Efficacy of homoeopathic treatment: Systematic review of meta-analyses of randomised placebo-controlled homoeopathy trials for any indication.

BACKGROUND AND OBJECTIVE: Since 1997, several meta-analyses (MAs) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAIs) have been published with different methods, results and conclusions. To date, a formal assessment of these MAs has not been performed. The main objective of this systematic review of MAs of PRETHAIs was to evaluate the efficacy of homoeopathic treatment. METHODS: The inclusion criteria were as follows: MAs of PRETHAIs in humans; all ages, countries, settings, publication languages; and MAs published from 1 Jan. 1990 to 30 Apr. 2023. The exclusion criteria were as follows: systematic reviews without MAs; MAs restricted to age or gender groups, specific indications, or specific homoeopathic treatments; and MAs that did not assess efficacy. We searched 8 electronic databases up to 14 Dec. 2020, with an update search in 6 databases up to 30 April 2023. The primary outcome was the effect estimate for all included trials in each MA and after restricting the sample to trials with high methodological quality, according to predefined criteria. The risk of bias for each MA was assessed by the ROBIS (Risk Of Bias In Systematic reviews) tool. The quality of evidence was assessed by the GRADE framework. Statistical analyses were performed to determine the proportion of MAs showing a significant positive effect of homoeopathy vs. no significant difference. RESULTS: Six MAs were included, covering individualised homoeopathy (I-HOM, n = 2), nonindividualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3). The MAs comprised between 16 and 110 trials, and the included trials were published from 1943-2014. The median trial sample size ranged from 45 to 97 patients. The risk of bias (low/unclear/high) was rated as low for three MAs and high for three MAs. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy compared to placebo (5 of 5 MAs, no data in 1 MA). Sensitivity analyses with sample restriction to high-quality trials were available from 4 MAs; the effect remained significant in 3 of the MAs (2 MAs assessed ALL-HOM, 1 MA assessed I-HOM) and was no longer significant in 1 MA (which assessed NI-HOM). DISCUSSION: The quality of evidence for positive effects of homoeopathy beyond placebo (high/moderate/low/very low) was high for I-HOM and moderate for ALL-HOM and NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MAs of PRETHAIs reveal significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing partially replicable effects of homoeopathically potentised preparations in physico-chemical, in vitro, plant-based and animal-based test systems. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020209661. The protocol for this SR was finalised and submitted on 25 Nov. 2020 and registered on 26 Dec. 2020.

Contributing to Global Health: Development of a Consensus-Based Whole Systems Research Strategy for Anthroposophic Medicine.

BACKGROUND: Whole medicine and health systems like traditional and complementary medicine systems (T&CM) are part of healthcare around the world. One key feature of T&CM is its focus on patient-centered and multimodal care and the integration of intercultural perspectives in a wide range of settings. It may contribute to good health and well being for people as part of the Sustainable Development Goals of the United Nations. The authentic, rigorous, and fair evaluation of such a medical system, with its inherent complexity and individualization, imposes methodological challenges. Hence, we propose a broad research strategy to test and characterize its possible contribution to health. METHODS: To develop a research strategy for a specific T&CM system, Anthroposophic Medicine (AM), applying multimodal integrative healthcare based on a four-level concept of man, we used a three-phase consensus process with experts and key stakeholders, consisting of (1) premeeting methodological literature and AM research review and interviews to supplement or revise items of the research strategy and tailor them to AM research, (2) face-to-face consensus meetings further developing and tailoring the strategy, and (3) postmeeting feedback and review, followed by finalization. RESULTS: Currently, AM covers many fields of medical specialties in varied levels of healthcare settings, such as outpatient and inpatient; primary, secondary, and tertiary care; and health education and pedagogy. It is by definition integrated with conventional medicine in the public healthcare system. It applies specific medicines, nursing techniques, arts therapies, eurythmy therapy, rhythmical massage, counseling, and psychotherapy, and it is provided by medical doctors, nurses, therapists, midwives, and nutritionists. A research strategy authentic to this level of complexity should comprise items with a focus on (I) efficacy and effectiveness, divided into (a) evaluation of the multimodal and multidisciplinary medical system as a whole, or of complex multimodal therapy concept, (b) a reasonable amount of methodologically rigorous, confirmatory randomized controlled trials on exemplary pharmacological and nonpharmacological therapies and indications, (c) a wide range of interventions and patient-centered care strategies with less extensive formats like well-conducted small trails, observational studies, and high-quality case reports and series, or subgroup analyses from whole-system studies, or health service research; (II) safety; (III) economics; (IV) evidence synthesis; (V) methodologic issues; (VI) biomedical, physiological, pharmacological, pharmaceutical, psychological, anthropological, and nosological issues as well as innovation and development; (VI) patient perspective and involvement, public needs, and ethics; (VII) educational matters and professionalism; and (IX) disease prevention, health promotion, and public health. CONCLUSION: The research strategy extends to and complements the prevailing hierarchical system by introducing a broad "evidence house" approach to evaluation, something many health technology assessment boards today support. It may provide transparent and comprehensive insight into potential benefits or risks of AM. It can serve as a framework for an evidence-informed approach to AM for a variety of stakeholders and collaborating networks with the aim of improving global health.

