The placebo effect and its ramifications for clinical practice and research. Villa La Collina at Lake Como, Italy, 4-6 May 2012.

INTRODUCTION: The purpose of this workshop was to further explore the implications of the placebo effect for both research and clinical practice from a variety of angles with a group of selected experts.

METHOD/APPROACH: The use of placebos in both clinical practice and research was explored in depth from a historical, methodological, ethical, legal and cultural point of view. The current state of knowledge regarding the placebo effect was established, knowledge gaps were identified, and the implications for both clinical research and practice were discussed in depth.

KEY MESSAGES: • Placebos have been consciously used in clinical practice since the 18th century, but only emerged as a research topic in the western world in the second half of the 20th century. • The placebo response consists of the placebo effect plus the natural course of the disease, and is a meaningful part of all medical treatments. • A variety of not fully understood individual, context and cultural factors contribute to the placebo response and interact in a non-linear way with the specific effects of medicines. • The assessment of a therapeutic effect in placebo-controlled RCTs is often difficult due to a strong placebo response, e.g. in Central Nervous System (CNS) indications like major depression or in Irritable Bowel Syndrome. • Placebo effects occur, and can affect the validity and appropriateness of placebo controlled trials in conventional as well as Complementary and Alternative Medicine (CAM) research. • It may be impossible to fully disentangle the verum and sham effects of both CAM and conventional medical procedures such as for instance acupuncture and surgery. • Context/meaning effects, including doctor empathy, are highly relevant and under-researched in both conventional and complementary medicine. • The use of 'impure placebos' (non-indicated/ineffective medicines) in clinical practice may be common, but little reliable data is available due to complexities around the definition of impure placebos and underreporting. • The assumption that placebo effects do not occur in veterinary research is likely to be incorrect, e.g. owner empathy and vet expectations can affect outcomes. • Various innovative trial designs that better deal with the placebo issue are available, but only as partial solutions. • Patient treatment will benefit from better understanding and appropriately utilising meaning/context effects.

CONCLUSIONS: There are many remaining knowledge gaps with regard to the placebo response. The evolving knowledge challenges the paradigm of the placebo controlled RCT as a gold standard for demonstrating benefit of treatments. There are a number of pointers towards alternative research designs and paradigms worthy of further exploration. The evolving knowledge can contribute to the further development of a 'meaning orientated' and patient centred healthcare system.