Clinical trial design during and beyond the pandemic: the I-SPY COVID trial

Calfee, Carolyn S.; Liu, Kathleen D.; Asare, Adam; Beitler, Jeremy R.; Berger, Paul; Coleman, Melissa H.; Crippa, Alessio; Discacciati, Andrea; Eklund, Martin; Files, D. Clark; Gandotra, Sheetal; Gibbs, Kevin W.; Henderson, Paul; Levitt, Joseph E.; Lu, Ruixiao; Matthay, Michael A.; Meyer, Nuala J.; Russell, Derek W.; Thomas, Karl W.; Esserman, Laura J.; Mittel, Aaron; Dzierba, Amy; Madahar, Purnema; Serra, Alexis; Rosen, Amanda; García, Iván; Muir, Justin; Schicchi, John; Darmanian, Anita; Wahab, Romina; Gosek, Katarzyna; Auld, Sara C.; Adelman, Max W.; Nugent, K.; Harris, Gavin; Creel-Bulos, Christina; Yang, Philip; Detelich, Joshua F.; Spainhour, Christine; Cobb, Nathan K.; Sonti, Rajiv; Orr, Lindsey A.; Robinson, Philip A.; Sarafian, Farjad; Martinez, Esmeralda; Jones, Patrice; Nguyen, Julie; Obermiller, Timothy; Weiler-Lisowski, Bethany; Kufa, Lucia; Saba, Paul L.; Wyatt, Jaime; Youssef, Fady; Tanios, Maged; Blevins, Daniel; Macías, L. Ramos; Suarez, Alexis; Reyes, María B.; Jung, Michelle; Melendrez, Marylee; Rosario-Remigio, Lissette; Su, Henry; Friedman, Eliot; Angelucci, Christina M.; Chaparro-Rojas, Fredy; Sternlieb, Mitchell; Sutter, Jacqueline B.; Whealon, Spencer; Nair, Rahul; López, Brenda; Amosu, Omowunmi; Tzehaie, Hiwet; Wunderink, Richard G.; Patel, Chirag; Simonson, Austin; Dodin, Jamal; Oliver, Tony; Lupu, Roxana; Meyers, Michelle; Albertson, Timothy E; Haczku, Angela Franciska; Hardy, Erin; Morrissey, Brian M.; Juarez, Maya; Pearson, Skyler J.; Lee, Richard Anthony; Amin, Alpesh; Jauregui, Alejandra; Fields, Scott; Ng, Diana Leh-Ching; Daniel, Brian; Yee, Kimberly; Jones, Chayse; Burnham, Ellen L.; McKeehan, Jeffrey; Ittner, C.A.G.; Reilly, John P.; Mangalmurti, Nilam S.; Rodrigues, Laura; Weisman, A.R.; Khan, Kashif; Wong, Se Fum; Yen, Albert; Peterfreund, Gregory; Kumar, Shubha; Marshall, Peter S.; Huerta, Luis E.; Lindgren, Brett; Lee, Jerry S.H.; Barker, Anna D.; Lang, Julie E.; LaRose, Mary; Landreth, Leigha; Parks, Lisa; Barot, Harsh V.; Koff, Jonathan L.; Kazianis, John; Boerger, Lindsie

doi:10.1038/s41591-021-01617-x

Cited by 18 publications

(5 citation statements)

References 9 publications

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“…This secondary analysis used de-identified data from the I-SPY COVID clinical trial (ClinicalTrials.gov identifier: NCT04488081), for which detailed design and methods have been published previously ( 8 , 9 ). The trial was overseen by a central institutional review board (IRB) at the Wake Forest School of Medicine (IRB00066805, “I-SPY COVID TRIAL: An Adaptive Platform Trial to Reduce Mortality and Ventilator Requirements for Critically Ill Patients,” approved on July 9, 2020).…”

Section: Methodsmentioning

confidence: 99%

Trend in Clinical Trial Participation During COVID-19: A Secondary Analysis of the I-SPY COVID Clinical Trial

