PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment

Elliot Israel, Loren C. Denlinger, Leonard B. Bacharier, Lisa M. LaVange, Wendy C. Moore, Michael C. Peters, Steve N. Georas, Rosalind J. Wright, David T. Mauger, Patricia Noel, Praveen Akuthota, Julia Bach, Eugene R. Bleecker, Juan Carlos Cardet, Tara F. Carr, Mario Castro, Angeles Cinelli, Suzy A.A. Comhair, Ronina A. Covar, Laura Crotty AlexanderEmily A. DiMango, Serpil C. Erzurum, John V. Fahy, Merritt L. Fajt, Benjamin M. Gaston, Eric A. Hoffman, Fernando Holguin, Daniel J. Jackson, Sonia Jain, Nizar N. Jarjour, Yuan Ji, Nicholas J. Kenyon, Michael R. Kosorok, Monica Kraft, Jerry A. Krishnan, Rajesh Kumar, Andrew H. Liu, Mark C. Liu, Ngoc P. Ly, M. Alison Marquis, Fernando D. Martinez, James N. Moy, Wanda K. O'Neal, Victor E. Ortega, David B. Peden, Wanda Phipatanakul, Kristie Ross, Lewis J. Smith, Stanley J. Szefler, W. Gerald Teague, Abigail F. Tulchinsky, Pandurangan Vijayanand, Michael E. Wechsler, Sally E. Wenzel, Steven R. White, Amir Zeki, Anastasia Ivanova

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Severe asthma accounts for almost half the cost associated with asthma. Severe asthma is driven by heterogeneous molecular mechanisms. Conventional clinical trial design often lacks the power and efficiency to target subgroups with specific pathobiological mechanisms. Furthermore, the validation and approval of new asthma therapies is a lengthy process. A large proportion of that time is taken by clinical trials to validate asthma interventions. The National Institutes of Health Precision Medicine in Severe and/or Exacerbation Prone Asthma (PrecISE) program was established with the goal of designing and executing a trial that uses adaptive design techniques to rapidly evaluate novel interventions in biomarker-defined subgroups of severe asthma, while seeking to refine these biomarker subgroups, and to identify early markers of response to therapy. The novel trial design is an adaptive platform trial conducted under a single master protocol that incorporates precision medicine components. Furthermore, it includes innovative applications of futility analysis, cross-over design with use of shared placebo groups, and early futility analysis to permit more rapid identification of effective interventions. The development and rationale behind the study design are described. The interventions chosen for the initial investigation and the criteria used to identify these interventions are enumerated. The biomarker-based adaptive design and analytic scheme are detailed as well as special considerations involved in the final trial design.

Original languageEnglish (US)
Pages (from-to)1594-1601
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume147
Issue number5
DOIs
StatePublished - May 2021

Keywords

  • adaptive design
  • biomarkers
  • clinical trial
  • master protocol
  • platform trial
  • precision medicine
  • Severe asthma
  • therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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