What do surrogate safety metrics measure? Understanding driving safety as a continuum.

Road safety is an important public health issue; technology, policy, and educational interventions to prevent crashes are of significant interest to researchers and policymakers. In particular, there is significant ongoing research to proactively evaluate the safety of new technologies, including autonomous vehicles, before enough crashes occur to directly measure their impact. We analyze the distributional form of five diverse datasets that approximate motor vehicle safety incident severity, including one dataset of hard braking events that characterizes the severity of non-crash incidents. Our empirical analysis finds that all five datasets closely fit a lognormal distribution (Kolmogorov-Smirnov distance < 0.013; significance of loglikelihood ratio with other distributions < 0.000029). We demonstrate a linkage between two well-known but largely qualitative safety frameworks and the severity distributions observed in the data. We create a formal model of the Swiss Cheese Model (SCM) and show through analysis and simulations that this formalization leads to a lognormal distribution of the severity continuum of safety-critical incidents. This finding is not only consistent with the empirical data we examine, but represents a quantitative restatement of Heinrich's Triangle, another heretofore largely qualitative framework that hypothesizes that safety events of increasing severity have decreasing frequency. Our results support the use of more frequent, low-severity events to rapidly assess safety in the absence of less frequent, high-severity events for any system consistent with our formalization of SCM. This includes any complex system designed for robustness to single-point failures, including autonomous vehicles.

Using integrated modeling to support the global eradication of vaccine-preventable diseases.

The long-term management of global disease eradication initiatives involves numerous inherently dynamic processes, health and economic trade-offs, significant uncertainty and variability, rare events with big consequences, complex and inter-related decisions, and a requirement for cooperation among a large number of stakeholders. Over the course of more than 16 years of collaborative modeling efforts to support the Global Polio Eradication Initiative, we developed increasingly complex integrated system dynamics models that combined numerous analytical approaches, including differential equation-based modeling, risk and decision analysis, discrete-event and individual-based simulation, probabilistic uncertainty and sensitivity analysis, health economics, and optimization. We discuss the central role of systems thinking and system dynamics in the overall effort and the value of integrating different modeling approaches to appropriately address the trade-offs involved in some of the policy questions. We discuss practical challenges of integrating different analytical tools and we provide our perspective on the future of integrated modeling.

Maintenance and Intensification of Bivalent Oral Poliovirus Vaccine Use Prior to its Coordinated Global Cessation.

OBJECTIVE: To examine the impact of different bivalent oral poliovirus vaccine (bOPV) supplemental immunization activity (SIA) strategies on population immunity to serotype 1 and 3 poliovirus transmission and circulating vaccine-derived poliovirus (cVDPV) risks before and after globally-coordinated cessation of serotype 1 and 3 oral poliovirus vaccine (OPV13 cessation). METHODS: We adapt mathematical models that previously informed vaccine choices ahead of the trivalent oral poliovirus vaccine to bOPV switch to estimate the population immunity to serotype 1 and 3 poliovirus transmission needed at the time of OPV13 cessation to prevent subsequent cVDPV outbreaks. We then examine the impact of different frequencies of SIAs using bOPV in high risk populations on population immunity to serotype 1 and 3 transmission, on the risk of serotype 1 and 3 cVDPV outbreaks, and on the vulnerability to any imported bOPV-related polioviruses. RESULTS: Maintaining high population immunity to serotype 1 and 3 transmission using bOPV SIAs significantly reduces 1) the risk of outbreaks due to imported serotype 1 and 3 viruses, 2) the emergence of indigenous cVDPVs before or after OPV13 cessation, and 3) the vulnerability to bOPV-related polioviruses in the event of non-synchronous OPV13 cessation or inadvertent bOPV use after OPV13 cessation. CONCLUSION: Although some reduction in global SIA frequency can safely occur, countries with suboptimal routine immunization coverage should each continue to conduct at least one annual SIA with bOPV, preferably more, until global OPV13 cessation. Preventing cVDPV risks after OPV13 cessation requires investments in bOPV SIAs now through the time of OPV13 cessation.

