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Ignoring the ICC in the sample size calculation might result in a severely underpowered study.
Disease heterogeneity and underpowered study designs are likely to be behind non-reproducible results in candidate gene association studies.
If the effect size is smaller than expected, sample size recalculation would be a reasonable choice in the face of an underpowered study.
In this current paper, we investigate this null result and find it cannot be explained by an underpowered study design, inaccurate measurements, low adoption of and compliance with the intervention, or crowding out through dietary substitution.
Therefore, when between-subject variations in outcome trends are anticipated to be significant, sample size determinations based on a fixed slope model can result in a seriously underpowered study.
However, inclusion of additional patients is still warranted in our possibly underpowered study before any definitive conclusion.
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Moreover, many of the included studies were underpowered, and underpowered studies contribute biased effect size estimates.
Most of these tests are based on small, underpowered studies.
However, results derived from individually underpowered studies are conflicting.
Higginson, A. D. & Munafò, M. Current incentives for scientists lead to underpowered studies with erroneous conclusions.
But summarizing small underpowered studies cannot eliminate the basic flaws in design.
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