Cohort studies - Hans Wolff

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Cohort studies<= /b>

Cohort study (CS)

Cohort study (CS)

Cohort study (CS)

Outline

Cohort Design

Example

Study design

Study design

Which is a fundamen= tal condition for the validity of this cohort design ?

�At risk of Respira= tory Cancer�

�Incident Respirato= ry Cancer�

What is the risk of respiratory cancer in this study ?

Cohort Design

Risk of respiratory cancer
in unexposed

What is the risk of respiratory cancer in unexposed ?

Calculating Risk in Unexposed

Risk in Unexposed

Cohort Design

Risk of respiratory cancer
in exposed to nickel

Calculating Risk in Exposed

Risk in Exposed=

What is an incidenc= e rate of
respiratory cancer in this study?

Notation

Incidence rate (IR)= =3D risk per unit of time

Slide 26

Incidence rate (IR)= =3D risk per unit of time

Study design

Example

Slide 30

What is an attribut= able risk
in this study?

Absolute Effect:
Attributable Risk (AR)� (2)=

Attributable Risk

What is a relative = risk in this study?

Relative Effect:
Relative Incidence Rate (RIR)*

Relative Effect=

Relative Effect=

Relative or Absolute Effect

Interpretation<= /b>

Example: Wrapping u= p

Prospective Studies= :� Advantages

Prospective Studies= :� Disadvantages
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Cohort studies<= /b>

Hans Wolff

Service d��pid�miol= ogie Clinique,

D�partement de m�de= cine communautaire
Hans.Wolff@hcuge.ch

Cohort study (CS)

Cohort study (CS)

Cohort study (CS)

Outline

Working Example

Welsh Nickel Worker= s Study

Description of the = study and raw� data in�

Breslow, N.E., Day = N.E. Statistical Methods in Cancer Research. IARC, 1987:369-74

Cohort Design

Example

Study design

Study design

Which is a fundamen= tal condition for the validity of this cohort design ?

�At risk of Respira= tory Cancer�

Never had respirato= ry cancer: exclude prevalent cases

Still have two lung= s � and a nose: exclude subjects who cannot travel from the denominator to the numerator

�Incident Respirato= ry Cancer�

Incident =3D �newly= diagnosed�

Between April 1,193= 4 and
December 31,1981

Risk Period =3D 47 = years

Employed in the fac= tory before 1925

What is the risk of respiratory cancer in this study ?

Cohort Design

Risk of respiratory cancer
in unexposed

What is the risk of respiratory cancer in unexposed ?

Calculating Risk in Unexposed

Risk in Unexposed

Interpretation:

Probability of deve= loping a respiratory cancer in workers unexposed to nickel is 20% over 47 years

Cohort Design

Risk of respiratory cancer
in exposed to nickel

Calculating Risk in Exposed

Risk in Exposed=

Interpretation:

Probability of deve= loping a respiratory cancer in workers exposed to nickel is 40% over 47 years

What is an incidenc= e rate of
respiratory cancer in this study?

Notation

Incidence rate (IR)= =3D risk per unit of time

Risk period =3D� 47 yrs.

Some subjects follo= wed-up for < 47 yrs.

E.g., cases, losses= to follow-up

Solution # 1=

=3D divide risk by = average duration
�� of follow-up (24yrs)<= /td>

Slide 26

Incidence rate (IR)= =3D risk per unit of time

Solution # 2=

Use person-time as = denominator

1 person followed f= or 2 years =3D 2 person-year

1 person followed f= or 1 year =3D 1 person-year

Study design

Example

Slide 30

What is an attribut= able risk
in this study?

The ratio of the ri= sk of RC in exposed to Nickel over the risk in unexposed?

The risk of RC that= is not due to Nickel exposure

The excess rate of = RC observed in subjects exposed to nickel compared to unexposed

The number of worke= rs that need to be exposed to nickel in order to observe an additional case of RC

All of the above

Absolute Effect:
Attributable Risk (AR)� (2)=

AR=3D I= R(E+) - IR(E-)

=3D IR (E+) - IR= (E -)

=3D 0.024/yr - 0= .008/yr =3D 0.016/yr

=3D 16 /1,000/y<= /font>

=3D Excess IR of= RC due to nickel

Attributable Risk

IR(E+) =3D�� IR(E-) + AR�� =3D� 0.008 + 0.016� =3D 0.024

Synonymous:<= /td>

Excess Risk<= /td>

Risk Difference

Excess Rate<= /td>

What is a relative = risk in this study?

The ratio of the IR= of RC in exposed to nickel over the IR in unexposed?

The IR of RC that i= s not due to nickel exposure

The excess risk of = RC observed among subjects exposed to nickel

The number of worke= rs that need to be exposed to nickel in order to observe an additional case of RC

None of the above

Relative Effect:
Relative Incidence Rate (RIR)*

Relative Effect=

Relative Effect=

Relative or Absolute Effect

Interpretation<= /b>

Example: Wrapping u= p

Prospective Studies= :� Advantages

Exposure to postula= ted cause is assessed before occurrence of disease

Possible to estimat= e all measures of incidence and effect

Possible to study s= everal outcomes to one cause

Prospective Studies= :� Disadvantages

Requires large inve= stments in time, human and financial resources

Requires large samp= le sizes (e.g., 110.000 nurses, 59.600 doctors, 1.2 millions volunteers)

Not easy to reprodu= ce (Re: consistency of the association)

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Click to edit Master title style

Click to edit Master text styles

Second Level

Third Level

Fourth Level

Fifth Level

WHO- Postgraduate course 2006 � Coh= ort studies

February 22, 2006
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Click to edit Master title style=

Click to edit Master subtitle st= yle

October 25, 2001

Mailman School of Public Health
<= span style=3D'mso-spacerun:yes'>�
Departm= ent of Epidemiology

Lecture 7
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------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/pres.xml Content-Transfer-Encoding: quoted-printable Content-Type: text/xml; charset="utf-8" ------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/v3_slide0626.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

Cohort studies

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Hans Wolff

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Cohort study (CS)

Environmental factors

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Cohort studies - Hans Wolff

Cohort study (CS)

Environmental factors

What is the outcome ?

Cohort studies - Hans Wolff

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Environmental factors

What is the outcome?

Cohort studies - Hans Wolff

Outline

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Cohort Design

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90

360

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Example

<= /td> <= /td>

450 Unexposed

To Nickel

Respiratory Cancer

1= 00

9= 0

Person-years

4= ,100

1= 1,000

Incidence Rate=

0= .024/yr

0= .008/yr

3= .0

Relative Incid= ence rate

0= .016/yr

Attributable R= isk

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Study design

<= /td>

� Po= pulation: a Nickel factory of South Wales

<= /td> =

� Ni= ckel production by decomposition of gaseous

ni= ckel compounds

<= /td> =

� Ex= posure: according to information on jobs at high

ri= sk of exposure held from 1902 to 1934

<= /td> =

� Ri= sk period: count cases of RC= * between April

19= 34 to December 1981

* RC =3D= respiratory cancer

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Study design

<= /td> <= /td>

Exposure

Period

<= /td> <= /td>

Risk

Period

= 1925

= 1902

= 1934

= 1981

<= /td>

Need to be

employed

before 1925

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=

Which is a fundamental condition for the

validity of this cohort design ?

<= /td>

� Subjects need to be:

<= /td>

1. A = random sample of the population?

<= /td>

2. At= risk of developing lung or nasal cancer ?

<= /td>

3. Un= likely to get colon cancer ?

<= /td>

4. Ra= ndomized to nickel exposure ?

<= /td> =

5. Wi= lling to answer questionnaires for

ma= ny years ?

