This funding opportunity announcement (FOA) is being issued by the Office of Behavioral and Social Sciences Research (OBSSR) of the National Institutes of Health (NIH) with participation from the following NIH components: FIC, NCI, NIA, NICHD, NCCAM, NHLBI, NIEHS, NIMH, NIAAA, NIDCR, NIDA, ODP, and ODS. This FOA solicits Exploratory/Developmental (R21) applications from institutions/organizations that propose to apply one or more specific system science methodologies (identified in Section I.1 Background, of this announcement) to public health and health care systems problems and contribute knowledge that will enhance effective decision making around the development of and prioritization of policies, interventions, and programs to improve population health, especially where resources are limited and only a limited number of programs/policies/interventions can be implemented. Applicants are encouraged to submit projects that tackle policy resistant health problems (i.e., ones in which the effects of planned interventions, programs or policies tend to be delayed, diluted or defeated by responses of the system to the intervention itself) using a systems science methodology.