Study Design with Staggered Sampling Times for Evaluating Sustained Unresponsiveness to Peanut Sublingual Immunotherapy
Sunday, March 4, 2018: 2:00 PM
S320CD (Convention Center)
Monica Chaudhari, ,
RATIONALE: The length of time off-therapy that would represent clinically meaningful sustained unresponsiveness (SU) to peanut allergen remains unexplored. Our work has two-fold objectives: first, to delineate aspects of the altered clinical trial design that would allow us to assess effectiveness of sublingual immunotherapy in achieving SU; second, to discuss methodology to evaluate the time to loss of SU and associated risk factors in context of the proposed study design.

METHODS: The salient feature of the new design is the allocation scheme of study subjects to staggered sampling timepoints following therapy suspension when a subsequent DBPCFC is administered. Due to a fixed sequence of increasing allergen doses administered in a challenge-test, the subject’s true threshold at either occasion is interval-censored. Additionally, due to the timing of subsequent DBPCFC, the time to loss of SU for subjects who pass the DBPCFC at study entry is either left- or right-censored. We examine performance of the proposed methodology specifically designed to analyze data arising from this trial.

RESULTS: The revised protocol not only eliminated the need for a two-arm trial and hence, the associated administrative burden, but also reduced the overall length of the clinical trial by almost fifteen months, potentially reducing non-compliance and drop-outs. The model is sufficiently powered for small sample sizes to detect risk factors associated with time to loss of SU.

CONCLUSIONS: Unlike typical protocol that has primary endpoint defined as the degree of desensitization measured at a fixed timepoint, the revised protocol has allowed to investigate new objectives of inquiry.