The impact of implementing a demand forecasting system into a low-income country's supply chain.

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.

Landscaping the structures of GAVI country vaccine supply chains and testing the effects of radical redesign.

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.

Only adding stationary storage to vaccine supply chains may create and worsen transport bottlenecks.

Although vaccine supply chains in many countries require additional stationary storage and transport capacity to meet current and future needs, international donors tend to donate stationary storage devices far more often than transport equipment. To investigate the impact of only adding stationary storage equipment on the capacity requirements of transport devices and vehicles, we used HERMES (Highly Extensible Resource for Modeling Supply Chains) to construct a discrete event simulation model of the Niger vaccine supply chain. We measured the transport capacity requirement for each mode of transport used in the Niger vaccine cold chain, both before and after adding cold rooms and refrigerators to relieve all stationary storage constraints in the system. With the addition of necessary stationary storage, the average transport capacity requirement increased from 88% to 144% for cold trucks, from 101% to 197% for pickup trucks, and from 366% to 420% for vaccine carriers. Therefore, adding stationary storage alone may worsen or create new transport bottlenecks as more vaccines flow through the system, preventing many vaccines from reaching their target populations. Dynamic modeling can reveal such relationships between stationary storage capacity and transport constraints.

Augmenting transport versus increasing cold storage to improve vaccine supply chains.

BACKGROUND: When addressing the urgent task of improving vaccine supply chains, especially to accommodate the introduction of new vaccines, there is often a heavy emphasis on stationary storage. Currently, donations to vaccine supply chains occur largely in the form of storage equipment. METHODS: This study utilized a HERMES-generated detailed, dynamic, discrete event simulation model of the Niger vaccine supply chain to compare the impacts on vaccine availability of adding stationary cold storage versus transport capacity at different levels and to determine whether adding stationary storage capacity alone would be enough to relieve potential bottlenecks when pneumococcal and rotavirus vaccines are introduced by 2015. RESULTS: Relieving regional level storage bottlenecks increased vaccine availability (by 4%) more than relieving storage bottlenecks at the district (1% increase), central (no change), and clinic (no change) levels alone. Increasing transport frequency (or capacity) yielded far greater gains (e.g., 15% increase in vaccine availability when doubling transport frequency to the district level and 18% when tripling). In fact, relieving all stationary storage constraints could only increase vaccine availability by 11%, whereas doubling the transport frequency throughout the system led to a 26% increase and tripling the frequency led to a 30% increase. Increasing transport frequency also reduced the amount of stationary storage space needed in the supply chain. The supply chain required an additional 61,269L of storage to relieve constraints with the current transport frequency, 55,255L with transport frequency doubled, and 51,791L with transport frequency tripled. CONCLUSIONS: When evaluating vaccine supply chains, it is important to understand the interplay between stationary storage and transport. The HERMES-generated dynamic simulation model showed how augmenting transport can result in greater gains than only augmenting stationary storage and can reduce stationary storage needs.

How influenza vaccination policy may affect vaccine logistics.

BACKGROUND: When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. PURPOSE: Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. METHODS: We Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand. A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. RESULTS: Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time-frame from 1 to 6 months decreases these bottlenecks. CONCLUSION: Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine.

Impact of introducing the pneumococcal and rotavirus vaccines into the routine immunization program in Niger.

OBJECTIVES: We investigated whether introducing the rotavirus and pneumococcal vaccines, which are greatly needed in West Africa, would overwhelm existing supply chains (i.e., the series of steps required to get a vaccine from the manufacturers to the target population) in Niger. METHODS: As part of the Bill and Melinda Gates Foundation-funded Vaccine Modeling Initiative, we developed a computational model to determine the impact of introducing these new vaccines to Niger's Expanded Program on Immunization vaccine supply chain. RESULTS: Introducing either the rotavirus vaccine or the 7-valent pneumococcal conjugate vaccine could overwhelm available storage and transport refrigerator space, creating bottlenecks that would prevent the flow of vaccines down to the clinics. As a result, the availability of all World Health Organization Expanded Program on Immunization vaccines to patients might decrease from an average of 69% to 28.2% (range = 10%-51%). Addition of refrigerator and transport capacity could alleviate this bottleneck. CONCLUSIONS: Our results suggest that the effects on the vaccine supply chain should be considered when introducing a new vaccine and that computational models can help assess evolving needs and prevent problems with vaccine delivery.

