The present invention relates to improved clotting compositions for producing high quality blood serum samples for analyte testing, such as for pathology testing and other biological assays. In particular, the present invention relates to the use of prothrombin activators in combination with stabilizing agents such as colloids for producing high quality blood serum samples. The present invention also relates to associated methods for preparing clotting compositions, tubes, kits and methods of diagnosis, prognosis and monitoring for responsiveness to therapy.