Mathematical Modelling for Optimal Vaccine Dose Finding: Maximising Efficacy and Minimising Toxicity.
Mathematical Modelling for Optimal Vaccine Dose Finding: Maximising Efficacy and Minimising Toxicity.
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DOI：
10.3390/vaccines10050756
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发表时间：
2022-05-11
期刊：
影响因子：
7.8
通讯作者：
White, Richard G.
中科院分区：
文献类型：
--
作者：
Benest, John;Rhodes, Sophie;Evans, Thomas G.;White, Richard G.
疫苗接种是减少全球疾病负担的关键工具。疫苗剂量会影响疫苗的效力和毒性。考虑到开发疫苗的费用，优化疫苗剂量至关重要。数学建模已被建议作为通过定量建立剂量与效力/毒性之间的关系来优化疫苗剂量的方法。在这项工作中，我们进行了模拟研究，以评估在确定最佳剂量的建模方法的性能。我们发现，建模方法确定最佳剂量的能力随着试验规模的增加而提高，特别是对于至少有30名试验参与者的研究，并且通常使用峰值或基于加权模型平均的剂量-疗效关系在寻找最佳剂量方面最有效。大多数试验剂量选择方法对于确定最佳剂量同样有效;然而，在试验期间包括调整剂量的建模可能导致更多试验受试者接受更佳剂量。在预测的最佳剂量附近进行临床试验给药，而不是仅以预测的最佳剂量给药，可能会改善最终剂量选择。这项工作表明，建模可以有效地用于疫苗剂量发现，促进这些方法在加速有效疫苗开发和拯救生命方面的潜在实际应用。
Vaccination is a key tool to reduce global disease burden. Vaccine dose can affect vaccine efficacy and toxicity. Given the expense of developing vaccines, optimising vaccine dose is essential. Mathematical modelling has been suggested as an approach for optimising vaccine dose by quantitatively establishing the relationships between dose and efficacy/toxicity. In this work, we performed simulation studies to assess the performance of modelling approaches in determining optimal dose. We found that the ability of modelling approaches to determine optimal dose improved with trial size, particularly for studies with at least 30 trial participants, and that, generally, using a peaking or a weighted model-averaging-based dose–efficacy relationship was most effective in finding optimal dose. Most methods of trial dose selection were similarly effective for the purpose of determining optimal dose; however, including modelling to adapt doses during a trial may lead to more trial participants receiving a more optimal dose. Clinical trial dosing around the predicted optimal dose, rather than only at the predicted optimal dose, may improve final dose selection. This work suggests modelling can be used effectively for vaccine dose finding, prompting potential practical applications of these methods in accelerating effective vaccine development and saving lives.
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