Cargando…
The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization
OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN:...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144687/ https://www.ncbi.nlm.nih.gov/pubmed/34034784 http://dx.doi.org/10.1186/s13063-021-05316-3 |
_version_ | 1783697011083575296 |
---|---|
author | Huang, David T. McCreary, Erin K. Bariola, J. Ryan Wadas, Richard J. Kip, Kevin E. Marroquin, Oscar C. Koscumb, Stephen Collins, Kevin Shovel, Judith A. Schmidhofer, Mark Wisniewski, Mary Kay Sullivan, Colleen Yealy, Donald M. Axe, Meredith Nace, David A. Haidar, Ghady Khadem, Tina Linstrum, Kelsey Snyder, Graham M. Seymour, Christopher W. Montgomery, Stephanie K. McVerry, Bryan J. Berry, Lindsay Berry, Scott Meyers, Russell Weissman, Alexandra Peck-Palmer, Octavia M. Wells, Alan Bart, Robert Albin, Debbie L. Minnier, Tami Angus, Derek C. |
author_facet | Huang, David T. McCreary, Erin K. Bariola, J. Ryan Wadas, Richard J. Kip, Kevin E. Marroquin, Oscar C. Koscumb, Stephen Collins, Kevin Shovel, Judith A. Schmidhofer, Mark Wisniewski, Mary Kay Sullivan, Colleen Yealy, Donald M. Axe, Meredith Nace, David A. Haidar, Ghady Khadem, Tina Linstrum, Kelsey Snyder, Graham M. Seymour, Christopher W. Montgomery, Stephanie K. McVerry, Bryan J. Berry, Lindsay Berry, Scott Meyers, Russell Weissman, Alexandra Peck-Palmer, Octavia M. Wells, Alan Bart, Robert Albin, Debbie L. Minnier, Tami Angus, Derek C. |
author_sort | Huang, David T. |
collection | PubMed |
description | OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN: Open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization PARTICIPANTS: We will evaluate patients who meet the eligibility criteria stipulated by the COVID-19 mAB EUAs who receive mABs within the UPMC Health System, including infusion centers and emergency departments. EUA eligibility criteria include patients with mild to moderate COVID-19, <10 days of symptoms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (elderly, obese, and/or with specific comorbidities). The EUA criteria exclude patients who require oxygen for the treatment of COVID-19 and patients already hospitalized for the treatment of COVID-19. We will use data collected for routine clinical care, including data entered into the electronic medical record and from follow-up calls. INTERVENTION AND COMPARATOR: The interventions are the COVID-19 specific mABs authorized by the EUAs. All aspects of mAB treatment, including eligibility criteria, dosing, and post-infusion monitoring, are as per the EUAs. As a comparative effectiveness trial, all patients receive mAB treatment, and the interventions are compared against each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mAB interventions will accordingly change. From November 2020 to February 2021, FDA issued EUAs for three mAB treatments (bamlanivimab; bamlanivimab and etesevimab; and casirivimab and imdevimab), and at trial launch on March 10, 2021 we evaluated all three. Due to a sustained increase in SARS-CoV-2 variants in the United States resistant to bamlanivimab administered alone, on March 24, 2021 the U.S. Government halted distribution of bamlanivimab alone, and UPMC accordingly halted bamlanivimab monotherapy on March 31, 2021. On April 16, 2021, FDA revoked the EUA for bamlanivimab monotherapy. At the time of manuscript submission, we are therefore evaluating the two mAB treatments authorized by EUAs (bamlanivimab and etesevimab; and casirivimab and imdevimab). MAIN OUTCOMES: The primary outcome is total hospital free days (HFD) at 28 days after mAB administration, calculated as 28 minus the number of days during the index stay (if applicable – e.g., for patients admitted to hospital after mAB administration in the emergency department) minus the number of days readmitted during the 28 days after treatment. This composite endpoint captures the number of days from the day of mAB administration to the 28 days thereafter, during which the patient is alive and free of hospitalization. Death within 28 days is recorded as -1 HFD, as the worst outcome. RANDOMISATION: We will start with equal allocation. Due to uncertainty in sample size, we will use a Bayesian adaptive design and response adaptive randomization to ensure ability to provide statistical inference despite variable sample size. When mABs are ordered by UPMC physicians as a generic referral order, the order is filled by UPMC pharmacy via therapeutic interchange. OPTIMISE-C19 provides the therapeutic interchange via random allocation. Infusion center operations teams and pharmacists use a mAB assignment application embedded in the electronic medical record to determine the random allocation. BLINDING (MASKING): This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size will be determined by case volume throughout the course of the pandemic, supply of FDA authorized mABs, and by that needed to reach a platform trial conclusion of inferiority, superiority, or futility of a given mAB. The trial will continue as long as more than one mAB type is available under EUA, and their comparative effectiveness is uncertain. TRIAL STATUS: Protocol Version 1.0, February 24, 2021. Recruitment began March 10, 2021 and is ongoing at the time of manuscript submission. The estimated recruitment end date is February 22, 2022, though the final end date is dependent on how the pandemic evolves, mAB availability, and when final platform trial conclusions are reached. As noted above, due to U.S. Government decisions, UPMC Health System halted bamlanivimab monotherapy on March 31, 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786. Registered March 10, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05316-3. |
format | Online Article Text |
