbeclearlydescribedinaresearchprotocol.TheprotocolshouldcontainastatementoftheethicalprinciplesinvolvedandindicatehowtheprinciplesinthisDeclarationhavebeenaddressed.Theprotocolshouldcontaininformationregardingfunding,sponsors,institutionalaffiliations,andotherpotentialconflictsofinterest,incentivesforsubjectsandprovisionsfortreatingand/orcompensatingsubjectswhoareharmedasaconsequenceofparticipatingintheresearchstudy.Theprotocolshoulddescribearrangementsforpost-studyaccessbystudysubjectstointerventionsidentifiedasbeneficialinthestudyoraccesstootherappropriatecareorbenefits.(2008-seeappendix)

TheprimaryfunctionofaRECwhenconsideringaproposedstudy,istoprotecttherights,safety,dignityandwell-beingofallactualorpotentialparticipants.TheRECalsohastherighttomonitorongoingtrials.Theresearcherhastheobligationtoprovidemonitoringinformationtothecommittee,especiallyanyseriousadverseevents.

IntheUKitisagainstthelaw,undertheMedicinesforHumanUse(ClinicalTrials)Regulations2004,tostartrecruitingforaclinicaltrialofaninvestigationalmedicinalproduct(CTIMP)untilthereisafavourableopinionfromarecognisedREC(andauthorisationfromthelicensingauthority–theMedicinesandHealthcareProductsRegulatoryAgency,MHRA).

EthicsCommitteesNHSResearchEthicsCommittees(RECs)havebeenestablishedthroughouttheUKformanyyearswiththepurposeofsafeguardingtherights,dignityandwelfareofpeopleparticipatinginresearchintheNHS.PotentialresearchparticipantsatNHSorganizationintheUKwillcomeundertheprotectionofaREC.The

RECisentirelyindependentoftheresearcherandtheorganisationsfundingandhostingtheresearch.EthicscommitteesareguidedbytheDeclarationofHelsinki.

ThemembersofaRECarespeciallytrainedinresearchethicsandoftenhavethetypeofexperiencewhichwillbeusefulinscrutinizingtheethicalaspectsofaresearchproposal.Theseincludepatients,membersofthepublic,nurses,GPs,hospitaldoctors,statisticians,pharmacistsandacademics,aswellaspeoplewithspecificethicalexpertisegainedthroughalegal,philosophicalortheologicalbackground.Therearecurrently155NHSRECsintheUK(02/01/2008).

TheNationalResearchEthicsServiceTheNationalResearchEthicsService(NRES)waslaunchedon1April2007.NREScomprisestheformerCentralOfficeforResearchEthicsCommitteesandResearchEthicsCommittees(RECs)inEngland.TheaimofNRESistoprotecttherights,safety,dignityandwell-beingofresearchparticipants,whilstfacilitatingandpromotingethicalresearch.Itdoesthisby:

• ProvidingethicalguidanceandmanagementsupporttoResearchEthicsCommitteesinEngland• DeliveringaqualityassuranceframeworkfortheResearchEthicsService• WorkingwithcolleaguesintheUKtomaintainaUK-wideframework• Workingwithcolleaguesinthewiderregulatoryenvironmenttostreamlinetheprocesses

NRESisacorefunctionoftheHealthResearchAuthorityisacorefunctionoftheHRAandiscommittedtoenablingandsupportingethicalresearchintheNHS.Itprotectstherights,safety,dignityandwellbeingofresearchparticipants.WehaveadutytoprovideanefficientandrobustethicsreviewservicethatmaximisesUKcompetitivenessforhealthresearchandmaximisesthereturnfrominvestmentintheUK,whilstprotectingparticipantsandresearchers.Moreinformation:http://www.hra.nhs.uk/about-the-hra/our-committees/nres/

EthicsApplicationsthroughtheNationalResearchEthicsService(NRES)AllapplicationstoResearchEthicsCommitteesmustbemadethroughtheIntegratedResearchApplicationSystem(IRAS),whichcanbefoundon-lineathttps://www.myresearchproject.org.uk/

Thisisanewsystemforapplyingforalloftheapprovalsrequiredtorunaresearchproject,andisdesignedtoenabletheapplicanttoentertheinformationabouttheirprojectonceinsteadofduplicatinginformationinseparateapplicationforms.

