Project Summary Over the past 5 years, the National Institutes of Health (NIH) established a Health Care Systems Research Collaboratory (Collaboratory) worked to strengthen the national capacity to implement cost-effective large- scale research studies that engage health care delivery organizations as research partners. The Collaboratory included a Coordinating Center (Collaboratory CC) that worked with the NIH to produce, documents, disseminate standards, and create durable infrastructure to facilitate multisite pragmatic studies and the reuse of electronic health care data from clinical settings to inform health care decisions. This program became a model for the type of cost-efficient, collaborative research that can build the foundation for a learning health care system. Real-world evidence generation, as has been demonstrated through the Collaboratory, is transforming the way clinical research is conducted, and building on this momentum remains a top national priority (Califf NEJM 2016). In the next phase, the Collaboratory CC intends to continue its efforts and undertake the critical responsibility of developing and disseminating generalizable lessons learned about embedded pragmatic clinical trials (ePCTs), and to enable the expansion of ePCTs in promotion of a learning health system. An important part of this next phase will be gathering data to estimate the value of ePCTs. This knowledge will help to promote the uptake of ePCT research methods by various stakeholders, including research sponsors, regulators, health plan executives, health system leaders, patients, scientific community members, and clinical researchers. Considering the Collaboratory's progress to date and future priorities, the Collaboratory CC will have the following Specific Aims: Specific Aim 1: Further develop, adapt and adopt technical and policy guidelines and best practices for the effective conduct of research studies in partnership with health care systems. Specific Aim 2: Work collaboratively with each Demonstration Project team supported through the Collaboratory program, including their partnering health care systems, to develop, test, and implement the proposed Demonstration Projects while providing technical, design, and coordination support. Specific Aim 3: Learn and disseminate the best strategies for engaging health care systems as research partners to improve health and care delivery. Specific Aim 4: Learn, develop, and disseminate the best means of conducting pragmatic clinical trials in health care systems to improve the scientific community's ability to perform future pragmatic trials.