Effect of grass sublingual tablet immunotherapy is similar in children and adults: A Bayesian approach to design pediatric sublingual immunotherapy trials

Amarjot Kaur, David Skoner, Joseph Ibrahim, Qing Li, Richard F Lockey, Michael Blaiss, Albrecht Bufe, Jens Strodl Andersen, Giorgio Walter Canonica, Hendrik Nolte

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials because of inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size.

OBJECTIVE: We sought to describe how a Bayesian framework using prior information from adult trials can be used to improve pediatric SLIT clinical development.

METHODS: Data were compiled by using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablets.

RESULTS: The treatment effect of timothy grass SLIT-tablets was considered similar between pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined symptom plus medication score improvement versus placebo of 21% (95% CI, 11.0% to 30.4%) and 20% (95% CI, 14.6% to 24.4%), respectively. Phleum pratense-specific IgG4and IgE-blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablets. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criteria for pediatric trials incorporating information from prior adult trials and thereby reduce the sample size.

CONCLUSIONS: Data support the similarity of efficacy and immunologic changes between children and adults treated with SLIT for allergic rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to design feasible trials in children, which might reduce unsafe off-label use by promoting more quickly proper labeling of approved products.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
DOIs
Publication statusE-pub ahead of print - Dec 5 2017

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Sublingual Immunotherapy
Poaceae
Tablets
Phleum
Pediatrics
Sample Size
Bayes Theorem
Product Labeling
Off-Label Use
Allergens
Immunoglobulin E
Placebos
Clinical Trials
Therapeutics

Keywords

  • Journal Article

Cite this

Effect of grass sublingual tablet immunotherapy is similar in children and adults : A Bayesian approach to design pediatric sublingual immunotherapy trials. / Kaur, Amarjot; Skoner, David; Ibrahim, Joseph; Li, Qing; Lockey, Richard F; Blaiss, Michael; Bufe, Albrecht; Andersen, Jens Strodl; Canonica, Giorgio Walter; Nolte, Hendrik.

In: Journal of Allergy and Clinical Immunology, 05.12.2017.

Research output: Contribution to journalArticle

Kaur, Amarjot ; Skoner, David ; Ibrahim, Joseph ; Li, Qing ; Lockey, Richard F ; Blaiss, Michael ; Bufe, Albrecht ; Andersen, Jens Strodl ; Canonica, Giorgio Walter ; Nolte, Hendrik. / Effect of grass sublingual tablet immunotherapy is similar in children and adults : A Bayesian approach to design pediatric sublingual immunotherapy trials. In: Journal of Allergy and Clinical Immunology. 2017.
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abstract = "BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials because of inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size.OBJECTIVE: We sought to describe how a Bayesian framework using prior information from adult trials can be used to improve pediatric SLIT clinical development.METHODS: Data were compiled by using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablets.RESULTS: The treatment effect of timothy grass SLIT-tablets was considered similar between pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined symptom plus medication score improvement versus placebo of 21{\%} (95{\%} CI, 11.0{\%} to 30.4{\%}) and 20{\%} (95{\%} CI, 14.6{\%} to 24.4{\%}), respectively. Phleum pratense-specific IgG4and IgE-blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablets. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criteria for pediatric trials incorporating information from prior adult trials and thereby reduce the sample size.CONCLUSIONS: Data support the similarity of efficacy and immunologic changes between children and adults treated with SLIT for allergic rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to design feasible trials in children, which might reduce unsafe off-label use by promoting more quickly proper labeling of approved products.",
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note = "Copyright {\circledC} 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.",
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T1 - Effect of grass sublingual tablet immunotherapy is similar in children and adults

T2 - A Bayesian approach to design pediatric sublingual immunotherapy trials

AU - Kaur, Amarjot

AU - Skoner, David

AU - Ibrahim, Joseph

AU - Li, Qing

AU - Lockey, Richard F

AU - Blaiss, Michael

AU - Bufe, Albrecht

AU - Andersen, Jens Strodl

AU - Canonica, Giorgio Walter

AU - Nolte, Hendrik

N1 - Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

PY - 2017/12/5

Y1 - 2017/12/5

N2 - BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials because of inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size.OBJECTIVE: We sought to describe how a Bayesian framework using prior information from adult trials can be used to improve pediatric SLIT clinical development.METHODS: Data were compiled by using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablets.RESULTS: The treatment effect of timothy grass SLIT-tablets was considered similar between pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined symptom plus medication score improvement versus placebo of 21% (95% CI, 11.0% to 30.4%) and 20% (95% CI, 14.6% to 24.4%), respectively. Phleum pratense-specific IgG4and IgE-blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablets. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criteria for pediatric trials incorporating information from prior adult trials and thereby reduce the sample size.CONCLUSIONS: Data support the similarity of efficacy and immunologic changes between children and adults treated with SLIT for allergic rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to design feasible trials in children, which might reduce unsafe off-label use by promoting more quickly proper labeling of approved products.

AB - BACKGROUND: Large sample sizes are needed for sublingual immunotherapy (SLIT) trials because of inherent data variability secondary to inconsistent allergen exposure. Obtaining large sample sizes for pediatric SLIT trials is challenging, but a Bayesian approach using prior adult data can reduce the necessary sample size.OBJECTIVE: We sought to describe how a Bayesian framework using prior information from adult trials can be used to improve pediatric SLIT clinical development.METHODS: Data were compiled by using a frequentist approach (conventional clinical trial approach independent of prior data) from trials conducted during the clinical development of timothy grass SLIT-tablets.RESULTS: The treatment effect of timothy grass SLIT-tablets was considered similar between pediatric (n = 795) and adult (n = 2299) data pools, with relative total combined symptom plus medication score improvement versus placebo of 21% (95% CI, 11.0% to 30.4%) and 20% (95% CI, 14.6% to 24.4%), respectively. Phleum pratense-specific IgG4and IgE-blocking factor increased from baseline in both children and adults treated with timothy grass SLIT-tablets. Given the reasonable assumption in similarity of treatment response between adults and children, a Bayesian approach is described to demonstrate rigorous efficacy criteria for pediatric trials incorporating information from prior adult trials and thereby reduce the sample size.CONCLUSIONS: Data support the similarity of efficacy and immunologic changes between children and adults treated with SLIT for allergic rhinoconjunctivitis. Therefore it is appropriate to use data from adult trials to design feasible trials in children, which might reduce unsafe off-label use by promoting more quickly proper labeling of approved products.

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DO - 10.1016/j.jaci.2017.09.051

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JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 0091-6749

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