id | pubmed-8144687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-81446872021-05-25 The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization Huang, David T. McCreary, Erin K. Bariola, J. Ryan Wadas, Richard J. Kip, Kevin E. Marroquin, Oscar C. Koscumb, Stephen Collins, Kevin Shovel, Judith A. Schmidhofer, Mark Wisniewski, Mary Kay Sullivan, Colleen Yealy, Donald M. Axe, Meredith Nace, David A. Haidar, Ghady Khadem, Tina Linstrum, Kelsey Snyder, Graham M. Seymour, Christopher W. Montgomery, Stephanie K. McVerry, Bryan J. Berry, Lindsay Berry, Scott Meyers, Russell Weissman, Alexandra Peck-Palmer, Octavia M. Wells, Alan Bart, Robert Albin, Debbie L. Minnier, Tami Angus, Derek C. Trials Letter OBJECTIVES: The primary objective is to evaluate the comparative effectiveness of COVID-19 specific monoclonal antibodies (mABs) with US Food and Drug Administration (FDA) Emergency Use Authorization (EUA), alongside UPMC Health System efforts to increase patient access to these mABs. TRIAL DESIGN: Open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization PARTICIPANTS: We will evaluate patients who meet the eligibility criteria stipulated by the COVID-19 mAB EUAs who receive mABs within the UPMC Health System, including infusion centers and emergency departments. EUA eligibility criteria include patients with mild to moderate COVID-19, <10 days of symptoms, and who are at high risk for progressing to severe COVID-19 and/or hospitalization (elderly, obese, and/or with specific comorbidities). The EUA criteria exclude patients who require oxygen for the treatment of COVID-19 and patients already hospitalized for the treatment of COVID-19. We will use data collected for routine clinical care, including data entered into the electronic medical record and from follow-up calls. INTERVENTION AND COMPARATOR: The interventions are the COVID-19 specific mABs authorized by the EUAs. All aspects of mAB treatment, including eligibility criteria, dosing, and post-infusion monitoring, are as per the EUAs. As a comparative effectiveness trial, all patients receive mAB treatment, and the interventions are compared against each other. When U.S. government mAB policies change (e.g., FDA grants or revokes EUAs), UPMC Health System policies and the evaluated mAB interventions will accordingly change. From November 2020 to February 2021, FDA issued EUAs for three mAB treatments (bamlanivimab; bamlanivimab and etesevimab; and casirivimab and imdevimab), and at trial launch on March 10, 2021 we evaluated all three. Due to a sustained increase in SARS-CoV-2 variants in the United States resistant to bamlanivimab administered alone, on March 24, 2021 the U.S. Government halted distribution of bamlanivimab alone, and UPMC accordingly halted bamlanivimab monotherapy on March 31, 2021. On April 16, 2021, FDA revoked the EUA for bamlanivimab monotherapy. At the time of manuscript submission, we are therefore evaluating the two mAB treatments authorized by EUAs (bamlanivimab and etesevimab; and casirivimab and imdevimab). MAIN OUTCOMES: The primary outcome is total hospital free days (HFD) at 28 days after mAB administration, calculated as 28 minus the number of days during the index stay (if applicable – e.g., for patients admitted to hospital after mAB administration in the emergency department) minus the number of days readmitted during the 28 days after treatment. This composite endpoint captures the number of days from the day of mAB administration to the 28 days thereafter, during which the patient is alive and free of hospitalization. Death within 28 days is recorded as -1 HFD, as the worst outcome. RANDOMISATION: We will start with equal allocation. Due to uncertainty in sample size, we will use a Bayesian adaptive design and response adaptive randomization to ensure ability to provide statistical inference despite variable sample size. When mABs are ordered by UPMC physicians as a generic referral order, the order is filled by UPMC pharmacy via therapeutic interchange. OPTIMISE-C19 provides the therapeutic interchange via random allocation. Infusion center operations teams and pharmacists use a mAB assignment application embedded in the electronic medical record to determine the random allocation. BLINDING (MASKING): This trial is open-label. However, outcome assessors conducting follow-up calls at day 28 are blinded to mAB assignment, and investigators are blinded to by-mAB aggregate outcome data until a statistical platform trial conclusion is reached. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size will be determined by case volume throughout the course of the pandemic, supply of FDA authorized mABs, and by that needed to reach a platform trial conclusion of inferiority, superiority, or futility of a given mAB. The trial will continue as long as more than one mAB type is available under EUA, and their comparative effectiveness is uncertain. TRIAL STATUS: Protocol Version 1.0, February 24, 2021. Recruitment began March 10, 2021 and is ongoing at the time of manuscript submission. The estimated recruitment end date is February 22, 2022, though the final end date is dependent on how the pandemic evolves, mAB availability, and when final platform trial conclusions are reached. As noted above, due to U.S. Government decisions, UPMC Health System halted bamlanivimab monotherapy on March 31, 2021. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04790786. Registered March 10, 2021 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-021-05316-3. BioMed Central 2021-05-25 /pmc/articles/PMC8144687/ /pubmed/34034784 http://dx.doi.org/10.1186/s13063-021-05316-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Letter Huang, David T. McCreary, Erin K. Bariola, J. Ryan Wadas, Richard J. Kip, Kevin E. Marroquin, Oscar C. Koscumb, Stephen Collins, Kevin Shovel, Judith A. Schmidhofer, Mark Wisniewski, Mary Kay Sullivan, Colleen Yealy, Donald M. Axe, Meredith Nace, David A. Haidar, Ghady Khadem, Tina Linstrum, Kelsey Snyder, Graham M. Seymour, Christopher W. Montgomery, Stephanie K. McVerry, Bryan J. Berry, Lindsay Berry, Scott Meyers, Russell Weissman, Alexandra Peck-Palmer, Octavia M. Wells, Alan Bart, Robert Albin, Debbie L. Minnier, Tami Angus, Derek C. The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