ResearchersneedtoregisterontheIRASwebsiteinordertocreateanapplicationform.FullguidanceforapplyingtoResearchEthicsCommitteesisgivenonthemainHRAwebsite:http://www.hra.nhs.uk/research-community/applying-for-approvals/

LocalTrustApprovalEachhospitalTrustorstudysitewillhaveanamedpersonwhoisresponsibleforensuringthatapprovalshavebeenobtained.S/hewillalsoberesponsibleforraisinganyotherissueswhicharepertinenttothelocalsite.Whenallchecksandlocalissueshavebeensatisfactorilycompleted,anapprovalletterwillbeissued.Onlythencanastudycommenceatthatsite.

ContactResearchandDevelopment,basedintheJointResearchOffices,ChurchillHospital,forfurtherinformationhttp://www.ouh.nhs.uk/researchers/

Appendix9:PharmacovigilanceintrialsofInvestigationalMedicinalProductsandSafetyReportingPharmacovigilanceisdefinedaswatchfulnessinguardingagainstdangerfromdrugsorprovidingforsafetyofdrugs.Ajointmedicalresearchcouncilanddepartmentofhealthworkstreamonpharmacovigilanceaimstodevelopworkableoperatingproceduresforthepubliclyfundedresearchcommunityforreporting,monitoringandmanagingadversereactionsandeventsthatwillsatisfytherequirementsoftheMedicinesforHumanUse(ClinicalTrials)Regulations.Tocomplywiththisactorganisationstakingonpharmacovigilanceresponsibilitiesneedtomakearrangementstorecord,notify,assess,report,analyseandmanageadverseeventsinthosetrials.

TheregulationsdistinguishbetweenAdverseEvents(AEs),SeriousAdverseEvents(SAEs),SeriousAdverseReactions(SARs)andSuspectedUnexpectedSeriousAdverseReactions(SUSARs).Itistheresponsibilityoftheresearchteamtonotifythetrialsunit/studysponsorofSAEs,SARsandSUSARSwithinthetimespecifiedintheprotocol.Systemsmustbeinplacetoensurethatadverseeventsareassessedfor:

• Causality(isitareactiontoatrialmedicineornot?)• Expectedness(isthereactionarecognisedadverseeffectofthemedicationorisitunexpected?)

TheregulationsallowtheSponsor/ChiefInvestigatortospecifyintheprotocolSAEsthatdonotneedtobenotifiedimmediately,forexampleiftheeventisoneofthemainexpectedoutcomesinthetrial.SponsorshavetomakesurethatSUSARSarereportedpromptlytoboththeregulatoryauthoritiesandtherelevantEthicsCommittee.TheRegulationssetthefollowingtimelimits.

FatalorlifethreateningSUSARS:notlaterthan7daysafterthepersonresponsibleforpharmacovigilancereceivedinformationthatthecasefulfilledthecriteriaforafatalorlifethreateningSUSAR.

AllotherSUSARs:notlaterthan15daysafterthesponsorhadinformationthatthecasefulfilledthecriteriaforaSUSAR.

Attheclinicallevel,therewillbealocalSOPforthereportingofSAEswhichmustbeadheredto.Inordertomeetthetightreportingdeadlinesabove,theclinicalresearchteammustreportanySAEtothetrialsofficeassoonaspossibleandnotlaterthan24hoursafterfirstdiscoveringthattheeventhasoccurred.

AnannualsafetyreportmustbesentbythetrialsofficetotheregulatoryauthoritiesandrelevantEthicsCommittee.Thereportshouldincludeadverseevents(AE)explicitlydetailedintheprotocol;allreportedSeriousAdverseEvents,SeriousAdverseReactionsandSUSARs.