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�At risk of Respiratory Cancer�

<= /td> = = <= /td> <= /td> <= /td>

� Ne= ver had respiratory cancer:

ex= clude prevalent cases

� St= ill have two lungs � and a nose:

ex= clude subjects who cannot travel

fr= om the denominator to the

nu= merator

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�Incident Respiratory Cancer�

<= /td> <= /td> <= /td> = <= /td> <= /td> <= /td>

� In= cident =3D �newly diagnosed�

� Be= tween April 1,1934 and

De= cember 31,1981

� Ri= sk Period =3D 47 years

� Em= ployed in the factory before 1925

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<= /td> =

1. Pr= obability of developing RC per 100,000

wo= rkers and per year

<= /td>

2. Pr= obability of developing RC over 47 years

<= /td>

3. Th= e excess probability of RC due to exposure

<= /td>

5. A = synonymous for the odds of RC

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Cohort Design

SOUTH WALES= REFINERY WORKERS

250

450

<= /td> <= /td>

No Respiratory

Cancer

<= /td> <= /td>

No Respiratory

Cancer

<= /td> <= /td>

Respiratory

Cancer

<= /td> <= /td>

Respiratory

Cancer

100

150

90

360

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<= /td> <= /td>

Unexposed to

Nickel

Respiratory Cancer

9= 0

Total

= 450

Person-years

= 11,000

Risk =3D=

Interpretation:

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= 90

= 450-90

= 90

3.

2.

1.

= 450-90

= 450

= 450

= 90

= �� 90

4.

5.

11,000 - 90

= 11,000

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New events

Risk_{time<=
/sub>� =3D}

Population �at risk� at baseline

90 cases of RC

Risk_{47 yr=
s} =3D

<= /td> <= /td>

450 subjects

= free of RC

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Risk in Unexposed

<= /td> <= /td> = <= /td> = <= /td>

� Interpretation:

� Pr= obability of developing a

re= spiratory cancer in workers

un= exposed to nickel is 20%

ov= er 47 years

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Cohort Design

SOUTH WALES= REFINERY WORKERS

250

450

<= /td> <= /td>

No Respiratory

Cancer

<= /td> <= /td>

No Respiratory

Cancer

<= /td> <= /td>

Respiratory

Cancer

<= /td> <= /td>

Respiratory

Cancer

100

150

90

360

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<= /td> <= /td>

Exposed to

Nickel

Respiratory Cancer

1= 00

Total

= 250

Person-years

= 4,100

Risk =3D=

Interpretation:

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Calculating Risk in Exposed

New events

Risk_{time<=
/sub>� =3D}

Population �at risk� at baseline

100 cases of RC

Risk_{47 yr=
s} =3D

<= /td> <= /td>

250 subjects

= free of RC

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Risk in Exposed

<= /td> <= /td> = <= /td> = <= /td>

� Interpretation:

� Pr= obability of developing a

re= spiratory cancer in workers

ex= posed to nickel is 40%

ov= er 47 years

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<= /td> =

1. Pr= obability of developing RC per 100,000

wo= rkers and per year

<= /td>

2. Pr= obability of developing RC over 47 years

<= /td>

3. Th= e excess probability of RC due to exposure

<= /td> <= /td> =

4. Th= e ratio of the probability of disease in

ex= posed over the probability of disease in

un= exposed

<= /td>

5. Eq= uivalent to the odds of disease (odds of RC)

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Notation

<= /td>

� R =3D Risk

<= /td>

� IR =3D Incidence rate

<= /td>

� E+ =3D� Exposed to nickel

<= /td>

� E�� =3D� Non-exposed to dime= s

<= /td>

� R(E+)� =3D� Risk in exposed to = nickel

<= /td>

� IR(E+)� =3D� Incidence rate in e= xposed to nickel

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New RC cases

= Risk =3D

Pop. at risk

<= /td> <= /td>

Incidence

Rate

New RC cases

= =3D

Pop. at risk * Duration

90 cases RC

IR (E�) =3D

450 men * 24 yrs

= 90

= =3D

= =3D

= 0.008/yr

<= /td> <= /td>

11,000 person-

= years

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Study design

<= /td> <= /td>

Exposure

Period

<= /td> <= /td>

Risk

Period

= 1925

= 1902

= 1934

= 1981

Py =3D 47=

RC

Py =3D 30=

lost

Py =3D 10=

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Example

<= /td> <= /td>

Unexposed to

Nickel

<= /td> <= /td>

Exposed to

Nickel

Respiratory Cancer

1= 00

9= 0

Person-years

4= ,100

1= 1,000

Incidence Rate=

?

0= .008

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100 cases RC

IR (E+) =3D

4,100 person-years

= =3D

0.024/yr

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<= /td> = <= /td> <= /td> = <= /td> <= /td>

1. Th= e ratio of the risk of RC in exposed to Nickel

ov= er the risk in unexposed?

2. T= he risk of RC that is not due to Nickel exposure

3. Th= e excess rate of RC observed in subjects

ex= posed to nickel compared to unexposed

4. Th= e number of workers that need to be

ex= posed to nickel in order to observe an

ad= ditional case of RC

5. Al= l of the above

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=

Absolute Effect:

Attributable Risk (AR)� (2)

= <= /td> <= /td> =

AR= =3D IR(E+) - IR(E-)

�� =3D IR (E+) - IR (E -)

�� =3D 0.024/yr - 0.008/yr =3D 0.0= 16/yr

�� =3D 16 /1,000/y

�� =3D Excess IR of RC due to nick= el

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/v3_slide0559.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

Attributable Risk

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<= /td> = <= /td> <= /td> <= /td> = <= /td> <= /td>

1. Th= e ratio of the IR of RC in exposed to nickel

ov= er the IR in unexposed?

2. Th= e IR of RC that is not due to nickel exposure

3. T= he excess risk of RC observed among subjects

ex= posed to nickel

4. Th= e number of workers that need to be

ex= posed to nickel in order to observe an

ad= ditional case of RC

5. No= ne of the above

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= IR(E+)

= 0.024

RIR =3D

= =3D 3.0

= =3D

= IR(E�)

= 0.008

* Also referred to as relative risk

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Relative Effect

<= /td> =

� Ri= sk in exposed is a multiple

of= risk in unexposed

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Relative Effect

=

Nickel exposur= e

in= creases RC risk

RIR� >� 1

=

No effect of

ni= ckel exposure

RIR� =3D� 1

=

Nickel exposur= e

pr= otects from RC

RIR� <� 1

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Relative or Absolute Effect

= IR(E+)

= IR(E�)

RR

AR

3.0

<= /td> <= /td>

16

/1000/yr

<= /td> <= /td>

= 8

/1000/yr

<= /td> <= /td>

= 24

/1000/yr

3.0

<= /td> <= /td>

= 20

/1000/yr

<= /td> <= /td>

40

/1000/yr

<= /td> <= /td>

= 60

/1000/yr

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Interpretation

<= /td> = <= /td>

� Attributable risk measures

cl= inical and public health importance

of= the causal relationship

<= /td> =

� Relative risk assesses strength

of= the association

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Example: Wrapping up

<= /td> <= /td>

450 Unexposed

To Nickel

Respiratory Cancer

1= 00

9= 0

Person-years

4= ,100

1= 1,000

Incidence Rate=

0= .024/yr

0= .008/yr

3= .0

Relative Incid= ence rate

0= .016/yr

Attributable R= isk

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Prospective Studies:� Advantages

<= /td> = = = <= /td> <= /td>

� Ex= posure to postulated cause is

as= sessed before occurrence of disease

� Po= ssible to estimate all measures of

in= cidence and effect

� Po= ssible to study several outcomes to

on= e cause

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/v3_slide0586.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

<= /td> = <= /td> <= /td> = <= /td>

� Re= quires large investments in time, human

an= d financial resources

� Re= quires large sample sizes (e.g., 110.000

nu= rses, 59.600 doctors, 1.2 millions

vo= lunteers)

� No= t easy to reproduce (Re: consistency of

th= e association)

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WHO- Postgraduate course 2006 � Cohort studies<= /b><= b>

February 22, 2006 =

Cohort studies

H= ans Wolff

Se= rvice d��pid�miologie Clinique,

D�partement de m�decine communautaire
Hans.Wolff@hcuge.ch

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Cohort study (CS)

Defined

population

Genetic factors

Environmental factors

exposed

non exposed

ill<= /span>

Not ill

T1

T2

hypothesis=

Life style

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file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0628.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Cohort study (CS)

Genetic factors

Populati= on
ill
Environmental factors

exposed
Not ill

What is the outcome ?