Modeling population immunity to support efforts to end the transmission of live polioviruses.

Eradication of wild poliovirus (WPV) types 1 and 3, prevention and cessation of circulating vaccine-derived polioviruses, and achievement and maintenance of a world free of paralytic polio cases requires active risk management by focusing on population immunity and coordinated cessation of oral poliovirus vaccine (OPV). We suggest the need for a complementary and different conceptual approach to achieve eradication compared to the current case-based approach using surveillance for acute flaccid paralysis (AFP) to identify symptomatic poliovirus infections. Specifically, we describe a modeling approach to characterize overall population immunity to poliovirus transmission. The approach deals with the realities that exposure to live polioviruses (e.g., WPV, OPV) and/or vaccination with inactivated poliovirus vaccine provides protection from paralytic polio (i.e., disease), but does not eliminate the potential for reinfection or asymptomatic participation in poliovirus transmission, which may increase with time because of waning immunity. The AFP surveillance system provides evidence of symptomatic poliovirus infections detected, which indicate immunity gaps after outbreaks occur, and this system represents an appropriate focus for controlling disease outbreaks. We describe a conceptual dynamic model to characterize population immunity to poliovirus transmission that helps identify risks created by immunity gaps before outbreaks occur, which provides an opportunity for national and global policymakers to manage the risk of poliovirus and prevent outbreaks before they occur. We suggest that dynamically modeling risk represents an essential tool as the number of cases approaches zero.

Current polio global eradication and control policy options: perspectives from modeling and prerequisites for oral poliovirus vaccine cessation.

As the Global Polio Eradication Initiative progresses toward the eradication of wild polioviruses, national and global health leaders must still actively consider options for managing poliovirus risks, including risks associated with using oral poliovirus vaccine. Oral poliovirus vaccine continues to represent a highly effective tool, but its use causes noticeable, rare cases of vaccine-associated paralytic polio and with low coverage it can evolve to become circulating vaccine-derived polioviruse that causes outbreaks. National leaders face a wide range of options, but their choices depend in part on global policies. This article explores the current set of global options for poliovirus eradication or control, discusses constraints and prerequisites for their implementation and offers some insights based on dynamic modeling to inform discussions and frame future economic analyses.

Trends in the risk of U.S. polio outbreaks and poliovirus vaccine availability for response.

OBJECTIVES: The United States eliminated indigenous wild polioviruses (WPVs) in 1979 and switched to inactivated poliovirus vaccine in 2000, which quickly ended all indigenous live poliovirus transmission. Continued WPV circulation and use of oral poliovirus vaccine globally allow for the possibility of reintroduction of these viruses. We evaluated the risk of a U.S. polio outbreak and explored potential vaccine needs for outbreak response. METHODS: We synthesized information available on vaccine coverage, exemptor populations, and population immunity. We used an infection transmission model to explore the potential dynamics of a U.S. polio outbreak and potential vaccine needs for outbreak response, and assessed the impacts of heterogeneity in population immunity for two different subpopulations with potentially low coverage. RESULTS: Although the risk of poliovirus introduction remains real, widespread transmission of polioviruses appears unlikely in the U.S., given high routine coverage. However, clusters of un- or underimmunized children might create pockets of susceptibility that could potentially lead to one or more paralytic polio cases. We found that the shift toward combination vaccine utilization, with limited age indications for use, and other current trends (e.g., decreasing proportion of the population with immunity induced by live polioviruses and aging of vaccine exemptor populations) might increase the vulnerability to poliovirus reintroduction at the same time that the ability to respond may decrease. CONCLUSIONS: The U.S. poliovirus vaccine stockpile remains an important resource that may potentially be needed in the future to respond to an outbreak if a live poliovirus gets imported into a subpopulation with low vaccination coverage.

