There has been considerable progress identifying pathophysiologic mechanisms of neuropathic pain, but analgesic medications with improved efficacy, safety, and tolerability still represent an unmet public health need. Numerous treatments examined in recent randomized clinical trials (RCTs) have failed to show efficacy for neuropathic pain, including treatments that had previously demonstrated efficacy. This suggests that at least some negative results reflect limited assay sensitivity of RCTs to distinguish efficacious treatments from placebo. Patient characteristics, clinical trial research designs and methods, outcome measures, approaches to data analysis, and statistical power may all play a role in accounting for difficulties in demonstrating the benefits of efficacious analgesic treatments vs placebo. The identification of specific clinical trial characteristics associated with assay sensitivity in existing data has the potential to provide an evidence-based approach to the design of analgesic clinical trials. The US Food and Drug Administration recently launched the Analgesic Clinical Trial Innovations, Opportunities, and Networks (ACTION) public-private partnership, which is designed to facilitate the discovery and development of analgesics with improved efficacy, safety, and tolerability for acute and chronic pain conditions. ACTION will establish a collaborative effort to prioritize research objectives, develop a standardized analgesic database platform, and conduct methodologically focused studies to increase the assay sensitivity and efficiency of analgesic clinical trials. The results of these activities have the potential to inform and accelerate the development of improved pain management interventions of all types, not just pharmacologic treatments.