T1

T2

Lifestyle

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0628_image057.png Content-Transfer-Encoding: base64 Content-Type: image/png iVBORw0KGgoAAAANSUhEUgAAAOUAAAAnCAYAAADw6Y+pAAAAAXNSR0ICQMB9xQAAAAlwSFlzAAAI NgAACDQBvpAePAAAABl0RVh0U29mdHdhcmUATWljcm9zb2Z0IE9mZmljZX/tNXEAAACiSURBVHja 7dWxDYAwDEVBD8ZQrJA9GIY9GIUiJBIFFaRJAOmKK9186cmRUgqgj5xjLfZiab0xHPSPMp+a4ozL ATBGjXPyKeH9T1ltd0GKEsZF+RijKGFMlHNrjKKEjzICiBIQJYgSECWIEhAliBIQJYjSCCBKQJQg SkCUIEpAlCBKQJQgSkCUgChBlIAoQZSAKEGUgChBlIAoAVGCKAFRwr8dPdkhcW+cpG4AAAAASUVO RK5CYIJ= ------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0629.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Cohort study = (CS)

Genetic factors

Populati= on
ill
Environmental factors

Not exposed

Not ill

What is the outcome?

T1

T2

Lifestyle

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0629_image058.png Content-Transfer-Encoding: base64 Content-Type: image/png iVBORw0KGgoAAAANSUhEUgAAAOUAAAAnCAYAAADw6Y+pAAAAAXNSR0ICQMB9xQAAAAlwSFlzAAAI NgAACDQBvpAePAAAABl0RVh0U29mdHdhcmUATWljcm9zb2Z0IE9mZmljZX/tNXEAAACiSURBVHja 7dWxDYAwDEVBD8ZQrJA9GIY9GIUiJBIFFaRJAOmKK9186cmRUgqgj5xjLfZiab0xHPSPMp+a4ozL ATBGjXPyKeH9T1ltd0GKEsZF+RijKGFMlHNrjKKEjzICiBIQJYgSECWIEhAliBIQJYjSCCBKQJQg SkCUIEpAlCBKQJQgSkCUgChBlIAoQZSAKEGUgChBlIAoAVGCKAFRwr8dPdkhcW+cpG4AAAAASUVO RK5CYIJ= ------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0528.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Outline

�Working Example

<= span style=3D'mso-special-format:bullet;color:#66CCFF;position:absolute;left:-7= .19%; font-family:Wingdings;font-size:80%'>� <= /span>

<= span style=3D'font-size:129%'>�Welsh Nickel Workers Study <= /span>

�&= #13;

�Description of the study and raw� data in�

�Breslow, N.E., Day N.E. <= span style=3D'position:absolute;top:77.0%;left:26.02%;width:67.97%;height:7.5%'= >Statistical Methods in Cancer Research. IARC, 1987:369-74

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0588.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Cohort Design

SOUTH WALES REFINERY WORKERS

Exposed to Nickel

Respiratory
Cancer

= No Respiratory
Cancer

150

100

Respiratory
Cancer

= No Respiratory
Cancer

360

90

250

Unexposed to Nickel

450

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0625.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Example

250 Exposed

To Nickel

450 Unexposed

To Nickel

Respiratory Cancer
Incidence Rate

Relative Incidence rate =

Attributable Risk

100

0.024/yr

3.0

90

Person-years

4,100

11,000

0.008/yr

0.016/yr

------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/slide0531.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252" Cohort studies - Hans Wolff

WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Study design

<= span style=3D'mso-special-format:bullet;color:#66CCFF;position:absolute;left:-4= .19%; top:.22em;font-family:Wingdings;font-size:80%'>�Pop= ulation: a Nickel factory of South Wales

<= span style=3D'mso-special-format:bullet;color:#66CCFF;position:absolute;left:-3= .86%; top:.22em;font-family:Wingdings;font-size:80%'>�Nic= kel production by decomposition of gaseous n= ickel compounds

�Exp= osure: according to information on jobs at high ri= sk of exposure held from 1902 to 1934

�Risk period: count cases of RC* between April <= /span>1934 to December 1981

<= span style=3D'mso-special-format:bullet;color:#66CCFF;position:absolute;left:-3= .5%; top:.22em;font-family:Wingdings;font-size:80%'>�Out= come: respiratory, mostly lung and nasal cancer

* RC =3D respiratory cancer

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

=

=

1902

=

=

1934

=

=

1925

=

=

1981

=

=

Need to= be employe= d
before 1925

Study design

Risk Period

Exposure
Period

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Which is a f= undamental condition for the validity of this cohort design ?

=

<= span style=3D'font-size:114%;color:yellow;mso-color-index:3'>�Subjects need to be:

2.At risk of develop= ing lung or nasal cancer ?

<= span style=3D'mso-special-format:"numbullet3\,3";color:#66CCFF;position:absolut= e; left:-7.31%'>3.Unlikely to get colon cancer ?

<= span style=3D'mso-special-format:"numbullet3\,4";color:#66CCFF;position:absolut= e; left:-7.31%'>4.Randomized to nickel exposure ?

5.Will= ing to answer questionnaires for
many years ?

<= span style=3D'mso-special-format:"numbullet3\,1";color:#66CCFF;position:absolut= e; left:-7.31%'>1.A random sample of the population?

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

=

=

�Never had respiratory cancer: exclude prevalent cases

�=

�Still have two lungs � and a nose: = exclude subjects who cannot travel from the denominator to the numerator

�At r= isk of Respiratory Cancer�

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

�Incid= ent Respiratory Cancer�

�Inc= ident =3D �newly diagnosed�

�

�Bet= ween April 1,1934 and
Decemb= er 31,1981

�Risk Period =3D 47 years

�

�Emp= loyed in the factory before 1925

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

What is the risk of respiratory cancer in this study ?

=

<= span style=3D'font-size:107%'>2.Probability of developing RC over 47 years=

=

3.The excess probability of RC due to exposure

=

4.The ratio of the probability of RC in exposed over the probability of RC in unexposed=

=

<= span style=3D'font-size:107%'>5.A synonymous for the odds of RC

=

1.Probability of developing RC per 100,000
workers and per y= ear

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Cohort Design

SOUTH WALES REFINERY WORKERS

Exposed to Nickel

Respiratory
Cancer

= No Respiratory
Cancer

150

100

Respiratory
Cancer

= No Respiratory
Cancer

360

90

250

Unexposed to Nickel

450

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Risk of respiratory cancer
in unexposed

Inte= rpretation:

Unexposed to
Nickel

Respiratory Cancer
Total

Risk =3D

90

450

Person-years

11,000

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

What is= the risk of respiratory cancer in unexposed ?

