Streamlining pediatric sublingual immunotherapy trial design

Published online: December 5, 2017

Sublingual immunotherapy (SLIT) may be an attractive treatment option for children with allergic rhinitis with or without conjunctivitis (AR/C), but currently only grass SLIT-tablets are approved for children in the United States. Conducting pediatric SLIT trials in a timely manner can be challenging given the large number of children needed to demonstrate efficacy as defined by the US Food and Drug Administration (FDA). The number of children needed in a trial can potentially be reduced using Bayesian methodology, which is the concept of borrowing information from historical information (such as adult trial data) and incorporating the information to other subgroups of patients (such as children). A Bayesian approach to trial design and data analysis of efficacy can only be used when the effect of the treatment has been established to be similar between patient subgroups (ie, adults and children). The safety assessment was beyond the scope of discussion in this article and should consider the regulatory requirements.
In The Journal of Allergy and Clinical Immunology (JACI), Kaur and colleagues compiled data from timothy grass SLIT-tablet trials to demonstrate that the treatment effect of the tablets was similar between adults and children. The authors then described a potential Bayesian framework in designing and analyzing a pediatric SLIT trial using specific assumptions and variables.

Using combined data from multiple trials, improvement in the total AR/C combined symptom plus medication score compared with placebo was 21% (95% CI: 11.0%, 30.4%) in children and 20% (95% CI: 14.6%, 24.4%) in adults. The authors also showed data that indicate antibody changes generated in response to the timothy grass SLIT-tablets are similar between adults and children. Having established the similarity in treatment effect for timothy grass SLIT-tablet between adults and children, the authors described the impact of using Bayesian methodology on the design of future pediatric SLIT trials. Using a traditional clinical trial design approach, the total number of children needed to demonstrate an effective SLIT response using the strict efficacy criterion could be very large, over 2000 in some scenarios. By borrowing historical adult trial data and applying Bayesian methodology, the number of children needed to demonstrate an effective SLIT response can be reduced manyfold.   

Implementing a Bayesian approach to future pediatric SLIT trial designs can potentially reduce the number of children and development needed to demonstrate efficacy of a SLIT product. Increasing the feasibility of conducting pediatric SLIT trials may encourage pharmaceutical companies to invest in the development of SLIT products for children.   

The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.

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