introduction to research - home - nihr oxford biomedical ......introduction to research v3 may 2018...
TRANSCRIPT
IntroductiontoResearch
forResearchNurses,MidwivesandotherResearchProfessionals
IntroductiontoResearchV3May2018 2
CompiledbySallyBeer,OxfordBiomedicalResearchCentre–EducationandTrainingCoordinator,basedonWestYorkshire/BradfordTeachingHospitalsNHSTrustInductionPack,LeedsTeachingHospitalsNHSTrustClinicalResearchNurseInductionPack&CompetencyFrameworkandYorkshireCancerResearchNetwork’sInductionHandbook.
Theamountofinformationinthisbookletmayseemdauntingrightnow;pleasebeassuredthatitismeanttosupportyouonyourjourneyinto
researchforaslongasyouneedit,andthereisnoexpectationthatyoureaditfromcovertocoveronyourfirstdayorweek.
Referenceisfrequentlymadeto‘researchnurses’whoarecurrentlythelargestsinglestaffgroupinclinicalresearch,buttheinformationisintended
tobeusefultoallresearchpractitioners
IntroductiontoResearchV3May2018 3
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
IntroductiontoResearchV3May2018 4
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.
IntroductiontoResearchV3May2018 5
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
IntroductiontoResearchV3May2018 6
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
NHSPatientCare
MRCProgrammes
NIHRProgrammes
NIHRInfrastructureCLAHRCs
NIHRInfrastructureClinicalResearchNetwork
NIHRInfrastructure
BRCs,BRUs,CRFs
IntroductiontoResearchV3May20188
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
OUH)
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)
IntroductiontoResearchV3May2018 9
ResearchStructureNationalInstituteforHealthResearchhttps://www.nihr.ac.uk/
TheNationalInstituteforHealthResearch(NIHR)isfundedthroughtheDepartmentofHealthtoimprovethehealthandwealthofthenationthroughresearch.TheNIHRprovidestheframeworkthroughwhichtheDepartmentofHealthcanposition,maintainandmanagetheresearch,researchstaffandresearchinfrastructureoftheNHSinEnglandasanationalresearchfacility. The NIHR systemsrepresentthemostintegratedclinicalresearchsystemintheworld,drivingresearchfrombenchtobedsideforthebenefitofpatientsandtheeconomy.
Sinceitsestablishment,theNIHRhastransformedresearchintheNHS.Ithasincreasedthevolumeofappliedhealthresearchforthebenefitofpatientsandthepublic,drivenfastertranslationofbasicsciencediscoveriesintotangiblebenefitsforpatientsandtheeconomy,anddevelopedandsupportedthepeoplewhoconductandcontributetoappliedhealthresearch.
AtthecentreofwhattheNIHRdoesisthePortfolio–acollectionofhigh-qualityclinicalstudiesthatbenefitfromtheinfrastructureprovidedbytheClinicalResearchNetwork.
Aims
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.
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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.
IntroductiontoResearchV3May2018 11
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.
IntroductiontoResearchV3May2018 12
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.
IntroductiontoResearchV3May2018 13
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.
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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:[email protected]
Allsessionsstartat12.30pmforonehourandwillbeheldinthemeetingroomoftheJointResearchOfficeattheChurchillHospital.
Researchbulletin• R+Dpublisharegularbulletinofupdatesandevents.TojointhemailinglistcontactKatie Flight:
01865 572233 Email: [email protected]
UKTrialManagersNetwork(Oxford)http://www.tmn.ac.uk/
AsteeringgrouphasbeenformedtoexploresettingupanOxfordHuboftheUKTrialManagersNetwork.Forfurtherinformation,[email protected]
IntroductiontoResearchV3May2018 15
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
IntroductiontoResearchV3May2018 16
GoodClinicalPractice(GCP)trainingAkeyrequirementforanyoneinvolvedintheconductofclinicalresearchisGoodClinicalPractice(GCP)training.GCPistheethicalandpracticalstandardtowhichallclinicalresearchisconducted.
Togetstarted,itisadvisabletocompleteanonlinecourse,buttothenattendaface-to-facesession,wherethereistheopportunitytoaskquestionsandlearnfromothersexperiences.
CRN:ThamesValleyandSouthMidlands
Forinformationaboutcoursedatesandavailability,contactCRNTrainingtraining.crnthamesvally@nihr.ac.ukor01865223292
OR
LocalR+DandOxfordUniversityofferjointGCPtraining
http://www.admin.ox.ac.uk/researchsupport/training/gcpoxford/
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
IntroductiontoResearchV3May2018 17
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
IntroductiontoResearchV3May2018 18
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
[email protected]• 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
IntroductiontoResearchV3May2018 19
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
IntroductiontoResearchV3May2018 20
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
IntroductiontoResearchV3May2018 21
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
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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
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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
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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
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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.
