Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19
Abstract Aim To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitali...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | Trials |
| Online Access: | https://doi.org/10.1186/s13063-022-06824-6 |
| _version_ | 1828217866759962624 |
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| author | Peter A. G. Sandercock Janet Darbyshire David DeMets Robert Fowler David G. Lalloo Mohammed Munavvar Natalie Staplin Adilia Warris Janet Wittes Jonathan R. Emberson |
| author_facet | Peter A. G. Sandercock Janet Darbyshire David DeMets Robert Fowler David G. Lalloo Mohammed Munavvar Natalie Staplin Adilia Warris Janet Wittes Jonathan R. Emberson |
| author_sort | Peter A. G. Sandercock |
| collection | DOAJ |
| description | Abstract Aim To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19. Methods and findings During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively ‘competing’ for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab. Conclusions RECOVERY’s streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial’s efficiency, without compromising the DMC’s ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination. |
| first_indexed | 2024-04-12T15:54:40Z |
| format | Article |
| id | doaj.art-0c0418070b5d44ec836582da1bbe6139 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-04-12T15:54:40Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-0c0418070b5d44ec836582da1bbe61392022-12-22T03:26:24ZengBMCTrials1745-62152022-10-012311910.1186/s13063-022-06824-6Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19Peter A. G. Sandercock0Janet Darbyshire1David DeMets2Robert Fowler3David G. Lalloo4Mohammed Munavvar5Natalie Staplin6Adilia Warris7Janet Wittes8Jonathan R. Emberson9Centre for Clinical Brain Sciences, University of EdinburghUniversity College LondonSchool of Medicine and Public Health, University of Wisconsin-MadisonDepartment of Medicine and Interdepartmental Division of Critical Care Medicine, University of TorontoLiverpool School of Tropical MedicineLancashire Teaching Hospitals and University of Central LancashireMedical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of OxfordMRC Centre for Medical Mycology, University of ExeterWittes LLCMedical Research Council Population Health Research Unit, Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of OxfordAbstract Aim To inform the oversight of future clinical trials during a pandemic, we summarise the experiences of the Data Monitoring Committee (DMC) for the Randomised Evaluation of COVID therapy trial (RECOVERY), a large-scale randomised adaptive platform clinical trial of treatments for hospitalised patients with COVID-19. Methods and findings During the first 24 months of the trial (March 2020 to February 2022), the DMC oversaw accumulating data for 14 treatments in adults (plus 10 in children) involving > 45,000 randomised patients. Five trial aspects key for the DMC in performing its role were: a large committee of members, including some with extensive DMC experience and others who had broad clinical expertise; clear strategic planning, communication, and responsiveness by the trial principal investigators; data collection and analysis systems able to cope with phases of very rapid recruitment and link to electronic health records; an ability to work constructively with regulators (and other DMCs) to address emerging concerns without the need to release unblinded mortality results; and the use of videoconferencing systems that enabled national and international members to meet at short notice and from home during the pandemic when physical meetings were impossible. Challenges included that the first four treatments introduced were effectively ‘competing’ for patients (increasing pressure to make rapid decisions on each one); balancing the global health imperative to report on findings with the need to maintain confidentiality until the results were sufficiently certain to appropriately inform treatment decisions; and reliably assessing safety, especially for newer agents introduced after the initial wave and in the small numbers of pregnant women and children included. We present a series of case vignettes to illustrate some of the issues and the DMC decision-making related to hydroxychloroquine, dexamethasone, casirivimab + imdevimab, and tocilizumab. Conclusions RECOVERY’s streamlined adaptive platform design, linked to hospital-level and population-level health data, enabled the rapid and reliable assessment of multiple treatments for hospitalised patients with COVID-19. The later introduction of factorial assessments increased the trial’s efficiency, without compromising the DMC’s ability to assess safety and efficacy. Requests for the release of unblinded primary outcome data to regulators at points when data were not mature required significant efforts in communication with the regulators by the DMC to avoid inappropriate early trial termination.https://doi.org/10.1186/s13063-022-06824-6 |
| spellingShingle | Peter A. G. Sandercock Janet Darbyshire David DeMets Robert Fowler David G. Lalloo Mohammed Munavvar Natalie Staplin Adilia Warris Janet Wittes Jonathan R. Emberson Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19 Trials |
| title | Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19 |
| title_full | Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19 |
| title_fullStr | Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19 |
| title_full_unstemmed | Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19 |
| title_short | Experiences of the Data Monitoring Committee for the RECOVERY trial, a large-scale adaptive platform randomised trial of treatments for patients hospitalised with COVID-19 |
| title_sort | experiences of the data monitoring committee for the recovery trial a large scale adaptive platform randomised trial of treatments for patients hospitalised with covid 19 |
| url | https://doi.org/10.1186/s13063-022-06824-6 |
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