Clinical trial : Types and Design (Pharmacovigilance)

Master's in Pharmacology 2nd semester
Pharmacovigilance notes

1. Presented by AYUSH ROY
M.PHARM, 2nd Semester Pharmacology
(2023-25)
Clinical Trials :Types and Design
SCHOOL OF PHARMACEUTICAL SCIENCES
GIRIJANANDA CHOWDHURY UNIVERSITY

2. CONTENT
i.Introduction
ii.Types of clinical trial
iii.Clinical trial design and its types

3. INTRODUCTION
▪Clinicaltrialsarescientificstudiesdesignedtoevaluatethesafetyandeffectivenessof
newmedicaltreatments,interventions,ortherapiesinhumans.
▪Thesetrialsinvolvecarefullyplannedexperimentsthataimtogatherreliabledataabout
howwellanewtreatmentworks,itspotentialsideeffects,andhowitcomparesto
existingtreatmentsoraplacebo.
▪Clinicaltrialsplayacrucialroleinadvancingmedicalknowledgeandimprovingpatient
carebyprovidingevidence-basedinformationtoguidemedicaldecisionsandthe
developmentofnewtherapies.

4. TYPES OF CLINICAL TRIALS
Thereareseveraltypesofclinicaltrials,eachservingdifferentpurposesandanswering
specificresearchquestions.Herearesomecommontypes:
i.Treatmenttrials:Thesetrialstestnewtreatments,suchasdrugs,medicaldevices,or
procedures,determinetheirsafetyandefficacyintreatingaparticulardiseaseor
condition.Treatmenttrialsmaycomparethenewtreatmentwithstandardtreatmentsora
placebo.
ii.Preventiontrials:Preventiontrialsinvestigateinterventionsaimedatpreventingthe
developmentofadiseaseorcondition.Thesetrialsmayinvolvelifestylechanges,
medications,vaccines,orotherstrategiestoreducetheriskofdiseaseoccurrence.

5. iv.Diagnostictrials:Diagnostictrialsassessnewmethodsortechnologiesfor
diagnosingdiseasesorconditions.Theyaimtodeterminetheaccuracy,safety,
andeffectivenessofdiagnostictestscomparedtostandardmethods.
v.Screeningtrials:Screeningtrialsevaluatetheeffectivenessofscreeningtestsin
identifyingindividualsatriskofdevelopingaparticulardiseaseorconditionat
anearlystagewhentreatmentmaybemoreeffective.
vi.Qualityoflifetrials:Qualityoflifetrialsassesstheimpactofmedical
interventionsonpatients'qualityoflife,includingtheirphysical,emotional,and
socialwell-being.Thesetrialsoftenusepatient-reportedoutcomemeasuresto
evaluatesubjectiveexperiences.

6. PHASES OF CLINICAL TRIALS
Phase Name of phase Conducted on Purpose
0 Micro Dosing StudiesHealthy volunteers (small
Number)
1.Toknowpharmacokinetics
2.CouldavoidcostlyphaseIstudiesfor
candidatedrugs with unsuitable
pharmacokinetics
I Human Pharmacology
and Safety
Healthy volunteers (20-100)1.Toknowmaximumtolerable
2.Safetyandtolerability
IITherapeutic ExploratoryPatients of homogenous
population(100-150)
1.Toestablishtherapeuticefficacy
2.Doserangingandceilingeffects
III Therapeutic
Confirmatory
Up to 5000 from several centres
(heterogenous population)
1.Toconfirmtherapeuticefficacy
2.Toestablishthevalueofdrugsinrelationto
existingtherapy
IV Post marketing
surveillance
Large number of patients being
treated by practicing physicians
1.Toknowrareandlong-termadverseeffects
2.Specialgrouplikechildren,pregnancycanbe
tested

7. CLINICAL TRIAL DESIGN
•The sequence or structure of activities which are carried out during the clinical trial to
know the actual cause and effect of new drug on human is called as clinical trial design.
•There are two major types of clinical study designs:

8. OBSERVATIONAL STUDY
•Anobservationalstudyiswhenresearcherswatchpeopleoreventswithoutchanging
anything.It'slikebeingasilentobserver,justnoticingwhat'shappening.Theydon't
interfere;theyjustobserve.
•Therearedifferenttypesofobservationalstudies:

9. 1.CohortStudy
•Cohortstudiesareatypeofresearchwherescientistscomparetwogroupsofpeople:one
grouphasbeenexposedtosomething(likeamedicationorenvironmentalfactor),whilethe
otherhasn’t.
•Cohortstudiesareparticularlyusefulfortestinghypotheses.
•Therearetwomaintypesofcohortstudies:
1.Prospectivecohortstudies:Thesestudiesstartbyidentifyingagroupofpeoplewitha
certainexposureandthenfollowthemovertimetoseeiftheydeveloptheoutcomeof
interest.
2.Retrospectivecohortstudies:Thesestudiesstartbylookingbackatpastdatatoseeif
there'salinkbetweenpastexposureandcurrentoutcomes.

12. 2.CaseControlStudy
•Case-control studies are a type of research method where scientists compare two groups:
one with a certain disease (cases) and one without (controls).
•They do this to see if there are differences in the things that might have caused the
disease. These studies are especially useful for investigating rare diseases.
•They're like experiments that test ideas about what might be causinga disease, but they
can't definitively prove a cause.
•They're cheaper and quicker than another type of study called cohort studies.
For example, in Pakistan, researchers looked at babies with and without neonatal tetanus.
They found that using ghee(a type of butter) was strongly linked to neonatal tetanus.
However, even though this link suggests that using ghee might cause neonatal tetanus, the
study can't say for sure. It just gives us a clue that needs more investigation.

