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

C.2 Annex: Methods for Statistical Power and Sample Size Calculations
C.2.4 Sample size requirements for validation/calibration sub-studies
When a sub-study with replicate measurements is used for regression calibration, e.g. of
blood-based exposure measurements, the accuracy of the adjustment will depend jointly
on the strength of correlation (ρ ,) between the replicate measurements, the size of the
m1,m2
sub-study (N), the strength of association (standardized difference A=βσ ) between exposure
measurements and disease risk and the number of cases with disease used for relative
risk modelling824, 825 . This can be expressed by the following equation, using the ratio of
observed number of cases (D) over the effective number of cases (D) left after calibration
correction as a relative efficiency criterion824 �1
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:
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D
2 m1,
m2
D
A 2
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For example, when the correlation ρ , between replicate measurements is at least 0.40,
m1,m2
and for a standardized difference (A) in exposure level between cases and controls corresponding
to an expected relative risk of 4.0 between the extreme quintiles of the exposure
measurement (i.e., A=0.50), a calibration sub-study should include at least 5.25 times the
number of cases with disease in a nested case-control study to limit the loss in effective
number of cases to 20% (i.e., D/D = 1/0.80 = 1.25). At higher correlations between replicate
measurements, or in situations where
~
relative risk estimates (association measure A) are
lower, this same criterion can be met by a smaller reproducibility/calibration sub-study. For
example, when the standardized difference in exposure between cases and controls corresponds
to an expected relative risk [odds ratio] of 2.0 between the extreme quintiles (i.e.,
A=0.25), the size of the sub-study should be only about 1.3 times the number of cases,
which is four times fewer than in the previous example. Table S6.8 shows the sample size
numbers (N) required for different combinations of ρ , A, D.
m1,m2 1
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On the basis of the estimated sample size requirements for calibration sub-studies (Table
S6.8), and anticipating that most relevant exposure measurements (i.e. those that in practice
can be expected to allow detection of a true relative risk of at least 1.5 or higher; see also
Table S6.9) will generally have a correlation of at least 0.30 between short-term replicate
measurements (e.g. over a one-year time interval), we propose a study size for validation/
calibration sub-studies of 10,000 subjects in total. Of these, 6,000 will be in the first (baseline)
recruitment round, and 4,000 in the second round of data collection, five years later.
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C.2