Formoreinformationvisit:EULegislation-Eudralex-EuropeanCommissionorhttp://www.ct-toolkit.ac.uk/

MedicinesandHealthcareproductsRegulatoryAgency(MHRA)

TheMHRAwassetupinApril2003fromamergeroftheMedicinesControlAgencyandtheMedicalDevicesAgency.TheMHRAisthegovernmentagencywhichisresponsibleforensuringthatmedicinesandmedicaldeviceswork,andareacceptablysafe.

TheMHRAisanexecutiveagencyoftheDepartmentofHealth.

TheMHRAaims:

• Toprotectpublichealththroughregulation,includingthedevelopmentofbenefitandriskprofilesformedicinesanddevices.

• Topromotepublichealthbyhelpingpeopletounderstandtherisksandbenefitsoftheproductstheyuse.

• Toimprovepublichealthbyfacilitatingthedevelopmentofproductsthatwillbenefitpeople.

Keyactivities:

• Toassessthesafety,qualityandefficacyofmedicines,includingtoauthorisetheirsaleorsupplyintheUKforhumanuse.

• Tooperaterigoroussurveillanceandinspectionsystemsfortheinvestigationofadversereactionstomedicines(theYellowCardScheme)andtoadverseincidentsinvolvingmedicaldevices,takinganynecessaryactiontosafeguardpublichealth.

• Tooperateaqualitysurveillancesystemtosampleandtestmedicinesandtoaddressqualitydefects,monitoringthesafetyandqualityofimportedunlicensedmedicinesandinvestigatinginternetsalesandpotentialcounterfeitingofmedicines.

• Toregulateclinicaltrialsofmedicinesandmedicaldevices.

• Tomonitorandensurecompliancewithstatutoryobligationsrelatingtomedicinesandmedicaldevicesthroughinspection,takingenforcementactionwherenecessary.

• Topromotegoodpracticeinthesafeuseofmedicinesandmedicaldevices.

• Toprovidethepublicandprofessionswithauthoritativeinformationtoenableinformeddialogueontreatmentchoices.

Formoreinformationvisit:http://www.mhra.gov.uk

Appendix10:CaseReportFormCompletionGuide

ACRFisarecordofallthedataandotherinformationoneachsubjectrequiredbytheresearchprotocol.TheICH-GCPguidelinesincludestrictguidancerelatingtoCRFcompletion,astheyaretheofficialdocumentationofthetrialfortheauthorities.TheCRFs,alongwithsourcedocumentationarecloselyexaminedintheeventofauditandinspection.

TheCRFshouldcollectnecessaryinformationabout:

•Theenrolledsubject.

•Administrationofthestudydrugorintervention.

•Studyspecificprocedures.

•Theoutcomeofanyassessments.

•Detailsofanyadverseevents,seriousadverseeventsandSUSARs.

OnlythosepersonnelidentifiedbytheprincipalinvestigatorshouldcompleteCRFs.Thesecaninclude:

•Co-investigators

•Clinicaltrialpractitioners

•Researchnurses/AHP

AnyonecompletingaCRFshouldhavecompletedthesignaturedelegationlogintheInvestigatorfile,andprovidedasignedanddatedcopyoftheirCV.

CRFsshouldbecompletedassoonaspossibleaftertheassociatedvisit/patientassessmenttoensurethattheinformationisuptodateandaccurate.Beforeanymonitoringorauditvisits,itisessentialtoensurethatCRFsareasuptodateaspossible.

ThereareguidelinestoCRFcompletionwitheachstudyprotocol.Somegeneralpointsaregivenhereforreference.

PaperCRF

•AlwaysuseablackballpointpentocompletepaperCRFs.

•IftheCRFisoncarbonlessduplicationpaper,ensurethatanappropriateseparatorisinserted.

•Neverleaveblankspaces.Ifasectioncannotbecompletedwrite,asappropriate,notknown,notcertain,testnotdone.

•Allentriesmustbelegible:

oCrossoutincorrectentrywithasingleline,sothattheoriginalentryisstilllegible

oEnterthecorrectdata

oInitialanddatacorrection

oIfitisnotobvious,thengiveanexplanationforalterations

•TheCRFforeachpatientMUSTbesignedoffbytheprincipleinvestigatortoindicatethattheybelievethattheyarecompleteandcorrect.