13. 3.Cross-SectionalStudy
•Cross-sectionalstudiesareatypeofresearchmethodusedtoexploretheconnection
betweenanexposure(likeariskfactor)andanoutcome(likeadisease)atthesametime.
•Sincecross-sectionalstudiescollectdataatonespecificpointintime,they'reusefulfor
figuringouthowcommonaparticularexposureoroutcomeisinapopulation
•Forexample,
•Inacross-sectionalstudyexaminingtheprevalenceofdiabetesinacommunity,researchers
surveyed500adultstodeterminetheproportionofindividualswiththedisease.Participants
providedinformationontheirage,gender,andlifestylefactors,alongwithundergoing
bloodglucosemeasurements.Thestudyfoundthat100individualswerediagnosedwith
diabetes,indicatingaprevalencerateof20%.Byanalyzingthedata,researchersgained
insightsintotheextentofdiabeteswithinthecommunityataspecificpointintime,aiding
inpublichealthplanningandinterventionstrategies.

14. •However,there'salimitationtothesestudies:theycan'testablishtheorderofevents,like
whetherariskfactorcamebeforeadisease,becausetheyonlycollectdataatonemoment.
Tosolvethis,researcherscanaskquestionsinaquestionnaireaboutwhensymptoms
startedorwhensomeonewasexposedtoariskfactorcomparedtowhentheygotsick.This
way,theycangetabetterideaofthetimingbetweenexposureandoutcome.So,while
cross-sectionalstudiesarehelpfulforunderstandingwhat'shappeningatacertaintime.

15. EXPERIMENTAL STUDY
•Anexperimentalstudydesignisawayoforganizingandconductingascientific
investigationtotestahypothesisoransweraresearchquestion.Ineasylanguage,it's
likesettingupaspecialkindofexperimenttoseeifsomethingworksorifthere'sa
relationshipbetweendifferentthings.
•Therearedifferenttypesofexperimentalstudies:

16. •Experimentalstudydesignscanbedividedinto3broadcategories:clinicaltrial,
communitytrial,fieldtrial.
•Clinicaltrialsarealsoknownastherapeutictrials,whichinvolvesubjectswithdisease
andareplacedindifferenttreatmentgroups.
•Clinicaltrialsarefurtherdividedinto
•Randomizedclinicaltrial(RCT)
•Non-randomizedclinicaltrial(Non-RCT)
•Cross-overclinicaltrial
•Factorialclinicaltrial.

17. •Anepidemiologicalexperimentinwhichsubjectsinapopulationarerandomlyallocatedinto
groups,usuallycalledstudyandcontrol.
•Groups,toreceiveornotreceiveanexperimentalpreventiveortherapeutic
•Patientsarerandomlyassignedtothestudyallgroupsthathelpinavoidingbiasinpatient.
Randomizedclinical trial (RCT)
Accordingtolevelofblinding
a.InOpenRCT-OpenRCT,everybodyinvolvedinthetrialknowswhichinterventionisgivento
eachparticipant.
b.SingleBlind-Patientorevaluatorisblindedastotreatment,butnotboth.
c.DoubleBlind-Neitherpatientnoroutcomeevaluatorknowstowhichtreatmentpatientwas
assigned.
d.TripleBlind-Patient,physician,anddataanalystareblindedastotreatmentidentity.
Classification of RCT

18. According to participants exposure
a.Parallel group RCTs
b.Cross-over RCTs
c.Cluster RCTs
a.Parallel-group RCTs: This is like comparing two different groups of people. Each group gets a different
treatment, and they stick with that treatment throughout the study.
b.Crossover RCTs: In this type, each person tries both treatments, one after the other. They start with one treatment,
then switch to the other later on. This helps to see how each treatment works for the same person.
c.Cluster RCTs: In a cluster RCT, groups of participants, such as schools, communities, or hospitals, are randomly
assigned to different treatments or interventions. The entire group receives the same treatment, rather than
individual participants. This design is useful when it's difficult to treat individuals separately or when the
intervention is applied at a group level.

19. •Aclinicaltrialsinwhichtheparticipantsarenotassignedbychancetodifferent
treatmentgroups.
•Participantsmaychoosewhichgrouptheywanttobein,ortheymaybeassignedto
thegroupsbytheresearchers.
Non-Randomizedclinical trial (Non-RCT)
Classification of Non-RCT
a.Non-randomizedconcurrentcontrolstudies
b.Non-randomizedhistoricalcontrolstudies

20. •Controlgroupispredetermined(alreadyselectionofpatientshasdone)
•Non-randomizedcontrolledtrialsrelayonparticipant
•Participantsvolunteerstojointhestudy
•Aregeographicallyclosetothestudysite.
a)Non-randomized concurrent control studies
b)Non-randomized historical control studies
•Historicalcontroltrialsareatypeofnon-randomizedclinicaltrialwherethe
outcomesofagroupofpatientsreceivinganewtreatmentorinterventionare
comparedwiththeoutcomesofasimilargroupofpatientswhoreceiveda
standardtreatmentinthepast.
•Thesetrialsusehistoricaldatafrompreviousstudiesordatabasesasacontrol
groupforcomparisonwiththecurrenttreatmentgroup.

21. THANK YOU
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