title | The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
title_full | The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
title_fullStr | The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
title_full_unstemmed | The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
title_short | The UPMC OPTIMISE-C19 (OPtimizing Treatment and Impact of Monoclonal antIbodieS through Evaluation for COVID-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
title_sort | upmc optimise-c19 (optimizing treatment and impact of monoclonal antibodies through evaluation for covid-19) trial: a structured summary of a study protocol for an open-label, pragmatic, comparative effectiveness platform trial with response-adaptive randomization |
topic | Letter |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144687/ https://www.ncbi.nlm.nih.gov/pubmed/34034784 http://dx.doi.org/10.1186/s13063-021-05316-3 |
work_keys_str_mv | AT huangdavidt theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT mccrearyerink theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT bariolajryan theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT wadasrichardj theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT kipkevine theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT marroquinoscarc theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT koscumbstephen theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT collinskevin theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT shoveljuditha theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT schmidhofermark theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT wisniewskimarykay theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT sullivancolleen theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT yealydonaldm theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT axemeredith theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT nacedavida theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT haidarghady theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT khademtina theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT linstrumkelsey theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT snydergrahamm theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT seymourchristopherw theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT montgomerystephaniek theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT mcverrybryanj theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT berrylindsay theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT berryscott theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT meyersrussell theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT weissmanalexandra theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT peckpalmeroctaviam theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT wellsalan theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT bartrobert theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT albindebbiel theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT minniertami theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT angusderekc theupmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT huangdavidt upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT mccrearyerink upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT bariolajryan upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT wadasrichardj upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT kipkevine upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT marroquinoscarc upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT koscumbstephen upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT collinskevin upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT shoveljuditha upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT schmidhofermark upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT wisniewskimarykay upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT sullivancolleen upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT yealydonaldm upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT axemeredith upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT nacedavida upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT haidarghady upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT khademtina upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT linstrumkelsey upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT snydergrahamm upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT seymourchristopherw upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT montgomerystephaniek upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT mcverrybryanj upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT berrylindsay upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT berryscott upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT meyersrussell upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT weissmanalexandra upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT peckpalmeroctaviam upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT wellsalan upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT bartrobert upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT albindebbiel upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT minniertami upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization AT angusderekc upmcoptimisec19optimizingtreatmentandimpactofmonoclonalantibodiesthroughevaluationforcovid19trialastructuredsummaryofastudyprotocolforanopenlabelpragmaticcomparativeeffectivenessplatformtrialwithresponseadaptiverandomization |