流行病研究性与偏倚预防2013

Bias

in

EpidemiologicalResearch流行病学研究中的偏倚1陈裕明教授医学统计与流行病学系Tel:

8733

0605Main

contents2Measurement

Error

测量误差Random

errorSystemic

error

(Bias)Bias

偏倚：sources,common

bias,and

control

methods来源、常见偏倚、控制方法Selection

bias

选择偏倚Information

bias

信息偏倚Confounding

bias

混杂偏倚

Should

I

believe

the

results?

CoffeeDiabetesRR

=

0.7

(95%CI,

0.65-0.84)Chance?Confounding?Bias?True

associationCausalNon-causal3Measurement

Error4Random

error:

leads

to

unreliable

measurementSystematic

error:

leads

to

biased

measurement5Measurement

error:Implications

for

epidemiologic

studies6RANDOM

ERRORBias

toward

thenull

(e.g.,

RR

=

1)Systematic

errorbias

ineitherdirectionMeasurement

error:Implications

for

epidemiologic

studies7Measurement

error

in

the

exposure

or

the

e

RANDOM

ERROR

–

Bias

toward

the

null

(e.g.,

RR

=

1)

Systematic

error

–

bias

in

either

directionMeasurement

error

in

a

confounder

Random

error

–

dilutes

ability

to

adjustSystematic

error

–

confounded

estimate

of

effectAttenuation

of

the

relations随机误差减弱关联强度Physiological

variables********R=0.96R=0.658Random

error随机误差9Error

due

tochance“that

part

of

our

experience

that

we cannot

predict”Usually

most

easily

conceptualizedas sampling

variabilityRandom

error

can

be

problematic,but

.

.

.Influence

can

be

controlled by…increasing

sample

sizechanging

designimproving

instrumentation10How

do

we

quantify

random

error

inatestorastudy?Foratestofexposures, es,

confoundersCoefficient

of

variation,

CVRepeat

measures,CV=

SD/mean

For

a

test

of

association,

incidence,prevalenceHypothesis

testing,

p-value,

95%CI11Bias12Definition

of

biasBias

is

systematic,non-random

deviation

of

results

orinferences

from

the

truth,or

processes

leading

to

suchdeviation.研究结果或推论系统地偏离真实值，或导致这种偏离的过程。Bias:

any

trend

in

the

design,

conduct,

analysis,interpretation,

publication

or

review

of

data

that

canlead

to

conclusions

which

are

systematically

differentfrom

the

truth.

(Dictionary

of

Epidemiology,

3rd

ed.)在设计、实施、分析、结果解释、发表或评阅过程中，能够导致结论系统地偏离真实值的任何趋势13Question?14Can

you

control

or

reducebias

by

increasingsample

size?Errors

in

epidemiological

studies15Classification

of

bias

分类Selection

bias

选择偏倚–differentialaccessto

the

studypopulationInformation

bias

信息偏倚–inaccuracy

inmeasurement

or

classificationConfounding

bias

混杂偏倚–unfaircomparison16SELECTION

BIAS

-

definitionSELECTION

BIAS

选择偏差:Errors

in

theprocess

of

identifying

the

study

population,which

causes

the

study

sample

does

notrepresent

the

target

population.在确定研究人群时出现的系统误差，使得研究样本不能代表总体17Sources

of

Selection

bias选择性偏倚的来源 Sampling

bias

抽样偏倚--the

degree

towhich

the

measured

subjects

are

notrepresentative

of

the

population,

is

due

to

:Convenience

Sample

方便样本Violated

random

sampling

scheme

偏离 随机抽样方案–

Haphazard

Sample偶然样本–

研究者有意或无意地基于某因素来选择18Sources

of

Selection

bias选择性偏倚的来源Participation

bias

参加者偏倚–due

to

participantsSelf-selection

(volunteerism)自我选择偏倚Healthy

(or

diseased)

