Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era

On behalf of the National Heart Lung and Blood Institute's “AsthmaNet”

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Precision medicine is expected to impact the care of people with asthma, given its high disease prevalence, heterogeneity of pathophysiologic mechanisms, and consequent clinical phenotypes. A novel phenotype-stratified clinical trial conducted by the NHLBI AsthmaNet Consortium, titled Steroids in Eosinophil Negative Asthma (SIENA), was a randomized, multicenter, clinical trial that prospectively stratified individuals according to their baseline level of sputum inflammation during a screening period. Two phenotypic strata were assigned based on an a priori defined extent of sputum eosinophilia (Eos Low versus Eos High). This article describes: the scientific premise for the trial design, including assumptions used for power calculations; modifications to the analysis plan implemented after the trial started due to a higher than expected prevalence of one phenotypic stratum which impacted the ability to accrue sufficient subjects within the planned budget and study period; investigator alternatives to address the strata imbalance weighing scientific impact and study feasibility; and the final modified SIENA study design and analysis plan. SIENA was successfully completed in a manner that maintained meaningful outcomes. We conclude with recommendations for incorporation of pre-specified contingency plans into phenotype-directed protocols, to address the potential for differences in observed compared to estimated prevalence of different phenotypes in a study population. These approaches can be applied to precision medicine trials for the future.

Original languageEnglish (US)
Pages (from-to)98-103
Number of pages6
JournalContemporary Clinical Trials
Volume77
DOIs
StatePublished - Feb 1 2019

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Precision Medicine
Multicenter Studies
Asthma
Eosinophils
Clinical Trials
Phenotype
Steroids
Sputum
National Heart, Lung, and Blood Institute (U.S.)
Eosinophilia
Feasibility Studies
Budgets
Randomized Controlled Trials
Research Personnel
Inflammation
Population

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

On behalf of the National Heart Lung and Blood Institute's “AsthmaNet”. / Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. In: Contemporary Clinical Trials. 2019 ; Vol. 77. pp. 98-103.
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Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. / On behalf of the National Heart Lung and Blood Institute's “AsthmaNet”.

In: Contemporary Clinical Trials, Vol. 77, 01.02.2019, p. 98-103.

Research output: Contribution to journalArticle

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AU - King, Tonya

AU - Dyer, Anne Marie

AU - Chinchilli, Vernon

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