Dried blood spot collection, sample quality, and fieldwork conditions: Structural validations for conversion into standard values

Objectives: SHARE, a pan-European panel study in 27 European countries and Israel, has collected dried blood spot (DBS) samples from approximately 27 000 respondents in 13 countries. We aim to obtain factors to convert analyte values between DBS and venous blood samples (VBS) taking account of adverse fieldwork conditions such as small spot size, high temperature and humidity, short drying time and long shipment times. Methods: We obtained VBS and DBS from a set of 20 donors in a laboratory setting, and treated the DBS in a systematic and controlled fashion simulating SHARE fieldwork conditions. We used the 3420 outcomes to estimate from DBS analyte values the values that we would have obtained had it been feasible to collect and analyze the donors' venous blood samples. Results: The influence of field conditions and sample quality on DBS analyte values is significant and differs among assays. Varying spot size is the main challenge and affects all markers except HbA1c. Smaller spots lead to overly high measured levels. A missing desiccant is detrimental for all markers except CRP and tHb. The temperature to which the samples are exposed plays a significant role for HDL and CysC, while too brief a drying time affects CRP and CysC. Lab-based adjustment formulae only accounting for the differences between re-liquefied DBS and venous blood do not address these fieldwork conditions. Conclusions: By simulating adverse fieldwork conditions in the lab, we were able to validate DBS collected under such conditions and established conversion formulae with high prediction accuracy.