Abstract
Although interim results from several large, placebo-controlled, phase 3 trials demonstrated high vaccine efficacy (VE) against symptomatic coronavirus disease 2019 (COVID-19), it is unknown how effective the vaccines are in preventing people from becoming asymptomatically infected and potentially spreading the virus unwittingly. It is more difficult to evaluate VE against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than against symptomatic COVID-19 because infection is not observed directly but rather is known to occur between 2 antibody or reverse-transcription polymerase chain reaction (RT-PCR) tests. Additional challenges arise as community transmission changes over time and as participants are vaccinated on different dates because of staggered enrollment of participants or crossover of placebo recipients to the vaccine arm before the end of the study. Here, we provide valid and efficient statistical methods for estimating potentially waning VE against SARS-CoV-2 infection with blood or nasal samples under time-varying community transmission, staggered enrollment, and blinded or unblinded crossover. We demonstrate the usefulness of the proposed methods through numerical studies that mimic the BNT162b2 phase 3 trial and the Prevent COVID U study. In addition, we assess how crossover and the frequency of diagnostic tests affect the precision of VE estimates.
Keywords: asymptomatic infection; seroconversion; symptomatic COVID-19; viral RNA; waning efficacy.
【저자키워드】 Seroconversion, asymptomatic infection, Viral RNA, symptomatic COVID-19, waning efficacy., 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, Efficacy, Vaccine, coronavirus, antibody, SARS-COV-2 infection, diagnostic test, Infection, severe acute respiratory syndrome Coronavirus, RT-PCR, virus, COVID, BNT162b2, polymerase chain reaction, Seroconversion, Asymptomatic, diagnostic tests, symptomatic, phase 3 trial, asymptomatic infection, community transmission, Viral RNA, estimates, change, placebo-controlled, Blood, Frequency, symptomatic COVID-19, Nasal sample, Chain Reaction, acute respiratory syndrome, Precision, Enrollment, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, placebo recipients, participant, nasal samples, interim results, crossover, Affect, effective, statistical, polymerase chain, evaluate, blinded, addition, occur, demonstrated, the vaccine, more difficult, placebo recipient, 【제목키워드】 coronavirus 2, respiratory, Against, Evaluating,