ElectronicCRF

•Adequateonlinetrainingwiththesystemtobeusedisrequiredandwillbefacilitatedbythestudysponsor.

•Apasswordwillbeissuedtoeachindividualauthorisedtoaccessthesystemtoenterdataandshouldbekeptsafeandneversharedwithothers.

•Datashouldbeenteredassoonaspossibleafterthesubjectsscheduledvisit.

•Correctionsandqueryresolutionisauditablethroughtheelectronicsystem.

•Provisionisrequiredatsitetofacilitatemonitoringvisits.Andaccesstotheelectronicsystem.

•Computersshouldnotbeleftunattendedwithpatientdataonscreeneventhoughanonymised.Adherencetotherelevantdataprotectionlegislationismandatory.

CRFcompletionisoneofthemostimportantrolesoftheclinicaltrialsco-ordinator,asitistheonlysourceofdatathatwillbereceivedbythesponsorcompany.Therefore,accurateandthoroughcompletionisessential.

Sourcedocumentation

Manyitemsofdatageneratedduringroutineandstudyrelatedcareepisodesconstitutesourcedocumentation.Forexample,bloodresults,radiologyreports,pharmacyprescriptions,lettersinmedicalnotes,handwrittennotesinthepatientsrecordallconstituteprimarysourcedata.

Thedevelopmentofstudyrelatedsourcedatasheetstocapturerelevantdataitemsatdesignatedstudyvisittime-pointsarehelpfulinensuringthatitemsarenotoverlookedormissedinerrorandcansignificantlyimprovedataqualityoverall.Suchsourcesheetsthenalsobecomeprimarysourcedataandshouldberetainedwiththesubject’smedicalnotesformonitoringanddataverification.Ifsourcedatasheetsarecreatedtheyneedtobeversioncontrolledandsignedanddataoncompletionofprimarydataentry.

Appendix11:IntroductiontoResearchMethodologyHealthresearchmethodologyisacomplexareaofstudyandonlyaverybriefoutlineofthemostrelevantinformationwillbediscussedinthissection.

Thereareanumberofdifferentresearchmethods,whichusedifferingrulesandareunderpinnedbydifferentphilosophies.Eachhavetheirstrengthsandweaknessesandwhenresearchneedstobecarriedout,thetypeorcombinationofmethodschosenwilldependonthetypeofresearchquestiontobeanswered,aswellastheskills,knowledgeandpreferencesoftheresearchers.

Epidemiology

Thisisthestudyoffactorsthatmightaffectthehealthandillnessofpopulations.Itisusedinpublichealthresearch,identifyingriskfactorsfordiseaseandcansometimesdemonstrateoptimaltreatmentapproachestomaintainpublichealth.

Observationalstudies

Theseincludeindividualcasestudies,casecontrolstudies,andcohortstudies(usingaparticulargroupofpeoplee.g.participantswithastrongfamilyhistoryofcancer).Thereisnoactiveinterventioninthesestudies.Investigatorsobservetheirparticipantsandmeasureoutcomes.Theyarelookingforcorrelations(associations)betweendifferentfactorse.g.variousriskfactorssuchaslifestyle,diet,environment,familyhistoryandgeneticpredisposition,andhealthstatusoroutcomesofdiseaseandtreatment.

ClinicalTrials

Thesearemedicalresearchstudiesinvolvingpatients.Carryingoutclinicaltrialsistheonlyreliablewaytofindoutifanewapproachtocancercareisbetterthanthestandardcancertreatmentsthatarecurrentlyavailable.Withouttrials,thereisariskthatpatientscouldbegiventreatments,whichhavenoadvantage,wasteresourcesandmightevenbeharmfultothem.Newtreatmentsforcancerareevaluatedinanumberofstagesorphases.

Itisnotonlynewtreatmentsthatareevaluatedintrials.Otherinterventionscanbestudied,suchaschangingthetiming,orthedurationofexistingtreatments,combiningexistingtreatments,orexaminingtheeffectsofstoppingastandardtreatmentcompletely,orintroducinganothertypeofinterventionsuchasgivingapsychologicalorsupportivetherapy.

