Methods, Quality Control and Specimen Management in an International Multi-Center Investigation of Type 1 Diabetes: TEDDY

The Environmental Determinants of Diabetes in the Young (TEDDY) is a multi-center, international prospective study (n = 8,677) designed to identify environmental triggers of type 1 diabetes (T1D) in genetically at-risk children from age 3 months until 15 years. The study is conducted through six primary clinical centers located in four countries. As of May 2012, over three million biological samples and 250 million total data points have been collected which will be analyzed to assess autoimmunity status, presence of inflammatory biomarkers, genetic factors, exposure to infectious agents, dietary biomarkers, and other potentially important environmental exposures in relation to autoimmunity and progression to T1D. The vast array and quantity of longitudinal samples collected in the TEDDY study present a series of challenges in terms of quality control procedures and data validity. To address this, pilot studies have been conducted to standardize and enhance both biospecimen collection and sample obtainment in terms of autoantibody collection, stool sample preservation, RNA, biomarker stability, metabolic biomarkers, and T-cell viability. This paper details the procedures utilized to standardize both data harmonization and management when handling a large quantity of longitudinal samples obtained from multiple locations. In addition, we provide a description of the available specimens that serve as an invaluable repository for the elucidation of determinants in T1D focusing on autoantibody concordance and harmonization, transglutaminase autoantibody (tGA), inflammatory biomarkers (T-cells), genetic proficiency testing, RNA lab internal quality control testing, infectious agents (monitoring cross contamination, virus preservation, and nasal swab collection validity), and HbA1c testing.