Questions to be addressed (using the PICO [population, intervention, comparator, outcome] format) 3 were prioritized by ALS Task Force members (by voting). Prioritization criteria included awareness of significant new data and new controversies or questions about practice. Questions about topics no longer relevant to contemporary practice or where little new research has occurred were given lower priority. The ALS Task Force prioritized 42 PICO questions for review. With the assistance of information specialists, a detailed search for relevant articles was performed in each of 3 online databases (PubMed, Embase, and the Cochrane Library).By using detailed inclusion and exclusion criteria, articles were screened for further evaluation. The reviewers for each question created a reconciled risk of bias assessment for each of the included studies, using state-of-the-art tools: Cochrane for randomized controlled trials (RCTs), 4 Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 for studies of diagnostic accuracy, 5 and GRADE for observational studies that inform both therapy and prognosis questions. 6 GRADE evidence profile tables 7 were then created to facilitate an evaluation of the evidence in support of each of the critical and important outcomes. The quality of the evidence (or confidence in the estimate of the effect) was categorized as high, moderate, low, or very low, 8 based on the study methodologies and the 5 core GRADE domains of risk of bias, inconsistency, indirectness, imprecision, and other considerations (including publication bias). 9 These evidence profile tables were then used to create a written summary of evidence for each outcome (the consensus on science statements). Whenever possible, consensus-based treatment recommendations were then created. These recommendations (designated as strong or weak) were accompanied by an overall assessment of the evidence and a statement from the task force about the values, preferences, and task force insights that underlie the recommendations. Further details of the methodology that underpinned the evidence evaluation process are found in "Part 2: Evidence Evaluation and Management of Conflicts of Interest."The task force preselected and ranked outcome measures that were used as consistently as possible for all PICO questions. Longer-term, patient-centered outcomes were considered more important than process variables and shorter-term outcomes. For most questions, we used the following hierarchy starting with the most important: long-term survival with neurologically favorable survival, long-term survival, short-term survival, and process variable. In general, longterm was defined as from hospital discharge to 180 days or longer, and short-term was defined as shorter than to hospital discharge. For certain questions (eg, related to defibrillation or confirmation of tracheal tube position), process variables such as termination of fibrillation and correct tube placement were important. A few questions (eg, organ donation) required unique outcomes....