DOI record:
{
"DOI": "10.1093/infdis/jiaf282",
"ISSN": [
"0022-1899",
"1537-6613"
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"URL": "http://dx.doi.org/10.1093/infdis/jiaf282",
"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>Virologic endpoints are used in Phase 2 trials for COVID-19 therapeutics, but they have not been established as surrogates for clinical endpoints. No meta-analysis using individual participant data (IPD) has been undertaken to identify viral load outcomes for which treatment effects are best associated with effects on hospitalization/death.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>This meta-analysis combined IPD from 23 COVID-19 treatment vs. control comparisons to calculate R2, a surrogacy measure quantifying the relationship between the treatment effect on 28-day hospitalization/death and the treatment effect on the surrogate. R2 ranges from 0-1, with a strong relationship ≥0.72, moderate 0.49&lt;R2&lt;0.72, and weak ≤0.49. We estimated R2 for various viral load outcomes at Days 3, 5, and 7, including change-from-baseline, slope, average area under the curve minus baseline (AAUCMB), and a change of at least 0.5 log10 copies/mL from baseline to Day 3.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>R2 was numerically highest for the change-from-baseline to Day 3 (0.53 [0.26, 0.79]), slightly lower for change-from-baseline to Day 5 (0.49 [0.24, 0.75]) and numerically lower for change-from-baseline to Day 7 (0.40 [0.15, 0.65]). All were statistically significant.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Discussion</jats:title>\n <jats:p>Our study is the first to use IPD, allowing us to evaluate viral load collected on various study days as a surrogate to clinical outcomes. Change in log10(viral load) from baseline to Day 3 or Day 5 are moderate surrogates for 28-day hospitalization/death and suitable primary endpoints in Phase 2 clinical trials and are preferred over change-from-baseline to Day 7. Slope and AAUCMB require more calculation but didn’t improve prediction so aren’t recommended.</jats:p>\n </jats:sec>",
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"title": "The choice of viral load endpoint in early phase trials of COVID-19 treatments aiming to reduce 28-day hospitalization and/or death",
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