To what extent are surgery and invasive procedures effective beyond a placebo response? A systematic review with meta-analysis of randomised, sham controlled trials.

OBJECTIVES: To 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. DESIGN: Systematic review and meta-analysis. DATA SOURCES: We 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 SELECTION: We 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 ANALYSIS: Three 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. RESULTS: 55 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; I(2)=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%). CONCLUSIONS: The 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.

Factors that influence practitioners' interpretations of evidence from alternative medicine trials: a factorial vignette experiment embedded in a national survey.

BACKGROUND: Clinical trial evidence in controversial areas such as complementary and alternative medicine (CAM) must be approached with an open mind. OBJECTIVE: To determine what factors may influence practitioners' interpretation of evidence from CAM trials. RESEARCH DESIGN: In a mailed survey of 2400 US CAM and conventional medicine practitioners we included 2 hypothetical factorial vignettes of positive and negative research results for CAM clinical trials. Vignettes contained randomly varied journal (Annals of Internal Medicine vs. Journal of Complementary and Alternative Medicine) and CAM treatment type (acupuncture, massage, glucosamine, meditation, and reiki). Response items also included randomly varied patient circumstances-chronic refractory symptoms and the patient requesting CAM. MEASURES: All practitioners rated the effectiveness and their willingness to recommend the therapy for a described patient. We used logistic regression to determine the independent influence of the 4 factors on respondents' effectiveness and legitimacy judgments. RESULTS: A total of 1561 practitioners responded (65%). Relative to Reiki, conventional medicine practitioners were most willing to recommend glucosamine (OR = 3.0; 95% CI [1.6-5.4]), than massage (1.9 [1.1-3.3]), acupuncture (1.3 [0.8-2.2]), and meditation (1.2 [0.7-2.0]). CAM practitioners rated acupuncture as effective more than other CAM therapies (OR = 5.8 [2.6-12.8] compared with Reiki), and were more willing to recommend acupuncture (OR = 12.3 [4.8-31.8]). When presented evidence of inefficacy, CAM practitioners were most willing to recommend acupuncture relative to other CAM therapies (OR = 15.5 [9.0-26.9]). CONCLUSIONS: Practitioners' judgments about CAM trial evidence depend on the type of treatments reported. Confirmation bias may play a role in the clinical translation of new evidence from clinical trials.

The legitimacy of placebo treatments in clinical practice: evidence and ethics.

Physicians commonly recommend 'placebo treatments', which are not believed to have specific efficacy for the patient's condition. Motivations for placebo treatments include complying with patient expectations and promoting a placebo effect. In this article, we focus on two key empirical questions that must be addressed in order to assess the ethical legitimacy of placebo treatments in clinical practice: 1) do placebo treatments have the potential to produce clinically significant benefit? and 2) can placebo treatments be effective in promoting a therapeutic placebo response without the use of deception? We examine evidence from clinical trials and laboratory experiments bearing on these two questions. The conclusion is reached that based on currently available evidence, it is premature to judge whether placebo treatments are ethically justifiable, with the possible exception of acupuncture for pain relief.

The placebo effect: illness and interpersonal healing.

The placebo effect has been a source of fascination, irritation, and confusion within biomedicine over the past 60 years. Although scientific investigation has accelerated in the past decade, with particular attention to neurobiological mechanisms, there has been a dearth of attention to developing a general theory of the placebo effect. In this article, we attempt to address this gap. To set the stage, we review evidence relating to the reality and clinical significance of the placebo effect. Next we investigate the scope and limits of the placebo effect by examining the hypothesis that the placebo effect operates predominantly by modifying the experience and perceptions of illness symptoms, such as pain, anxiety, and fatigue, rather than by modifying the pathophysiology of disease. Based on this background, we characterize the placebo effect as a form of interpersonal healing, as distinct from spontaneous natural healing and from technological healing dependent on physiologically active pharmaceuticals or procedures. Finally, we argue that research on the placebo effect has the potential to revitalize the art of medicine.

Religion, clinicians, and the integration of complementary and alternative medicines.

OBJECTIVE: The aim of this study was to compare religious characteristics of general internists, rheumatologists, naturopaths, and acupuncturists, as well as to examine associations between physicians' religious characteristics and their openness to integrating complementary and alternative medicine (CAM). DESIGN: The design involved a national mail survey. The subjects were internists, rheumatologists, naturopaths, and acupuncturists. MEASURES: Physician outcome measures were use of and attitudes toward six classes of CAM. Predictors were religious affiliation, intrinsic religiosity, spirituality, and religious traditionalism. RESULTS: There was a 65% response. Naturopaths and acupuncturists were three times as likely as internists and rheumatologists to report no religious affiliation (35% versus 12%, p < 0.001), but were more likely to describe themselves as very spiritual (51% versus 20%, p < 0.001) and to agree they try to carry religious beliefs into life's dealings (51% versus 44%, p < 0.01). Among physicians, increased spirituality and religiosity coincided with more personal use of CAM and willingness to integrate CAM into a treatment program. CONCLUSIONS: Current and future integrative medicine will be shaped in part by religious and spiritual characteristics of providers.

Alternative medicine research in clinical practice: a US national survey.

