Clinical Research Methods

8/4/2019 Clinical Research Methods

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Clinical Research MethodsClinical Research Methods

in Ophthalmologyin Ophthalmology

OverviewOverview


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GoalsGoals

Provide introduction to key aspectsProvide introduction to key aspects

DesignDesign

ConductConduct AnalysisAnalysis

Basic resourcesBasic resources

Information to include in manuscriptsInformation to include in manuscripts

Encourage critical readingEncourage critical reading


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Lecture TopicsLecture Topics

Case seriesCase series

CaseCase--control studycontrol study

CrossCross--sectional studysectional study

Cohort studyCohort study

Randomized trials and related studiesRandomized trials and related studies


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Case ReportCase Report

Describes what has happened in 1 case:Describes what has happened in 1 case:

New cataract surgical technique had goodNew cataract surgical technique had good

results.results.

Rabbit retina retained function after drug ABC.Rabbit retina retained function after drug ABC.

Pathology specimen from CNV showed basalPathology specimen from CNV showed basal

linear deposits.linear deposits.


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Pyramid of EvidencePyramid of Evidence

AnecdotalAnecdotal

case reportscase reports


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Case SeriesCase Series

Describes a series of similar events:Describes a series of similar events:

8 patients afterLasik report 20/25 vision.8 patients afterLasik report 20/25 vision.

10 rabbits are injected with antibiotics.10 rabbits are injected with antibiotics. Spindle cells were found in 5 choroidalSpindle cells were found in 5 choroidal

melanoma tumors.melanoma tumors.


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Case series w/o controlsCase series w/o controls


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Comparative case seriesComparative case series


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Ecologic orGeographic StudyEcologic orGeographic Study

Describes the relationship between factor A andDescribes the relationship between factor A and

outcome B (population level):outcome B (population level):

Is sun exposure related to cataractIs sun exposure related to cataract

development?development?

Is pigment level related to CNV?Is pigment level related to CNV?


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Ecologic StudyEcologic Study


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CaseCase--control Studycontrol Study

Describes the association between factor ADescribes the association between factor A

and outcome B (individual level):and outcome B (individual level):

Is sunlight exposure related to CNV?Is sunlight exposure related to CNV?

Do blondes have more fundus problems?Do blondes have more fundus problems?

Do antioxidants protect against CNV?Do antioxidants protect against CNV?


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CaseCase--control studiescontrol studies


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CrossCross--Sectional StudySectional Study

Describes the state of a sample/population:Describes the state of a sample/population:

How many blind people live in Baltimore?How many blind people live in Baltimore?

How many people in Maryland have glaucoma?How many people in Maryland have glaucoma? How many people with Geographic Atrophy alsoHow many people with Geographic Atrophy also

have CNV?have CNV?

How many children < 2 yrs have strabismus?How many children < 2 yrs have strabismus?

How many uveitis patients have allele A?How many uveitis patients have allele A?


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CrossCross--sectional (prevalence) studiessectional (prevalence) studies


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Cohort StudyCohort Study

Describes a group that is followed over time:Describes a group that is followed over time:

How fast do Chesapeake Bay WatermenHow fast do Chesapeake Bay Watermen

develop cataracts?develop cataracts?

How many new cases of CNV develop in 5How many new cases of CNV develop in 5

years?years?

How does vision change in a group ofHow does vision change in a group of

diabetics?diabetics?


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Cohort or followCohort or follow--up studiesup studies


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Randomized TrialRandomized Trial

Evaluates different treatments for XYZ:Evaluates different treatments for XYZ:

Does preDoes pre--enucleation radiation therapy prolongenucleation radiation therapy prolong

survival with choroidal melanoma compared tosurvival with choroidal melanoma compared to

enucleation alone?enucleation alone?

Does submacular surgery preserve vision inDoes submacular surgery preserve vision in

patients with CNV compared to observation?patients with CNV compared to observation?

Does azithromycin prevent trachoma comparedDoes azithromycin prevent trachoma comparedto face washing?to face washing?


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Single randomized clinical trialSingle randomized clinical trial


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MetaMeta--analysis of multiple randomizedanalysis of multiple randomized

clinical trialsclinical trials


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Match Vocabulary to DesignMatch Vocabulary to Design

Prevalence: Number of people with condition /Prevalence: Number of people with condition /

number of people in population.number of people in population.

What research design would you use ?What research design would you use ? Incidence: Number of NEW CASES / number ofIncidence: Number of NEW CASES / number ofpeople at risk.people at risk.

What research design would you use ?What research design would you use ?


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Prospective: Look forward in time.Prospective: Look forward in time.

What research design ?What research design ?

Retrospective: Look backward in time.Retrospective: Look backward in time. What research design ?What research design ?


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Observational: Look and describe.Observational: Look and describe.

What research design ?What research design ?

Interventional: Change and describe.Interventional: Change and describe. What research design ?What research design ?


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Which Research Design ?Which Research Design ?

Is Zinc associated with CNV?Is Zinc associated with CNV?

Is enucleation better than radiation?Is enucleation better than radiation?

