Table 2.

Key observations and future opportunities

	Key observation/implication	TrialNet current activities and future opportunities
Natural history of type 1 diabetes
Stages of type 1 diabetes	• Intervention in those with two or more autoantibodies represents treatment of islet autoimmunity	• The objective of the abatacept prevention trial is to delay progression from stage 1 to stage 2
	• Progression between stages can be used to define intermediate end points for clinical trials	• Studies into mechanisms underlying progression between stages 1, 2, and 3 and key transition from single to multiple autoantibodies
Rapid decline in β-cell function occurs 6–12 months prior to clinical diagnosis	• This “cliff edge” for loss of β-cell function suggests this is a key time for intervention	• Future studies may use β-cell function as entry/end point for trials at stage 1 and/or stage 2
	• The cause of this rapid change in β-cell function needs to be understood	• Studies into immune mechanisms associated with onset of rapid decline
Age is a major determinant of the clinical course of type 1 diabetes at all stages of disease	• Mechanisms underlying the effect of age are unknown	• Studies into immune and genetic mechanisms underlying age effect
	• Age of participants must be considered in clinical trial design	• Inclusion criteria and analytic plan for the teplizumab prevention trial vary by age
Disease-modifying therapies	• Immunotherapy “works” in type 1 diabetes, though the effect wanes	• Future studies with sequential therapy and/or repeat dosing
	• Changes in C-peptide after clinical diagnosis are predictable	• Standard definitions of responder/nonresponder to disease-modifying therapy
	• C-peptide secretion falls most rapidly over the first 6 months after diagnosis	• Characterizing immune changes in the “therapeutic window” 0–6 months post-diagnosis
	• Heterogeneity of the disease process, both within and between stages, is likely to demand appropriately tailored therapeutic approaches	• Investigating how “early” disease differs from “late” disease, including drug responsiveness and determinants of persistent C-peptide secretion after diagnosis
Efficiencies in clinical trials	• Social media and peer-to-peer outreach	• Metrics to determine best practices
	• Processes and procedures to ease burdens for participants	• Home capillary testing
	• Use of CIRB in U.S.	• Online consenting
		• Evaluate impact of transition on sites and network