180124 ethics in medical research & intro to gcp...

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ETHICSINMEDICALRESEARCH&INTRODUCTIONTOTHEGCP

RovinaRuslami

Pelatihan Etik Dasar dan Lanjutan, 24 Januari 2018

Theprimarypurposeofmedicalresearch(involvinghumansubjects)is

tounderstandthecauses,developmentandeffectsofdiseasesandtoimprovepreventive,diagnosticandtherapeuticinterventions(methods,proceduresandtreatments).

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WMADeclarationofHelsinki,v2013:A6

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Eventhebestproveninterventionsmustbeevaluatedcontinuallythroughresearchfortheirsafety,effectiveness,efSiciency,accessibilityandquality.

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WMADeclarationofHelsinki,v2013:A6

Howcantherightsofindividualpersonsbereconciledwiththedemandsofmedicalresearch?§  BeneSitsofmedicalresearchhavecomewithaheavyprice

§  Therearemanyexamplesofstudiesthathaveviolatedtherightsand

dignityofparticipants

§  Insomecases,costingparticipantstheirhealthoreventheirlives

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§  Thegoodphysician,Sirst,donoharm§  Butthen…historyshowsus…L

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WWIII

(NAZI

experiments)

1939-1945

TuskegeeSyphilis

experiment1932-1972

Willowbrook1963-1966

AsthmaStudy2001

Trovan(PSiz

er)

1996

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NAZIdoctors(WWII)

TheTuskegeeSyphilisStudy(1932-1972)

WillowbrookHepatitisStudy(1950s)

TheJewishChronicDiseaseHospital(1960s)

SanAntonioContraceptionStudy(1970s)

TheThalidomideExperience

JohnHopkinsStudy

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•  ExperimentationtoHolocaustVictims

•  Novoluntaryconsent•  Subjectsnotkilledby

experimentswouldbekilledanddissected

•  1947:Doctor’strialatNuremberg

1947:theNurembergCode

•  MentallycompromisedchildrenattheWillowbrookStateSchoolinNYCwhowerepurposelyexposedtohepatitisvirus.

•  Problemofhepatitis(theriskofhavinghepatitisis30-50%).

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•  HealthychildrenintentionallygivenhepatitisCvirus•  Monitoredtoseeeffectsof

γ-globulin“Theywillgetitanyway”

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•  22elderlychronicallyill(old)patientsinjectedwithlivecancercells•  Purposewasto“discoverthesecretofhowthebodiesSightthe

invasionofmalignantcells”•  Covered-upbyhospitaladministration

“Theywilldieanyway”

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•  Evaluatetheeffectivenessoffemalebirthcontrolpills.

•  Indigentpatientswithnootherplacetogoforadviceormedicationbuttheclinic.

•  Randomized:activecontraceptiveandPLACEBO.

•  Womennotinformed.•  Results:Highnumberofunplanned

pregnanciesinplacebogroup.

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•  Safetyinpregnantwomenhasnotbeenestablished.•  Itcaused10,000-20,000birthdefectsWITHINYEARS

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THEESSENCE&LESSONSLEARNT

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UnfairnessDishonesty

Researchactivitiesé

Competitioninresearchenvironment

Interests•  Sponsor•  Researchers•  Subjects•  Government

Needsofethicalguidelines

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NationalCommissionfortheProtectionofHumanSubjectofBiomedicalandBehavioralResearch

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•  Treatindividualsasautonomousagents(Autonomy)&selfdetermination•  Voluntary•  Informedconsent•  ConUidentiality•  Canstopparticipationanytime

•  personswithdiminishedautonomy(vulnerablesubjects)

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•  Children•  MentallyChallenged•  InstitutionalizedIndividuals•  Subordinates/Staff/employee•  Students•  Prisoners•  Pregnant/Lactatingwomen•  Disease/condition•  Poor•  Military•  Tribal•  Uneducated•  Ethnicminorities/refugees•  Homeless/frailandold

•  Nottoincludeunlessthestudydemandsspecialgroups

•  Informedconsentfromthelegalguardians

•  Informedconsentfromtheindividualswhereverpossible

•  Noinducementofguardians•  Assentfromminors•  Respecttheirrighttorefuse

participation

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•  DONOHARM•  MaximizepossiblebeneSitandminimizepotentialrisk

“Do unto others as you would have them do unto you”

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•  Totreateachpersonaccordingtowhatismorallyrightandproper

•  EquitabledistributionofbothburdensandbeneUitsoftheresearch

•  Individualjustice&Socialjustice(we’lldiscussedinthenexttopic)

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•  TheHelsinkiDeclaration,theBelmontReport&otherdocumentsgive“ethicalprinciples”toguidedecision-makinginmedicalresearch.

•  Thisprinciplesaretranslatedinpracticalstandardsof

workingintheGoodClinicalPractices(GCP)guidelines•  WorldHealthOrganization,1995•  InternationalConferenceofHarmonization,1996•  NationalGuidelines

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GCP(GoodClinicalPractices)isaninternationalstandard(ethical&scienti>icquality)in:

trialsthatinvolveparticipationofhumansubjects

Designing

Conducting

Recording

Reporting

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•  Ensurepatients’protection•  Ensurequalityofdata

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ethics

quality

Thisguidelineshouldbefollowed:

generatingCTdatathatintendedtobesubmittedtoregulatoryauthority/bepublished

anyresearchthatmayhaveanimpactonthesafety&well-beingofhumansubjects

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critical

always

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1.ethicalprinciplesinconductingclinicaltrial(CT)

2.Performrisk-beneUitanalysisbeforeinitiationofthetrial

3.Safeguardingtheparticipants

4.Adequatedata(preclinicaldata)tosupportproposedCT

5.ScientiUicallysoundàclearlydescribedinprotocol

6.ComplywithprotocolwhenconductingtheCT

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7.Medicareforparticipant(qualiUiedphysician)

8.QualiUiedtrialpersonnel

9.Freelygiveninformedconsent(beforeandduringthestudy)

10.Qualityofthedata

11.RespectparticipantconUidentiality

12.InvestigationalProduct

13.Qualityassurance

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•  a-3-dayscourse•  byacompetenttrainer/institution

•  itisencouragedthatallresearcher&supervisorsofresearcherstakethecourse

•  in-housetrainingispossible(capacitybuilding)

moreandmoreofferscomefromtheCROtoconducttheCT(phase2-3CT)

àAndthisisoneoftherequirement

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renewalevery2years

thesystematicanalysisofsuchquestionstoensurethatstudyparticipantsareprotected,

andultimately,thatclinicalresearchisconductedinawaythatservestheneedsofsuchparticipantsandofsocietyasawhole.

(Weijer,Dickens&Meslin,1997)

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•  ClinicalTrialisapartofmedicalresearch(involvinghumansubject)

•  Indoingso…•  ICH-GCPistheinternationalethical&scientiSicqualitystandard

•  allinvestigatorsshouldbeawareofthis

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Betterresearch

Betterresults(evidence)

Betterpatientcare

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“Mostpeoplesaythatitistheintellectwhichmakesagreat

scientist.Theyarewrong:itischaracter.” 33

THANKYOU