; and (C) considers pain, pain control, or pain management in assessing whether a disease or condition is a serious or life-threatening disease or condition; (2) the methods by which sponsors may evaluate acute and chronic pain, endpoints for non-addictive medical products intended to treat pain, the manner in which endpoints and evaluations of efficacy will be applied across and within review divisions, taking into consideration the etiology of the underlying disease, and the manner in which sponsors may use surrogate endpoints, intermediate endpoints, and real world evidence; (3) the manner in which the Food and Drug Administration will assess evidence to support the inclusion of opioid-sparing data in the labeling of non-addictive medical products intended to treat acute or chronic pain, including— (A) alternative data collection methodologies, including the use of novel clinical trial designs (consistent with section 3021 of the 21st Century Cures Act ( Public Law 114–255 )) and real world evidence (consistent with section 505F of the Federal Food, Drug, and Cosmetic Act ( 21 U.S.C. 355g )), including patient registries and patient reported outcomes, as appropriate, to support product labeling; (B) ethical considerations of exposing subjects to controlled substances in clinical trials to develop opioid-sparing data and considerations on data collection methods that reduce harm, which may include the reduction of opioid use as a clinical benefit; (C) endpoints, including primary, secondary, and surrogate endpoints, to evaluate the reduction of opioid use; (D) best practices for communication between sponsors and the agency on the development of data collection methods, including the initiation of data collection; and (E) the appropriate format in which to submit such data results to the Secretary