Structural integration as an adjunct to outpatient rehabilitation for chronic nonspecific low back pain: a randomized pilot clinical trial.

Structural Integration (SI) is an alternative method of manipulation and movement education. To obtain preliminary data on feasibility, effectiveness, and adverse events (AE), 46 outpatients from Boston area with chronic nonspecific low back pain (CNSLBP) were randomized to parallel treatment groups of SI plus outpatient rehabilitation (OR) versus OR alone. Feasibility data were acceptable except for low compliance with OR and lengthy recruitment time. Intent-to-treat data on effectiveness were analyzed by Wilcoxon rank sum, n = 23 per group. Median reductions in VAS Pain, the primary outcome, of -26 mm in SI + OR versus 0 in OR alone were not significantly different (P = 0.075). Median reductions in RMDQ, the secondary outcome, of -2 points in SI + OR versus 0 in OR alone were significantly different (P = 0.007). Neither the proportions of participants with nor the seriousness of AE were significantly different. SI as an adjunct to OR for CNSLBP is not likely to provide additional reductions in pain but is likely to augment short term improvements in disability with a low additional burden of AE. A more definitive trial is feasible, but OR compliance and recruitment might be challenging. This trial is registered with ClinicalTrials.gov (NCT01322399).

Participants' experiences of being debriefed to placebo allocation in a clinical trial.

Participants in placebo-controlled clinical trials give informed consent to be randomized to verum or placebo. However, researchers rarely tell participants which treatment they actually received. We interviewed 4 participants in a trial of acupuncture for irritable bowel syndrome before, during, and after they received a course of placebo treatments over 6 weeks. During the final interview, we informed participants that they had received a course of placebo treatments. We used an idiographic phenomenological approach based on the Sheffield School to describe each participant's experiences of being blinded to and then debriefed to placebo allocation. The participants' experiences of blinding and debriefing were embodied, related to their goals in undertaking the study, and social (e.g., embedded in trusting and valued relationships with acupuncturists). We suggest ways in which debriefing to placebo allocation can be managed sensitively to facilitate positive outcomes for participants.

Scientific tools, fake treatments, or triggers for psychological healing: how clinical trial participants conceptualise placebos.

Placebos are an essential tool in randomised clinical trials, where they are used to control for bias and contextual healing effects. Placebos and their effects are also studied from multiple diverse perspectives, but the perspectives of placebo recipients are seldom considered. Research shows that people form cognitive and affective representations of active treatments such as medicines, and that they use these representations to guide their behaviour; it seems reasonable to suggest that people might also think about and develop representations of placebos. We adopted a qualitative approach to examine in detail how participants in one RCT, conducted in the USA, conceptualised placebos. 12 people were interviewed 3 times each, at the start, middle, and end of a trial of placebo effects and acupuncture for Irritable Bowel Syndrome (IBS). The interview data were analysed inductively and we identified four ways in which the participants conceptualised placebos: placebos are necessary for research; placebo effects are fake; placebo acupuncture is not real acupuncture; placebos have real effects mediated by psychological mechanisms. Participants' conceptualisations of placebos were dynamic and situated in a broader psychological and socio-cultural context. Seeing placebo effects as legitimate seemed to be facilitated by having more holistic models of healing, viewing IBS as psychological, and seeing treatment as multifactorial. However, some participants maintained a negative view of placebo effects (e.g. as illusions) that was apparently inconsistent with their other beliefs (e.g. in mind-body healing mechanisms). This may indicate a dominance of negative discourses around placebos at a socio-cultural level. Negative views of placebos are inconsistent with evidence that placebo treatments can have positive effects on symptoms. RCT participants should be informed about potential benefits of placebo treatments to avoid misunderstandings and unease. Future work should improve methods of providing participants with full accurate information about placebos and their effects.

Patient and practitioner influences on the placebo effect in irritable bowel syndrome.