Anthroposophic vs. conventional therapy for chronic low back pain: a prospective comparative study.

OBJECTIVE: To compare anthroposophic treatment (eurythmy, rhythmical massage or art therapy; counselling, anthroposophic medication) and conventional treatment for low back pain (LBP) under routine conditions. METHODS: 62 consecutive outpatients from 38 medical practices in Germany, consulting an anthroposophic (A-) or conventional (C-) physician with LBP of >or= 6 weeks duration participated in a prospective non-randomised comparative study. Main outcomes were Hanover Functional Ability Questionnaire (HFAQ), LBP Rating Scale Pain Score (LBPRS), Symptom Score, and SF-36 after 6 and 12 months. RESULTS: At baseline, LBP duration was > 6 months in 85% (29/34) of A-patients and 54% (15/28) of C-patients (p = 0.004). Unadjusted analysis showed significant improvements in both groups of HFAQ, LBPRS, Symptom Score, SF-36 Physical Component Summary, and three SF-36 scales (Physical Function, Pain, Vitality), and improvements in A-patients of three further SF-36 scales (Role Physical, General Health, Mental Health). After adjustment for age, gender, LBP duration, and education, improvements were still significant in both groups for Symptom Score (p = 0.030), SF-36 Physical Component Summary (p = 0.004), and three SF-36-scales (Physical Function, p = 0.025; Role Physical, p = 0.014; Pain, p = 0.003), and in A-patients for SF-36-Vitality (p = 0.032). Compared to C-patients, A-patients had significantly more pronounced improvements of three SF-36 scales (Mental Health: p = 0.045; General Health: p = 0.006; Vitality: p = 0.005); other improvements did not differ significantly between the two groups. CONCLUSION: Compared to conventional therapy, anthroposophic therapy for chronic LBP was associated with at least comparable improvements.

Complementary cancer therapy: a systematic review of prospective clinical trials on anthroposophic mistletoe extracts.

BACKGROUND: Anthroposophic Mistletoe therapy is a widely used complementary cancer treatment. OBJECTIVE: To evaluate prospective clinical trials on the effectiveness of anthroposophic mistletoe therapy for cancer. DESIGN: Systematic review. MATERIAL AND METHODS: Search of 9 electronic databases, reference lists and extensive expert consultations. Criteria-based assessment of methodological study quality. RESULTS: 16 randomized (RCT) and 9 non-randomized (N-RCT) controlled trials were identified that investigated mistletoe treatment of malignant diseases. Statistically significant benefit for survival was reported in 8 of 17 trials (in 5 of 10 RCTs), for disease-free survival and tumour recurrence in none of 2 RCTs, for remission of tumour and malignant effusion in 1 RCT and 1 N-RCT of 4 controlled trials, for quality of life (QoL) in 3 of 5 RCTs, and for QoL and reduction of side effects of cytoreductive therapies (chemotherapy, radiation or surgery) in 5 of 7 trials (3 of 5 RCTs). Methodological quality of the controlled trials differed substantially; some had major limitations while others were reasonably well conducted. 12 single-arm cohort studies were identified. 5 of 7 studies found substantial tumour remission in various cancers, one study reported remission of CIN, and 4 studies remission of malignant pleural effusion or ascites. Quality of reporting in cohort studies was mostly reasonably good. Mistletoe application was well tolerated. CONCLUSIONS: Regarding quality of studies and consistency of results, the best evidence for efficacy of mistletoe therapy exists for improvement of QoL and reduction of side effects of cytotoxic therapies (chemotherapy, radiation). Survival benefit has been shown but not beyond critique. Tumour remissions are described in cohort studies that investigate the application of high dose or local mistletoe extracts. As several reasonably well-conducted studies indicate beneficial effects, further properly designed trials should be encouraged to investigate clinical efficacy and its possible dependency on the mode of application.