people

may

seek

out

participation

in

thestudyNon-response,refusal

无应答偏倚Response,orlack

ofit,

dependsonexposureHealthy

worker

effect

健康工人效应Differential

loss

tofollow-up

选择性失访Bias

due

to

differences

in

completeness

of

follow-upbetween

comparison

groups19Sources

of

Selection

bias选择性偏倚的来源 Ascertainment

bias确认偏倚--systematicerror

due

to

a

difference

in

characteristics

between

whochoose

to

participate

in

a

study

and

whose

who

do

not.Prevalence-incidence

bias

现患与新发病例偏差Prevalent

case

is

likely

to

bemild,

andsurvivelongerReferral

bias

转诊偏倚Sicker

patients

are

referred

to

major

health

centers20Sources

of

Selection

bias选择性偏倚的来源3.

Ascertainment

bias

确认偏倚Diagnostic

bias

诊断偏倚Diagnosis

of e

associated

with

exposureAdmission

rate

bias

(Berkson’s

bias)入院偏差Hospitalization

rates

differ

for

by

disease

andpresence/absence

ofthe

exposureofinterestLead

time

bias

领先时间偏倚21Sampling

bias抽样偏倚Casesliver

cirrhosisControls

A

trauma

wardHeavy

alcohol

useLight/no

alcohol

use80402060OR=6How

representative

are

hospitalised

trauma

patients

of

thepopulation

which

gave

rise

to

the

cases?22Sampling

bias抽样偏倚Cases

liver

cirrhosisControls

A

trauma

wardControls

B

non-traumaHeavy

alcohol

useLight/no

alcohol

use804010206090OR=6OR=3623Diagnostic

bias

诊断偏倚Casesuterine

cancerControlsTakesoralcontraceptivesDoes

not

take

oralcontraceptivesabcdDiagnostic

approach

related

to

knowing

exposure

statusOral

Contraceptive

use

breakthrough

bleeding

increased

chance

of

detecting

uterine

cancerOverestimation

of “a”

overestimation

ofOR24Non-response

bias

无应答偏倚Cases

ofcervical

cancerControlsPapanicolau

testDid

not

have

testHad

testabcdTotal10001060Controls

chosen

among

women

at

their

homes:

13000

homescontacted

1060

controlsControls

mainly

housewives

with

lower

chance

of

havingtest

than

women

gainfully

employedUnderestimation

of “b”

overerestimation

of

OR25Paper

smearHad

testDidn’t

have

testHealthy

worker

effect健康工人效应ExposedGeneralworkerspopulationDeaths507,000Person-time1,000100,000in

yearsMortality(cases/year)0.050.07RR=0.726Healthy

worker

effectGeneral

populationExposed

Workers

Non-

Totalworkers

workersDeaths504,5002,5007,000Person-time1,00090,00010,000100,000Mortality(cases/yr)0.050.050.250.072728Loss

to

follow-up

bias失访偏倚Bias

due

to

differences

in

completeness

offollow-up

between

comparison

groupsExampleStudy

of

disease

risk

in

migrantsMigrants

more

likely

to

return

to

place

oforigin

when

having

disease

lost

to

follow-up

lower

disease

rate

among

exposed(=migrant)29Methods

to

reduce

selection

biasRigorous,

but

feasible

random

samplingscheme

严谨可行的随机抽样方案Clear

definition

of

study

population清楚定义研究人群Explicit

case/control,

expose/non-exposedefinitions明确病例/对照,暴露/非暴露的定义Cases

and

controls

from

same

population病例和对照来自同一人群30Methods

to

reduce

selection

biasSelection

of

cases

and

controls

without knowing

exposure

status

(case-control study)选择病例对照不要知道暴露状态Selection

of

exposed

and

non-exposedwithout

knowing

disease

status(retrospective

cohort)选择暴露与非暴露人群不要知道结局–

Strive

for

high

participation

rate

(incentive)–

尽量提高参与率Information

bias信息偏倚31Information

biasSystematic

error

in

the

measurement

ofinformation

on

exposure

or

e在测量暴露或结局时发生的系统误差Differences

in

accuracyof

exposure

data

between

cases

andcontrolsof e

data

between

different

exposuregroups32Sources

of

Information

bias偏倚的来源Respondent

应答者,:inability

to

understand,recall,articulate;unwillingness

to

disclose

or

socialdesirabilityData

collector

资料收集者: unclear

orambiguous

questions,

lack

of

a

neutral

demeanor,insufficiently

conscientious,

inaccurate

transcription,fraudInstrument

测量工具:inaccurate

instrument33Sources

of

information

biasData

managers

资料管理者:

