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

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A.3 Study design
and from there to the competence center on imaging. However, as a considerable amount
of time may be required to transmit this amount of data, further analysis in the course of
the respective feasibility study may find that it is appropriate to deviate from this standard
procedure (described in Sect. A.4) in the case of imaging.
Image evaluation; centralized reading core
The present proposal does not include funding for detailed imaging evaluation with respect
to the scientific hypotheses. However, in order to address the issue of incidental findings,
a so-called ”first-line reading” of the images will be performed centrally. Subsequently a
“second-line”, hypothesis-driven reading will be performed. Thus, similar to the approach
proposed by the Imaging Group of the UK Biobank, MRI data will be regarded as infrastructure
for future scientific projects that are funded by subsequent grant applications.
The ”first-line reading” will only include those findings which will be potentially reported to
the participants. They include acute diseases such as stroke or acute infectious diseases,
which urgently need to be further diagnosed, and abnormalities suggesting tumor diseases.
Given the standardization requirements and financial constraints, we propose centralized
reading with several participating radiologists. The reading is performed during or directly
after the MRI examination, and the subjects receive the results directly after the examinations
from the radiologists via phone calls or video conferences. This interaction will include
recommendations for further diagnostic work-up.
Use of contrast agents
Gadolinium-based contrast agents, which are associated with a very low risk, have been
routinely used in clinical MRI mainly to characterize suspected tumors, to detect inflammation,
and for myocardial enhancement and vessel visualization. However, there are four
disadvantages of using contrast agents in an epidemiologic study: Firstly, contrast dye requires
intravenous administration, which is invasive (although minimally) and relatively time
consuming. Secondly, there is a risk, albeit low, of adverse events and, considering the
large size of the study population, it is likely that some of the participants will suffer from
such adverse events. Thirdly, logistic concerns would require that valid information on allergies
and renal dysfunction be available. Fourthly, there are financial constraints (additional
cost of contrast agent administration per patient is approx. 75 Euro).
Therefore, contrast agents will not be administered, and only non-contrast-enhanced whole
body MRI protocols will be applied.
A.3.4.5 International scientific advisory and data safety monitoring board
The proposed MRI substudy was developed and will be further specified in close collaboration
with an international expert scientific advisory board with advisers from the United
States, the Netherlands, and Great Britain who have extensive experience in populationbased
imaging.
We anticipate that other experts and experienced investigators will be added to the advisory
board, which will be continued over the study period and meet on a regular basis (i.e., once
a year). We also anticipate that some members of the advisory board will be elected into
the Data Safety and Monitoring Board (DSMB), which will also contain statisticians and ethicists.
The DSMB will meet on a regular basis (i.e., every 4 months). The major task of the
DSMB will be to ensure the safety of the substudy by reviewing potential adverse events.
A.3