The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations

Anastasia Ivanova; Elliot Israel; Lisa M. LaVange; Michael C. Peters; Loren C. Denlinger; Wendy C. Moore; Leonard B. Bacharier; M. Alison Marquis; Nathan M. Gotman; Michael R. Kosorok; Chalmer Tomlinson; David T. Mauger; Steve N. Georas; Rosalind J. Wright; Patricia Noel; Gary L. Rosner; Praveen Akuthota; Dean Billheimer; Eugene R. Bleecker; Juan Carlos Cardet; Mario Castro; Emily A. DiMango; Serpil C. Erzurum; John V. Fahy; Merritt L. Fajt; Benjamin M. Gaston; Fernando Holguin; Sonia Jain; Nicholas J. Kenyon; Jerry A. Krishnan; Monica Kraft; Rajesh Kumar; Mark C. Liu; Ngoc P. Ly; James N. Moy; Wanda Phipatanakul; Kristie Ross; Lewis J. Smith; Stanley J. Szefler; W. Gerald Teague; Michael E. Wechsler; Sally E. Wenzel; Steven R. White

doi:10.1080/10543406.2020.1821705

The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations

Anastasia Ivanova^*, Elliot Israel, Lisa M. LaVange, Michael C. Peters, Loren C. Denlinger, Wendy C. Moore, Leonard B. Bacharier, M. Alison Marquis, Nathan M. Gotman, Michael R. Kosorok, Chalmer Tomlinson, David T. Mauger, Steve N. Georas, Rosalind J. Wright, Patricia Noel, Gary L. Rosner, Praveen Akuthota, Dean Billheimer, Eugene R. Bleecker, Juan Carlos CardetMario Castro, Emily A. DiMango, Serpil C. Erzurum, John V. Fahy, Merritt L. Fajt, Benjamin M. Gaston, Fernando Holguin, Sonia Jain, Nicholas J. Kenyon, Jerry A. Krishnan, Monica Kraft, Rajesh Kumar, Mark C. Liu, Ngoc P. Ly, James N. Moy, Wanda Phipatanakul, Kristie Ross, Lewis J. Smith, Stanley J. Szefler, W. Gerald Teague, Michael E. Wechsler, Sally E. Wenzel, Steven R. White

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

Abstract

The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving up to five interventions and at least one placebo. Treatment assignments are based on the patients’ biomarker profiles and precision health methods are incorporated into the interim and final analyses. We describe key elements of the PrecISE study including the multistage adaptive enrichment strategy, early stopping of an intervention for futility, power calculations, and the primary analysis strategy.

Original language	English (US)
Pages (from-to)	1026-1037
Number of pages	12
Journal	Journal of Biopharmaceutical Statistics
Volume	30
Issue number	6
DOIs	https://doi.org/10.1080/10543406.2020.1821705
State	Published - 2020

Funding

This trial was funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH). The request for funding called for a Phase 2 proof-of-concept clinical trial to assess a number of novel interventions in biomarker-defined subgroups of patients with severe asthma and obtain information on the utility of the biomarkers in identifying patients with a higher likelihood to respond to a specific treatment. Rather than propose more standard, non-adaptive, biomarker-stratified, parallel group designs, applicants were encouraged to propose adaptive trial designs that made use of accumulating data on biomarker-outcome relationships to modify design features during the trial. The PrecISE study is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, grant U24 HL138998. The study also gratefully acknowledges receiving contributed product from Vitaeris, owned and operated by CSL group (clazakizumab), Vitaflo (MCT), Sun Pharma (imatinib), OM Pharma, a Vifor Pharma Group Company (OM-85, Broncho-Vaxom), Incyte (itacitinib), Laurel Venture (cavosonstat) and GlaxoSmithKline (Advair Diskus and Ventolin). The authors thank anonymous reviewers for their helpful comments.

Keywords

Master protocol
adaptive enrichment
compex
covariate adaptive randomization
platform trial
severe asthma

ASJC Scopus subject areas

Statistics and Probability
Pharmacology
Pharmacology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1080/10543406.2020.1821705

Cite this

Ivanova, A., Israel, E., LaVange, L. M., Peters, M. C., Denlinger, L. C., Moore, W. C., Bacharier, L. B., Marquis, M. A., Gotman, N. M., Kosorok, M. R., Tomlinson, C., Mauger, D. T., Georas, S. N., Wright, R. J., Noel, P., Rosner, G. L., Akuthota, P., Billheimer, D., Bleecker, E. R., ... White, S. R. (2020). The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations. Journal of Biopharmaceutical Statistics, 30(6), 1026-1037. https://doi.org/10.1080/10543406.2020.1821705