What is the risk of developing CNV in 5What is the risk of developing CNV in 5years? How quickly does Geographicyears? How quickly does Geographic

Atrophy spread into the fovea? What is theAtrophy spread into the fovea? What is the

prognosis of children who have blunt traumaprognosis of children who have blunt traumato the eye?to the eye?


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Which Research Design ?Which Research Design ?

Is iris color associated with presence ofIs iris color associated with presence of

CNV? Is iris color associated withCNV? Is iris color associated with

developing CNV? Is iris color associateddeveloping CNV? Is iris color associatedwith vision loss?with vision loss?

Is iris color associated with survival?Is iris color associated with survival?

Is iris color associated with treatmentIs iris color associated with treatmentoutcome?outcome?


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The Research QuestionThe Research Question

General concern MUSTGeneral concern MUST be narrowed down.be narrowed down.

ConcreteConcrete

ResearchableResearchable


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The Research QuestionThe Research Question

5 essential characteristics5 essential characteristics

FeasibleFeasible

InterestingInteresting NovelNovel

EthicalEthical

RelevantRelevant


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Concerns for All DesignsConcerns for All Designs

Type of design does not = quality of study. AType of design does not = quality of study. A

poorly done randomized trial is NOT betterpoorly done randomized trial is NOT better

than a well done comparative case series.than a well done comparative case series.Factors that affect quality.Factors that affect quality.


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ErrorError

RandomRandom

SystematicSystematic

Bias: Any systematic error in the design, conduct orBias: Any systematic error in the design, conduct or

analysis of a study that results in a mistaken estimateanalysis of a study that results in a mistaken estimate

of an exposures effect on the risk of disease.of an exposures effect on the risk of disease. ----

SchlesselmanSchlesselman


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Choosing SubjectsChoosing Subjects

Target populationTarget population

Study sampleStudy sample GeneralizingGeneralizing

Inclusion/ExclusionInclusion/Exclusion

RecruitmentRecruitment

Ethical PrinciplesEthical Principles


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MeasurementsMeasurements

Continuous/Discrete/Categorical/OrdinalContinuous/Discrete/Categorical/Ordinal

Precision/Reproducible/ReliablePrecision/Reproducible/Reliable AccuracyAccuracy

Sensitivity/SpecificitySensitivity/Specificity

ObjectivityObjectivity


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Sample size/PowerSample size/Power

HypothesisHypothesis

Errors (Type I, Type II)Errors (Type I, Type II) Effect sizeEffect size

FormulasFormulas

SoftwareSoftware


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Data collectionData collection

Data cleaningData cleaning

Data analysisData analysis


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Data CollectionData Collection

Form designForm design

OpenOpen--ended/Closedended/Closed--endedended

FormatFormat OrderOrder

Spreadsheets/DatabasesSpreadsheets/Databases

Define variablesDefine variables

Data entryData entry


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Data CleaningData Cleaning

Edit checksEdit checks

Range checksRange checks

Date checksDate checks Impossible valuesImpossible values

Scatter diagramsScatter diagrams

Exploratory data analysisExploratory data analysis


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Data AnalysisData Analysis

Exploratory AnalysisExploratory Analysis

Scatter plotsScatter plots

Box and whisker plotsBox and whisker plots BlandBland--Altman plotsAltman plots

Summary statistics (mean, median, std dev)Summary statistics (mean, median, std dev)

Frequency countsFrequency counts

Proportion with eventProportion with event


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Hypothesis testingHypothesis testing

ContinuousContinuous

tt--testtest

ANOVAANOVA

regressionregression

CategoricalCategorical

Chi squared testChi squared test Test of proportionsTest of proportions


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Hypothesis testingHypothesis testing

Paired dataPaired data

Paired tPaired t--testtest

McNemarMcNemar

PP--valuesvalues

If there were no difference between the groups,If there were no difference between the groups,

how likely would I be to see this result in thehow likely would I be to see this result in thedata or a result more extreme than this?data or a result more extreme than this?


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Evaluation of test/screening/gradingEvaluation of test/screening/grading Reliability (repeatability)Reliability (repeatability)

% agreement% agreement

KappaKappa CorrelationCorrelation

Validity (accuracy)Validity (accuracy)

GoldGold--standardstandard

SensitivitySensitivity SpecificitySpecificity

Predictive valuePredictive value


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Spurious associationsSpurious associations

Due to chanceDue to chance

Due to biasDue to bias Real associationsReal associations

EffectEffect--causecause

ConfoundingConfounding

CauseCause--effecteffect


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ConclusionConclusion

OVERVIEWOVERVIEW

Familiar with different designsFamiliar with different designs

Familiar with vocabularyFamiliar with vocabulary Read, understand, and evaluate publishedRead, understand, and evaluate published

research reportsresearch reports

Write your own research reportsWrite your own research reports

Much left unsaidMuch left unsaid


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Discuss your research with aDiscuss your research with a

statisticianstatistician BEFORE you begin your researchBEFORE you begin your research

WHILE you are collecting dataWHILE you are collecting data

WHEN you are ready to analyzeWHEN you are ready to analyze

WHEN you are writing your manuscriptWHEN you are writing your manuscript

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Clinical Research Methods