Optimal vaccine stockpile design for an eradicated disease: application to polio.

Eradication of a disease promises significant health and financial benefits. Preserving those benefits, hopefully in perpetuity, requires preparing for the possibility that the causal agent could re-emerge (unintentionally or intentionally). In the case of a vaccine-preventable disease, creation and planning for the use of a vaccine stockpile becomes a primary concern. Doing so requires consideration of the dynamics at different levels, including the stockpile supply chain and transmission of the causal agent. This paper develops a mathematical framework for determining the optimal management of a vaccine stockpile over time. We apply the framework to the polio vaccine stockpile for the post-eradication era and present examples of solutions to one possible framing of the optimization problem. We use the framework to discuss issues relevant to the development and use of the polio vaccine stockpile, including capacity constraints, production and filling delays, risks associated with the stockpile, dynamics and uncertainty of vaccine needs, issues of funding, location, and serotype dependent behavior, and the implications of likely changes over time that might occur. This framework serves as a helpful context for discussions and analyses related to the process of designing and maintaining a stockpile for an eradicated disease.

The risks, costs, and benefits of possible future global policies for managing polioviruses.

OBJECTIVES: We assessed the costs, risks, and benefits of possible future major policy decisions on vaccination, surveillance, response plans, and containment following global eradication of wild polioviruses. METHODS: We developed a decision analytic model to estimate the incremental cost-effectiveness ratios and net benefits of risk management options for polio for the 20-year period and stratified the world according to income level to capture important variability between nations. RESULTS: For low-, lower-middle-, and upper-middle-income groups currently using oral poliovirus vaccine (OPV), we found that after successful eradication of wild polioviruses, OPV cessation would save both costs and lives when compared with continued use of OPV without supplemental immunization activities. We found cost-effectiveness ratios for switching from OPV to inactivated poliovirus vaccine to be higher (i.e., less desirable) than other health investment opportunities, depending on the actual inactivated poliovirus vaccine costs and assumptions about whether supplemental immunization activities with OPV would continue. CONCLUSIONS: Eradication promises billions of dollars of net benefits, although global health policy leaders face difficult choices about future policies. Until successful eradication and coordination of posteradication policies, health authorities should continue routine polio vaccination and supplemental immunization activities.

Eradication versus control for poliomyelitis: an economic analysis.

BACKGROUND: Worldwide eradication of wild polioviruses is likely to yield substantial health and financial benefits, provided we finish the job. Challenges in the four endemic areas combined with continuing demands for financial resources for eradication have led some to question the goal of eradication and to suggest switching to a policy of control. METHODS: We developed a dynamic model, based on modelling of the currently endemic areas in India, to show the importance of maintaining and increasing the immunisation intensity to complete eradication and to illustrate how policies based on perception about high short-term costs or cost-effectiveness ratios without consideration of long-term benefits could undermine any eradication effort. An extended model assesses the economic implications and disease burden of a change in policy from eradication to control. FINDINGS: Our results suggest that the intensity of immunisation must be increased to achieve eradication, and that even small decreases in intensity could lead to large outbreaks. This finding implies the need to pay even higher short-run costs than are currently being spent, which will further exacerbate concerns about continued investment in interventions with high perceived cost-effectiveness ratios. We show that a wavering commitment leads to a failure to eradicate, greater cumulative costs, and a much larger number of cases. We further show that as long as it is technically achievable, eradication offers both lower cumulative costs and cases than control, even with the costs of achieving eradication exceeding several billion dollars more. A low-cost control policy that relies only on routine immunisation for 20 years with discounted costs of more than $3500 million could lead to roughly 200 000 expected paralytic poliomyelitis cases every year in low-income countries, whereas a low-case control policy that keeps the number of cases at about 1500 per year could cost around $10 000 million discounted over the 20 years. INTERPRETATION: Focusing on the large costs for poliomyelitis eradication, without assessing the even larger potential benefits of eradication and the enormous long-term costs of effective control, might inappropriately affect commitments to the goal of eradication, and thus debate should include careful consideration of the options.

