Scientific Concept of the National Cohort (status ... - Nationale Kohorte

C.2
C.2 Annex: Methods for Statistical Power and Sample Size Calculations
The differences in case numbers for cancer over 10 or 15 years’ follow-up based on registry
data or on extrapolations from different ongoing German cohort studies document a degree
of uncertainty with regard to numbers of cases with disease that may be expected in practice,
depending on possible self-selection of cohort participants. Apart from current health
status, these self-selection effects are likely to be associated with different background risks
for chronic disease in different geographic and socio-economic strata of the German population,
which are difficult to fully describe in advance.
C.2.2 minimally detectable odds ratios in main effects models
In addition to the Figures 6.2 to 6.4 in the main protocol text (Chapter 5), Table S6.2 provides
minimum detectable odds ratios (MDOR; statistical power 0.80, significance level of
either 0.05 or 0.01) for a binary main effect, as function of exposure prevalence, number of
disease cases, and number of controls per case. Likewise, Table S6.3 provides minimum
detectable odds ratios (MDOR; statistical power 0.80, significance level of either 0.05 or
10 -4 ) for comparison of top to bottom quartiles of a continuous exposure variable, for a number
of scenarios.
figure S6.1 provides estimates for study size (number of cases with 2 control each) required
to detect with statistical power 0.80 minimal odds ratios [MDOR]), at a significance
level of 10 -4 . This figure shows that a nested case-control study with 1000 cases of disease
and two controls per case will allow detection of a MDOR of 1.5 for a dominant allele that
has carrier frequencies of about 0.14 or higher. For smaller MDOR, considerably larger
study sizes are generally needed.
figure S6.1: Study size (number of cases with 2 control each) required to detect minimally detectable
odds ratios [MDOR] varying from 1.2 to 2.5 for a genetic main effect (statistical power
0.80, significance level 10 -4 ).**
Genetic main effect, alpha=10e-4
N cases
10000
9000
8000
7000
6000
5000
4000
3000
2000
1000
0
0 0.05 0.1 0.15 0.2 0.25 0.3 0.35 0.4 0.45 0.5
N cases
10000
9000
Allele frequency
RG 1.2 1.3 1.5 1.7 2 2.5
Assuming dominant model, unmatched case-control study with 2 controls per case
** Assuming Hardy-Weinberg equilibrium between high- and low-risk alleles – that is, for
2
allele frequency af the carrier frequency cf is computed as ).
Genetic main effect, alpha=10e-4
274
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cf � af � 2af
1�
�1
� �0
A
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