Phasesofclinicaltrials

Clinicaltrialsareusuallyconductedinphases.Thetrialsateachphasehaveadifferentpurposeandhelpscientistsanswerdifferentquestions:

PhaseItrialsareinitialclinicaltestsofnewpotentialtreatments.Theyareusedtodeterminewhetherornotatreatmentissafeandtodefineamaximumtolerateddose.Theygenerallyareatthelaboratoryphaseanduseveryfewhumansubjects(typically3-6).Oftenthesearehealthyvolunteers,butinthecaseofcancertreatmentsthiswouldbeunethicalasthetreatmentsareoftentoxic.Thereforephase1trialstendtobeofferedtopatientswithadvancedcancerwhohaveexhaustedallothertreatmentoptions.Thesetrialscanbeexpectedtodetectcommonsideeffects.

PhaseIItrialsinvolvelargernumbersofpatients,startingwithabout15andcontinuingtoapproximately40.Theyaredesignedtostarttotesttheefficacyofthenewtreatment.Informationonsideeffectsandtolerabilitycontinuestobecollected,sothatsomelesscommonsideeffectsandcumulativeeffectsmightbecomevisibleinphaseII.

AllphaseIandnon-randomised(seebelow)phaseIItrialsfallundertheheadingoftranslationalresearch.Thisisatermusedtodefineexperimentalresearchofnewtreatmentsanddiagnosticproceduresforalldiseases,includingcancer.Itcoversallexperimentationtodevelopnewtreatments,ratherthancomparingthemagainstastandardtreatment.Manytrialsdonotproceedtothenextphase.

PhaseIIItrialsarelargenationalorinternationaltrialsinvolvinghundredsorthousandsofpatients.Theyarecomparativestudiesdesignedtocomparetheeffectsofnewdrugs,treatmentmethods,orotherinterventions(whichcouldmeannointervention)withthestandardtreatment.Patientsareusuallydividedatrandomintoeitherthetreatmentinterventiongroup,oracontrolgroup.Patientsinbothgroupswillbeassimilaraspossible.Furtherandmorereliableinformationcanbegatheredaboutefficacy:howwellthetreatmentworksandhowlongthebenefitslastonaverage.Lesscommonsideeffectsandpossiblyanylongertermproblemswillberevealedatthisstage.

Statisticiansestimatehowmanyresearchparticipantswillberequiredtoprove,withanacceptabledegreeofconfidence(usuallydescribedas95%confidenceinterval)thatanyresultsarenotduetochancealone.Generally,iftheexpectedimprovementsfromthetrialtreatmentarelarge,thedifferenceswillbemeasurableafterarelativelysmallernumberofpatientshavebeentreated.Ifonlyasmallimprovementisexpected,alargernumberwillneedtobetreatedbeforethemeasuredeffectcanbeclassedassignificant(meaningthechangeisnotduetochancealone).

PhaseIVtrialsarepost-marketingstudies,carriedoutafteratreatmenthasbeenshowntoworkandalicensehasbeengranted.Furtherinformationisgainedabouttheeffectsofwiderparticipation,longer-termrisksandbenefits,andmoreaboutpossibleraresideeffectssothatoptimalusecanbedecided.

Trialdesign

Clinicaltrialsaredesignedinmanydifferentwaysaccordingtotheresearchquestion.Manyofthetrialsthatyouwillbeinvolvedwitharecomparingnewtreatmentswiththetriedandtestedor“goldstandard”treatment.Themosteffectivewayofcomparingtreatmentsinthiswayisthroughrandomisedcontrolledtrials

RandomisedControlledTrials(RCTs)

Acrosstheworld,RCTsarenowseenasthemostreliablewaytotestnewtreatmentsandtocomparetwo(ormore)existingtreatments,toseewhichoneworksbest.

