In contrast to drug therapy, interventional pain therapies involve a complex "interaction" between the clinician ("the operator"), the clinical procedure and medical device/equipment. An appreciation of this interaction is fundamental to the understanding of the challenges of designing clinical trials for interventional procedures in chronic pain. This article overviews the evolving evidence requirements of healthcare policy makers and payers, discusses the specific challenges of designing clinical trials of interventional procedures, and outlines some potential clinical trial design solutions to these challenges.