Assessment of specific immunotherapy efficacy using a novel placebo score–based method

Abstract Background In trials of allergen immunotherapy, allergen exposure is typically assessed by pollen counts, but these may misrepresent exposure if performed remotely from multiple study centers. Objective To assess whether symptomatology in placebo-treated patients is a better measure of local allergen burden at individual centers in such trials. Methods Data from a multicenter, placebo-controlled trial of preseasonal grass pollen immunotherapy were reanalyzed to identify the 4 weeks at each center in which the placebo-treated subjects had the highest combined symptom/medication scores (CSMS). The difference in CSMS between active and placebo groups was compared during the 4 peak placebo score weeks (PlSW) and the 4 peak pollen count weeks (PoCW). Results The benefit of immunotherapy over placebo in the PlSW analysis (18.5%) was greater than in the PoCW analysis (13.6%), with increased statistical significance ( P = .0001, .0038, respectively). Similar improved discrimination was observed when analyzing benefits in subgroups of patients with severe symptoms, a high disease burden, and in different geographical locations. Conclusion This novel PlSW analysis results in better discrimination of the effects of allergen immunotherapy compared with placebo and may be widely applicable in similar studies, both prospectively and retrospectively.