Systematic biases arising from pre-analytical variables seem to represent a relevant issue. Examples of non-disease-associated factors include: 1) within-class biological variability, which may comprise unknown sub-phenotypes among study populations; 2) pre-analytical variables, such as systematic differences in study populations and/or sample collection, handling, and pre-processing procedures; 3) analytical variables, such as inconsistency in instrument conditions, resulting in poor reproducibility; and 4) measurement imprecision [22].