TABLE 2.

Explanations for the paucity of antigen-specific immunotherapy studies in the intervention setting

	“Biologics” and other nonantigen-specific approaches	Antigen-specific immunotherapy
Biomarkers	Facile (e.g., reduction in B-cells during anti-CD20 therapy)	Emerging but remain typically site and study-specific; lack of consensus
Dosing and route of administration	Clear treatment pathways from Phase I studies and/or other diseases	Often difficult and complex in ASI; issues over use of adjuvants unresolved; optimal routes remain to be determined
Preclinical models	Generally robust and informative	Translation not always straightforward (e.g., is the intranasal route appropriate in humans; antigen or peptide choice; timing of therapy in relation to natural history)
Success in other autoimmune diseases	Yes	Not yet (but whole allergen and allergen peptide immunotherapy are effective)
Target population	All patients with type 1 diabetes	Inclusion criteria may require staging to presence of selected autoantibodies and their titre, and to HLA type for peptides
Efficacy	Often effective as interventions	Intervention is a tough arena for trials with metabolic outcomes (i.e., C-peptide preservation)
Safety	Variable but generally predictable	Good
Biotechnology/Pharmaceutical involvement	High	Variable; e.g., there is still no Good Manufacturing Practice (GMP) grade proinsulin; new Intellectual Property (IP) relies upon novel modes of delivery