Benest John, Rhodes Sophie, Evans Thomas G, White Richard G
Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Vaccitech Ltd., The Schrodinger Building, Heatley Road, The Oxford Science Park, Oxford OX4 4GE, UK.
Vaccines (Basel). 2022 May 11;10(5):756. doi: 10.3390/vaccines10050756.
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.
疫苗接种是减轻全球疾病负担的关键工具。疫苗剂量会影响疫苗效力和毒性。鉴于开发疫苗的成本高昂，优化疫苗剂量至关重要。数学建模已被提议作为一种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，以评估建模方法在确定最佳剂量方面的性能。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，并且一般来说，使用基于峰值或加权模型平均的剂量-效力关系在找到最佳剂量方面最有效。大多数试验剂量选择方法在确定最佳剂量方面同样有效；然而，在试验期间纳入建模以调整剂量可能会使更多试验参与者接受更优剂量。围绕预测的最佳剂量而非仅在预测的最佳剂量进行临床试验给药，可能会改善最终剂量选择。这项工作表明，建模可有效地用于确定疫苗剂量，促使这些方法在加速有效疫苗开发和拯救生命方面具有潜在的实际应用。