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abstract = "The Precision Interventions for Severe and/or Exacerbation-prone Asthma (PrecISE) study is an adaptive platform trial designed to investigate novel interventions to severe asthma. The study is conducted under a master protocol and utilizes a crossover design with each participant receiving up to five interventions and at least one placebo. Treatment assignments are based on the patients{\textquoteright} biomarker profiles and precision health methods are incorporated into the interim and final analyses. We describe key elements of the PrecISE study including the multistage adaptive enrichment strategy, early stopping of an intervention for futility, power calculations, and the primary analysis strategy.",

keywords = "Master protocol, adaptive enrichment, compex, covariate adaptive randomization, platform trial, severe asthma",

author = "Anastasia Ivanova and Elliot Israel and LaVange, {Lisa M.} and Peters, {Michael C.} and Denlinger, {Loren C.} and Moore, {Wendy C.} and Bacharier, {Leonard B.} and Marquis, {M. Alison} and Gotman, {Nathan M.} and Kosorok, {Michael R.} and Chalmer Tomlinson and Mauger, {David T.} and Georas, {Steve N.} and Wright, {Rosalind J.} and Patricia Noel and Rosner, {Gary L.} and Praveen Akuthota and Dean Billheimer and Bleecker, {Eugene R.} and Cardet, {Juan Carlos} and Mario Castro and DiMango, {Emily A.} and Erzurum, {Serpil C.} and Fahy, {John V.} and Fajt, {Merritt L.} and Gaston, {Benjamin M.} and Fernando Holguin and Sonia Jain and Kenyon, {Nicholas J.} and Krishnan, {Jerry A.} and Monica Kraft and Rajesh Kumar and Liu, {Mark C.} and Ly, {Ngoc P.} and Moy, {James N.} and Wanda Phipatanakul and Kristie Ross and Smith, {Lewis J.} and Szefler, {Stanley J.} and Teague, {W. Gerald} and Wechsler, {Michael E.} and Wenzel, {Sally E.} and White, {Steven R.}",

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doi = "10.1080/10543406.2020.1821705",

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Ivanova, A, Israel, E, LaVange, LM, Peters, MC, Denlinger, LC, Moore, WC, Bacharier, LB, Marquis, MA, Gotman, NM, Kosorok, MR, Tomlinson, C, Mauger, DT, Georas, SN, Wright, RJ, Noel, P, Rosner, GL, Akuthota, P, Billheimer, D, Bleecker, ER, Cardet, JC, Castro, M, DiMango, EA, Erzurum, SC, Fahy, JV, Fajt, ML, Gaston, BM, Holguin, F, Jain, S, Kenyon, NJ, Krishnan, JA, Kraft, M, Kumar, R, Liu, MC, Ly, NP, Moy, JN, Phipatanakul, W, Ross, K, Smith, LJ, Szefler, SJ, Teague, WG, Wechsler, ME, Wenzel, SE & White, SR 2020, 'The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations', Journal of Biopharmaceutical Statistics, vol. 30, no. 6, pp. 1026-1037. https://doi.org/10.1080/10543406.2020.1821705

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AU - Ivanova, Anastasia

AU - Israel, Elliot

AU - LaVange, Lisa M.

AU - Peters, Michael C.

AU - Denlinger, Loren C.

AU - Moore, Wendy C.

AU - Bacharier, Leonard B.

AU - Marquis, M. Alison

AU - Gotman, Nathan M.

AU - Kosorok, Michael R.

AU - Tomlinson, Chalmer

AU - Mauger, David T.

AU - Georas, Steve N.

AU - Wright, Rosalind J.

AU - Noel, Patricia

AU - Rosner, Gary L.

AU - Akuthota, Praveen

AU - Billheimer, Dean

AU - Bleecker, Eugene R.

AU - Cardet, Juan Carlos

AU - Castro, Mario

AU - DiMango, Emily A.

AU - Erzurum, Serpil C.

AU - Fahy, John V.

AU - Fajt, Merritt L.

AU - Gaston, Benjamin M.

AU - Holguin, Fernando

AU - Jain, Sonia

AU - Kenyon, Nicholas J.

AU - Krishnan, Jerry A.

AU - Kraft, Monica

AU - Kumar, Rajesh

AU - Liu, Mark C.

AU - Ly, Ngoc P.

AU - Moy, James N.

AU - Phipatanakul, Wanda

AU - Ross, Kristie

AU - Smith, Lewis J.

AU - Szefler, Stanley J.

AU - Teague, W. Gerald

AU - Wechsler, Michael E.

AU - Wenzel, Sally E.

AU - White, Steven R.

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KW - Master protocol

KW - adaptive enrichment

KW - compex

KW - covariate adaptive randomization

KW - platform trial

KW - severe asthma

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The precision interventions for severe and/or exacerbation-prone asthma (PrecISE) adaptive platform trial: statistical considerations

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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