Yang¹,

Dickert²,

Haczku³

et al. 2023

Critical Care Explorations

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OBJECTIVES: To analyze the temporal trend in enrollment rates in a COVID-19 platform trial during the first three waves of the pandemic in the United States. DESIGN: Secondary analysis of data from the I-SPY COVID randomized controlled trial (RCT). SETTING: Thirty-one hospitals throughout the United States. PATIENTS: Patients who were approached, either directly or via a legally authorized representative, for consent and enrollment into the I-SPY COVID RCT. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Among 1,338 patients approached for the I-SPY COVID trial from July 30, 2020, to February 17, 2022, the number of patients who enrolled (n = 1,063) versus declined participation (n = 275) was used to calculate monthly enrollment rates. Overall, demographic and baseline clinical characteristics were similar between those who enrolled versus declined. Enrollment rates fluctuated over the course of the COVID-19 pandemic, but there were no significant trends over time (Mann-Kendall test, p = 0.21). Enrollment rates were also comparable between vaccinated and unvaccinated patients. In multivariable logistic regression analysis, age, sex, region of residence, COVID-19 severity of illness, and vaccination status were not significantly associated with the decision to decline consent. CONCLUSIONS: In this secondary analysis of the I-SPY COVID clinical trial, there was no significant association between the enrollment rate and time period or vaccination status among all eligible patients approached for clinical trial participation. Additional studies are needed to better understand whether the COVID-19 pandemic has altered clinical trial participation and to develop strategies for encouraging participation in future COVID-19 and critical care clinical trials.

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Section: Methodsmentioning

confidence: 99%

Trend in Clinical Trial Participation During COVID-19: A Secondary Analysis of the I-SPY COVID Clinical Trial

Yang¹,

Dickert²,

Haczku³

et al. 2023

Critical Care Explorations

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“…Carolyn Calfee (San Francisco, CA, USA) introduced adaptive trials (trials with pre-planned capabilities to adjust design factors) as a proposal to deal with the ARDS phenotype heterogeneity, the stratified randomisation and a response adaptation [ 37 – 39 ]. They had a considerable impact during COVID-19: for example, RECOVERY evaluated 10 treatments in 47 879 participants in 199 sites, and I-SPY-COVID is an adaptive platform for a phase 2 clinical trial to identify agents with potential therapeutic benefit [ 40 , 41 ].…”

Section: Beyond Covid-19: Translating Covid-19 Treatment Successes To...mentioning

confidence: 99%

ERS International Congress 2022: highlights from the Respiratory Intensive Care Assembly

et al. 2023

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Early Career Members of Assembly 2 (Respiratory Intensive Care) attended the 2022 European Respiratory Society Annual Congress in Barcelona. The conference covered acute and chronic respiratory failure. Sessions of interest to our Assembly members and to those interested in respiratory critical care included the state-of-the-art session on respiratory critical care, the journal session (ERS/Lancet) on acute respiratory distress syndrome (ARDS) phenotyping into precision medicine, specificity of COVID-19 ARDS and its post critical care. A symposium on treatment of acute respiratory failure in patients with chronic obstructive pulmonary disease and innovations in mechanical ventilation either in intensive care unit or at home were also reported. These sessions are summarized in this article.

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“…A fifth ad-RCT, the I-SPY Covid Trial [10] , is built on the experience investigators gained in a previous ad-RCT on breast cancer. This trial is a unique collaborative effort by a consortium that included the US FDA, industry, patient advocates, philanthropic sponsors, and clinicians from major US medical research centers [11] .…”

mentioning

confidence: 99%

“…This trial is a unique collaborative effort by a consortium that included the US FDA, industry, patient advocates, philanthropic sponsors, and clinicians from major US medical research centers [11] . Unlike the other ad-RCTs mentioned above, which are phase 3 RCTs, it is a phase 2 trial for rapidly screening and triaging potential treatments [10] . The I-SPY Covid Trial, which started in July 2020, evaluates in parallel up to four (repurposed and novel) medications vs a control (remdesivir; dexamethasone was added later) on top of the standard care for severe COVID-19 patients.…”

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confidence: 99%

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Participants’ informed consent in adaptive, platform drug trials in hospitalized COVID-19 patients: Not all approaches are ethically acceptable

Dal‐Ré¹,

Caplan²,

Voo³

2022

European Journal of Internal Medicine

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Clinical trial design during and beyond the pandemic: the I-SPY COVID trial

Cited by 18 publications

References 9 publications

Trend in Clinical Trial Participation During COVID-19: A Secondary Analysis of the I-SPY COVID Clinical Trial

Trend in Clinical Trial Participation During COVID-19: A Secondary Analysis of the I-SPY COVID Clinical Trial

ERS International Congress 2022: highlights from the Respiratory Intensive Care Assembly

Participants’ informed consent in adaptive, platform drug trials in hospitalized COVID-19 patients: Not all approaches are ethically acceptable

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