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

A.6
A.6 Planned statistical analyses and statistical power considerations
for correct estimation of FPR. Thus, as the underlying TPR 1 is further away from the targeted
TPR 0 , a smaller number of cases would be needed, but at some point the numbers of
cases and controls are kept constant by the demand of securing accurate joint estimation
of FPR 0 (shaded areas in Table 6.7).
In practice, the variance of a diagnostic marker may differ between subjects developing
disease (cases) and control subjects who remain disease-free and often will show wider
spread among the cases. As the FPR is estimated from control subjects, a smaller marker
variance among controls, compared to that among cases, will generally improve estimation
of FPR 0 . Thus, comparing the situation in which biomarker variances for cases and controls
are equal to the one in which variance of biomarker among control patients is half of the
biomarker variance of cases, smaller numbers of cases are needed in the latter situation.
To be able to study the validity of candidate markers within a prospective cohort, the cohort
should have accumulated certain numbers of prospectively identified (“incident”) cases of
disease, detected within a reasonably short period of the blood sample collection. In general,
a diagnostic marker, e.g., for cancer, may be able to detect a disease only within a
limited time span (often no more than 1–2 years) before its natural diagnosis. Table 6.6
indicates numbers of cancer cases occurring within 1, 2, or 3 years after visit to a study
center and collection of biological specimens, assuming either a single recruitment visit for
the full cohort or also a second visit.
Table 6.6: Expected counts of incident cancer cases within 1, 2, or 3 years after blood
donation.
Table 6.6: Expected counts of incident cancer cases within 1, 2, or 3 years after blood donation
Number of cases after baseline blood
donation from full cohort
within
1 year
within
2 years
within
3 years
188
Baseline blood sample from full cohort,
and second blood sample
from 75% of participants
within
1 year
within
2 years
within
3 years
Prostate 182 365 547 319 639 958
Breast 161 322 483 282 563 845
Colon 88 177 265 155 309 464
Lung 59 117 176 103 205 308
Kidney 34 68 101 59 118 177
Bladder 24 49 73 43 85 128
Pancreas 19 38 57 33 66 99
Brain 18 36 54 32 63 95
Non-Hodgkin 17 35 52 30 61 91
Corpus Uteri 13 27 40 24 47 71
Ovary 12 25 37 22 43 65
*3-year incident cases calculated as 0.2-fold 10-year incidence from EPIC-HD-sample; 2-year incident cases as
2/3 of cases in 3 years and 1-year incidence cases as 1/3 of cases in 3 years.