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Table 1.

Study components based on hypothetical target trial, emulated trial and original cohort.

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Fig 1.

Study design using target trial emulation with cloning and censoring.

A total of 3,193 eligible patients were initially assigned to one of three treatment groups: favipiravir with dexamethasone (FPV with Dexa), favipiravir (FPV) alone, or symptomatic treatment (ST). The cloning process expanded each patient across the three treatment arms (n = 9,579), ensuring comparability. Patients who deviated from their assigned protocol were censored, and follow-up was conducted for 30 days. Time-to-event analysis was performed using inverse probability of censoring weights to estimate treatment effects.

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Fig 2.

Exclusions of participants.

From all patients with COVID-19 admitted to Bussarakham Field Hospital (n = 18,184), asymptomatic patients (n = 2,789) and those with mild severity (n = 9,747) were excluded. The remaining eligible patients were 3,193.

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Table 2.

Demographic, clinical characteristics, treatment, and outcome of the original patient cohort.

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Fig 3.

Standardize differences of each baseline characteristic between treatment strategies (A) unweighted standardized difference; (B) weighted standardized difference.

The reference lines at ±0.1 indicate the threshold for acceptable similarity between characteristics. Between ST and FPV with Dexa, 13 baseline characteristics differed (STD > 0.1). Comparisons between ST vs. FPV and FPV with Dexa vs. FPV showed fewer differences, with 10 and 9 out of 25 characteristics differing, respectively.

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Fig 4.

Kaplan-Meier estimation of 30-day in-hospital mortality (right) and the predicted survival curve based on flexible parametric survival regression.

The Kaplan-Meier curve shows empirical survival probabilities over 30 days for patients receiving symptomatic treatment (blue), favipiravir alone (red), and favipiravir combined with dexamethasone (green). The flexible parametric model provides a smoothed survival estimate, accounting for time-dependent effects. Both models indicate that survival probabilities differ across treatment groups, with the symptomatic treatment group showing a slightly lower survival probability over time.

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Table 3.

Restricted mean survival time of in-hospital mortality for each treatment strategy.

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Table 3 Expand