Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity
Abstract Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the $$S/F$$ S / F ratio. Because of the ceiling effect in oxyhaemoglob...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-42205-6 |
| _version_ | 1827709510863552512 |
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| author | Maaike C. Swets Steven Kerr James Scott-Brown Adam B. Brown Rishi Gupta Jonathan E. Millar Enti Spata Fiona McCurrach Andrew D. Bretherick Annemarie Docherty David Harrison Kathy Rowan Neil Young ISARIC4C Investigators Geert H. Groeneveld Jake Dunning Jonathan S. Nguyen-Van-Tam Peter Openshaw Peter W. Horby Ewen Harrison Natalie Staplin Malcolm G. Semple Nazir Lone J. Kenneth Baillie |
| author_facet | Maaike C. Swets Steven Kerr James Scott-Brown Adam B. Brown Rishi Gupta Jonathan E. Millar Enti Spata Fiona McCurrach Andrew D. Bretherick Annemarie Docherty David Harrison Kathy Rowan Neil Young ISARIC4C Investigators Geert H. Groeneveld Jake Dunning Jonathan S. Nguyen-Van-Tam Peter Openshaw Peter W. Horby Ewen Harrison Natalie Staplin Malcolm G. Semple Nazir Lone J. Kenneth Baillie |
| author_sort | Maaike C. Swets |
| collection | DOAJ |
| description | Abstract Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the $$S/F$$ S / F ratio. Because of the ceiling effect in oxyhaemoglobin saturation, $$S/F$$ S / F ratio ceases to reflect pulmonary oxygenation function at high $${S}_{p}{O}_{2}$$ S p O 2 values. We found that the correlation of $$S/F$$ S / F with the reference standard ( $${P}_{a}{O}_{2}$$ P a O 2 / $${F}_{I}{O}_{2}$$ F I O 2 ratio) improves substantially when excluding $${S}_{p}{O}_{2} > 0.94$$ S p O 2 > 0.94 and refer to this measure as $$S/{F}_{94}$$ S / F 94 . Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that $$S/{F}_{94}$$ S / F 94 is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using $$S/{F}_{94}$$ S / F 94 . We demonstrate that $$S/{F}_{94}$$ S / F 94 is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power. |
| first_indexed | 2024-03-10T17:23:00Z |
| format | Article |
| id | doaj.art-009fd47cdad84e04b276c3c4dbe7d8d5 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:23:00Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-009fd47cdad84e04b276c3c4dbe7d8d52023-11-20T10:15:35ZengNature PortfolioNature Communications2041-17232023-11-0114111010.1038/s41467-023-42205-6Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severityMaaike C. Swets0Steven Kerr1James Scott-Brown2Adam B. Brown3Rishi Gupta4Jonathan E. Millar5Enti Spata6Fiona McCurrach7Andrew D. Bretherick8Annemarie Docherty9David Harrison10Kathy Rowan11Neil Young12ISARIC4C InvestigatorsGeert H. Groeneveld13Jake Dunning14Jonathan S. Nguyen-Van-Tam15Peter Openshaw16Peter W. Horby17Ewen Harrison18Natalie Staplin19Malcolm G. Semple20Nazir Lone21J. Kenneth Baillie22Roslin Institute, University of EdinburghRoslin Institute, University of EdinburghSchool of Informatics, University of EdinburghRoslin Institute, University of EdinburghInstitute for Global Health, University College LondonRoslin Institute, University of EdinburghMedical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health (NDPH)EMERGE, NHS Lothian, Royal Infirmary EdinburghMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General HospitalCentre for Medical Informatics, Usher Institute, University of EdinburghIntensive Care National Audit & Research CentreIntensive Care National Audit & Research CentreDepartment of Anaesthesia, Critical Care and Pain Medicine, Royal Infirmary of EdinburghDepartment of Infectious Diseases, Leiden University Medical Center, Leiden UniversityPandemic Sciences Institute, University of OxfordPopulation and Lifespan Health, University of Nottingham School of MedicineNational Heart and Lung Institute, Imperial College LondonPandemic Sciences Institute, University of OxfordCentre for Medical Informatics, Usher Institute, University of EdinburghMedical Research Council Population Health Research Unit at the University of Oxford, Nuffield Department of Population Health (NDPH)Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of LiverpoolCentre for Medical Informatics, Usher Institute, University of EdinburghRoslin Institute, University of EdinburghAbstract Choosing optimal outcome measures maximizes statistical power, accelerates discovery and improves reliability in early-phase trials. We devised and evaluated a modification to a pragmatic measure of oxygenation function, the $$S/F$$ S / F ratio. Because of the ceiling effect in oxyhaemoglobin saturation, $$S/F$$ S / F ratio ceases to reflect pulmonary oxygenation function at high $${S}_{p}{O}_{2}$$ S p O 2 values. We found that the correlation of $$S/F$$ S / F with the reference standard ( $${P}_{a}{O}_{2}$$ P a O 2 / $${F}_{I}{O}_{2}$$ F I O 2 ratio) improves substantially when excluding $${S}_{p}{O}_{2} > 0.94$$ S p O 2 > 0.94 and refer to this measure as $$S/{F}_{94}$$ S / F 94 . Using observational data from 39,765 hospitalised COVID-19 patients, we demonstrate that $$S/{F}_{94}$$ S / F 94 is predictive of mortality, and compare the sample sizes required for trials using four different outcome measures. We show that a significant difference in outcome could be detected with the smallest sample size using $$S/{F}_{94}$$ S / F 94 . We demonstrate that $$S/{F}_{94}$$ S / F 94 is an effective intermediate outcome measure in COVID-19. It is a non-invasive measurement, representative of disease severity and provides greater statistical power.https://doi.org/10.1038/s41467-023-42205-6 |
| spellingShingle | Maaike C. Swets Steven Kerr James Scott-Brown Adam B. Brown Rishi Gupta Jonathan E. Millar Enti Spata Fiona McCurrach Andrew D. Bretherick Annemarie Docherty David Harrison Kathy Rowan Neil Young ISARIC4C Investigators Geert H. Groeneveld Jake Dunning Jonathan S. Nguyen-Van-Tam Peter Openshaw Peter W. Horby Ewen Harrison Natalie Staplin Malcolm G. Semple Nazir Lone J. Kenneth Baillie Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity Nature Communications |
| title | Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity |
| title_full | Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity |
| title_fullStr | Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity |
| title_full_unstemmed | Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity |
| title_short | Evaluation of pragmatic oxygenation measurement as a proxy for Covid-19 severity |
| title_sort | evaluation of pragmatic oxygenation measurement as a proxy for covid 19 severity |
| url | https://doi.org/10.1038/s41467-023-42205-6 |
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