Comparative effectiveness research (CER) aims to inform healthcare decisions by providing evidence on the benefits and harms of different alternatives in cancer care. While randomized controlled trials are often considered to be the gold standard of research and have high internal validity due to their controlled environment, they are often not generalizable to `real-world' populations. Clinical trials often exclude large segments of the population, particularly those who are older or have comorbid conditions, threatening the external validity of the findings. Furthermore, explanatory trials typically compare only two or three interventions. As the number of cancer therapies and technologies increases exponentially, additional methods are necessary to adequately compare benefits and harms across several different interventions. While the emphasis in the past was on determining whether an intervention could work under the best conditions, increasing importance is given to whether interventions also work in `real-world' settings, and how they compare to other available alternatives. Real-world evidence and CER are vital to adequately evaluate and position new health interventions and technologies as they emerge. Few training programs specifically address CER methodologies. The overarching goal of this application is to implement a comprehensive national CER training program for junior cancer investigators, encompassing the broad spectrum of healthcare delivery in cancer care. Training will encompass three major CER methodologies: 1) Knowledge synthesis including systematic reviews, meta-analysis, and decision analysis; 2) Observational studies and secondary data analysis of registries and other sources of data, and 3) Pragmatic clinical trials, and. After first completing a series of interactive online courses in these topics to acquire a strong knowledge base in CER, participants will complete an intensive, hands-on training small group workshop in one or more of the three CER methodologies. Each participant will develop an individual protocol for a CER study, for a research question of their interest. Topics of interest can address any of the stages of care throughout the cancer continuum, including prevention, screening, diagnosis, treatment, supportive care, end-of-life care, and survivorship. Program faculty will provide individual methods guidance and support to participants during the 12 months after enrolling in the course. Participants will be junior investigators, recruited nationally, and affiliated with academic institutions, cancer centers or non-profit organizations (junior faculty, research scientists or post- doctoral or clinical fellows with an expectation of a research career path). Enrollment methods will include engaging underrepresented minorities. This education program is designed to support the National Cancer Institute's educational mission by arming cancer researchers with innovative tools needed to conduct CER. Expanding ...