The research objective of this award is to formulate and analyze Markov decision process models to enable vaccine clinicians to optimally balance the tradeoffs inherent to vaccine administration, especially in remote locations, e.g., rural areas and developing countries. The main tradeoff is one between vaccine "wastage" and missed opportunities for vaccine administration. Wastage is especially acute for vaccines that are packaged in large, multi-dose vials which once opened, must be used within a matter of hours; hence clinicians face difficult tradeoffs between opening a vial to satisfy a potentially small immediate demand, versus retaining the vial to satisfy a potentially large future demand. Furthermore, because the power supply in remote areas of developing countries is often unreliable, the development of -passive cold boxes- that maintain temperature over several weeks - provided they are not opened excessively often is being considered; clinicians deciding when to retrieve vials from these cold boxes will face difficult tradeoffs between retrieving vials for potential immediate use, versus not having vaccines available in the face of future demand. Moreover, the design specifications for these cold boxes are open questions that depend heavily on how their use will impact wastage and coverage in the field. Anticipated outcomes of this research include: (i) optimal vaccine administration policies (e.g., vial opening decisions and cold box retrieval decisions) for different situations (e.g., vaccine type(s), vial size(s), demand profile(s)) as a function of many variables (e.g., time of day, vial inventory, history of cold box openings); (ii) dissemination of operational guidelines that can be easily implemented by clinicians in the field; and (iii) insights into various cold box designs in with respect to vaccine coverage and wastage. The results of the research will be disseminated within the US and internationally through the WHO website and potentially enable millions of additional vaccines to be administered annually throughout the world.