Arm
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
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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.
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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
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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.
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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.
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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.
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TrialSteeringCommittee
TheroleoftheTrialSteeringCommittee(TSC)istoprovidetheoverallsupervisionofthetrial.Ideally,theTSCshouldincludememberswhoareindependentoftheinvestigators,theiremployingorganisations,fundersandsponsors.TheTSCshouldmonitortrialprogressandconductandadviseonscientificcredibility.TheTSCwillconsiderandact,asappropriate,upontherecommendationsoftheDataMonitoringCommittee(DMC)orequivalentandultimatelycarriestheresponsibilityfordecidingwhetheratrialneedstobestoppedongroundsofsafetyorefficacy.
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Pleaseseewww.ct-toolkit.ac.ukforaninteractiveversion,withlinkstoextensivefurtherinformation
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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
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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• 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.
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• 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.
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Organisationsprovidingcare
• Mustensurethesponsorhasassumedresponsibility,researchhasbeenreviewedbyappropriatebodies,andthatanauthorisedpersonhasgivenwrittenpermissiononbehalfofthecareorganisationfortheresearchtobegin.
• MustarrangeforresearchersnotemployedbyanyNHSorganisationtoholdanNHShonorarycontract.
• Mustensureadverseincidentsarereported.
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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.
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TeamContactGillRoweHeadofResearchServices,[email protected]://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
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• 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@[email protected]://www.ouh.nhs.uk/researchers/
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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)[email protected]://www.admin.ox.ac.uk/researchsupport/
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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.
Or:
1. EmployedbytheOUHTrust–completeaResearchAccesstoNotesRegistrationFormandsendtoR&Dforverification.
2. Onceapproved–takewithyoueverytimeyouwishtorequestresearchparticipant’smedicalrecords.
TheResearchAccesstoNotesRegistration(RANR)formcanbedownloadedfromtheR&DWebsiteorwillbesenttoyouonrequestbytheR&[email protected].
TheMedicalRecordsLibrarystaffwillrequesttoseetheRANRformbeforeretrievingnotesforresearchersorallowstafftoretrievenotesthemselvesoneachoccasiontheresearchattendstheMedicalRecordsLibrary.
WherenewstaffjointheresearchteamtheRANRformshouldbeupdatedwiththeirnamesthroughcontactwithR&D.[Ifstaffareconductingastudyandtheydonothavearesearchnumberasignedletterfromtheheadofthestudyandalistofpatientsshouldbegiventothelibrarystaff.]
AllstaffusingthelibraryarerequiredtoattendLibrary&HIMTrackertraining.Thisistoensurethatstaffareableto‘track’medicalnotesandhowtolookfornoteswithinthelibraries.ResearcherscancontacttheMedicalRecordsTrainingTeamviaemailmedrecstraining@ouh.nhs.uk
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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
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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.
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• 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
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(andtheresultingdose)shouldbethatnecessarytoprovidetheinformationrequired.AllARSACcertificatesaresite-specific,thereforeinthecaseofmulticentrestudies;eachstudysiterequiresitsowncertificate.
https://www.gov.uk/government/organisations/administration-of-radioactive-substances-advisory-committee
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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
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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/
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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/
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MedicinesandHealthcareproductsRegulatoryAgency(MHRA)
TheMHRAwassetupinApril2003fromamergeroftheMedicinesControlAgencyandtheMedicalDevicesAgency.TheMHRAisthegovernmentagencywhichisresponsibleforensuringthatmedicinesandmedicaldeviceswork,andareacceptablysafe.
TheMHRAisanexecutiveagencyoftheDepartmentofHealth.
Aims
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
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IntroductiontoResearchV3May2018 60
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
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•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.
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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.
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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.
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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
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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
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Outcomemeasuresinclinicaltrials
Anoutcomemeasuresisthemeansbywhichwemeasuretheimpactofaninterventiononpatients.Outcomemeasuresarealsoknownasresponsevariables,eventsorendpoints.Theoutcomemeasure/sselectedforatrialwilldependonthephaseoftrial,stageofdiseaseandtheinterventionbeingtested.
Earlyphasetrialscommonlyuseoutcomemeasuresoftumourresponsewhilstlatephasetrialsuseoutcomemeasuresthatincludesurvival(diseasefreeoroverallsurvival).Almostallcancertrialswillincludesomemeasureoftoxicityandtreatmentcompliance.
Forinformationanda’processmap’ofplanningaresearchstudy,seehttps://processmap.tghn.org/
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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.
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• 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