Background: Placebo and nocebo effects occur in clinical or laboratory medical contexts after administration of an inert treatment or as part of active treatments and are due to psychobiological mechanisms such as expectancies of the patient. Placebo and nocebo studies have evolved from predominantly methodological research into a far-reaching interdisciplinary field that is unravelling the neurobiological, behavioural and clinical underpinnings of these phenomena in a broad variety of medical conditions. As a consequence, there is an increasing demand from health professionals to develop expert recommendations about evidence-based and ethical use of placebo and nocebo effects for clinical practice. Methods: A survey and interdisciplinary expert meeting by invitation was organized as part of the 1st Society for Interdisciplinary Placebo Studies (SIPS) conference in 2017. Twenty-nine internationally recognized placebo researchers participated. Results: There was consensus that maximizing placebo effects and minimizing nocebo effects should lead to better treatment outcomes with fewer side effects. Experts particularly agreed on the importance of informing patients about placebo and nocebo effects and training health professionals in patient-clinician communication to maximize placebo and minimize nocebo effects. Conclusions: The current paper forms a first step towards developing evidence-based and ethical recommendations about the implications of placebo and nocebo research for medical practice, based on the current state of evidence and the consensus of experts. Future research might focus on how to implement these recommendations, including how to optimize conditions for educating patients about placebo and nocebo effects and providing training for the implementation in clinical practice.

BackgroundThe use of placebo interventions outside clinical trials is ethically, professionally and legally controversial. Little is known about the frequency and circumstances of placebo use in clinical practice. Our aim was to summarize the available empirical studies addressing these issues.MethodsWe searched PubMed and EMBASE from inception to July 2009 in order to identify cross-sectional surveys, qualitative or longitudinal studies among health care professionals, students or patients which investigated at least one of the following issues - frequency of placebo use or attitudes to, or motivations for, the use of placebo interventions. At least two reviewers extracted information on the study methods, participants and findings. Descriptive summaries were prepared in an iterative process by at least two reviewers per study.ResultsTwenty-two studies from 12 different countries met the inclusion criteria. Most studies had relevant shortcomings. The proportion of respondents reporting that they had applied 'pure' placebos (for example, saline injection) during their professional life varied between 17% and 80% among physicians and between 51% and 100% among nurses, but it seems that the actual frequency of such use seems to be rare. The use of 'impure' or 'active' placebos (for example, antibiotics for viral infections) is likely to be much more frequent. However, it is impossible to make a reliable estimation because there is no agreement of what an impure placebo might be. Studies using qualitative methods or asking participants to judge case examples suggest that motivations and attitudes towards placebo use are complex and health care providers are often faced with a dilemma.ConclusionsAlthough the available evidence is incomplete and confusing at times there can be little doubt that the prevalence of placebo use outside of clinical trials is not negligible and that views and attitudes on placebos use differ considerably among individuals, both health care professionals and patients. Further research is needed to clarify these issues.

No abstract

BackgroundWhile several recent large randomized trials found clinically relevant effects of acupuncture over no treatment or routine care, blinded trials comparing acupuncture to sham interventions often reported only minor or no differences. This raises the question whether (sham) acupuncture is associated with particularly potent nonspecific effects. We aimed to investigate the size of nonspecific effects associated with acupuncture interventions.MethodsMEDLINE, Embase, Cochrane Central Register of Controlled Clinical Trials and reference lists were searched up to April 2010 to identify randomized trials of acupuncture for any condition, including both sham and no acupuncture control groups. Data were extracted by one reviewer and verified by a second. Pooled standardized mean differences were calculated using a random effects model with the inverse variance method.ResultsThirty-seven trials with a total of 5754 patients met the inclusion criteria. The included studies varied strongly regarding patients, interventions, outcome measures, methodological quality and effect sizes reported. Among the 32 trials reporting a continuous outcome measure, the random effects standardized mean difference between sham acupuncture and no acupuncture groups was -0.45 (95% confidence interval, -0.57, -0.34; I2 = 54%; Egger's test for funnel plot asymmetry, P = 0.25). Trials with larger effects of sham over no acupuncture reported smaller effects of acupuncture over sham intervention than trials with smaller nonspecific effects (β = -0.39, P = 0.029).ConclusionsSham acupuncture interventions are often associated with moderately large nonspecific effects which could make it difficult to detect small additional specific effects. Compared to inert placebo interventions, effects associated with sham acupuncture might be larger, which would have considerable implications for the design and interpretation of clinical trials.