inaccuratetranscription,

mis-reading,

miscoding,

programmingerrorsData

analysts资料分析者: variable

coding

andprogramming

errorsData

interpreters

资料解释者:

inadequateappreciation

of

the

characteristics

of

the

measure

orof

the

relations

being

studied34Main

types

of

informationbiasReporting

bias

报告偏倚Recall

bias

回忆偏倚Biased reporting

偏倚的报告Observer

bias

观察者偏倚Data

collection

bias

资料收集偏倚Interviewer

bias

访问者偏倚Biased

follow-up

偏性随访detection

bias

检测偏倚Measurement

bias

测量偏倚35Definition

of

common

information

Bias-136Data

collection

bias资料收集偏倚Biasthat

resultsfrom

abstracting

charts,interviews

or

surrogateinterviewsRecall

bias

回忆偏倚Disease

occurrence

enhances

recall

aboutpotential

exposuresDetection

bias

检测偏倚The

exposure

promoted

morecarefulevaluation

for

the e

ofinterestDefinition

of

common

information

Bias-137Interviewer

bias

访问者偏倚Systematic

difference

in

soliciting,

recording,interpreting

information.Reporting

bias

报告偏倚Exposure

may

be

under-reported

because

of attitudes,

perceptions,

or

beliefsMothers

of

children

with

malformations

will

remember

pastexposures

better

than

mothers

with

healthy

childrenRecall

bias

回忆偏倚Children

withmalformationControlsTook

tobacco,alcohol,

drugsDid

not

takeabcdCases

remember

exposure

differently

than

controlsMothers

ofOverestimation

of “a”

overestimation

ofOR•38Investigator

may

probe

listeriosis

cases

about

consumption

ofsoft

cheeseInterviewer

bias

访问者偏倚Investigator

asks

cases

and

controls

differently

about

exposureCases

oflisteriosisControlsEats

soft

cheeseDoes

not

eatsoft

cheeseabcdOverestimation

of “a”

overestimation

ofOR•39Biased

follow-up

偏性随访Unexposed

are

less

diagnosed

for

disease

thanexposedExampleCohort

study

to

investigate

risk

factors

for mesothelioma

间皮瘤Difficult

histological

diagnosisHistologist

more

likely

to

diagnose

specimen as

mesothelioma

if

asbestos(石棉)exposure kown40Impact

of

information

bias:MisclassificationMeasurement

error

leads

toassigning

wrong

exposure

or

ecategory41Impact

of

information

bias:Misclassification42Non-differential

无差异错误分类（错分）Error

in

assessing

exposure

or

disease

is

similar between

study

groupsMeasure

of

effect

tends

toward

1Differential差异错分Error

in

assessing

exposure

(or

disease)

differs in

different

study

groupsMay

increase

or

decrease

measure

of

effectHypothetical

Case-Control

study43OR

=

60*60/40*40

=

2.25DDˉE6040Eˉ4060100100DDˉE4832Eˉ5268100100Percent

ExposureMisclassification:20%

20%OR

=

48*64/36*52

=

1.96

OR

DifferentialmisclassificationDifferentialmisclassification44Hypothetical

Case-Control

studyOR

=

60*60/40*40

=

2.25DDˉE6040Eˉ4060100100DDˉE5732Eˉ4368100100Percent

ExposureMisclassification:5%

20%OR

=

48*64/36*52

=

2.74Techniques

to

reduce

information

bias(1)Standardize

measurement

instrumentsAdminister

instruments

equally

to

cases/controls

or

exposed/unexposedUse

objective

parameters

ifpossibleUse

multiple

sources

of

informationQuestionnairesDirect

measurementsRegistriesCase

records45Techniques

to

reduce

information

bias

(2)Use

multiple

controlsUse

re-classified

subjects

to

check

forbiasUse

memory

aids

and

validateexposuresProvide

standardized

training

sessionsand

protocols46Techniques

to

reduce

information

bias

(3)Blinding:Blind

participants

as

to

study

goals

and participants’