AnRCTisastudyinwhichpeopleareallocatedatrandomtoreceiveoneoftwoormoreclinicalinterventions.Oneoftheseinterventionsisthestandardofcomparisonorcontrol.Thecontrolmaybeastandardpractice,aplacebo,ornointerventionatall.RCTsseektomeasureandcomparetheoutcomesaftertheparticipantsreceivetheinterventions.RCTstypicallyfollowaprescribedseriesofstudyphases,whichmaylastuptotwentyyears,althoughthetimeframesassociatedwithdevelopment,areincreasing.

Ethically,equipoiseshouldexistforarandomisedtrialtobeundertaken:thatis,thereshouldbegenuineuncertaintyabouttheadditionalbenefitsandrisksofthenewinterventionoverthecurrentstandardintervention.

QuantitativeResearch

QuantitativeResearchmethodsarebasedonmeasuringandcountingobservedphenomenaandusemathematicalmodelsandstatistics,usuallywithlargenumbersofsubjects.RCTsareusuallyquantitativestudiesbecausetheoutcomesaremeasured.

Randomisationmethods

Randomisationisnotalwaysasimplecaseofrandomlyallocatingpatientstooneoftwoormoregroups.Thefollowingtechniquescanbeappliedtotherandomisationprocess

Simplerandomisationallocationisnowusuallydecidedbyacomputerprogramme,(previouslyusedmethodsincludedtossingacoin,orusingarandomnumbertable.)

Minimisationimprovesthebalancebetweengroupsintermsofimportantcharacteristics,especiallyinsmallsamples.Itisbasedontheideathatthenextparticipanttoenterthetrialismorelikelytobeallocatedtheinterventionthatwouldminimisetheoverallimbalanceofselectedcharacteristicsbetweenthegroupsatthatstage.

Blocked/restrictedrandomisationsareassignedrandomlywithinblockstoensurebalancewithintheblocks.Blockscanbeofanysizebutamultipleofthenumberoftrialgroupsislogical.Theblocksizeshouldbesmallandvariable,andunknowntotheinvestigators,topreventpredictabilityandmaintainconcealment.

Stratifiedrandomisationgivesabalancewithinsub-groupsdefinedbyimportantvariablessuchascentre/countryinamulti-centretrial.Blockedrandomisationmustbeusedwithineachstrata.Stratificationisnotfeasibleforsmallstudiesorformanyvariables.NCRNInductionManualSeptember200960

Clusterrandomisationiswhentheunitofrandomisationisnottheindividualparticipantbeingstudiedbutgroupsofparticipants(clusters)suchasGPpracticeorvillagecommunity.

Blinding

Sometimesinclinicaltrialsitisnecessarytodisguisetheidentityofthetreatmenttolimitconsciousandunconsciouspotentialbias.Thisisachievedthroughatechniquecalled“blinding”.

Blindingisusedincombinationwithrandomisationtolimittheoccurrenceofconsciousandunconsciousbiasintheconductofclinicaltrials(performancebias)andinterpretationofoutcomes(ascertainmentbias).

Therearetwotypesofblinding:

DoubleBlind:Bothinvestigatorandparticipantareignorantoftheinterventionallocation

SingleBlind:Eithertheparticipantortheinvestigatorisunawareoftheinterventionallocated.Usuallyitistheparticipantwhois“blind”.

Placebos

Ifthereisnostandardtreatment,patientstakingpartinatrialmaybegivenadummydrug,whichlookslikethedrugbeingtested.Thisdummydrugiscalledaplacebo.Placebosareusedbecausesometimespeoplegetbetterwithouttreatment.

Insometrialswhereanewtreatmentisbeingcomparedwiththestandardtreatment,placebosarealsoused.Thisisusuallybecausethetreatmentscanbeeasilydistinguishedbytheappearanceofthedrugbeingsuppliedandthepatientcouldbecomeawareofwhattheyaretaking.Inthiscasetwoplacebosareused,onemadetolooklikeeachofthedrugsandeachpersonreceivesoneoftheseplacebosandonerealdrug.