PURPOSE We performed a systematic review of the currently available evidence on whether psychological treatments are effective for treating depressed primary care patients in comparison with usual care or placebo, taking the type of therapy and its delivery mode into account. METHODSRandomized controlled trials comparing a psychological treatment with a usual care or a placebo control in adult, depressed, primary care patients were identified by searches in MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and PsycINFO up to December 2013. At least 2 reviewers extracted information from included studies and assessed the risk of bias. Random effects meta-analyses were performed using posttreatment depression scores as outcome. RESULTSA total of 30 studies with 5,159 patients met the inclusion criteria. Compared with control, the effect (standardized mean difference) at completion of treatment was -0.30 (95% CI, -0.48 to -0.13) for face-to-face cognitive behavioral therapy (CBT), -0.14 (-0.40 to 0.12) for face-to-face problem-solving therapy, -0.24 (-0.47 to -0.02) for face-to-face interpersonal psychotherapy, -0.28 (-0.44 to -0.12) for other face-to-face psychological interventions, -0.43 (-0.62 to -0.24) for remote therapist-led CBT, -0.56 (-1.57 to 0.45) for remote therapist-led problem-solving therapy, -0.40 (-0.69 to -0.11) for guided selfhelp CBT, and -0.27 (-0.44 to -0.10) for no or minimal contact CBT.CONCLUSIONS There is evidence that psychological treatments are effective in depressed primary care patients. For CBT approaches, substantial evidence suggests that interventions that are less resource intensive might have effects similar to more intense treatments.

ObjectivesTo assess the quantity and quality of randomised, sham-controlled studies of surgery and invasive procedures and estimate the treatment-specific and non-specific effects of those procedures.DesignSystematic review and meta-analysis.Data sourcesWe searched PubMed, EMBASE, CINAHL, CENTRAL (Cochrane Library), PILOTS, PsycInfo, DoD Biomedical Research, clinicaltrials.gov, NLM catalog and NIH Grantee Publications Database from their inception through January 2015.Study selectionWe included randomised controlled trials of surgery and invasive procedures that penetrated the skin or an orifice and had a parallel sham procedure for comparison.Data extraction and analysisThree authors independently extracted data and assessed risk of bias. Studies reporting continuous outcomes were pooled and the standardised mean difference (SMD) with 95% CIs was calculated using a random effects model for difference between true and sham groups.Results55 studies (3574 patients) were identified meeting inclusion criteria; 39 provided sufficient data for inclusion in the main analysis (2902 patients). The overall SMD of the continuous primary outcome between treatment/sham-control groups was 0.34 (95% CI 0.20 to 0.49; p<0.00001; I2=67%). The SMD for surgery versus sham surgery was non-significant for pain-related conditions (n=15, SMD=0.13, p=0.08), marginally significant for studies on weight loss (n=10, SMD=0.52, p=0.05) and significant for gastroesophageal reflux disorder (GERD) studies (n=5, SMD=0.65, p<0.001) and for other conditions (n=8, SMD=0.44, p=0.004). Mean improvement in sham groups relative to active treatment was larger in pain-related conditions (78%) and obesity (71%) than in GERD (57%) and other conditions (57%), and was smaller in classical-surgery trials (21%) than in endoscopic trials (73%) and those using percutaneous procedures (64%).ConclusionsThe non-specific effects of surgery and other invasive procedures are generally large. Particularly in the field of pain-related conditions, more evidence from randomised placebo-controlled trials is needed to avoid continuation of ineffective treatments.

