Hidden sources of bias in diagnostic studies: the example of visceral leishmaniasis in east Africa.

A clear understanding of the accuracy of diagnostic tests is essential for the management of infections such as visceral leishmaniasis in endemic areas. Using both published and unpublished datasets from field diagnostic trials of visceral leishmaniasis in the past ten years, we show the potential effects of unrecognised sources of bias including work-up bias, referral bias, and reference test bias on the results. We outline why these biases, which can occur in diagnostic studies of any disease, can go unrecognised despite adherence to current STARD and QUADAS-2 guidelines. Using these examples and referring to others seen in studies of bacterial and viral infections, we make specific recommendations on how these biases might be avoided through specific steps in study design, study reporting, and the locations where studies are conducted.