During the early stages of any epidemic, simple interventions such as quarantine and isolation may be sufficient to halt the spread of a novel pathogen. However, should this opportunity be missed, substantially more resource-intensive, complex, and societally intrusive interventions may be required to achieve an acceptable outcome. These disparities place a differential on the value of a given unit of knowledge across the time-domains of an epidemic. Within this dissertation we explore these value-differentials via extension of the business concept of the time-value of knowledge and propose the C4 Response Model for organizing the research response to novel pathogenic outbreaks. First, we define the C4 Response Model as a progression from an initial data-hungry collect stage, iteration between open-science-centric connect stages and machine-learning centric calibrate stages, and a final visualization-centric convey stage. Secondly we analyze the trends in knowledge-building across the stages of epidemics with regard to open and closed access article publication, referencing, and citation. Thirdly, we demonstrate a Twitter message mapping application to assess the virality of tweets as a function of their source-profile category, message category, timing, urban context, tone, and use of bots. Finally, we apply an agent-based model of influenza transmission to explore the efficacy of combined antiviral, sequestration, and vaccination interventions in mitigating an outbreak of an influenza-like-illness (ILI) within a simulated military base population. We find that while closed access outbreak response articles use more recent citations and see higher mean citation counts, open access articles are published and referenced in significantly greater numbers and are growing in proportion. We observe that tweet viralities showed distinct heterogeneities across message and profile type pairing, that tweets dissipated rapidly across time and space, and that tweets published before high-tweet-volume time periods showed higher virality. Finally, we saw that while timely responses and strong pharmaceutical interventions showed the greatest impact in mitigating ILI transmission within a military base, even optimistic scenarios failed to prevent the majority of new cases. This body of work offers significant methodological contributions for the practice of computational epidemiology as well as a theoretical grounding for the further use of the C4 Response Model. / Doctor of Philosophy / During the early stages of an outbreak of disease, simple interventions such as isolating those infected may be sufficient to prevent further cases. However, should this opportunity be missed, substantially more complex interventions such as the development of novel pharmaceuticals may be required. This results in a differential value for specific knowledge across the early, middle, and late stages of epidemic. Within this dissertation we explore these differentials via extension of the business concept of the time-value of knowledge, whereby key findings may yield greater benefits during early epidemics. We propose the C4 Response Model for organizing research regarding this time-value. First, we define the C4 Response Model as a progression from an initial knowledge collection stage, iteration between knowledge connection stages and machine learning-centric calibration stages, and a final conveyance stage. Secondly we analyze the trends in knowledge-building across the stages of epidemics with regard to open and closed access scientific article publication, referencing, and citation. Thirdly, we demonstrate a Twitter application for improving public health messaging campaigns by identifying optimal combinations of source-profile categories, message categories, timing, urban origination, tone, and use of bots. Finally, we apply an agent-based model of influenza transmission to explore the efficacy of combined antiviral, isolation, and vaccination interventions in mitigating an outbreak of an influenza-like-illness (ILI) within a simulated military base population. We find that while closed access outbreak response articles use more recent citations and see higher mean citation counts, open access articles are growing in use and are published and referenced in significantly greater numbers. We observe that tweet viralities showed distinct benefits to certain message and profile type pairings, that tweets faded rapidly across time and space, and that tweets published before high-tweet-volume time periods are retweeted more. Finally, we saw that while early responses and strong pharmaceuticals showed the greatest impact in preventing influenza transmission within military base populations, even optimistic scenarios failed to prevent the majority to new cases. This body of work offers significant methodological contributions for the practice of computational epidemiology as well as a theoretical grounding for the C4 Response Model.