The Third Factor

7/25/2019 The Third Factor

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The third factor

Effect modification

Confounding factorFETP India


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Competency to be gained

from this lectureIdentify and describe an effect modification

Eliminate a confounding factor


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Key elements

Describing an effect modification

Eliminating a confounding factor


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Stratification

Sub-groups can be defined according to

various characteristics in a population

ge Se!

Socio-economic status

n association bet"een a ris# factor and an

outcome may be studied "ithin these various

strata


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Key elements



Effect modification


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Spotting effect modification

in a stratified analysis Effect modification $% Interaction& occurs

"hen the ans"er about a measure of

association is' (it depends)

E!amples' Efficacy of measles vaccine

*ariation according to the age +is# of myocardial infarction among "omen

ta#ing oral contraceptives *ariation according to smo#ing habits

Effect modification


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Conduct crude analysis

Stratify data by suspected modifier

,bserve the association strata by strata

udge the heterogeneity of'

,dds ratios

+elative ris#s Test a potential difference

+eport the effect modification

Effect modification


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,bserve the association strata by strata

udge the heterogeneity of'

,dds ratios



Effect modification


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,bserve the association strata by strata udge the heterogeneity of'

,dds ratios



Effect modification


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Diarrhoea Controls Total

No breastfeeding 120 136 256

Breastfeeding 50 204 254

Total 170 340 510

Death from diarrhoea according to

breastfeeding. /ra0il. 1234s

$Crude analysis&

Odds ratio: 3.6 !5" C#: 2.4$ 5.5 % & 0.0001

Effect modification


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,dds ratios

+elative ris#s

Test a potential difference

+eport the effect modificationEffect modification


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Infants 5 1 month of age

Cases Controls Total


Breastfeeding 7 6' 75

Total 17 71 ''

Infants 6 1 month of ageCases Controls Total


Breastfeeding 43 136 17!

Total 153 26! 422

Death from diarrhoea according

to breastfeeding. /ra0il. 1234s


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,dds ratios



Effect modification


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Breastfeeding 7 6' 75

Total 17 71 ''


to breast feeding. /ra0il. 1234s'

nalysis among infants 5 1 month of age

Odds ratio: 32.4 !5" C#: 6$ 203 % & 0.0001

Effect modification


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Breastfeeding 43 136 17!

Total 153 26! 422


to breast feeding. /ra0il. 1234s'

nalysis among infants 6 1 month of age

Odds ratio: 2.6 !5" C#: 1.7$ 4.1 % & 0.0001

Effect modification


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,dds ratios



Effect modification


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udge the heterogeneity of the

measures of association To be a difference. a difference should ma#e

a difference

+evie" public health implications ,dds ratios in the specific e!ample'

Strata 1' ,+ % 789 2:; CI' - ?=1

Effect modification


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,dds ratios



Effect modification


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@oolfAs test for heterogeneity

of the odds ratios Statistical testing of the heterogeneity of the

odds ratios

Bac#s statistical po"er

Calculation'

In statistical te!tboo#s

In the soft"areAs analysis output

udgement is important

Effect modification


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andling heterogeneous

measures of association

E f f e c t m o d i f i c a t i o n

, + s + + s 2 : ; C = I =

d o n o t o v e r l a p


@ o o l f s t e s t s i g n i f i c a n t

D i s c u s s l a c # o f p o " e r

o f @ o l l f s t e s t


u n l i # e l y

@ o o l f s t e s t n o t s i g n i f i c a n t

F s e @ o o l f s t e s t

, + s + + s C = I =

d o o v e r l a p

, + s + + s a r e

d i f f e r e n t a c r o s s s t r a t a


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,dds ratios



Effect modification


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Conclusion of the /ra0ilian case-control

study on breastfeeding

and death from diarrhoea The protective efficacy of breastfeeding is

more mar#ed among infants under the age of

one month This may correspond to a biological

phenomenon that must be reported as part

of the results

Effect modification


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+eporting results in the presence of

an effect modification ,nce the effect modification "as detected

the study population is split

+esults for the ris# factor considered arereported stratum by stratum

Effect modification


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*accination against hepatitis / among

institutionali0ed children in +omania epatitis / is highly endemic in +omania

Gany children live in institutions

Institutionali0ed children are at higher ris# 122:' epatitis / immuni0ation initiated