BACKGROUND: Little is known about whether federally funded complementary and alternative medicine (CAM) research is translating into clinical practice. We sought to describe the awareness of CAM clinical trials, the ability to interpret research results, the acceptance of research evidence, and the predictors of trial awareness among US clinicians. METHODS: We conducted a cross-sectional mailed survey of 2400 practicing US acupuncturists, naturopaths, internists, and rheumatologists. RESULTS: A total of 1561 clinicians (65%) responded. Of the respondents, 59% were aware of at least 1 major CAM clinical trial; only 23% were aware of both trials. A minority of acupuncturists (20%), naturopaths (25%), internists (17%), and rheumatologists (33%) were "very confident" in interpreting research results (P < .001). Fewer acupuncturists (17%) and naturopaths (24%) than internists (58%) and rheumatologists (74%) rated the results of randomized controlled trials as "very useful" (P < .001). Twice as many internists (53%) and rheumatologists (64%) rated patient preferences as "least important" compared with acupuncturists (27%) and naturopaths (31%) (P < .001). In multivariate analyses, for clinicians aware of at least 1 trial, male sex (odds ratio [OR], 1.30 [95% confidence interval {CI}, 1.05-1.62]), prior research experience (OR, 1.45 [95% CI, 1.13-1.86]), institutional or academic practice setting (ORs, 1.98 [95% CI, 1.01-3.91], and 1.23 [95% CI, 0.73-2.09], respectively), and rating randomized trials as "very useful" (OR, 1.46 [95% CI, 1.12-1.91]) (P < .001) for clinical decision making were positively associated with CAM trial awareness. Acupuncturists, naturopaths, and internists (ORs, 0.15 [95% CI, 0.10-0.23], 0.15 [95% CI, 0.09-0.24], and 0.18 [95% CI, 0.12-0.28], respectively) were all similarly less aware of CAM trial results compared with rheumatologists. CONCLUSION: For clinical research in CAM to achieve its social value, concerted efforts must be undertaken to train clinicians and improve the dissemination of research results.

Does the evidence make a difference in consumer behavior? Sales of supplements before and after publication of negative research results.

OBJECTIVE: To determine if the public consumption of herbs, vitamins, and supplements changes in light of emerging negative evidence. METHODS: We describe trends in annual US sales of five major supplements in temporal relationship with publication of research from three top US general medical journals published from 2001 through early 2006 and the number of news citations associated with each publication using the Lexus-Nexis database. RESULTS: In four of five supplements (St. John's wort, echinacea, saw palmetto, and glucosamine), there was little or no change in sales trends after publication of research results. In one instance, however, dramatic changes in sales occurred following publication of data suggesting harm from high doses of vitamin E. CONCLUSION: Results reporting harm may have a greater impact on supplement consumption than those demonstrating lack of efficacy. In order for clinical trial evidence to influence public behavior, there needs to be a better understanding of the factors that influence the translation of evidence in the public.

Responding to medical pluralism in practice: a principled ethical approach.

The popularity of complementary and alternative medicine (CAM) raises a range of ethical issues for practicing clinicians. Principles of biomedical ethics define obligations of health care professionals, but applying principles in particular cases at the interface of CAM and biomedicine may be particularly challenging. "Recognition of medical pluralism" can help clinicians' ethical deliberations related to CAM. Here we outline a 3-point practical approach to applying basic principles of biomedical ethics in light of medical pluralism: (1) inquiring about CAM use and the scientific evidence related to CAM, (2) acknowledging the health beliefs and practices of patients, and (3) accommodating diverse healing practices. Construed as such, recognition of medical pluralism encourages pragmatic willingness to examine the personal and cultural meaning associated with CAM use, the biases and assumptions of biomedicine, as well as the risk-benefit ratio of CAM practices. In this way, recognition of medical pluralism can help clinicians enhance patient care in a manner consistent with basic ethical principles.

William James, faith, and the placebo effect.

Long considered a fact of medicine and of clinical investigation, the placebo effect has recently been challenged. The thought of the great American psychologist and philosopher William James, particularly his understanding of the practical value of faith, helps to illuminate the nature of the placebo effect and the implications of this puzzling phenomenon for understanding healing and the practice of medicine.

Viewpoint: what is the best and most ethical model for the relationship between mainstream and alternative medicine: opposition, integration, or pluralism?

Despite radical improvements in medicine over the past 60 years, patients maintain multiple health care pathways that include high utilization of unconventional treatments. The authors examine three possible relationships between mainstream and alternative medicine: opposition, integration, and pluralism. Opposition, the traditional ethical position that the medical profession must eradicate unconventional medicine for the good of the patient, has withered away. Integration of mainstream and alternative medicine is increasingly advocated in tandem with hospital-based programs that amalgamate the use of conventional and alternative therapies. While advocates of integrative medicine often speak of "evidence-based" complementary and alternative medicine (CAM), integration fosters double standards for validating conventional and unconventional treatments. Integration also ignores unbridgeable epistemological beliefs and practices between mainstream and alternative medicine. Pluralism, which has been relatively ignored, calls for cooperation between the different medical systems rather than their integration. By recognizing the value of freedom of choice in medical options, pluralism is compatible with the principle of patient autonomy. Nonetheless, the pluralistic model does not amount to a relativistic stance according in which there would be no objective standards for comparing the therapeutic merit of conventional and CAM treatments. As an ethical model, pluralism realizes that physicians must be prepared to disagree with patient choices to pursue alternative therapies, and urge patients not to forgo medically indicated treatment. Pluralism encourages cooperation, research, and open communication and respect between practitioners despite the possible existence of honest disagreement, and preserves the integrity of each of the treatment systems involved.

Ethical issues concerning research in complementary and alternative medicine.

The use of complementary and alternative medicine (CAM) has grown dramatically in recent years, as has research on the safety and efficacy of CAM treatments. Minimal attention, however, has been devoted to the ethical issues relating to research on CAM. We argue that public health and safety demand rigorous research evaluating CAM therapies, research on CAM should adhere to the same ethical requirements for all clinical research, and randomized, placebo-controlled clinical trials should be used for assessing the efficacy of CAM treatments whenever feasible and ethically justifiable. In addition, we explore the legitimacy of providing CAM and conventional therapies that have been demonstrated to be effective only by virtue of the placebo effect.