90

450-90

90

450

90

11,000

450-90

450

1.

2.

4.

5.

3.

�� 90

11,000 - 90

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

New events

Population �at risk� at baseli= ne

Risktime� =3D

90 cases of RC

450 subjects
free of RC

Risk47 yrs�=3D

=3D 0.2� =3D 20%

Calculating Risk in Unexposed

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Risk in Unexposed

=

�Interpretation:

= �Probability of developing a respiratory cancer in workers unexposed to nickel is 20% over 47 years

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Cohort Design

SOUTH WALES REFINERY WORKERS

Exposed to Nickel

Respiratory
Cancer

= No Respiratory
Cancer

150

100

Respiratory
Cancer

= No Respiratory
Cancer

360

90

250

Unexposed to Nickel

450

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Risk of respiratory cancer
in exposed to nickel

Inte= rpretation:

Exposed to
Nickel

Respiratory Cancer
Total

Risk =3D

100

250

Person-years

4,100

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

New events

Population �at risk� at baseli= ne

Risktime� =3D

100 cases of RC

250 subjects
free of RC

Risk47 yrs�=3D

=3D 0.4� =3D 40%

Calculating Risk in Exposed

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Risk in Exposed

=

�Interpretation:

= �Probability of developing a respiratory cancer in workers exposed to nickel is 40% over 47 years

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

What is an <= span style=3D'font-size:93%;color:yellow;mso-color-index:3'>incidence rate of
respiratory cancer in this stud= y?

=

<= span style=3D'font-size:107%'>2.Probability of developing RC over 47 years=

=

3.The excess probability of RC due to exposure

=

4.The ratio of the probability of disease in exposed over the probability of disease in unexposed

=

<= span style=3D'font-size:107%'>5.Equivalent to the odds of disease (odds of RC)

=

1.Probability of developing RC per 100,000
workers and per y= ear

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Notat= ion

=

<= span style=3D'font-size:114%;color:yellow;mso-color-index:3'>�= IR =3D Incidence rate

=

�= E+ =3D� Exposed to nickel

=

<= span style=3D'font-size:114%;color:yellow;mso-color-index:3'>�= R(E+)= � =3D� Risk in exposed to nickel

=

<= span style=3D'font-size:114%;color:yellow;mso-color-index:3'>�= R= =3D Risk

=

�= E�� =3D� Non-exposed to dimes

=

<= span style=3D'font-size:114%;color:yellow;mso-color-index:3'>= �IR(E+= )� =3D� Incidence rate in exposed to nickel

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Incidence rate (IR) =3D risk per unit of ti= me

�Risk period =3D�= 47 yrs.

�

�Some subjects followed-up for < 47 yrs.

�E.g., cases, losses to follow-up

�

Solution # 1

�=3D divide risk by average duration
�� of follow-up (24yrs)

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New RC cases

Pop. at risk * Duration

Incidence
Rate =

90 cases RC

450 men * 24 yrs

IR (E�) =3D

90

11,000 pers= on-years

=3D =

0.008/yr

=3D

New RC cases

Pop. at risk

Risk =3D

=3D =

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

=

Solution # 2

<= span style=3D'font-size:114%'>�Use person-time as denominator

<= span style=3D'font-size:107%'>�1 person followed for 2 years =3D 2 person-year

�1 person followed for 1 year =3D 1 pers= on-year

Incidence rate (IR) =3D risk per unit of ti= me

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

=

=

1902

=

=

1934

=

=

1925

=

=

1981

Study design

Exposure
Period

Risk Period

=

=

RC

=

=

Py =3D 47

=

=

Py =3D 30

=

=

Py =3D 10

=

=

lost

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Example

Exposed to
Nickel

Unexposed to
Nickel

Respiratory Cancer
Person-years

Incidence Rate

100

4,100

?

90

11,000

0.008

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100 cases RC

4,100 person-years

IR (E+) =3D

0.024/yr

=3D =

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

What is an attributable risk
in this study?

1.The ratio of the risk of RC in exposed to Nickel over the risk in unexposed?

2.The = risk of RC that is not due to Nickel exposure

3.The excess rate of RC observed in subjects exposed to nickel compare= d to unexposed

4.The number of workers that need to be exposed to nickel in order= to observe an additional case of RC

5.All = of the above

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Absolute Effect:<= br> Attributable Risk (AR)� (2)

AR =3D IR(E+) - IR(E-)

=3D IR (E+) - IR (E -)

=3D 0.024/yr - 0.008/yr =3D 0.016/yr

=3D 16 /1,000/y

=3D Excess IR of RC due to nickel

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Attrib= utable Risk

=

IR(E+) =3D�� IR(E-) + AR�� =3D� 0.008 + 0.016� =3D 0.024

�

�= Synonymous:
�Excess Risk= 3;

�Risk Differenc= e

�Excess Rate

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

What is a relative risk i= n this study?

1.The ratio of the IR of RC in exposed to nickel over the IR in unexposed?&= #13;

2.The = IR of RC that is not due to nickel exposure

3.The excess risk of RC observed among subjects exposed to nickel�

4.The number of workers that need to be exposed to nickel in orde= r to observe an additional case of RC

5.None= of the above

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Relative Effect:
Rel= ative Incidence Rate (RIR)*

IR(E+)

IR(E�)

RIR =3D

=3D

0.024

0.008

=3D 3.0

* Also referred to as relative risk

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Relat= ive Effect

=

�IR(E+)� =3D� = [ IR(E-) * RIR ] =3D [ 0.008 * 3.0 ]
�� =3D� 0.024/yr

=

�Risk in exposed is a multiple
of ris= k in unexposed

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Relati= ve Effect

RIR� >= ;� 1

Nickel exposure
increases RC risk

RIR� =3D= � 1

No effect of
nickel exposure

RIR� <= ;� 1

Nickel exposure
protects from RC

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Relative or Absolute Effect

IR(E+)

IR(E�)

RR

AR

24 <= /span>/1000/yr

8
/1000/yr

3.0

16
/1000/yr

60 <= /span>/1000/yr

20 <= /span>/1000/yr

3.0

40 /1000/yr<= /span>

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Interpretation

�Attributable risk = measures clinical and public health importance <= /span>of the causal relationship

�Relative risk assesses strength <= /span>of the association

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Example: Wrapping up

250 Exposed

To Nickel

450 Unexposed

To Nickel

Respiratory Cancer
Incidence Rate

Relative Incidence rate =

Attributable Risk

100

0.024/yr

3.0

90

Person-years

4,100

11,000

0.008/yr

0.016/yr

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

Prospective Studies:� Advantages

�Exposure to postulated cause is assessed before occurrence of disease

�

�Possible to estimate all measures of incidence and effect

�

�Possible to study several outcomes to one cause

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WH= O- Postgraduate course 2006 � Cohort studies

February 22, 2006

�Requires large investments in time, human = and financial resources

�

�Requires large sample sizes (e.g., 110.000 nurses, 59.600 doctors, 1.2 millions volunteers)

�

�Not easy to reproduce (Re: consistency of = the association)

Prospective Studies:� Disadvantages

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<= /div>
<= /div>
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�header�=

<= /div>
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<= /div>

�date/time�

Click to edit Master text styles

Second level

Third level

Fourth level

Fifth level

<= /div>
<= /div>
<= /div>

�footer�=

<= /div>
<= /div>
<= /div>

�#�&= #13;

