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

A.6 Planned statistical analyses and statistical power considerations
A.6 planned statistical analyses and statistical power
considerations
A.6.1 General issues and structure of the section
As stated in Sect. A.1, the major specific aims for the National Cohort include identifying
lifestyle, nutritional, occupational, environmental, (pre)clinical, and (epi)genetic risk factors
for the development of chronic diseases and aging-related declines in health and determinants
of the progression of early-stage (preclinical) morbidity to overt clinical-stage disease
and/or related losses of autonomy. A related aim is to develop risk prediction models and
algorithms that may help identify individuals at increased risk of developing major chronic
diseases. These latter models may include questionnaire assessments of risk factors, as
well as genetic and other biological markers, and clinical examination data. For each of
these objectives, quantitative risk associations – in terms of relative and attributable risk
– will be estimated for a range of chronic disease outcomes. Finally, it is also anticipated
that the cohort will be used to evaluate candidate blood or urine-based markers or clinical
examinations (e.g., imaging) for early detection of disease.
The design of the National Cohort as a large-scale, population-based prospective cohort
study guides the general strategy for planned statistical analyses. This has a number of
direct implications:
� Whenever indicated and feasible, and contingent upon the exposure or risk factor
information collected, statistical analyses will be based on data from the full cohort. If
a study question of interest is only relevant for a certain subpopulation, relevant subcohorts
will be considered.
� This study does not have one single hypothesis or even a limited number of hypotheses
that can be taken as a single basis for confirmatory statistical testing and for
sample size considerations and power calculations. Rather, research questions as
outlined in Sects. A.1 and A.2 have been defined from diverse areas in epidemiology.
A wide range of scientific questions and related statistical analyses follow from these two
general statements, which are summarized in Sect. A.6.2.
To structure the statistical models used for the National Cohort, we need to account for
the different types of outcome that will be observed during study follow-up. Thus, we have
outlined a possible series of general types of analysis and a list of selected approaches,
without any claim of completeness, in Sect. A.6.2.1.
Within this general model (by type of outcome), the risk factors or intermediate factors
presenting along the pathway from exposure to a health event will be related using a wide
range of specialized models. Therefore, the directional and undirectional association and
correlation structures between the different exposure variables must be incorporated in
statistical analyses and the general models must be adapted accordingly. Models for exposures
with a clustered structure such as environmental exposures, which require (variance)
component models, for repeated measurements, and for missing values (e.g., due to losses
by follow-up) must also be adapted. On the basis of the general models, some of these
model adaptations are therefore described in Sect. A.6.2.3.
Calculations for the expected numbers of incident cases of several relevant diseases are
outlined in Sect. A.6.3. These calculations are based on the source population presented in
Sect. A.3.1. The numbers, combined with the aforementioned statistical methods, serve as
examples for the general power calculations of the cohort of 200,000.
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A.6