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

Publication ,  Journal Article
Sorkness, CA; King, TS; Dyer, A-M; Chinchilli, VM; Mauger, DT; Krishnan, JA; Blake, K; Castro, M; Covar, R; Israel, E; Kraft, M; Lang, JE ...
Published in: Contemp Clin Trials
February 2019

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.

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Published In

Contemp Clin Trials

DOI

EISSN

1559-2030

Publication Date

February 2019

Volume

77

Start / End Page

98 / 103

Location

United States

Related Subject Headings

  • Sputum
  • Research Design
  • Public Health
  • Precision Medicine
  • Phenotype
  • Middle Aged
  • Male
  • Humans
  • General Clinical Medicine
  • Female
 

Citation

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Sorkness, C. A., King, T. S., Dyer, A.-M., Chinchilli, V. M., Mauger, D. T., Krishnan, J. A., … National Heart Lung and Blood Institute’s “AsthmaNet,” . (2019). Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. Contemp Clin Trials, 77, 98–103. https://doi.org/10.1016/j.cct.2018.12.012
Sorkness, Christine A., Tonya S. King, Anne-Marie Dyer, Vernon M. Chinchilli, David T. Mauger, Jerry A. Krishnan, Kathryn Blake, et al. “Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era.Contemp Clin Trials 77 (February 2019): 98–103. https://doi.org/10.1016/j.cct.2018.12.012.
Sorkness CA, King TS, Dyer A-M, Chinchilli VM, Mauger DT, Krishnan JA, et al. Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era. Contemp Clin Trials. 2019 Feb;77:98–103.
Sorkness, Christine A., et al. “Adapting clinical trial design to maintain meaningful outcomes during a multicenter asthma trial in the precision medicine era.Contemp Clin Trials, vol. 77, Feb. 2019, pp. 98–103. Pubmed, doi:10.1016/j.cct.2018.12.012.
Sorkness CA, King TS, Dyer A-M, Chinchilli VM, Mauger DT, Krishnan JA, Blake K, Castro M, Covar R, Israel E, Kraft M, Lang JE, Lugogo N, Peters SP, Wechsler ME, Wenzel SE, Lazarus SC, 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. Contemp Clin Trials. 2019 Feb;77:98–103.
Journal cover image

Published In

Contemp Clin Trials

DOI

EISSN

1559-2030

Publication Date

February 2019

Volume

77

Start / End Page

98 / 103

Location

United States

Related Subject Headings

  • Sputum
  • Research Design
  • Public Health
  • Precision Medicine
  • Phenotype
  • Middle Aged
  • Male
  • Humans
  • General Clinical Medicine
  • Female