Anthroposophic therapies in chronic disease: the Anthroposophic Medicine Outcomes Study (AMOS).

CONTEXT: Anthroposophic medicine (AM) is used worldwide for chronic diseases. OBJECTIVE: To study clinical outcomes and costs in patients treated with AM therapies for chronic conditions. DESIGN: Prospective cohort study. SETTING: 141 medical practices in Germany providing AM treatment. PARTICIPANTS AND INTERVENTIONS: 898 outpatients aged 1-75 years referred to AM therapies (art, eurythmy or rhythmical massage, n = 665) or starting AM medical treatment (counselling, medicines, n = 233). MAIN OUTCOME MEASURES: Disease severity assessed independently by physician (Disease Score) and patient (Symptom Score), and health-related quality of life (SF-36, KINDL, KITA) after 3, 6, 12, 18, and 24 months; health costs in pre-study year and first study year. RESULTS: Most common indications were mental disorders (32.0%), and musculoskeletal disorders (18.9%). Disease duration at baseline was median 3.0 years (interquartile range = i.q.r. 1.0-8.5, mean 6.5 +/- 8.4 years). Median number of AM therapy sessions was 12 (i.q.r. 10-20), median therapy duration was 120 days (i.q.r. 81-195). From baseline to 6-month follow-up, Disease Score (0-10) improved from 6.40 +/- 1.76 to 3.43 +/- 2.23 (p < 0.001), Symptom Score (0-10) improved from 5.89 +/- 1.75 to 3.35 +/- 2.09 (p < 0.001). In adults, SF-36 Physical Component Summary improved from mean 43.34 +/- 10.58 at baseline to 47.44 +/- 10.32 after 6 months (p < 0.001), SF-36 Mental Component Summary improved from 38.83 +/- 12.45 to 44.93 +/- 10.92 (p < 0.001). Similar HRQoL improvements were observed in children (KINDL, KITA). All improvements remained stable until 24-month follow-up. Adverse effects from AM therapies occurred in 2.7% (19/712) of patients. Three (0.5%) patients stopped therapy due to adverse effects. Health costs were 3,637 Euro per patient in the pre-study year and 3,484 Euro in the first study year, a decrease of 152 Euro (4.2%) per patient. CONCLUSION: Anthroposophic therapies were associated with long-term reduction of chronic disease symptoms, improvement of health-related quality of life, and health cost reduction.

Mistletoe in cancer - a systematic review on controlled clinical trials.

