Identifying and Alleviating Bias Due to Differential Depletion of Susceptible People in Postmarketing Evaluations of COVID-19 Vaccines
Identifying and Alleviating Bias Due to Differential Depletion of Susceptible People in Postmarketing Evaluations of COVID-19 Vaccines
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DOI：
10.1093/aje/kwac015
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发表时间：
2022-01-27
影响因子：
5
通讯作者：
Lipsitch, Marc
中科院分区：
文献类型：
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作者：
Kahn, Rebecca;Schrag, Stephanie J.;Lipsitch, Marc
最近的研究提供了关于SARS-CoV-2疫苗的功效和有效性（VE）的关键信息。仍然存在的一个重要问题是，疫苗提供的保护是否会随着时间的推移而减弱。然而，随着时间的推移，由于接种疫苗组和未接种疫苗组之间易感个体的差异耗竭，估计可能存在偏差。我们检查了在不同情况下偏倚发生的程度，并评估血清学检测是否有可能纠正这种偏倚。通过识别非疫苗抗体，这些测试可以识别先前感染的个体。我们发现，在基线VE较高的情况下，易感个体的差异消耗在VE估计中产生了最小的偏差，这表明任何观察到的下降可能不仅仅是由于虚假的减弱。然而，如果基线VE较低，则漏性疫苗（在接触后降低个体感染概率）的偏倚较大，如果机制已知是漏性的，则应通过排除既往感染的个体来加以纠正。对过去感染进行未调整和调整的分析可以给出真实VE的下限和上限。因此，对VE的研究应纳入个体，而不考虑先前的感染史，但也应收集有关这一关键变量的信息，最好是通过血清学检测。
Recent studies have provided key information about SARS-CoV-2 vaccines' efficacy and effectiveness (VE). One important question that remains is whether the protection conferred by vaccines wanes over time. However, estimates over time are subject to bias from differential depletion of susceptible individuals between vaccinated and unvaccinated groups. We examined the extent to which biases occur under different scenarios and assessed whether serological testing has the potential to correct this bias. By identifying nonvaccine antibodies, these tests could identify individuals with prior infection. We found that in scenarios with high baseline VE, differential depletion of susceptible individuals created minimal bias in VE estimates, suggesting that any observed declines are likely not due to spurious waning alone. However, if baseline VE was lower, the bias for leaky vaccines (which reduce individual probability of infection given contact) was larger and should be corrected for by excluding individuals with past infection if the mechanism is known to be leaky. Conducting analyses both unadjusted and adjusted for past infection could give lower and upper bounds for the true VE. Studies of VE should therefore enroll individuals regardless of prior infection history but also collect information, ideally through serological testing, on this critical variable.