Introduction

Aside from the provision of a specific therapeutic regimen, a medical encounter might elicit non-specific or contextual benefits or what are most often called placebo effects. Experimental settings seek to contain these “nuisance” effects with placebo controls. Such non-specific effects in a clinical setting can theoretically be separated into three components: a patient’s response to observation and assessment (Hawthorne effects), the patient’s response to the administration of a therapeutic ritual (placebo treatment), and the patient’s response to the patient-practitioner interaction.1 2 3 We tested this by determining whether these distinct potential contributions to clinical care can be separated and then combined incrementally under controlled conditions to produce progressive improvement in clinical outcomes in a manner resembling a graded dose escalation of component parts. We also quantified the extent to which the patient-practitioner relationship enhances the effects of a placebo treatment alone and whether a placebo intervention is more effective than no treatment/natural course of the illnessalone.

We carried out the trial on patients with irritable bowel syndrome. This is a chronic, functional gastrointestinal disorder characterised by recurrent abdominal pain and disturbed bowel function—that is, diarrhoea, constipation, or alternation between the two.4 Irritable bowel syndrome is one of the top 10 reasons for seeking primary care and is the reason for nearly a third of all consultations with gastroenterologists,5 with an estimated direct and indirect cost in the eight major industrial countries of over $41bn (£20bn, €27bn).6 Irritable bowel syndrome seemed a suitabledisease to study because previous randomised controlled trials of treatments have shown a large positive response (about 40%) in placebo groups.7 This also suggests that it might be possible to show a graded response when the three hypothetical non-specific components of the clinical encounter were added individually or in combinations.

Study design

We conducted this randomised controlled trial in a single centre in 262 participants over two study periods of three weeks (fig 1) ⇓ For the first three week period, participants were randomised to one of three groups: a “waiting list” that controlled for any effects of assessment and observation (Hawthorne effects) as well as the effects of the natural course of the illnessand regression to the mean; “limited interaction,” providing placebo treatment with minimal interaction with the practitioner; or “augmented interaction,” providing placebo treatment with a defined positive patient-practitioner relationship. Our placebo treatment was delivered with a validated sham acupuncture device. We therefore assumed that the three study groups represented the successive addition of the three postulated elements of the non-specific clinical interactions: group 1 (waiting list) having only observation alone, group 2 (limited) adding a dummy treatment, and group 3 (augmented) adding a warm, empathetic, and confident patient-practitioner relationship. All participants were evaluated at entry to the trial and after three and six weeks.