fenoldopam mesylate, atrial natriuretic peptide, statins, mannitol, MENSA fluid, allopurinol, furosemide, trimetazidine, anisodamine, probucol, and pentoxifline. ‡ Includes studies that compared all hydration regimens (oral and IV). 7 Organization of This Report The following results section reports on a number of comparisons. We report in detail on comparisons for which substantial evidence exists, starting with the comparisons that have received the most attention in the literature (N-acetylcysteine plus IV saline versus IV saline, IV sodium bicarbonate versus IV saline, N-acetylcysteine plus IV saline versus IV sodium bicarbonate, statins plus IV saline versus IV saline, adenosine antagonists plus IV saline versus IV saline, renal replacement therapy versus IV saline, and ascorbic acid plus IV saline versus IV saline). At the end of the results section, we refer to information about other “miscellaneous comparisons” for which the studies were too few or too small to draw conclusions. Details on those comparisons appear in Appendixes H and I. 8 Methods Topic Refinement and Protocol Review We developed the Key Question with the input of a key informant panel that included: experts in nephrology, radiology, cardiology, and primary care; patient advocates; representatives from the Food and Drug Administration; and oversight by our Task Order Officer from the Agency for Health Care Research and Quality. We also recruited a technical expert panel to provide input on the protocol for the comparative effectiveness review. Literature Search Strategy We searched the following databases for primary studies through July 8, 2015: MEDLINE®, EMBASE®, and the Cochrane Library (see Appendix B for a detailed search strategy). We did not add any date limits to the search and developed a search strategy for MEDLINE, accessed via PubMed®, based on medical subject headings (MeSH®) terms and text words of key articles that we identified a priori. The search was not limited by language. In addition, we looked for conference proceedings and other reports by searching the Scopus database. We reviewed the reference lists of relevant articles and related systematic reviews to identify original journal articles and other reports the database searches might have missed. Scientific Information Packages were requested from a number of manufacturers, but no information was provided. We also searched ClinicalTrials.gov to identify on-going studies. We searched for publicly available data held by the U.S. Food and Drug Administration, but it has not approved any interventions for the prevention of CIN. We uploaded articles into DistillerSR (Evidence Partners, Ottawa, Ontario, Canada), a Webbased service for systematic review and data management. We used this database to track search results at the levels of title review, abstract review, article inclusion/exclusion, and data abstraction. Study Selection We followed the PICOTS framework (Table 1) in developing the criteria for including studies in the review, and included studies of patients of all ages with low, moderate, or high risk of developing CIN. We anticipated heterogeneity in the pre-procedure risk assessment and reported on the heterogeneity as it was defined by the studies, which had to assess serum creatinine or glomerular filtration rate prior to and after contrast media injection. We only included studies in which the intervention group received either IOCM or LOCM via IV or intraarterial injection. Studies had to report on at least one of the outcomes listed in the PICOTS framework. We included RCTs of comparisons detailed in the PICOTS, but focused the review on comparisons for which two or more studies reported on the same comparison. When we found interventions for which the comparisons were too heterogeneous to support an overall conclusion, we included a summary of the studies in the main report and placed details in an appendix. We included observational studies where available for all comparisons of interest. We evaluated previous systematic reviews on this topic to determine the extent to which they addressed our specific Key Question. 9 Data Extraction Due to the volume of literature, we first screened titles and then screened abstracts for relevance to the Key Question. The titles and abstracts were screened independently by two reviewers. Inclusion at the title screening level was liberal; if a single reviewer believed an article might contain relevant information, the article was moved to the abstract level for further screening. When reviewing abstracts followed by the full text of articles, both reviewers had to agree on inclusion or exclusion. Disagreements that could not be resolved by the two reviewers were resolved by a third expert member of the team (see Appendix C for screening forms). At random intervals during screening, quality checks by senior team members were performed to ensure that the eligibility criteria were applied consistently. Quality (Risk of Bias) Assessment of Individual Studies Two reviewers independently assessed each study’s risk of bias using five items from the Cochrane Risk of Bias tool for randomized studies22: • Was the allocation sequence adequately generated? • Was allocation adequately concealed? • Was knowledge of the allocated intervention adequately prevented during the study? • Were incomplete outcome data