I-SPY COVID adaptive platform trial for COVID-19 acute respiratory failure: rationale, design and operations
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Abstract
The COVID-19 pandemic brought an urgent need to discover novel effective therapeutics for patients hospitalised with severe COVID-19. The Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular Analysis (ISPY COVID-19 trial) was designed and implemented in early 2020 to evaluate investigational agents rapidly and simultaneously on a phase 2 adaptive platform. This manuscript outlines the design, rationale, implementation and challenges of the ISPY COVID-19 trial during the first phase of trial activity from April 2020 until December 2021.
Methods and analysis
The ISPY COVID-19 Trial is a multicentre open-label phase 2 platform trial in the USA designed to evaluate therapeutics that may have a large effect on improving outcomes from severe COVID-19. The ISPY COVID-19 Trial network includes academic and community hospitals with significant geographical diversity across the country. Enrolled patients are randomised to receive one of up to four investigational agents or a control and are evaluated for a family of two primary outcomes—time to recovery and mortality. The statistical design uses a Bayesian model with ‘stopping’ and ‘graduation’ criteria designed to efficiently discard ineffective therapies and graduate promising agents for definitive efficacy trials. Each investigational agent arm enrols to a maximum of 125 patients per arm and is compared with concurrent controls. As of December 2021, 11 investigational agent arms had been activated, and 8 arms were complete. Enrolment and adaptation of the trial design are ongoing.
Ethics and dissemination
ISPY COVID-19 operates under a central institutional review board via Wake Forest School of Medicine IRB00066805. Data generated from this trial will be reported in peer-reviewed medical journals.
Trial registration number
NCT04488081 .
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SciScore for 10.1101/2022.05.05.22274628: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: If the agent is selected for inclusion, the chaperones prepare the materials necessary for IRB approval and implementation, including agent-specific appendices to the master protocol, informed consent documents and technical guides on dosing and administration. Sex as a biological variable not detected. Randomization 2 The I-SPY COVID Trial is a phase 2, multi-center, multi-arm, adaptive, open-label, randomized controlled trial designed to rapidly screen agents to identify those with potential impact to meaningfully improve outcomes for severe COVID-19 patients (Figure 1). Blinding While the open-label approach does potentially allow for investigator bias, a similar open label approach … SciScore for 10.1101/2022.05.05.22274628: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: If the agent is selected for inclusion, the chaperones prepare the materials necessary for IRB approval and implementation, including agent-specific appendices to the master protocol, informed consent documents and technical guides on dosing and administration. Sex as a biological variable not detected. Randomization 2 The I-SPY COVID Trial is a phase 2, multi-center, multi-arm, adaptive, open-label, randomized controlled trial designed to rapidly screen agents to identify those with potential impact to meaningfully improve outcomes for severe COVID-19 patients (Figure 1). Blinding While the open-label approach does potentially allow for investigator bias, a similar open label approach has also been used successfully in the RECOVERY Platform for COVID-19 in the United Kingdom.8 Ultimately, the open label design of the I-SPY COVID trial was deemed to be the most efficient approach to rapidly and safely evaluate novel therapeutics for severe COVID-19, with the goal that promising agents could be further tested in a closed, double blinded placebo-controlled format upon trial graduation. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources Examples of the type of analyses that will be conducted include testing whether previously identified phenotypes of ARDS are relevant in COVID-199, replicating innovative analyses of immunotypes within severe COVID-19,10 testing for anti-Type I interferon antibodies in serum from enrolled patients,11 and measuring plasma viral antigen levels and SARS-CoV-2 endogenous antibody levels. anti-Type Isuggested: NoneSoftware and Algorithms Sentences Resources Lastly, site conduct is audited by Quantum Leap Healthcare Collaborative and trial conduct by other study sponsors. Leap Healthcaresuggested: (Ohio State University College of Medicine; Ohio; USA, RRID:SCR_012866)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04488081 Recruiting I-SPY COVID-19 TRIAL: An Adaptive Platform Trial for Critica… Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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