Retrospective cost-effectiveness analyses for polio vaccination in the United States.

The history of polio vaccination in the United States spans 50 years and includes different phases of the disease, multiple vaccines, and a sustained significant commitment of resources. We estimated cost-effectiveness ratios and assessed the net benefits of polio vaccination applicable at various points in time from the societal perspective and we discounted these back to appropriate points in time. We reconstructed vaccine price data from available sources and used these to retrospectively estimate the total costs of the U.S. historical polio vaccination strategies (all costs reported in year 2002 dollars). We estimate that the United States invested approximately US dollars 35 billion (1955 net present value, discount rate of 3%) in polio vaccines between 1955 and 2005 and will invest approximately US dollars 1.4 billion (1955 net present value, or US dollars 6.3 billion in 2006 net present value) between 2006 and 2015 assuming a policy of continued use of inactivated poliovirus vaccine (IPV) for routine vaccination. The historical and future investments translate into over 1.7 billion vaccinations that prevent approximately 1.1 million cases of paralytic polio and over 160,000 deaths (1955 net present values of approximately 480,000 cases and 73,000 deaths). Due to treatment cost savings, the investment implies net benefits of approximately US dollars 180 billion (1955 net present value), even without incorporating the intangible costs of suffering and death and of averted fear. Retrospectively, the U.S. investment in polio vaccination represents a highly valuable, cost-saving public health program. Observed changes in the cost-effectiveness ratio estimates over time suggest the need for living economic models for interventions that appropriately change with time. This article also demonstrates that estimates of cost-effectiveness ratios at any single time point may fail to adequately consider the context of the investment made to date and the importance of population and other dynamics, and shows the importance of dynamic modeling.

Risks of paralytic disease due to wild or vaccine-derived poliovirus after eradication.

After the global eradication of wild polioviruses, the risk of paralytic poliomyelitis from polioviruses will still exist and require active management. Possible reintroductions of poliovirus that can spread rapidly in unprotected populations present challenges to policymakers. For example, at least one outbreak will likely occur due to circulation of a neurovirulent vaccine-derived poliovirus after discontinuation of oral poliovirus vaccine and also could possibly result from the escape of poliovirus from a laboratory or vaccine production facility or from an intentional act. In addition, continued vaccination with oral poliovirus vaccines would result in the continued occurrence of vaccine-associated paralytic poliomyelitis. The likelihood and impacts of reintroductions in the form of poliomyelitis outbreaks depend on the policy decisions and on the size and characteristics of the vulnerable population, which change over time. A plan for managing these risks must begin with an attempt to characterize and quantify them as a function of time. This article attempts to comprehensively characterize the risks, synthesize the existing data available for modeling them, and present quantitative risk estimates that can provide a starting point for informing policy decisions.

The costs of future polio risk management policies.

Decisionmakers need information about the anticipated future costs of maintaining polio eradication as a function of the policy options under consideration. Given the large portfolio of options, we reviewed and synthesized the existing cost data relevant to current policies to provide context for future policies. We model the expected future costs of different strategies for continued vaccination, surveillance, and other costs that require significant potential resource commitments. We estimate the costs of different potential policy portfolios for low-, middle-, and high-income countries to demonstrate the variability in these costs. We estimate that a global transition from routine immunization with oral poliovirus vaccine (OPV) to inactivated poliovirus vaccine (IPV) would increase the costs of managing polio globally, although routine IPV use remains less costly than routine OPV use with supplemental immunization activities. The costs of surveillance and a stockpile, while small compared to routine vaccination costs, represent important expenditures to ensure adequate response to potential outbreaks. The uncertainty and sensitivity analyses highlight important uncertainty in the aggregated costs and demonstrates that the discount rate and uncertainty in price and administration cost of IPV drives the expected incremental cost of routine IPV vs. OPV immunization.