=

=

=

=
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stIndexOf('/')+1) } function HideMenu() { if( frames["PPTSld"] && PPTSld.document.all.item("ctx= tmenu") && PPTSld.ctxtmenu.style.display!=3D"none" ) { PPTSld.ctxtmenu.styl= e.display=3D'none'; return true } return false } function IsWin( name ) { return window.name =3D=3D name } function IsNts() { return IsWin("PPTNts") } function IsSldOrNts() { return( IsWin("PPTSld")||IsWin("PPTNts") ) } function SupportsPPTAnimation() { return( navigator.platform =3D=3D "Win32"= && navigator.appVersion.indexOf("Windows")>0 ) } function SupportsPPTHTML() { var appVer=3Dnavigator.appVersion, msie=3DappVer.indexOf("MSIE "), ver=3D0 if( msie >=3D 0 ) ver=3DparseFloat( appVer.substring( msie+5, appVer.indexOf(";",msie) ) ) else ver=3DparseInt(appVer) return( ver >=3D 4 && msie >=3D 0 ) } function _RSW() { if( !g_supportsPPTHTML || IsNts() || ( !g_scaleInFrame && (!IsWin("PPTSld") || !parent.IsFullScrMode()) ) ) return var padding=3D0; if( IsWin("PPTSld") && parent.IsFramesMode() ) padding=3D6 cltWidth=3Ddocument.body.clientWidth-padding cltHeight=3Ddocument.body.clientHeight-padding factor=3D(1.0*cltWidth)/g_origW if( cltHeight < g_origH*factor ) factor=3D(1.0*cltHeight)/g_origH newSize =3D g_origSz * factor if( newSize < 1 ) newSize=3D1 s=3DSlideObj.style s.fontSize=3DnewSize+"px" s.posWidth=3Dg_origW*factor s.posHeight=3Dg_origH*factor s.posLeft=3D(cltWidth-s.posWidth+padding)/2 s.posTop=3D(cltHeight-s.posHeight+padding)/2 if( g_scaleHyperlinks ) ScaleHyperlinks( factor ) } function _InitAnimations() { animRuntimeInstalled =3D ''+document.body.localTime !=3D 'undefined'; isFullScreen =3D (window.name =3D=3D "PPTSld") && !parent.IsFramesMode(); g_animUseRuntime =3D g_showAnimation && animRuntimeInstalled && !(isFullSc= reen && parent.IsSldVisited()); if( g_animUseRuntime ) { collSeq =3D document.all.tags("seq"); if( collSeq !=3D null ) { for(ii=3D0;ii numSlds ) gSldJumpIdx =3D numSlds; if ( gSldJumpIdx >=3D 0 ) { if ( gSldJumpIdx =3D=3D 0 ) gSldJumpIdx =3D 1; var jumpTo =3D parseInt(gSldJumpIdx); gSldJump =3D 0; gSldJumpIdx =3D ""; win.GoToSld( parent.GetSldList().mList[jumpTo-1].mSldHref ) } } } function _KDH() { if( event.keyCode =3D=3D 8 ) { event.returnValue =3D 0; parent.GoToPrevSld(); } }function DocumentOnClick() { if( IsNts() || parent.HideMenu() ) return; if( ( g_allowAdvOnClick && (window.name=3D=3D"PPTSld") && !parent.IsFrames= Mode() ) || (event && event.keyCode=3D=3D32) ) { =09 if( g_animUseRuntime && g_animMainSequence && g_animMainSequence.cangonex= t ) return; parent.GoToNextSld(); } } var g_supportsPPTHTML =3D SupportsPPTHTML(), g_scaleInFrame =3D 1, gId=3D""= , g_bgSound=3D"", g_scaleHyperlinks =3D false, g_allowAdvOnClick =3D 1, g_showInBrowser = =3D 0, gLoopCont =3D 0, gUseSldTimings =3D 1; var g_showAnimation =3D g_supportsPPTHTML && SupportsPPTAnimation() && ( (w= indow.name=3D=3D"PPTSld" && !parent.IsFramesMode()) || g_showInBrowser );va= r g_animManager =3D null; var g_animUseRuntime =3D false; var g_animItemsToHide, g_animInteractiveItems, g_animSlideTime; var g_animMainSequence =3D null; var ENDSHOW_MESG=3D"End of slide show, click to exit.", SCREEN_MODE=3D"Fram= es", gIsEndShow=3D0, NUM_VIS_SLDS=3D42, SCRIPT_HREF=3D"script.js", FULLSCR_= HREF=3D"fullscreen.htm"; var gCurSld =3D gPrevSld =3D 1, g_offset =3D 0, gNtsOpen =3D gHasNts =3D gO= tlTxtExp =3D 0, gHasNarration =3D 0, gOtlOpen =3D true window.gPPTHTML=3DSupportsPPTHTML() var gMainDoc=3Dnew Array(new hrefList("slide0626.htm",1,-1,1),new hrefList(= "slide0627.htm",1,-1,1),new hrefList("slide0628.htm",1,-1,1),new hrefList("= slide0629.htm",1,-1,1),new hrefList("slide0528.htm",1,-1,1),new hrefList("s= lide0588.htm",1,-1,1),new hrefList("slide0625.htm",1,-1,1),new hrefList("sl= ide0531.htm",1,-1,1),new hrefList("slide0532.htm",1,-1,1),new hrefList("sli= de0534.htm",1,-1,1),new hrefList("slide0535.htm",1,-1,1),new hrefList("slid= e0590.htm",1,-1,1),new hrefList("slide0595.htm",1,-1,1),new hrefList("slide= 0589.htm",1,-1,1),new hrefList("slide0543.htm",1,-1,1),new hrefList("slide0= 596.htm",1,-1,1),new hrefList("slide0545.htm",1,-1,1),new hrefList("slide05= 46.htm",1,-1,1),new hrefList("slide0608.htm",1,-1,1),new hrefList("slide060= 9.htm",1,-1,1),new hrefList("slide0611.htm",1,-1,1),new hrefList("slide0612= .htm",1,-1,1),new hrefList("slide0597.htm",1,-1,1),new hrefList("slide0598.= htm",1,-1,1),new hrefList("slide0549.htm",1,-1,1),new hrefList("slide0607.h= tm",1,-1,1),new hrefList("slide0551.htm",1,-1,1),new hrefList("slide0605.ht= m",1,-1,1),new hrefList("slide0606.htm",1,-1,1),new hrefList("slide0599.htm= ",1,-1,1),new hrefList("slide0556.htm",1,-1,1),new hrefList("slide0592.htm"= ,1,-1,1),new hrefList("slide0559.htm",1,-1,1),new hrefList("slide0560.htm",= 1,-1,1),new hrefList("slide0600.htm",1,-1,1),new hrefList("slide0563.htm",1= ,-1,1),new hrefList("slide0564.htm",1,-1,1),new hrefList("slide0601.htm",1,= -1,1),new hrefList("slide0566.htm",1,-1,1),new hrefList("slide0624.htm",1,-= 1,1),new hrefList("slide0577.htm",1,-1,1),new hrefList("slide0586.htm",1,-1= ,1)); /********************************************* Frameset functions These functions control slide navigation and state of the frameset. **********************************************/ function FullScrInit() { g_allowAdvOnClick =3D GetCurSld().mAdvOnClk document.body.style.backgroundColor=3D"black" document.oncontextmenu=3Dparent._CM; document.onkeydown =3D _KDH; document.ondragstart=3DCancel document.onselectstart=3DCancel self.focus() } function Redirect( frmId ) {=09 var str=3Ddocument.location.hash,idx=3Dstr.indexOf('#'), sId=3DGetSldId() if(idx>=3D0) str=3Dstr.substr(1); if( window.name !