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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:147

Article

Israel, Elliot^1,2  Denlinger, Loren C.³  Bacharier, Leonard B.⁴  LaVange, Lisa M.⁵  Moore, Wendy C.⁶  Peters, Michael C.⁷  Georas, Steve N.⁸  Wright, Rosalind J.⁹  Mauger, David T.¹⁰  Noel, Patricia¹¹  Akuthota, Praveen¹²  Bach, Julia³  Bleecker, Eugene R.¹³  Cardet, Juan Carlos¹⁴  Carr, Tara F.¹³  Castro, Mario¹⁵  Cinelli, Angeles¹⁶  Comhair, Suzy A. A.¹⁷  Covar, Ronina A.¹⁸  Alexander, Laura Crotty¹²  DiMango, Emily A.¹⁹  Erzurum, Serpil C.¹⁷  Fahy, John, V⁷  Fajt, Merritt L.²⁰  Gaston, Benjamin M.²¹  Hoffman, Eric A.²²  Holguin, Fernando²³  Jackson, Daniel J.³  Jain, Sonia¹²  Jarjour, Nizar N.³  Ji, Yuan²⁴  Kenyon, Nicholas J.²⁵  Kosorok, Michael R.⁵  Kraft, Monica¹³  Krishnan, Jerry A.²⁶  Kumar, Rajesh²⁷  Liu, Andrew H.^23,28  Liu, Mark C.²⁹  Ly, Ngoc P.⁷  Marquis, M. Alison⁵  Martinez, Fernando D.¹³  Moy, James N.³⁰  O'Neal, Wanda K.³¹  Ortega, Victor E.⁶  Peden, David B.³²  Phipatanakul, Wanda^33,34  Ross, Kristie³⁵  Smith, Lewis J.³⁶  Szefler, Stanley J.^23,28  Teague, W. Gerald³⁷  Tulchinsky, Abigail F.¹⁶  Vijayanand, Pandurangan³⁸  Wechsler, Michael E.^18,23  Wenzel, Sally E.²⁰  White, Steven R.³⁹  Zeki, Amir A.²⁵  Ivanova, Anastasia⁵ 

[1] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA

[2] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Allergy & Immunol, Boston, MA 02115 USA

[3] Univ Wisconsin, Sch Med & Publ Hlth, Dept Med, Madison, WI USA

[4] Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA

[5] Univ N Carolina, Dept Biostat, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA

[6] Wake Forest Univ Sch Med, Winston Salem, NC USA

[7] Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA

[8] Univ Rochester, Med Ctr, Dept Med, Div Pulm & Crit Care Med, Rochester, NY 14642 USA

[9] Icahn Sch Med Mt Sinai, New York, NY 10029 USA

[10] Penn State Univ, Sch Med, Hershey, PA USA

[11] NIH, NHLBI, Div Lung Dis, Bldg 10, Bethesda, MD 20892 USA

[12] Univ Calif San Diego, Dept Med, Pulm Div, La Jolla, CA 92093 USA

[13] Univ Arizona, Asthma & Airway Dis Res Ctr, Tucson, AZ USA

[14] Univ S Florida, Allergy & Immunol, Tampa, FL 33620 USA

[15] Univ Kansas, Sch Med, Kansas City, KS USA

[16] Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA

[17] Cleveland Clin, Lerner Res Inst, Cleveland, OH 44106 USA

[18] Natl Jewish Hlth, Denver, CO USA

[19] Columbia Univ, Med Ctr, New York, NY USA

[20] Univ Pittsburgh, Asthma Inst, Pittsburgh, PA USA

[21] Indiana Univ, Wells Ctr Pediat Res, Indianapolis, IN 46204 USA

[22] Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA

[23] Univ Colorado, Sch Med, Aurora, CO USA

[24] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA

[25] Univ Calif Davis, Dept Internal Med, Sch Med, Div Pulm Crit Care & Sleep Med, Davis, CA 95616 USA

[26] Univ Illinois, Dept Med, Div Pulm, Chicago, IL USA

[27] Lurie Childrens Hosp, Chicago, IL USA

[28] Childrens Hosp Colorado, Aurora, CO USA

[29] Johns Hopkins Univ, Dept Med, Pulm & Crit Care Med, Baltimore, MD USA

[30] Rush Univ, Med Ctr, Chicago, IL USA

[31] Univ N Carolina, Ctr Environm Med, Asthma & Lung Biol, Chapel Hill, NC 27515 USA

[32] Univ N Carolina, UNC CF Res Ctr, Mars Lung Inst, Chapel Hill, NC USA

[33] Boston Childrens Hosp, Boston, MA USA

[34] Harvard Med Sch, Boston, MA 02115 USA

[35] UH Rainbow Babies & Childrens Hosp, Cleveland, OH USA

[36] Northwestern Univ, Chicago, IL 60611 USA

[37] Univ Virginia, Sch Med, Charlottesville, VA 22903 USA

[38] La Jolla Inst Immunol, La Jolla, CA USA

[39] Univ Chicago, Dept Med, Sect Pulm & Crit Care Med, 5841 S Maryland Ave, Chicago, IL 60637 USA

关键词: Severe asthma;    therapy;    clinical trial;    biomarkers;    precision medicine;    adaptive design;    master protocol;    platform trial;   

DOI  :  10.1016/j.jaci.2021.01.037

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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