Pain leads the way: the development of evidence-based medicine for pain relief

This paper describes the development of evidence based methods in pain medicine since the 1980s at the Pain Research Department of the Nuffield Department of Clinical Neurosciences, Oxford University. Pain medicine can be said to have led the way in terms of developing registers of randomized controlled trials (RCTs) and in developing appropriate methodology for assessing clinical trials and developing metanalytical techniques. This paper tells the story of that development which occurred in conjunction with the development of the Cochrane Collaboration. Pain has a larger body of evidence than many medical specialties with more than 30,000 RCTs and over 2,500 published systematic reviews. Our work continues to raise methodological challenges and a number of key ones are described: Size: We have added to the existing literature to show that small studies overestimate treatment effects. We consider studies with less than 50 participants per treatment group to be at high risk of bias. Mean pain scores: We have shown these to be unhelpful and misleading. We illustrate that response to analgesics is a U-shaped curve with a larger proportion of participants having either a poor response or a good response. Imputation: We discuss the problems of current methods. Tiers of evidence: We propose a way to assess evidence for pain studies. Duplicate publication of data can lead to inflated benefits in systematic reviews. In addition we touch on fraud, pharmaceutical company funding. The final sections cover developments in several areas of pain medicine, and suggest some developments going forward.