classification

statusBlind

researchers

as

to

subjects’

study

statusTry

to

ensure

that

question

are

clearlyunderstood

through

careful

wording

andpretesting47Confounding48混杂49Confounding局联系的扭曲。Latin:

confundere

–

“to

mix

together”Confounding

is

a

distortion

inan association

between

a

study

exposure and

disease

brought

about

by

the influence

of

extraneous

factors混杂是由于外来因素的影响导致的暴露与结50ConfoundingConfounders

混杂因素:extraneous

factor that

biases

the

association

we

are interested

inare

calledconfounders.混杂因素：扭曲暴露与结局之间联系的外来因 素51Example

1:Case-control:

OC–

breast

Ca;

Covariate:

SmokingSocialOC

Users

NonusersORstatusDNon-DDNon-DLow2550751501Middle505050501High1204030101Total1951401552101.89Confounding

occurred

because

smoking

is

positivelyassociated

with

OC

and

breast

Ca52Example

2:Cohort:

Physical

activity–

CHD;

Covariate:

age,sexActive

SedentarySex-age

RRDPTDPTM:50-59709,50038628,5000.54M:60-69666,00036418,0000.54F:50-591510,0008330,0000.54F:60-69417,50022622,5000.54Total19233,0001,05999,0000.54Confounding

didn’t

occurbecause

activity

was

not

associated

withageand

sex,

though

both

age

and

sex

werepredictors

of

CHDProperties

of

confoundersTo

be

a

confounder

,A

covariate

(C)must

bearisk

factor

forthe

disease

(D)inthe unexposed

basepopulation,

orit

must

bea

marker(proxy)

for another

(usually

unmeasured)

riskfactor.C

must

be

associated

with

exposure

in

the

total

base populationCE?D53Properties

of

confoundersC

is

NOT

a

confounderif

its

association

with

D

in

the

date

is

due

to

chance

or

biasIf

the

association

is

due

to

the

effect

of

D

on

CIf

the

effect

of

C

on

D

is

not

independent

of

E4）C

is

an

intermediate

variable

in

the

causalpathway

between

E-DECCE?DEC1)2)D3)?D54Summary:Properties

of

confounders55The

confounding

variableisCAUSALLY

associated

with

the

disease

(

e),but

is

not

a

consequence

of

thedisease.Noncausally

or

causally

associated

with

theexposure,but

is

not

a

consequence

oftheexposure.56A

variable

cannot

be

a

confounder

if

it

is

a

stepin

the

causal

chain

or

pathway.Example

Moderate

alcohol

consumption高脂高热能饮食TC

TG

LDLHDL

FG

Insulin

冠心病糖尿病高血压低体力活动Question?57Which

variables

are

potentialconfounders?•Usually,

risk

factors

fordisease.Howdoyouknowifavariableisaconfounder

in

your

data

or

not?Compare

crude

and

adjusted

measures

ofassociation.If

they

differ

appreciably,

the

answer

is

“yes.”Controlof

confounding58Design

strategiesRandomizationRestrictionMatchingAnalysis

strategiesStandardizationStratificationMultivariate

analysesPartIII:Validity59Validity60Definition

:

thedegreeto

whichameasurement

orstudy

reachesacorrect

conclusion.Types:internalvsexternalvalidityStudy

Validity61Internal

validityThe

degree

to

which

the

observed

results

of

the study

are

true.Inferences

are

correct

regarding

the

participants in

the

studyExternal