122>' Evaluation through serologic survey

Effect modification


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epatitis / vaccine efficacy among

institutionali0ed children over < months

of age H. +omania. 122>

nti-/c $& nti-/c $-& ++ 2:; C=I=

7 doses 1: 737 4=?3 4=1>-1=?

5 7 doses ? ?> +ef=

H /orn after implementation of routine vaccination

(a))ine e*)a)+, 52", !5" C# 0$'3"

-B(

(a))ine

Effect modification


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institutionali0ed children over < months

of age H. by district. +omania. 122>nti-/c $& nti-/c $-& ++ 2:; C=I=

7 doses 18


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+omanian children in institutions'

Conclusions The protective efficacy of hepatitis /

vaccine appears lo" overall

This overall lo" efficacy does notcorrespondto a biological phenomenon

In fact. the efficacy is' Jormal in most districts $33;&

Bo" in district

This points to"ards programme errors thatmust be identified and prevented

Effect modification


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Describing an effect modification'

Summary The analysis plan'

nticipates effect modifiers to collect data

The analysis' Boo#s for effect modification to test it

The report'

/rea#s do"n the population in strata to report

the effect modification

Effect modification


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Key elements



Confounding factor


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@hat may e!plain an association

bet"een a ris# factor and an outcomeLL Chance

L /ias

L Third factorL Causal association

Confounding factor


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@hat may e!plain an association

bet"een a ris# factor and an outcomeLL Chance

L /ias

L Third factorL Causal association

Confounding factor


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Exposure

Characteristics of a third.

confounding factor ssociated "ith the e!posure

@ithout being a conseMuence of e!posure

ssociated "ith the outcome Independently from the e!posure

Outcome

Confounding factor

Confounding factor


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The nuisance introduced by

confounding factors Gay simulate an association

Gay hide an association that does e!ist

Gay alter the strength of the association Increased

Decreased

Confounding factor


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Outcome

E!ample of confounding factor

Exposure 1

pparent association

Confounding

factor

Confounding factor


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Pneumonia

E!ample of confounding factor $1&

Ethnicity

pparent association

Crowding

Confounding factor


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Pneumonia

E!ample of confounding factor $8&

Crowding

ltered strength of association

Malnutrition

Confounding factor


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Eliminating confounding in the

pneumonia e!ample

Estimate the strength of the associationbet"een malnutrition and pneumonia

Estimate the strength of the associationbet"een cro"ding and pneumonia dNusted for the effect of malnutrition

Eliminate the confounding effect of cro"ding

on the false association bet"een ethnicityand pneumonia

Confounding factor


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Controlling a confounding factor

Stratification

+estriction

Gatching +andomi0ation

Gultivariate analysis

Confounding factor


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Stratification

+estriction



Confounding factor


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dNustment to eliminate confounding

E!amine strength of association across strata

Chec# for the absence of effect modification

If there is an effect modification. brea# invarious strata. report= End of the story

,bservation of a strength of association' omogeneous across strata

Different from the crude measure Calculate "eighted average of stratum-

specific measures of association

Confounding factor


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Galaria and radio sets

ypothesis' Could radio "aves be a repellent

for female anophelesL

Cohort study on the ris# factors for malariain an endemic area

Confounding factor


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Incidence of malaria according to the

presence of a radio set.