OBJECTIVE: To determine whether placebo responses can be explained by characteristics of the patient, the practitioner, or their interpersonal interaction. METHODS: We performed an analysis of videotape and psychometric data from a clinical trial of patients with irritable bowel syndrome who were treated with placebo acupuncture in either a warm empathic interaction (Augmented, n = 96), a neutral interaction (Limited, n = 97), or a waitlist control (Waitlist, n = 96). We examined the relationships between the placebo response and a) patient personality and demographics; b) treating practitioner; and c) the patient-practitioner interaction as captured on videotape and rated by the Psychotherapy Process Q-Set. RESULTS: Patient extraversion, agreeableness, openness to experience, and female gender were associated with placebo response, but these effects held only in the augmented group. Regression analyses controlling for all other independent variables suggest that only extraversion is an independent predictor of placebo response. There were significant differences between practitioners in outcomes; this effect was twice as large as the effect attributable to treatment group assignment. Videotape analysis indicated that the augmented group fostered a treatment relationship similar to a prototype of an ideal healthcare interaction. CONCLUSIONS: Personality and gender influenced the placebo response, but only in the warm, empathic, augmented group. This suggests that, to the degree a placebo effect is evoked by the patient-practitioner relationship, personality characteristics of the patient will be associated with the placebo response. In addition, practitioners differed markedly in effectiveness, despite standardized interactions. We propose that the quality of the patient-practitioner interaction accounts for the significant difference between the groups in placebo response.

"Maybe I made up the whole thing": placebos and patients' experiences in a randomized controlled trial.

Patients in the placebo arms of randomized controlled trials (RCT) often experience positive changes from baseline. While multiple theories concerning such "placebo effects" exist, peculiarly, none has been informed by actual interviews of patients undergoing placebo treatment. Here, we report on a qualitative study (n = 27) embedded within a RCT (n = 262) in patients with irritable bowel syndrome. Besides identical placebo acupuncture treatment in the RCT, the qualitative study patients also received an additional set of interviews at the beginning, midpoint, and end of the trial. Interviews of the 12 qualitative subjects who underwent and completed placebo treatment were transcribed. We found that patients (1) were persistently concerned with whether they were receiving placebo or genuine treatment; (2) almost never endorsed "expectation" of improvement but spoke of "hope" instead and frequently reported despair; (3) almost all reported improvement ranging from dramatic psychosocial changes to unambiguous, progressive symptom improvement to tentative impressions of benefit; and (4) often worried whether their improvement was due to normal fluctuations or placebo effects. The placebo treatment was a problematic perturbation that provided an opportunity to reconstruct the experiences of the fluctuations of their illness and how it disrupted their everyday life. Immersion in this RCT was a co-mingling of enactment, embodiment and interpretation involving ritual performance and evocative symbols, shifts in bodily sensations, symptoms, mood, daily life behaviors, and social interactions, all accompanied by self-scrutiny and re-appraisal. The placebo effect involved a spectrum of factors and any single theory of placebo--e.g. expectancy, hope, conditioning, anxiety reduction, report bias, symbolic work, narrative and embodiment--provides an inadequate model to explain its salubrious benefits.

A treatment trial of acupuncture in IBS patients.

OBJECTIVES: This study aimed to compare the effects of true and sham acupuncture in relieving symptoms of irritable bowel syndrome (IBS). METHODS: A total of 230 adult IBS patients (75 % females, average age: 38.4 years) were randomly assigned to 3 weeks of true or sham acupuncture (6 treatments) after a 3-week "run-in" with sham acupuncture in an "augmented" or "limited" patient-practitioner interaction. A third arm of the study included a waitlist control group. The primary outcome was the IBS Global Improvement Scale (IBS-GIS) (range: 1 - 7); secondary outcomes included the IBS Symptom Severity Scale (IBS-SSS), the IBS Adequate Relief (IBS-AR), and the IBS Quality of Life (IBS-QOL). RESULTS: Although there was no statistically significant difference between acupuncture and sham acupuncture on the IBS-GIS (41 vs. 32 % , P = 0.25), both groups improved significantly compared with the waitlist control group (37 vs. 4 % , P = 0.001). Similarly, small differences that were not statistically significant favored acupuncture over the other three outcomes: IBS-AR(59 vs. 57 % , P = 0.83), IBS-SSS (31 vs. 21 % , P = 0.18), and IBS-QOL (17 vs. 13 % , P = 0.56). Eliminating responders during the run-in period did not substantively change the results. Side effects were generally mild and only slightly greater in the acupuncture group. CONCLUSIONS: This study did not find evidence to support the superiority of acupuncture compared with sham acupuncture in the treatment of IBS.

Adequate relief in a treatment trial with IBS patients: a prospective assessment.

