Finally, the majority of data available were from prepost studies conducted in self-identified persons who use heroin; therefore, our findings may be considered limited if approached from the perspective of traditional evidence hierarchies. However, randomized controlled trials or cluster randomized trials to evaluate the impact of OEND on various outcomes described previously would likely present formidable practical and ethical challenges.[48] With our use of theumbrellareviewmethodology, our findings indicate that there are numerousreviewsthat provide unanimous support regarding the effectiveness of OEND programs. While these results may be difficult to generalize to persons who use prescription opioids, injection drug useparticularly with heroin in communities with illicit drug supplies contaminated with superpotent opioidsis the largest contributor to opioid mortality.[49] As a consequence, OEND programs are likely to have the most significant impact within these high-risk populations