Insummary,RCTsarequantitative,comparative,controlledexperimentsinwhichinvestigatorsstudytwoormoreinterventionsinaseriesofindividualswhoreceivetheminrandomorder.Randomisedcontrolledtrialsarethemostrigorouswayofdeterminingwhetheracause-effectrelationexistsbetweentreatmentandoutcomeandforassessingthecosteffectivenessofatreatment.

QualitativeResearch

Derivingasimpledefinitionofqualitativeresearchisdifficultduetoalackofconsensusonthefundamentaltenetsofqualitativeresearchmethods.Itisusuallybasedonamoreindepthstudyofthesubjectmatter,usingasmallernumberofparticipants.Therearecertainprinciplesofqualitativeresearchthatseparateitfromquantitativeapproaches.Firstly,thatthisapproachtoresearchisconstructedwithinandisnotremovedfromsocialprocesses.Secondly,thattheresearcherispartoftheresearchprocessandisnotremovedfromit.Thirdlythatqualitativeresearchinvolvesdescriptionratherthanmeasurement.NCRNInductionManualSeptember200961

AlthoughRCTsareconsideredtobethe„goldstandard‟methodwhentryingtomeasurethe

effectsofadiscretemedicalintervention,qualitativemethodsmightbebetterwhenadeeperanalysisisrequired,forexamplewhentryingtounderstandhumanbehaviourorcomplexsocialphenomena.Qualitativemethodscanbeusedtoevaluatetheeffectsofmorecomplexhealthorsocialinterventions.Somehealthandsocialstudieswilluseamixedmethodsapproach.

SystematicReviews

Asystematicreviewisclassedassecondaryresearch.Thisistheanalysisofpublishedorrecordeddatafrompreviouslyconductedresearchprojects.Systematicandexplicitcriteriaareadoptedtoidentifyselectandcriticallyappraiseresearchstudiestoestablishwheretheeffectsandeffectivenessofhealthcareinterventionsareconsistentandwheretheyvary.

Meta-analyses

Meta-analysesoccurswhenstatisticalmethodsareappliedtothereviewandanalysisofcombineddatafromstudiesincludedinasystematicreview

Outcomemeasuresinclinicaltrials

Anoutcomemeasuresisthemeansbywhichwemeasuretheimpactofaninterventiononpatients.Outcomemeasuresarealsoknownasresponsevariables,eventsorendpoints.Theoutcomemeasure/sselectedforatrialwilldependonthephaseoftrial,stageofdiseaseandtheinterventionbeingtested.

Earlyphasetrialscommonlyuseoutcomemeasuresoftumourresponsewhilstlatephasetrialsuseoutcomemeasuresthatincludesurvival(diseasefreeoroverallsurvival).Almostallcancertrialswillincludesomemeasureoftoxicityandtreatmentcompliance.

Forinformationanda’processmap’ofplanningaresearchstudy,seehttps://processmap.tghn.org/

Appendix12:Whydidyoubecomearesearchnurse?POSTEDONMAR9,2015BYKELLYGLEASONINRESEARCHLikemanyofyouI‘fell’intoresearchnursing.Somearescoutedbyaprofessorwithaprojectandagrantoraseniorresearchnursewhospottedyour‘talent’whileworkingalongsideyouinout-patientclinic.Todayevenscientistsaredrawntoclinicalresearchexchangingpetridishesforpatients.

Whateveritwasthatbroughtyoutoclinicalresearchyouwerelikelylookingforsomething:achange,achallenge,anadventure,adesiretogrowandexpand.Inthosefirstfewmonths,youbegantopiecetogetherapictureofwhatclinicalresearchwas‘really’about,allyouneededtolearn,whoyouneededtobecome,whoyouwouldnowconsideryour‘colleagues’andthatnoteverybodywasgoingtoseeresearchasimportantasyoudid.

Butifafterlearningallthat,youstayed:

• Itislikelybecauseyoufeltyoufoundsomethingyouliked.• Itfeltgoodtolearnnewthings.

• Itfeltgoodtobechallenged–evenifitwasdaily.

• Itfeltgoodtocontributetomakingthingsbetter.

• Itfeltgoodtoworkmoreautonomously.

