PCORI is seeking applications for comparative clinical effectiveness research (CER) designed to provide information that would inform critical decisions that face patients and caregivers, clinicians, policy makers, and healthcare system leaders. These decisions must be consequential and be occurring now in the absence of sound evidence about the comparative effectiveness of alternative approaches. There must be substantial potential that patients and caregivers will benefit from the new knowledge in ways that are important to them. The premise of this research is that the new knowledge will inform critical healthcare choices by patients and other stakeholders. This knowledge will provide insight about the comparative benefits and harms of the options and provide information about outcomes that are important to patients.