MRC Centre for Outbreak Analysis & Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, London, UK.
Malar J. 2010 Mar 23;9:82. doi: 10.1186/1475-2875-9-82.
Phase III trials of the malaria vaccine, RTS, S, are now underway across multiple sites of varying transmission intensity in Africa. Heterogeneity in exposure, vaccine response and waning of efficacy may bias estimates of vaccine efficacy.
Theoretical arguments are used to identify the expected effects of a) heterogeneity in exposure to infectious bites; b) heterogeneity in individual's response to the vaccine; and c) waning efficacy on measures of vaccine efficacy from clinical trials for an infection-blocking vaccine.
Heterogeneity in exposure and vaccine response leads to a smaller proportion of trial participants becoming infected than one would expect in a homogeneous setting. This causes estimates of vaccine efficacy from clinical trials to be underestimated if transmission heterogeneity is ignored, and overestimated if heterogeneity in vaccine response is ignored. Waning of vaccine efficacy can bias estimates of vaccine efficacy in both directions.
Failure to account for heterogeneities in exposure and response, and waning of efficacy in clinical trials can lead to biased estimates of malaria vaccine efficacy. Appropriate methods to reduce these biases need to be used to ensure accurate interpretation and comparability between trial sites of results from the upcoming Phase III clinical trials of RTS, S.
疟疾疫苗 RTS，S 的 III 期临床试验目前正在非洲多个不同传播强度的地点进行。暴露、疫苗反应和疗效衰减的异质性可能会使疫苗疗效的估计产生偏差。
理论论证用于确定以下因素对传染病阻断疫苗临床试验中疫苗疗效衡量标准的预期影响：a）传染性叮咬暴露的异质性；b）个体对疫苗的反应的异质性；c）疗效衰减。
暴露和疫苗反应的异质性导致临床试验中感染的参与者比例低于在同质环境中预期的比例。如果忽略传播异质性，临床试验中疫苗疗效的估计会被低估，如果忽略疫苗反应的异质性，估计则会被高估。疫苗疗效的衰减会使疫苗疗效的估计产生偏差。
临床试验中未考虑暴露和反应的异质性以及疗效衰减，可能导致疟疾疫苗疗效的估计出现偏差。需要使用适当的方法来减少这些偏差，以确保即将进行的 RTS，S III 期临床试验结果在不同试验地点的准确解释和可比性。
