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Induction%20and%20latency%20(J-F%20Boivin,%20March%202006)

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Induction and latency (J-F Boivin, March 2006) Introduction ... (nondifferential misclassification) RR. No exposure. In utero. DES. 1. 1/10 000. 1/10 000 ... – PowerPoint PPT presentation

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Title: Induction%20and%20latency%20(J-F%20Boivin,%20March%202006)


1
Induction and latency (J-F Boivin, March 2006)
  • Introduction
  • Rothmans model of induction
  • Analysis largest estimate methods
  • Modelling approaches
  • Thomas 1983
  • Rachet et al. 2003

Version 28 February 2006 (abbreviated)
2
  • Point exposures

3
Point exposure, fixed induction period
Disease initiation
Disease detection
Exposure
Latent period
Induction period
In practice, induction and latent period can
rarely be be separated
4
Point exposure, variable induction period
5
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6
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7
Analysis
Two simultaneous goals
  1. Estimate the mode of the distribution of
    empirical induction periods
  2. Estimate the effect of the exposure on disease
    risk without bias due to inappropriate assumption
    about induction period

8
  • Principle
  • Measures of effect are reduced if an
    inappropriate assumption is used for the
    empirical induction period
  • (nondifferential misclassification)

9
RR
No exposure
In utero DES
1
1/10 000
1/10 000
09 yr
10
  • Estimate the measure of association repeatedly
    with different assumptions about the induction
    period
  • The maximum point estimate of the measure of
    association corresponds to the most appropriate
    assumption about induction period and
    simultaneously offers an estimate of the maximum
    effect relatively unobscured by an inappropriate
    assumption

11
Limitation of largest estimate methods (Rothman-Gr
eenland 1998, pp. 298-299)
12
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14
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15
Alternative approach
  • Estimate the effects for each time window
  • while adjusting for the exposures from other
  • windows
  • Sharpe et al. British Journal of Cancer 2002

16
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18
Multiple time-windows approach
  • Problem

19
Modelling
Thomas 1983
20
dose
21
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22
a and b determined by trial and error
23



E
10/10,000
55/10,000
100/10,000



E-
10/10,000
10/10,000
10/10,000
0 10 20
30 yr
RE-R0
0
45/10,000
90/10,000
24
E
E-
165/30,000 55/10,000
30/30,000 10/10,000
0 10 20 30
RE-R0 45/10,000
RE-R0 (45/10,000) x 1
25
E
E-
10/10,000
155/20,000 77.5/10,000
10/10,000
20/20,000 10/10,000
RE-R0 0
67.5/10,000
26



E
10/10,000
55/10,000
100/10,000



E-
10/10,000
10/10,000
10/10,000
27
ER (T) b
?
T
d(t) f (T-t) dt
0
Values of 5, 10, 15 yr for induction period are
fitted
Standard deviation of 0.17609 log t units is
assumed
28
Complexities of modelling
  • Relevant exposure may be a complex function of
    the intensity of the exposure and time
    (Rothman-Greenland, p. 83)
  • Influence of intensity
  • Influence of age at exposure
  • atomic bomb survivors

29
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30
  • Rachet et al.
  • Statistics in Medicine 2003

31
Limitation of Thomas approach
32
Rachet et al.
  • no strong a priori assumptions
  • however dichotomous point exposure

33
Rachet et al.
  • Overall hazard ratio (HR) represents weighted
    average of
  • HR1 1
  • HR2 gt 1
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