OBJECTIVES: Adequate relief (AR) of irritable bowel syndrome (IBS) symptoms (IBS-AR) has been used as a primary end point in many randomized controlled trials of IBS and is considered by the Rome III committee to be an acceptable primary end point. However, controversy exists on whether baseline severity confounds the effect of the treatment outcome. The aim (1) is to compare a subjective report of IBS-AR with global assessment of improvement (IBS-GAI), change in IBS symptom severity scale (IBS-SSS), and IBS quality of life (IBS-QOL); (2) to explore whether initial IBS symptom severity influences the ability of these outcome measures to detect differences post treatment; and (3) to determine whether psychological symptoms influence the sensitivity of these measures, in a randomized controlled treatment trial. METHODS: A total of 289 adult IBS patients were recruited to a treatment trial. Baseline IBS-SSS scores were used to classify IBS severity as mild (<175), moderate (175-300), or severe (>300). Questionnaires were completed at baseline and after 3 weeks of treatment with sham acupuncture or wait-list control. RESULTS: IBS baseline severity (IBS-SSS) significantly affected the proportion of patients who reported IBS-AR at 3 weeks (mild, 70%; moderate, 49.7%; severe, 38.8%) (P<0.05). However, once the patients who reported IBS-AR at baseline (28.0%) were excluded from the analysis, baseline severity no longer affected the proportion of patients reporting IBS-AR. Baseline severity did not have a significant effect on patients reporting moderate or significant improvement on the IBS-GAI (mild, 30%; moderate, 25.3%; severe, 18.8%) (P=NS). Psychological symptoms had no significant correlations with responders after adjusting for baseline severity. CONCLUSIONS: These data suggest that IBS-AR as an end point is inversely related to baseline symptom severity. However, if patients who report AR at screening were excluded from study participation, baseline symptom severity was no longer confounded with a report of AR at the study end point.

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

OBJECTIVE: To investigate whether placebo effects can experimentally be separated into the response to three components-assessment and observation, a therapeutic ritual (placebo treatment), and a supportive patient-practitioner relationship-and then progressively combined to produce incremental clinical improvement in patients with irritable bowel syndrome. To assess the relative magnitude of these components. DESIGN: A six week single blind three arm randomised controlled trial. SETTING: Academic medical centre. PARTICIPANTS: 262 adults (76% women), mean (SD) age 39 (14), diagnosed by Rome II criteria for and with a score of > or =150 on the symptom severity scale. INTERVENTIONS: For three weeks either waiting list (observation), placebo acupuncture alone ("limited"), or placebo acupuncture with a patient-practitioner relationship augmented by warmth, attention, and confidence ("augmented"). At three weeks, half of the patients were randomly assigned to continue in their originally assigned group for an additional three weeks. MAIN OUTCOME MEASURES: Global improvement scale (range 1-7), adequate relief of symptoms, symptom severity score, and quality of life. RESULTS: At three weeks, scores on the global improvement scale were 3.8 (SD 1.0) v 4.3 (SD 1.4) v 5.0 (SD 1.3) for waiting list versus "limited" versus "augmented," respectively (P<0.001 for trend). The proportion of patients reporting adequate relief showed a similar pattern: 28% on waiting list, 44% in limited group, and 62% in augmented group (P<0.001 for trend). The same trend in response existed in symptom severity score (30 (63) v 42 (67) v 82 (89), P<0.001) and quality of life (3.6 (8.1) v 4.1 (9.4) v 9.3 (14.0), P<0.001). All pairwise comparisons between augmented and limited patient-practitioner relationship were significant: global improvement scale (P<0.001), adequate relief of symptoms (P<0.001), symptom severity score (P=0.007), quality of life (P=0.01). Results were similar at six week follow-up. CONCLUSION: Factors contributing to the placebo effect can be progressively combined in a manner resembling a graded dose escalation of component parts. Non-specific effects can produce statistically and clinically significant outcomes and the patient-practitioner relationship is the most robust component. TRIAL REGISTRATION: Clinical Trials NCT00065403.

Investigating placebo effects in irritable bowel syndrome: a novel research design.

Little is known about placebo effects with scientific precision. Poor methodology has confounded our understanding of the magnitude and even the existence of the placebo effect. Investigating placebo effects presents special research challenges including: the design of appropriate controls for studying placebo effects including separating such effects from natural history and regression to the mean, the need for large sample sizes to capture expected small effects, and the need to understand such potential effects from a patient's perspective. This article summarizes the methodology of an ongoing NIH-funded randomized controlled trial aimed at investigating whether the placebo effect in irritable bowel syndrome (IBS) exists and whether the magnitude of such an effect can be manipulated to vary in a manner analogous to "dose dependence." The trial also uses an innovative combination of quantitative and qualitative methods.