Impact of changing the measles vaccine vial size on Niger's vaccine supply chain: a computational model.

BACKGROUND: Many countries, such as Niger, are considering changing their vaccine vial size presentation and may want to evaluate the subsequent impact on their supply chains, the series of steps required to get vaccines from their manufacturers to patients. The measles vaccine is particularly important in Niger, a country prone to measles outbreaks. METHODS: We developed a detailed discrete event simulation model of the vaccine supply chain representing every vaccine, storage location, refrigerator, freezer, and transport device (e.g., cold trucks, 4 × 4 trucks, and vaccine carriers) in the Niger Expanded Programme on Immunization (EPI). Experiments simulated the impact of replacing the 10-dose measles vial size with 5-dose, 2-dose and 1-dose vial sizes. RESULTS: Switching from the 10-dose to the 5-dose, 2-dose and 1-dose vial sizes decreased the average availability of EPI vaccines for arriving patients from 83% to 82%, 81% and 78%, respectively for a 100% target population size. The switches also changed transport vehicle's utilization from a mean of 58% (range: 4-164%) to means of 59% (range: 4-164%), 62% (range: 4-175%), and 67% (range: 5-192%), respectively, between the regional and district stores, and from a mean of 160% (range: 83-300%) to means of 161% (range: 82-322%), 175% (range: 78-344%), and 198% (range: 88-402%), respectively, between the district to integrated health centres (IHC). The switch also changed district level storage utilization from a mean of 65% to means of 64%, 66% and 68% (range for all scenarios: 3-100%). Finally, accounting for vaccine administration, wastage, and disposal, replacing the 10-dose vial with the 5 or 1-dose vials would increase the cost per immunized patient from $0.47US to $0.71US and $1.26US, respectively. CONCLUSIONS: The switch from the 10-dose measles vaccines to smaller vial sizes could overwhelm the capacities of many storage facilities and transport vehicles as well as increase the cost per vaccinated child.

Replacing the measles ten-dose vaccine presentation with the single-dose presentation in Thailand.

Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes involved in distributing vaccines from manufacturers to patients). We developed a computational model of Thailand's Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose measles-mumps-rubella vaccine (which Thailand is currently considering) or a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations' storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage.

Postconcussive symptoms are associated with compensatory cortical recruitment during a working memory task.

BACKGROUND: The severity of sports-related concussion is often characterized by the number and severity of postconcussive symptoms (eg, headache, dizziness, difficulty concentrating). Although the level of postconcussive symptoms after injury is believed to index the severity of the neurological insult sustained, studies examining the relationship between symptom severity and neural functioning in concussed athletes remain rare. OBJECTIVE: This exploratory study examined the association between self-reported symptom severity and functional activation on a working memory task in a group of 16 recently concussed student athletes. METHODS: Functional magnetic resonance imaging was used to examine the relationship of symptom severity to brain activation during a working memory task in 16 concussed subjects. RESULTS: Findings indicated that symptom severity was associated with regionally specific hyperactivation during a working memory task, even though symptom severity was not significantly related to task accuracy. CONCLUSION: The results add to a growing body of literature that demonstrates that functional neuroimaging may have the potential to serve as a sensitive biomarker of the severity of concussion and mild traumatic brain injury.

Pursuit and saccadic eye movement subregions in human frontal eye field: a high-resolution fMRI investigation.

Recent positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) studies in humans have localized the frontal eye field (FEF) to the precentral sulcus (PCS). In macaque monkeys, low-threshold microstimulation and single unit recording studies have located a saccadic subregion of FEF in a restricted area along the anterior wall of the arcuate sulcus and a pursuit subregion located deeper in the sulcus close to the fundus. The functional organization and anatomical location of these two FEF subregions are still to be defined in humans. In the present study, we used fMRI with high spatial resolution image acquisition at 3.0 Tesla to map the saccade- and pursuit-related areas of FEF within the two walls of the PCS in 11 subjects. We localized the saccade-related area to the upper portion of the anterior wall of the precentral sulcus and the pursuit-related area to a deeper region along the anterior wall, extending in some subjects to the fundus or deep posterior wall. These findings localize distinct pursuit and saccadic subregions of FEF in humans and demonstrate a high degree of homology in the organization of these FEF subregions in the human and the macaque monkey.