When do platform trials in chronic pain make sense?

Abstract

Clinical trials to develop new, non-addictive, pain medications are costly and labor intensive and might benefit from consolidation within platform trials to allow rapid testing of new agents. We describe our experience with the first National Institutes of Health (NIH)-sponsored attempt at a platform trial for a chronic pain condition (the Early Phase Pain Investigation Clinical Network Platform Protocol (EPPIC-Net-PP) for painful diabetic peripheral neuropathy) and contextualize the EPPIC-Net-PP within platform trials more broadly. A search of clinicaltrials.gov revealed 350 platform trials, the majority of which were cancer-related or targeting an acute illness usually in the inpatient setting (e.g., COVID-19). The remainder (other than EPPIC-Net-PP) fell into one or more categories: 1) industry-sponsored, 2) rare serious diseases, 3) pragmatic trials in common chronic diseases. Among the industry-sponsored studies, Eli Lilly’s Chronic Pain Master Protocol (CPMP) was the only other pain-focused platform; the CPMP successfully studied four investigational agents in three pain conditions over approximately three years, suggesting that the streamlined infrastructure available in industry is an important benefit. Outside industry, successful platforms were launched from within longstanding, clinical trials experienced, research networks with diverse funding sources. The key finding from the EPPIC-Net experience and literature review is that in a successful platform the efficiency of shared infrastructure will outweigh the cost of increased complexity. Efficiency depends on an adequate flow of treatments and funding, which will be challenging for chronic pain platforms outside of industry. Thus, such platforms should focus especially on minimizing complexity through disciplined streamlining of procedures.