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Vaccines reside in a complex multiscale system that includes biological, clinical, behavioral, social, operational, environmental, and economical relationships. Not accounting for these systems when making decisions about vaccines can result in changes that have little effect rather than solutions, lead to unsustainable solutions, miss indirect (e.g., secondary, tertiary, and beyond) effects, cause unintended consequences, and lead to wasted time, effort, and resources. Mathematical and computational modeling can help better understand and address complex systems by representing all or most of the components, relationships, and processes. Such models can serve as "virtual laboratories" to examine how a system operates and test the effects of different changes within the system. Here are ten lessons learned from using computational models to bring more of a systems approach to vaccine decision making: (i) traditional single measure approaches may overlook opportunities; (ii) there is complex interplay among many vaccine, population, and disease characteristics; (iii) accounting for perspective can identify synergies; (iv) the distribution system should not be overlooked; (v) target population choice can have secondary and tertiary effects; (vi) potentially overlooked characteristics can be important; (vii) characteristics of one vaccine can affect other vaccines; (viii) the broader impact of vaccines is complex; (ix) vaccine administration extends beyond the provider level; and (x) the value of vaccines is dynamic., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the potential impact and value of applications (e.g. adjusting ordering levels, storage capacity, transportation capacity, distribution frequency) of data from demand forecasting systems implemented in a lower-income country's vaccine supply chain with different levels of population change to urban areas., Materials and Methods: Using our software, HERMES, we generated a detailed discrete event simulation model of Niger's entire vaccine supply chain, including every refrigerator, freezer, transport, personnel, vaccine, cost, and location. We represented the introduction of a demand forecasting system to adjust vaccine ordering that could be implemented with increasing delivery frequencies and/or additions of cold chain equipment (storage and/or transportation) across the supply chain during varying degrees of population movement., Results: Implementing demand forecasting system with increased storage and transport frequency increased the number of successfully administered vaccine doses and lowered the logistics cost per dose up to 34%. Implementing demand forecasting system without storage/transport increases actually decreased vaccine availability in certain circumstances., Discussion: The potential maximum gains of a demand forecasting system may only be realized if the system is implemented to both augment the supply chain cold storage and transportation. Implementation may have some impact but, in certain circumstances, may hurt delivery. Therefore, implementation of demand forecasting systems with additional storage and transport may be the better approach. Significant decreases in the logistics cost per dose with more administered vaccines support investment in these forecasting systems., Conclusion: Demand forecasting systems have the potential to greatly improve vaccine demand fulfilment, and decrease logistics cost/dose when implemented with storage and transportation increases. Simulation modeling can demonstrate the potential health and economic benefits of supply chain improvements., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Many of the world's vaccine supply chains do not adequately provide vaccines, prompting several questions: how are vaccine supply chains currently structured, are these structures closely tailored to individual countries, and should these supply chains be radically redesigned?, Methods: We segmented the 57 GAVI-eligible countries' vaccine supply chains based on their structure/morphology, analyzed whether these segments correlated with differences in country characteristics, and then utilized HERMES to develop a detailed simulation model of three sample countries' supply chains and explore the cost and impact of various alternative structures., Results: The majority of supply chains (34 of 57) consist of four levels, despite serving a wide diversity of geographical areas and population sizes. These four-level supply chains loosely fall into three clusters [(1) 18 countries relatively more bottom-heavy, i.e., many more storage locations lower in the supply chain, (2) seven with relatively more storage locations in both top and lower levels, and (3) nine comparatively more top-heavy] which do not correlate closely with any of the country characteristics considered. For all three cluster types, our HERMES modeling found that simplified systems (a central location shipping directly to immunization locations with a limited number of Hubs in between) resulted in lower operating costs., Conclusion: A standard four-tier design template may have been followed for most countries and raises the possibility that simpler and more tailored designs may be warranted., (Copyright © 2015 Elsevier Ltd. All rights reserved.)