Research Review by Dr. Michael Haneline©

Date:

Aug. 2008

Study Title:

Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome

Authors:

Kaptchuk T et al.

Authors’ Affiliations: Osher Research Center, Harvard Medical School, Boston MA, USA

Publication Information:

British Medical Journal 2008; 336(7651):999-1003.

Summary:

In addition to the actual therapeutic effects of a given treatment, there are non-specific or contextual benefits (i.e. placebo effects) that are thought to be associated with not only the interventions themselves, but also with the medical encounter. Non-specific effects in the clinical setting have been divided into three elements:
  1. the Hawthorne effect, wherein the patient improves as a result of being observed;
  2. improvement related to the administration of a therapeutic ritual; and
  3. improvement due to the interaction between the practitioner and patient.
It should be noted that these non-specific components may also bring about negative effects (nocebo effects), resulting in a worsening of a patient’s condition.

The purpose of this study was to determine whether the three elements of non-specific effects could be separated. If so, could they be combined incrementally to produce progressive improvement in clinical outcomes based on which of the three elements the patients were exposed to. The authors also sought to quantify how much the relationship between practitioner and patient would improve the effects of a placebo treatment and whether a placebo treatment is more effective than no treatment.

The study sample consisted of 262 subjects with irritable bowel syndrome (IBS) who were recruited through various advertisements and by referrals from health providers. Subjects were allowed to continue their existing IBS medications.

There were two study periods, each lasting three weeks. In the first period, participants were randomized to one of three groups:
  1. Waiting List where Hawthorne effects, natural progression of the disease, and regression to the mean could be observed
  2. “Limited” Interaction that involved placebo treatment plus minimal patient-practitioner interaction; or
  3. “Augmented” Interaction that also involved a placebo treatment, plus a defined positive patient-practitioner relationship.
In the second period, subjects from the “limited” and “augmented” groups were randomized again to receive either continued sham or real acupuncture. The results of this part of the study will be reported elsewhere.

Interventions
Subjects in group 1 (waiting list) did not receive sham acupuncture and they did not have interactions with the practitioners. All they received were evaluations at baseline, at three weeks, and at six weeks.

Subjects in group 2 (limited interaction) received a validated form of sham acupuncture that has been shown to be indistinguishable from real acupuncture. A total of 6 sham treatments were given during the first study period and, if randomized to receive more sham treatments, an additional 6 during the second period. The practitioners drastically limited their conversations with the subjects and specifically did not give them any from of encouragement.

Subjects in group 3 (augmented interaction) were given the same placebo intervention as group 2 for the same period of time, but they also received feedback that was based on an optimal patient-practitioner relationship model. Practitioners systematically asked subjects questions about their condition and offered them encouragement by displaying a warm, friendly manner; active listening; empathy; 20 seconds of thoughtful silence; and communication of confidence and positive expectation.

Outcome measures
  • The global improvement scale, which asks: “Compared to the way you felt before you entered the study, have your IBS symptoms over the past 7 days been: 1=substantially worse, 2=moderately worse, 3=slightly worse, 4=no change, 5=slightly improved, 6=moderately improved, or 7=substantially improved.”
  • Adequate relief, a single question that asks: “Over the past week have you had adequate relief of your IBS symptoms?”
  • The symptom severity scale, which is a questionnaire that measures the sum of the subject’s evaluation on a 100 point scale based on five items: 1) severity of abdominal pain, 2) frequency of abdominal pain, 3) severity of abdominal distension, 4) dissatisfaction with bowel habits, and 5) interference with quality of life.
  • The quality of life scale, which determines how much the condition interferes with the patient’s quality of life.
Pertinent results of this study include: The following table shows the changes in outcome scores that occurred for each group during the study period.
Table of study outcomes showing how group scores were progressively higher depending on the level of intervention the subjects received.
Outcome Measure Mean (SD) Waiting list (n=87) Limited (n=88) Augmented (n=87)
At 3 Weeks
Global Improvement 3.8 (1.0) 4.3 (1.4) 5.0 (1.3)
Adequate Relief 28% 44% 62%
Change in Symptom Severity 30 (63) 42 (67) 82 (89)
Change in Quality of Life 3.6 (8.1) 4.1 (9.4) 9.3 (14.0)
At 6 Weeks
Global Improvement 3.7 (1.0) 4.6 (1.2) 5.1 (1.5)
Adequate Relief 35% 53% 61%
Change in Symptom Severity 35 (80) 53 (80) 108 (91)
Change in Quality of Life 5.5 (10.8) 5.4 (9.9) 12.4 (15.1)
  • The authors hypothesized that there would be a trend in scores between groups, wherein the outcomes of the waiting list group would be less than the limited interaction group, which would be less than the augmented interaction group. (i.e., Group 1 < Group 2 < Group 3).
  • Trend was supported (statistically significant), as can be seen in the table above.
  • Almost 20% of the subjects reported side effects, most commonly pain during needle placement and redness, swelling, or pain after needle removal. Even though needles did not actually penetrate the skin during the sham acupuncture.
  • Other side effects subjects thought were possibly related to their treatment included increased constipation, increased diarrhea, and dry mouth. A small number of subjects (< 1%) reported bad dreams, loss of appetite, sleepiness, fatigue, insomnia, nausea, giddiness, weakness, dizziness, and headache.
  • 76% of the limited group and 84% of the augmented group thought they had received authentic acupuncture after three weeks, while 56% and 84% respectively thought so at the six-week follow-up.
Limitations to the study:
  • The effects of observation and assessment could not be separated in this study, which the authors thought could have been handled by including another wait list group in which participants were followed without their knowledge. However, they did not think this was feasible.
  • The outcome measures were all subjective, which the authors thought was necessary because non-specific effects would have been difficult to demonstrate using objective measures.
  • It was not possible to determine whether the study outcomes were related to actual biological changes that occurred in subjects or because they shifted their selective attention to diffuse symptoms.

Conclusions & Practical Application:

This study reported on three components of placebo effects that are capable of demonstrating an incremental improvement in symptoms. The strongest effect was placebo treatment together with an enhanced patient-practitioner relationship. Placebo treatment together with limited patient-practitioner interaction was superior to waiting list on only two of the four measures. Therefore, the strongest component of non-specific treatment effects is probably a supportive interaction with a practitioner.

The findings of this study are important for clinicians to consider for several reasons:
  1. A patient’s condition might improve while receiving a given treatment due to, at least in part, a positive relationship established between the practitioner and patient. While this element of improvement is in actuality a non-specific effect of treatment, practitioners would be well-advised to make the most of it.
  2. Likewise, a patient’s condition might fail to improve in the absence of supportive interaction.
  3. Further research is necessary in order to sort out treatment effects from non-specific effects.
Practitioners should not rely entirely on patient reports of improvement as the sole validation of the procedures they utilize in practice. In addition to evaluating patient progress using valid and reliable clinical outcome measures, research is necessary to establish whether therapeutic procedures are actually effective as compared with a placebo or another type of treatment.