临床试验设计的类型

Lea

Drye,

PhDJohnsHopkinsUniversityTypesofTrialDesignCopyright©2023JohnsHopkinsUniversityandLeaDrye.

AllRightsReserved.

Phase

I:First

stage

in

testing

a

new

intervention

in

humansUsually

10-30

peopleIdentify

tolerable

dose,

provide

information

on

drug

metabolism,excretion,

and

toxicityOften

not

controlled

Phase

II:Usually

30-100

peoplePreliminary

information

on

efficacy,

additional

information

onsafety

and

side

effects

Phase

III:Usually

100+

peopleAssess

efficacy

and

safetyControlled,

usually

randomized2Phases

of

trialsLectureOutline

DiscussvarioustrialdesigntypesParallelCrossoverGroupallocationFactorialLargesimpleEquivalencyNon-inferiorityAdaptive3ComparisonStructure:Parallel,Crossover,andGroupAllocationDesignsSectionAThematerialinthisvideoissubjecttothecopyrightoftheownersofthematerialandisbeingprovidedforeducationalpurposesunderrulesoffairuseforregisteredstudentsinthiscourseonly.Noadditionalcopiesofthecopyrightedworkmaybemadeordistributed.ParallelDesign5

Simultaneoustreatmentandcontrolgroups

Eachpersonisrandomlyassignedtoonetreatmentgroup

Randomizationremovestreatmentselectionbiasandpromotescomparabilityoftreatmentgroups

Statisticalcomparisonsmadebetweentreatmentgroups|P叫ωe G巾Randomized「占v1，白6iJHSPHParallelDesignExample:NETTSource:NETT

ResearchGroup(1999).Chest1999;116:

1750-61;

NETT

Research

Group

(1999).

JThoracCardiovascSurg,118:

518-528;

Fishman,

A.,&Martinez,F.,et

al.(2023).

NEnglJMed348:

2059-73.7

National

Emphysema

Treatment

Trial

(NETT)- PhaseIIItrial,unmaskedPopulationPeoplewithsevereemphysemaSamplesize1,200AllocationtotreatmentRandomizedTreatments—Lungvolumereductionsurgeryplusmedical

therapy—Medical

therapy(standardtherapycontrol)ParallelDesignExample:NETTSource:NETT

ResearchGroup(1999).Chest1999;116:

1750-61;

NETT

Research

Group

(1999).

JThoracCardiovascSurg,118:

518-528;

Fishman,

A.,&Martinez,F.,et

al.(2023).

NEnglJMed348:

2059-73.8HypothesistestingSuperiorityOutcomes—Primary:mortality,exercisecapacity—Secondary:qualityoflife,symptoms,lungfunctionandmechanics,functionalcapacityFollow-upUpto

7.5

yearsNumberofrecruitingcentersMulti-center

(17)CrossoverDesign9

RandomizationoforderinwhichtreatmentsarereceivedABorBARandomizationpromotesbalancebetweentreatmentgroupsintimingofexposure

TestingofbothtreatmentsineachpatientEachpatientservesashis/herowncontrolVariabilityreduced

becauselessvariabilitywithin

patient

thanbetween

patients

FewerpatientsneededCrossoverDesignGraphWashout10Group1,

Tx

AGroup1,

TxBGroup2,

TxBGroup2,

Tx

ACrossoverDesign:Disadvantages11

Treatmentcan’thavepermanent

effects

orcures

Potentialcarry-overeffectsoffirst-periodtreatmenttosecondperiodWashoutneedstobelongenoughUnequal

carry-over

effectsTreatmentduringwashout

Testforperiodbytreatmentinteractionsnotpowerful

Dropoutsmoresignificant

AnalysismaybemoredifficultCrossoverDesign:Uses12

ConstantintensityofunderlyingdiseaseChronic

diseases—asthma,

hypertension,

arthritis

Short-termtreatmenteffectsReliefofsignsorsymptomsofdisease

Metabolic,bioavailability,ortolerabilitystudiesCrossoverDesign:Examples13

Evening-dosevs.morning-dosedtravoprostinopen-angleglaucomafor24-hourintraocularpressurecontrol

Montelukastvs.salmeterol

as

adjuvant

to

inhaled

fluticasone

forexercise-inducedasthmainchildren

Topicaloilvs.placeboforneuropathicpainGroupAllocationDesign14

Alsoknownas

“cluster

randomization”

Randomizationunitisagroupofindividuals(community,school,clinic)

Individual

randomizationand

interventionis

notfeasibleor

isunacceptableTrackingContamination

Ifthereisacorrelationintheresponseswithinagroup,designlosessomeefficiency(moreindividualsrequired)lα[Ij川臼15Randomized〈〈Group

Allocation

Example:

Sommer

Vit

A

trial16Lancet.

1986

May

24;1(8491):1169-73

PopulationPreschool

children

in

northern