BackgroundA growing body of evidence suggests that healthcare practitioners who enhance how they express empathy can improve patient health, and reduce medico-legal risk. However we do not know how consistently healthcare practitioners express adequate empathy. In this study, we addressed this gap by investigating patient rankings of practitioner empathy.MethodsWe conducted a systematic review and meta-analysis of studies that asked patients to rate their practitioners’ empathy using the Consultation and Relational Empathy (CARE) measure. CARE is emerging as the most common and best-validated patient rating of practitioner empathy. We searched: MEDLINE, Embase, PsycINFO, Cinahl, Science & Social Science Citation Indexes, the Cochrane Library and PubMed from database inception to March 2016. We excluded studies that did not use the CARE measure. Two reviewers independently screened titles and extracted data on average CARE scores, demographic data for patients and practitioners, and type of healthcare practitioners.ResultsSixty-four independent studies within 51 publications had sufficient data to pool. The average CARE score was 40.48 (95% CI, 39.24 to 41.72). This rank s in the bottom 5th percentile in comparison with scores collected by CARE developers. Longer consultations (n = 13) scored 15% higher (42.60, 95% CI 40.66 to 44.54) than shorter (n = 9) consultations (34.93, 95% CI 32.63 to 37.24). Studies with mostly (>50%) female practitioners (n = 6) showed 16% higher empathy scores (42.77, 95% CI 38.98 to 46.56) than those with mostly (>50%) male (n = 6) practitioners (34.84, 95% CI 30.98 to 38.71). There were statistically significant (P = 0.032) differences between types of providers (allied health professionals, medical students, physicians, and traditional Chinese doctors). Allied Health Professionals (n = 6) scored the highest (45.29, 95% CI 41.38 to 49.20), and physicians (n = 39) scored the lowest (39.68, 95% CI 38.29 to 41.08). Patients in Australia, the USA, and the UK reported highest empathy ratings (>43 average CARE), with lowest scores (<35 average CARE scores) in Hong Kong.ConclusionsPatient rankings of practitioner empathy are highly variable, with female practitioners expressing empathy to patients more effectively than male practitioners. The high variability of patient rating of practitioner empathy is likely to be associated with variable patient health outcomes. Limitations included frequent failure to report response rates introducing a risk of response bias. Future work is warranted to investigate ways to reduce the variability in practitioner empathy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12909-017-0967-3) contains supplementary material, which is available to authorized users.

IMPORTANCE When analyzing results of randomized clinical trials, the treatment with the greatest specific effect compared with its placebo control is considered to be the most effective one. Although systematic variations of improvements in placebo control groups would have important implications for the interpretation of placebo-controlled trials, the knowledge base on the subject is weak. OBJECTIVE To investigate whether different types of placebo treatments are associated with different responses using the studies of migraine prophylaxis for this analysis. DESIGN, SETTING, AND PARTICIPANTS We searched relevant sources through February 2012 and contacted the authors to identify randomized clinical trials on the prophylaxis of migraine with an observation period of at least 8 weeks after randomization that compared an experimental treatment with a placebo control group. We calculated pooled random-effects estimates according to the type of placebo for the proportions of treatment response. We performed meta-regression analyses to identify sources of heterogeneity. In a network meta-analysis, direct and indirect comparisons within and across trials were combined. Additional analyses were performed for continuous outcomes. EXPOSURE Active migraine treatment and the placebo control conditions. MAIN OUTCOMES AND MEASURES Proportion of treatment responders, defined as having an attack frequency reduction of at least 50%. Other available outcomes in order of preference included a reduction of 50% or greater in migraine days, the number of headache days, or headache score or a significant improvement as assessed by the patients or their physicians. RESULTS Of the 102 eligible trials, 23 could not be included in the meta-analyses owing to insufficient data. Sham acupuncture (proportion of responders, 0.38 [95% CI, 0.30-0.47]) and sham surgery (0.58 [0.37-0.77]) were associated with a more pronounced reduction of migraine frequency than oral pharmacological placebos (0.22 [0.17-0.28]) and were the only significant predictors of response in placebo groups in multivariable analyses (P = .005 and P = .001, respectively). Network meta-analysis confirmed that more patients reported response in sham acupuncture groups than in oral pharmacological placebo groups (odds ratio, 1.88 [95% CI, 1.30-2.72]). Corresponding analyses for continuous outcomes showed similar findings. CONCLUSIONS AND RELEVANCE Sham acupuncture and sham surgery are associated with higher responder ratios than oral pharmacological placebos. Clinicians who treat patients with migraine should be aware that a relevant part of the overall effect they observe in practice might be due to nonspecific effects and that the size of such effects might differ between treatment modalities.