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Fig 1.

Simulation framework.

For each Monte Carlo simulation path, we simulate patient-level infections data based on input trial design assumptions and attack rates from the population epidemiological model (for an RCT, ORCT, and ARCT). At the end of the trial (or, at each interim analysis for an ARCT), we determine if the vaccine candidate is approved under superiority or superiority-by-margin testing. Finally, we compute the expected net value of the trial design over 100,000 simulation paths.

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Fig 1 Expand

Table 1.

Sensitivity analysis with respect to trial design, epidemiological model, and population vaccination schedule assumptions.

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Table 1 Expand

Table 2.

Expected number of incremental infections and deaths avoided in the U.S. under different trial designs, vaccine efficacies, and epidemiological scenarios, assuming trials start on August 1, 2020, superiority testing, and 10M doses of a vaccine per day are available after licensure, compared to the baseline case in which no vaccine is ever approved.

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Table 2 Expand

Fig 2.

Dates of licensure under RCT, ORCT, ARCT, HCT (30-day set-up time), and HCT (90-day set-up time), assuming superiority testing, a vaccine efficacy of 50%, and a population vaccination schedule of 10M doses per day.

(a) Under the behavioral epidemiological model. (b) Under the status quo epidemiological model.

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Fig 2 Expand