=3D frmId && ( sId !=3D str) ) { obj =3D GetObj("Main-File") window.location.href=3Dobj.href+"#"+sId return 1 } return 0 } var MHTMLPrefix =3D CalculateMHTMLPrefix();=20 function CalculateMHTMLPrefix() { if ( document.location.protocol =3D=3D 'mhtml:') {=20 href=3Dnew String(document.location.href)=20 Start=3Dhref.indexOf('!')+1=20 End=3Dhref.lastIndexOf('/')+1=20 if (End < Start)=20 return href.substring(0, Start)=20 else=20 return href.substring(0, End)=20 } return ''; } function GetTags(base,tag) { if(g_supportsPPTHTML) return base.all.tags(tag); else return base.getElementsByTagName(tag); } function UpdNtsPane(){ if(frames["PPTNts"]) PPTNts.location.replace( MHTMLP= refix+GetHrefObj( gCurSld ).mNtsHref ) } function UpdNavPane( sldIndex ){ if(gNavLoaded) PPTNav.UpdNav() } function UpdOtNavPane(){ if(gOtlNavLoaded) PPTOtlNav.UpdOtlNav() } function UpdOtlPane(){ if(gOtlLoaded) PPTOtl.UpdOtl() } function SetHasNts( fVal ) { if( gHasNts !=3D fVal ) { gHasNts=3DfVal UpdNavPane() } } function ToggleOtlText() { gOtlTxtExp=3D!gOtlTxtExp UpdOtlPane() } function ClearMedia() { // Clear any sounds playing before launching another browser window. Other= wise, // in fullscreen mode, you'll continue to hear the sound in the frames mod= e. if (PPTSld.pptSound) PPTSld.pptSound.loop =3D 0; } function FullScreen() {=20 if ( PPTSld.g_animUseRuntime ) PPTSld.document.body.pause(); ClearMedia(); var href =3D ( document.location.protocol =3D=3D 'mhtml:') ? FULLSCR_HREF = : FULLSCR_HREF+"#"+GetHrefObj(gCurSld).mSldHref; if(PPTNav.event.ctrlKey) { var w =3D (window.screen.availWidth * 1.0) / 2.0 var h =3D w * (PPTSld.g_origH * 1.0) / PPTSld.g_origW win =3D window.open( MHTMLPrefix+href,null,"toolbar=3D0,resizable=3D1,top= =3D0,left=3D0," + "width=3D"+ w + ",height=3D" + h ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } else { win =3D window.open( MHTMLPrefix+href,null,"fullscreen=3Dyes" ); if( win.document.body && PPTSld.g_animUseRuntime ) win.document.body.PPTSldFrameset=3Dwindow; } } function ToggleVNarration() { rObj=3DPPTSld.document.all("NSPlay") if( rObj && !PPTSld.g_animUseRuntime ) { if( (rObj.playState =3D=3D 1)||(rObj.playState =3D=3D 0) ) rObj.Play() else if( rObj.playState =3D=3D 2 ) rObj.Pause() else return; } else if( PPTSld.g_animUseRuntime ) { narObj =3D PPTSld.document.all("narrationID") if( narObj ) narObj.togglePause() } } function GetCurSldNum() { =20 obj=3DGetHrefObj(gCurSld) if( obj.mOrigVis =3D=3D 1 ) return obj.mSldIdx else =20 return gCurSld } function GetNumSlds() { =20 if( GetHrefObj(gCurSld).mOrigVis =3D=3D 1 ) return GetSldList().mNumVisSlds; else return GetSldList().mList.length } function GetSldNum( href ) { for(ii=3D0; ii 1 ) PopSldList(); else if( !IsFramesMode() ) { if( gLoopCont ) GoToFirst() else EndShow() } } function GoToPrevSld() { ii=3DgCurSld-1 if( ii > 0 ) { obj=3DGetHrefObj(ii) while ( obj && ( obj.mVis =3D=3D 0 ) && ( ii>0 ) ) obj=3DGetHrefObj(--ii) if( ii =3D=3D 0 ) ii=3D1 GoToSldNum(ii) } } function GoToFirst(){ GoToSld( GetHrefObj(1).mSldHref ) } function GoToLast() { ii=3DGetSldList().mList.length if( ii !=3D gCurSld ) GoToSld( GetHrefObj(ii).mSldHref ) } function GoToSldNum( num ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue obj =3D GetHrefObj( num ) obj.mVis=3D1 gPrevSld=3DgCurSld gCurSld =3D num; PPTSld.location.replace(MHTMLPrefix+obj.mSldHref) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function GoToSld( href ) { if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue GetHrefObj( GetSldNum(href) ).mVis=3D1 PPTSld.location.replace(MHTMLPrefix+href) } function SldUpdated( id ) { if( id =3D=3D GetHrefObj(gCurSld).mSldHref ) return gPrevSld=3DgCurSld gCurSld=3DGetSldNum(id) if( IsFramesMode() ) { UpdNavPane(); UpdOtlPane(); UpdNtsPane() } } function PrevSldViewed(){ GoToSld( GetHrefObj(gPrevSld).mSldHref ) } function HasPrevSld() { return ( gIsEndShow || ( gCurSld !=3D 1 && GetHrefO= bj( gCurSld-1 ).mVis =3D=3D 1 )||( GetCurSldNum() > 1 ) ) } function HasNextSld() { return (GetCurSldNum() !=3D GetNumSlds()) } function CloseWindow() { if( HideMenu() ) return; =09 var event =3D PPTSld.event; if( !IsFramesMode() && event && (event.keyCode=3D=3D27 || event.keyCode=3D= =3D32 || event.type=3D=3D"click" ) ) window.close( self ); CatchNumKeys( self, event ); } function Unload() { gIsEndShow=3D0; } function SetupEndShow() { gIsEndShow=3D1; PPTSld.document.body.scroll=3D"no"; PPTSld.document.onkeypress=3DCloseWindow; PPTSld.document.onclick=3DCloseWindow; PPTSld.document.oncontextmenu=3D_CM; } function EndShow() { if( IsFramesMode() ) return if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue doc=3DPPTSld.document var dir =3D doc.body.dir if( dir !=3D "rtl" ) dir =3D "ltr"; doc.open() doc.writeln('