• Itfeltgoodtobepartofamotivatedteam.

WhenIaskpeopleattending‘DevelopingYourselfinClinicalResearch’whattheyfeelthebenefitsoftheirroleare,theyusuallysay:

• Autonomy

• Innovation

• Creatingchange

• Moretimewithpatients

• Variety

Jobsinclinicalresearchdefinitelygivepeopletheopportunitytoexperiencealloftheabove.Justthinkbackforamomenttoallyouhavelearntsincetakingonyourfirstroleinresearch:

• YoulearntaboutTMFs,ISFs,CRFsandSVDs.Thingsyoulikelyknewnothingaboutbeforeenteringintoresearch.

• Youlearntnewlawsandregulations.

• Youlearntsomescience.

• Youlearnttherealmeaningofinformedconsentandthatrobustinformedconsenttakestime,moretimethanweusuallycostfor.

• Youprobablythoughtdeeplyabouttheethicalprinciplesofresearch.

• Youlearnttobalanceacentrifuge,pipettewithnoairbubbles,andsomemayevenhavebecomefamiliarwiththe‘buffycoat’.

• Youlearnttopackagedryicewithoutputtingyourcourier’slifeatrisk.

• YoulearnttouseencryptedUSBsticks.

• Youlearnttoasknicely…andsometimesdesperatelyforanurgentMRIorPETscan.

• Afteryourfirstinspection,youleanttotakeprideinmaintainingsitefiles.TotheMHRA,thatfileisareflectionofyourwork.

• You’veprobablylearnttohaveyourvoiceheardinmeetingsandcircleswhereyoumaynothaveeverspokenbefore.

• YouhavedevelopedyourPR,yourmarketing&yourpublicspeakingskills.

• Youhaveredefinedassertiveness.

• Mappedpatientpathwaysfrompartsoftheserviceyoudidn’tevenknowexisted.

• You’velearnttoworkwithdifferentpersonalities,stakeholdersandagendas.

• Youcreatedrecruitmentstrategies.

• Youestablishedyourselfasthe‘hub’oftheteam.

• Youlearnthowfara‘can-do’attitudegetsyou.

Youhavelikelygrowninwaysyouneverthoughtpossible.Youareatrailblazer.

Rolesinthefieldofclinicalresearcharestill‘new’.Youarecreatingnewpathwaysforotherstofollow.ThisisbynomeansaneasytaskbutsomehowIknowyouareupforthechallenge.Therearesomanywaystogrowandexpandskills.ProfessionalpathwaysneedtobeforgedbutwealsoneedtobuildbridgesbetweenculturesifresearchisgoingtotrulybecomepartofhealthcareintheUK.Whateveryoutalentorinterest,thereisaplaceforyoutocontributeandmakeyourmark.

MoreresearchthaneverishappeningintheNHS.Wehaveagreaternumberofopenstudiesandagreaternumberofpatientstakingpartinstudiesthaneverbefore.YouarethelargestbodyofprofessionalscarryingoutclinicalresearchintheNHS.Youaretheenginethatismakingitallpossible.YouarechangingthecultureintheNHS.Youarecreatingopportunitiestoimproveservicesanddevelopnewcareerpathways.

Whateverbroughtyouhere,Iamgladyoustayed.Itisfantastictobepartofthisnetworkofindividualsdedicatedtoimprovinghealthcarethroughresearch.Itisenergisingtobewith,andtosharewithlike-mindedpeoplewhohavealsodesiredtobreakout,explorenewterritory,learnnewskillsanddiscoverhiddentalents.Ifyouarenewtoclinicalresearch,hanginthere…thegoodtimesdocome,bepatientandgiveyourselftimetotransitionintothisnewworldofclinicalresearch.Itisworthit,Ipromise.

https://clinfield.com/why-did-you-become-a-research-nurse/

Seehttp://www.futuremorph.org/11-13/case-studies/john-clinical-trial-coordinator/fortheexperiencesofaTrialCo-ordinator

introduction to research - home - nihr oxford biomedical ......introduction to research v3 may 2018...

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