This supplemental issue describes the individual studies and collaborative efforts of the Helping to End Addiction Long-term Prevention Cooperative's (HPC's) innovative approaches to rapidly develop evidence-based prevention programs for widespread dissemination. This introduction succinctly reviews (1) the context that demands the rapid development of efficacious prevention programs and their scale-ups, (2) the unique objectives of the individual HPC research projects, and (3) collective efforts to harmonize research across studies to advance the prevention of opioid misuse and gain insight into opioid misuse etiology to inform improvements in preventive interventions. At the conclusion of HPC studies, we anticipate the availability of multiple evidence-based programs to prevent opioid misuse and use disorder for persons who experience particular sources of risk and for delivery in settings where prevention has traditionally been lacking. By harmonizing and coordinating efforts across 10 distinct outcomes studies of prevention programs and making data available for analysis by non-HPC researchers, the HPC's efficacy and etiology evidence will far surpass the additive contributions of 10 individual research projects.