' + ENDSHOW_MESG + '
') doc.close() } function SetSldVisited(){ GetSldList().mList[gCurSld-1].mVisited=3Dtrue } function IsSldVisited(){ return GetSldList().mList[gCurSld-1].mVisited } function hrefList( sldHref, visible, advDelay, advClk ) { this.mSldHref=3D this.mNtsHref =3D sldHref this.mOrigVis=3D this.mVis =3D visible this.mVisited=3D false this.mAdvDelay=3D advDelay this.mAdvOnClk=3D advClk } function SldList(arr,curSld,fEnd) { this.mCurSld =3D curSld; this.mList =3D new Array(); var idx =3D 1; for(ii=3D0;ii 0) { PushSldList(sldList,fEnd); gCurSld =3D 1; } else if( PPTSld.event ) PPTSld.event.cancelBubble=3Dtrue } function PushSldList(arr,fEnd) { var ii =3D gSldStack.length; gSldStack[ii] =3D new SldList(arr,gCurSld,fEnd); GoToSld( gSldStack[ii].mList[0].mSldHref ); } function PopSldList() { if (gSldStack[gSldStack.length-1].fEndShow) EndShow() else { gCurSld =3D gSldStack[gSldStack.length-1].mCurSld; gSldStack[gSldStack.length-1] =3D null; gSldStack.length--; var sldList =3D gSldStack[gSldStack.length-1]; GoToSld( sldList.mList[gCurSld - 1].mSldHref ); } } var custShowList=3Dnew Array(); /********************************************* Navigation button implementation There are 2 types of buttons: ImgBtn, TxtBtn implemented as function objects. They share a similiar interface so the event handlers can call SetActive, for example, on a button=20 object without needing to know exactly=20 what type of button it is. **********************************************/ //---------------------------------- function ImgBtn( oId,bId,w,action ) //---------------------------------- { var t=3Dthis t.Perform =3D _IBP t.SetActive =3D _IBSetA t.SetInactive=3D _IBSetI t.SetPressed =3D _IBSetP t.SetDisabled=3D _IBSetD t.Enabled =3D _IBSetE t.ChangeIcon =3D null t.UserAction =3D action t.ChgState =3D _IBUI t.mObjId =3D oId t.mBorderId=3D bId t.mWidth =3D w t.mIsOn =3D t.mCurState =3D 0 } function _IBSetA() { if( this.mIsOn ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _IBSetI() { if( this.mIsOn ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0=20 } } function _IBSetP() { if( this.mIsOn ) { obj=3Dthis.ChgState( gShadowClr,gHiliteClr,2 ) obj.style.posLeft+=3D1; obj.style.posTop+=3D1 } } function _IBSetD() { =20 obj=3Dthis.ChgState( gFaceClr,gFaceClr,0 ) obj.style.posTop=3D0=20 } function _IBSetE( state ) { var t=3Dthis GetObj( t.mBorderId ).style.visibility=3D"visible" if( state !=3D t.mIsOn ) { t.mIsOn=3Dstate if( state ) t.SetInactive() else t.SetDisabled() } } function _IBP() { var t=3Dthis if( t.mIsOn ) { if( t.UserAction !=3D null ) t.UserAction() if( t.ChangeIcon ) { obj=3DGetObj(t.mObjId) if( t.ChangeIcon() ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-4)*t.mWidth else obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-0)*t.mWidth } t.SetActive() } =20 } function _IBUI( clr1,clr2,nextState ) { var t=3Dthis SetBorder( GetObj( t.mBorderId ),clr1,clr2 ) obj=3DGetObj( t.mObjId ) obj.style.posLeft=3Dobj.style.posLeft+(t.mCurState-nextState)*t.mWidth-obj= .style.posTop t.mCurState=3DnextState return obj } //----------------------------------------- function TxtBtn( oId,oeId,action,chkState ) //----------------------------------------- { var t=3Dthis t.Perform =3D _TBP t.SetActive =3D _TBSetA t.SetInactive=3D _TBSetI t.SetPressed =3D _TBSetP t.SetDisabled=3D _TBSetD t.SetEnabled =3D _TBSetE t.GetState =3D chkState t.UserAction =3D action t.ChgState =3D _TBUI t.mObjId =3D oId t.m_elementsId=3D oeId t.mIsOn =3D 1 } function _TBSetA() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gHiliteClr,gShadowClr,0,0 ) } function _TBSetI() { var t=3Dthis if( t.mIsOn && !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) } function _TBSetP() { if( this.mIsOn ) this.ChgState( gShadowClr,gHiliteClr,1,1 ) } function _TBSetD() { =20 this.ChgState( gFaceClr,gFaceClr,0,0 ) this.mIsOn =3D 0 } function _TBSetE() { var t=3Dthis if( !t.GetState() ) t.ChgState( gFaceClr,gFaceClr,0,0 ) else t.ChgState( gShadowClr,gHiliteClr,1,1 ) t.mIsOn =3D 1 } function _TBP() { var t=3Dthis if( t.mIsOn ) {=20 if( t.UserAction !=3D null ) t.UserAction() if( !t.GetState ) return if( t.GetState() ) t.SetPressed() else t.SetActive() } =20 } function _TBUI( clr1,clr2,lOffset,tOffset ) { SetBorder( GetObj( this.mObjId ),clr1,clr2 ) Offset( GetObj( this.m_elementsId ),lOffset,tOffset ) } function Offset( obj, top, left ){ obj.style.top=3Dtop; obj.style.left=3Dle= ft } function SetBorder( obj, upperLeft, lowerRight ) { s=3Dobj.style; s.borderStyle =3D "solid" s.borderWidth =3D 1=20 s.borderLeftColor =3D s.borderTopColor =3D upperLeft s.borderBottomColor=3D s.borderRightColor =3D lowerRight } function GetBtnObj(){ return gBtnArr[window.event.srcElement.id] } function BtnOnOver(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetActive() } function BtnOnDown(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetPressed() } function BtnOnOut(){ b=3DGetBtnObj(); if( b !=3D null ) b.SetInactive() } function BtnOnUp() { b=3DGetBtnObj() if( b !=3D null ) b.Perform() else Upd() } function GetNtsState(){ return parent.gNtsOpen } function GetOtlState(){ return parent.gOtlOpen } function GetOtlTxtState(){ return parent.gOtlTxtExp } function NtsBtnSetFlag( fVal ) { s=3Ddocument.all.item( this.m_flagId ).style s.display=3D"none" if( fVal ) s.display=3D"" else s.display=3D"none" } function _BSetA_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etActive() } function _BSetI_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etInactive() } function _BSetP_Border(){ b =3D gBtnArr[this.mObjId]; if( b !=3D null ) b.S= etPressed() } function _BSetA_BorderImg() {=20 b =3D gBtnArr[this.mBorderId]=20 if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gHiliteClr,gShadowClr,2 ) obj.style.posTop=3D0 } } function _BSetI_BorderImg() {=20 b =3D gBtnArr[this.mBorderId] if( b !=3D null && this.mIsOn && !b.GetState() ) { obj=3Dthis.ChgState( gFaceClr,gFaceClr,1 ) obj.style.posTop=3D0 } } var gHiliteClr=3D"THREEDHIGHLIGHT",gShadowClr=3D"THREEDSHADOW",gFaceClr=3D"= THREEDFACE" var gBtnArr =3D new Array() gBtnArr["nb_otl"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOtlPan= e,GetOtlState ) gBtnArr["nb_otlElem"] =3D new TxtBtn( "nb_otl","nb_otlElem",parent.ToggleOt= lPane,GetOtlState ) gBtnArr["nb_nts"] =3D new ImgBtn( "nb_nts","nb_ntsBorder",10,parent.ToggleN= tsPane ) gBtnArr["nb_nts"].SetActive =3D _BSetA_BorderImg; gBtnArr["nb_nts"].SetInactive =3D _BSetI_BorderImg; gBtnArr["nb_ntsBorder"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.= ToggleNtsPane,GetNtsState ) gBtnArr["nb_ntsElem"] =3D new TxtBtn( "nb_ntsBorder","nb_ntsElem",parent.To= ggleNtsPane,GetNtsState ) gBtnArr["nb_prevBorder"] =3D gBtnArr["nb_prev"]=3D new ImgBtn( "nb_prev","n= b_prevBorder",30,parent.GoToPrevSld ) gBtnArr["nb_nextBorder"] =3D gBtnArr["nb_next"]=3D new ImgBtn( "nb_next","n= b_nextBorder",30,parent.GoToNextSld ) gBtnArr["nb_sldshw"]=3D new ImgBtn( "nb_sldshw","nb_sldshwBorder",18,parent= .FullScreen ) gBtnArr["nb_sldshwBorder"] =3D new TxtBtn( "nb_sldshw","nb_sldshwBorder",pa= rent.FullScreen,null ) gBtnArr["nb_sldshwBorder"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwBorder"].SetInactive =3D _BSetI_Border; gBtnArr["nb_sldshwText"] =3D new TxtBtn( "nb_sldshw","nb_sldshwText",parent= .FullScreen,null ) gBtnArr["nb_sldshwText"].SetActive =3D _BSetA_Border; gBtnArr["nb_sldshwText"].SetInactive =3D _BSetI_Border; gBtnArr["nb_voice"] =3D gBtnArr["nb_voiceBorder"] =3D new ImgBtn( "nb_voice= ","nb_voiceBorder",18,parent.ToggleVNarration ) gBtnArr["nb_otlTxtBorder"] =3D gBtnArr["nb_otlTxt"]=3D new ImgBtn( "nb_otlT= xt","nb_otlTxtBorder",23,parent.ToggleOtlText ) gBtnArr["nb_ntsBorder"].m_flagId=3D "nb_nts" gBtnArr["nb_ntsBorder"].SetFlag =3D NtsBtnSetFlag gBtnArr["nb_otlTxt"].ChangeIcon=3D GetOtlTxtState /********************************************* Context menu implementation _CM() is the function that's hooked up to the oncontextmenu event. Once we're asked to show the menu, we first build it by creating DIVs on-the-fly. Then we position it=20 within the screen area so it doesn't get clipped. Creating the DIVs using createElement() means we don't have to write out any extra HTML into the slide HTML files. **********************************************/ var sNext=3D"Next",sPrev=3D"Previous",sEnd=3D"End Show",sFont=3D"Arial",sAr= row=3D"Arrow",sFreeform=3D"Freeform",sRect=3D"Rectangle",sOval=3D"Oval" function ShowMenu() { BuildMenu(); var doc=3DPPTSld.document.body,x=3DPPTSld.event.clientX+doc.scrollLeft,y= =3DPPTSld.event.clientY+doc.scrollTop m =3D PPTSld.document.all.item("ctxtmenu") m.style.pixelLeft=3Dx if( (x+m.scrollWidth > doc.clientWidth)&&(x-m.scrollWidth > 0) ) m.style.pixelLeft=3Dx-m.scrollWidth m.style.pixelTop=3Dy if( (y+m.scrollHeight > doc.clientHeight)&&(y-m.scrollHeight > 0) ) m.style.pixelTop=3Dy-m.scrollHeight m.style.display=3D"" } function _CM() { if( !parent.IsFullScrMode() ) return; if(!PPTSld.event.ctrlKey) { ShowMenu() return false } else HideMenu() } function BuildMenu() { if( PPTSld.document.all.item("ctxtmenu") ) return var mObj=3DCreateItem( PPTSld.document.body ) mObj.id=3D"ctxtmenu" mObj.style.visibility=3D"hidden" var s=3DmObj.style s.position=3D"absolute" s.cursor=3D"default" s.width=3D"120px" SetCMBorder(mObj,"menu","black") var iObj=3DCreateItem( mObj ) SetCMBorder( iObj, "threedhighlight","threedshadow" ) iObj.style.padding=3D2 CreateMenuItem( iObj,sNext,M_GoNextSld,M_True ) CreateMenuItem( iObj,sPrev,M_GoPrevSld,M_HasPrevSld ) =09 CreateSeparator( iObj ) CreateMenuItem( iObj,sEnd,M_End,M_True ) mObj.style.visibility=3D"visible" } function Cancel() { window.event.cancelBubble=3Dtrue; 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charset="windows-1252" Cohort studies - Hans Wolff ------=_NextPart_01C63A74.80BB6560 Content-Location: file:///C:/5209C636/Cohort_OMS_Wolff_2006_files/outline.htm Content-Transfer-Encoding: quoted-printable Content-Type: text/html; charset="windows-1252"

