Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 147, Issue 5, Pages 1594-1601Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2021.01.037
Keywords
Severe asthma; therapy; clinical trial; biomarkers; precision medicine; adaptive design; master protocol; platform trial
Categories
Funding
- National Heart, Lung, and Blood Institute, National Institutes of Health [U24 HL138998, 1UG1HL139054, 1UG1HL139098, 1UG1HL139106, 1UG1HL139117, 1UG1HL139118, 1UG1HL139119, 1UG1HL139123, 1UG1HL139124, 1UG1HL139125, 1UG1HL139126]
- National Institute of Health Clinical & Translational Science Award [UL1TR002451, UL1TR000427, UL1TR002366, UL1TR002389, UL1TR002489, UL1TR001857, UL1TR001442, UL1TR001872]
- Duke/Vanderbilt Trial Innovation Center [5U24TR001608]
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Severe asthma accounts for a significant amount of asthma-related costs, but traditional clinical trial designs lack efficiency. The National Institutes of Health launched the PrecISE program to rapidly evaluate novel interventions for severe asthma using adaptive design techniques that incorporate precision medicine components.
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.
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