SynthesisThe Journal of infectious diseases2025
The Choice of Viral Load End Point in Early Phase Trials of COVID-19 Treatments Aiming to Reduce 28-Day Hospitalization and/or Death.
Synthesis in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- Accurate Measurement of Viral Clearance in Early-Phase Antiviral Studies in Coronavirus Disease 2019.The Journal of infectious diseases · 2026Article
- Evaluating Viral Load Sampling Schemes and Swabbing Methods for Optimal Surrogacy.The Journal of infectious diseases · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors.
Funding
Abstract
backgroundVirologic end points are used in phase 2 trials for COVID-19 therapeutics, but they have not been established as surrogates for clinical end points. 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.
methodsThis meta-analysis combined IPD from 23 COVID-19 treatment versus 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 to 1, with a strong relationship ≥ 0.72, moderate 0.49 < R2 < 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.
resultsR 2 was numerically highest for the change-from-baseline to day 3 (0.53; 95% confidence interval [CI], .26-.79), slightly lower for change-from-baseline to day 5 (0.49; 95% CI, .24-.75) and numerically lower for change-from-baseline to day 7 (0.40; 95% CI, .15-.65). All were statistically significant. DISCUSSION: 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 end points in phase 2 clinical trials and are preferred over change-from-baseline to day 7. Slope and AAUCMB require more calculation but did not improve prediction so are not recommended.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.