No= tes

Slide Show

Outline

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Cohort studies

Hans Wolff

Service d��pid�miologie Clinique,

D�partement de m�decine communautaire
Hans.Wolff@hcuge.ch

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Cohort study (CS= )

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Cohort study (CS= )

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Cohort study (CS= )

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Outline

Working Example

Welsh Nickel Workers Study

Description of the study and raw� data in�

Breslow, N.E., Day N.E. Statistical Methods in Cancer Research. I= ARC, 1987:369-74

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Cohort Design

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Example

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Study design=

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Study design=

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Which is a fund= amental condition for the validity of this cohort design ?

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�At risk of Res= piratory Cancer�

Never had respiratory cancer: exclude prevalent cases

Still have two lungs � and a nose: exclude subjects who cannot travel from the denominator to the numerator

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�Incident Respi= ratory Cancer�

Incident =3D �newly diagnosed�

Between April 1,1934 and
December 31,1981

Risk Period =3D 47 years

Employed in the factory before 1925

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What is the ris= k of respiratory cancer in this study ?

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Cohort Design

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Risk of respira= tory cancer
in unexposed

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What is the ris= k of respiratory cancer in unexposed ?

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Calculating Ris= k in Unexposed

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Risk in Unexpos= ed

Interpretation:

Probability of developing a respiratory cancer in workers unexposed= to nickel is 20% over 47 years

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Cohort Design

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Risk of respira= tory cancer
in exposed to nickel

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Calculating Ris= k in Exposed

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Risk in Exposed=

Interpretation:

Probability of developing a respiratory cancer in workers exposed to nickel is 40% over 47 years

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What is an inci= dence rate of
respiratory cancer in this study?

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Notation

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Incidence rate = (IR) =3D risk per unit of time

Risk period =3D� 47 yrs.

Some subjects followed-up for < 47 yrs.

E.g., cases, losses to follow-up

Solution # 1

=3D divide risk by average duration
�� of follow-up (24= yrs)

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�

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Incidence rate = (IR) =3D risk per unit of time

Solution # 2

Use person-time as denominator

1 person followed for 2 years =3D 2 person-year

1 person followed for 1 year =3D 1 person-year

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Study design

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Example

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�

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What is an attr= ibutable risk
in this study?

The ratio of the risk of RC in exposed to Nickel over the risk in unexposed?

The risk of RC that is not due to Nickel exposure

The excess rate of RC observed in subjects exposed to nickel compare= d to unexposed

The number of workers that need to be exposed to nickel in order to observe an additional case of RC

All of the above

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Absolute Effect= :
Attributable Risk (AR)� (2)=

AR=3D IR(E+) - IR(E-)

=3D IR (E+) - IR (E -)

=3D 0.024/yr - 0.008/yr =3D 0.016/yr

=3D 16 /1,000/y

=3D Excess IR of RC due to nickel

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Attributable Ri= sk

IR(E+) =3D�� IR(E-) + AR�� =3D� 0.008 + 0.016� =3D 0.= 024

Synonymous:

Excess Risk

Risk Difference

Excess Rate

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What is a relat= ive risk in this study?

The ratio of the IR of RC in exposed to nickel over the IR in unexpo= sed?

The IR of RC that is not due to nickel exposure

The excess risk of RC observed among subjects exposed to nickel

The number of workers that need to be exposed to nickel in order to observe an additional case of RC

None of the above

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Relative Effect= :
Relative Incidence Rate (RIR)*

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Relative Effect=

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Relative Effect=

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Relative or Abs= olute Effect

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Interpretation<= /a>

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Example: Wrappi= ng up

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Prospective Stu= dies:� Advantages

Exposure to postulated cause is assessed before occurrence of diseas= e

Possible to estimate all measures of incidence and effect

Possible to study several outcomes to one cause

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Prospective Stu= dies:� Disadvantages

Requires large investments in time, human and financial resources

Requires large sample sizes (e.g., 110.000 nurses, 59.600 doctors, 1= .2 millions volunteers)

Not easy to reproduce (Re: consistency of the association)

<= /a>= =
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