Kahinbhi Pradesh

Cr/de dataalaria No alaria Total

adio '0 440 520

No radio 220 '60 10'0

Total 300 1300 1600

: 0.7 !5" C#: 0.6$ 0.! % & 0.02

Confounding factor


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Kahinbhi Pradesh

trata 1: lee%ing /nder a os/ito netalaria No alaria Total

adio 30 370 400

No radio 50 630 6'0

Total '0 1000 10'0

: 1.02 !5" C#: 0.7$ 1.6 % & 0.!7

Confounding factor


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Kahinbhi Pradesh

trata 2: lee%ing itho/t a os/ito netalaria No alaria Total

adio 50 70 120

No radio 170 230 400

Total 220 300 520

: 0.!' !5" C#: 0.'$ 1.2 % & 0.!5

Confounding factor


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Gantel-aens0el adNusted relative ris#

$-

[(ai80i9 Ti;

[()i 81i9 Ti;

Confounding factor


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Galaria and radio sets'

Conclusion

Jo association bet"een radio and malaria

"ithin each strata

The ne" adNusted relative ris# replaces thecrude one

MalariaRadio sets

pparent association

Mosquito nets

Confounding factor


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OR M-H

[(ai!di" # $i%

[(&i!ci" # $i%

Gantel-aens0el adNusted odds ratio

Confounding factor


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Stratification

+estriction



Confounding factor


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epatitis / and blood transfusion in

Goldova

epatitis / virus infection is highly endemic

in Goldova

+outes of transmission are un#no"n case control study "as initiated to assess

potential modes of transmission

Confounding factor


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Transf/sion 3 1 4

Non$transf/sion 6! 1'! 25'

Total 72 1!0 262

Odds ratio: '.2 !5" C# : 0.'$220

cute hepatitis / and receiving a

transfusion in Goldova. 122?-122:

Confounding factor


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cute hepatitis / and receiving a

transfusion in Goldova. 122?-122:

$ccording to receiving inNections&

Case Control Total

Transf/sion 3 1 6

No transf/sion 22 6 2'

Total 25 7 32

Case Control Total

Transf/sion 0 0 0

No transf/sion 47 1'3 230

Total 47 1'3 230

Odds ratio: $

#n


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Stratification

+estriction



Confounding factor


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Stratification

+estriction



Confounding factor


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+andomi0ation

Distribution of e!posure of interest at

random in the study population for a

prospective cohort

n association bet"een an e!posure and a

confounding factor "ill be'

Secondary to chance alone

Improbable

Confounding factor


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Stratification

+estriction


Gultivariateanalysis

Confounding factor


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Gathematical model

Simultaneous adNustment of all confounding

and ris# factors Can address effect modification

Confounding factor


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Ta#ing into account a third factor

in practice

1= Thin# of potential confounding factors

8= Collect accurate data on them

7= Conduct crude analysis

?= Stratify:= Boo# for effect modification

re the ++ or ,+ different to each otherL


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naly0ing a third factor

+ e p o r t , J E c r u d e , + + +

T h i r d f a c t o r d o e s n o t p l a y a r o l e

S t r a t a , + s + + s s i m i l a r t o c r u d e

$ C r u d e v a l u e f a l l s b e t " e e n s t r a t a &

E l i m i n a t e t h e c o n f o u d i n g

+ e p o r t , J E a d N u s t e d , + + +

d N u s t u s i n g t h eG - t e c h n i M u e

C o n f o u n d i n g f a c t o r

S t r a t a , + s + + s d i f f e r e n t f r o m c r u d e

$ C r u d e v a l u e d o e s n o t f a l l b e t " e e n s t r a t a &

I d e n t i c a l , + s + + s a c r o s s s t r a t a

+ e p o r t G F B T I P B E , + s + + s f o r e a c h s t r a t u m

S t o p t h e a n a l y s i s =

D , J , T a d N u s t O


D i f f e r e n t , + s + + s a c r o s s s t r a t a

E ! a m i n e , + s + + s i n e a c h s t r a t u m

E ! a m i n e c r u d e , + + +


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Ta#e-home messages

Describe effect modifications

The analysis must TEST for their occurrences

Control confounding factors The analysis must EBIGIJTE their influence

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The Third Factor