BACKGROUND: Mistletoe preparations are among the most widely used unconventional cancer therapies in Central Europe. Their clinical effectiveness, however, is controversial. OBJECTIVE: To investigate whether prospective controlled clinical trials provide evidence for efficacy of mistletoe therapy in cancer. DESIGN: Systematic review. MATERIAL AND METHODS: Search of 11 electronic databases, reference lists and expert consultations. Criteria based analysis was performed to assess methodological quality of the studies. RESULTS: Twenty-three studies were identified: 16 randomized, 2 quasi-randomized and 5 non-randomized. Cancer sites included breast, lung, stomach, colon, rectum, head and neck, kidney, bladder, melanoma, glioma, and genital. Among these studies, statistically significant positive outcomes were reported for survival (n = 8), tumor remission (n = 1), overall quality of life (QOL) (n = 3), and QOL in relation to side effects during cytoreductive therapy (n = 3). Further, positive trends were reported for survival (n = 8), disease-free-survival (n = 1), and tumor remission (n = 2). Several studies reported no effect on survival (n = 4), disease-free-survival (n = 1), recurrence (n = 2), remission (n = 3), and QOL (n = 1). One study showed a negative trend for disease-free-survival. However, methodological quality of the studies was sometimes far below the standard that is today regarded as optimal or necessary. In view of substantial heterogeneity of the studies and potential positive and negative biases, we considered effect size estimation by quantitative synthesis to be unreliable and decided on a non-quantitative synthesis and discussion. Mistletoe therapy was well tolerated, and no major side effects were noted. CONCLUSIONS: Among 23 identified studies evaluated for clinically relevant outcome measures, 12 studies showed one or more statistically significant, positive results, another 7 studies showed at least one positive trend, 3 showed no effect and 1 had a negative trend. All studies, however, suffered from methodological shortcomings to some degree, and many of the studies are not conclusive. As several reasonably well conducted studies indicate beneficial effects, further properly designed trials should be encouraged. Future controlled studies should take into account the methodological limitations and potential biases of these past mistletoe trials.

Use of Iscador, an extract of European mistletoe (Viscum album), in cancer treatment: prospective nonrandomized and randomized matched-pair studies nested within a cohort study.

CONTEXT: In anthroposophical medicine, total extracts of Viscum album (mistletoe) have been developed to treat cancer patients. The oldest such product is Iscador. Although Iscador is regarded as a complementary cancer therapy, it is the most commonly used oncological drug in Germany. OBJECTIVE: To determine whether Iscador treatment prolongs survival time of patients with carcinoma of the colon, rectum, or stomach; breast carcinoma with or without axillary or remote metastases; or small cell or non-small-cell bronchogenic carcinoma; and to explore synergies between Iscador treatment and psychosomatic self-regulation. DESIGN: Prospective nonrandomized and randomized matched-pair studies nested within a cohort study. SETTING: General community in Germany. PARTICIPANTS: 10,226 cancer patients involved in a prospective long-term epidemiological cohort study, including 1668 patients treated with Iscador and 8475 who had taken neither Iscador nor any other mistletoe product (control patients). INTERVENTION: Iscador. MAIN OUTCOME MEASURE: Survival time. RESULTS: In the nonrandomized matched-pair study, survival time of patients treated with Iscador was longer for all types of cancer studied. In the pool of 396 matched pairs, mean survival time in the Iscador groups (4.23 years) was roughly 40% longer than in the control groups (3.05 years; P < .001). Synergies between Iscador treatment and self-regulation manifested in a longer survival advantage for Iscador patients with good self-regulation (56% relative to control group; P = .03) than for patients with poor self-regulation. Results of the 2 randomized matched-pair studies largely confirmed the results of the non-randomized studies. CONCLUSION: Iscador treatment can achieve a clinically relevant prolongation of survival time of cancer patients and appears to stimulate self-regulation.

[Does the study "Complementary medicine in health insurance" provide a basis for scientifically valid conclusions?]. / Können aus der Studie <> wissenschaftlich tragfähige Schlüsse gezogen werden?

In Switzerland public attention was caught by a health economic analysis of health insurance's reimbursement of complementary medical procedures. Objectives of the study were 1) cost development, 2) health status development of insured citizens, 3) substitutional/additional use of complementary medical procedures. However, several conceptual, methodical and statistical flaws limit the conclusions that can be drawn from this study: The analysis claimed to be based on a large randomized trial. However, the attempt to achieve an unbiased equality in experimental and control group through stratified sampling grossly failed. Effects of complementary medical procedures on health status were inappropriately assessed and only based on 10 patients. The question whether complementary medicine is being used as a substitution or addition to conventional medicine was not even explored (the published result is based on a misleading interpretation of the health insurance's database). Finally, statements on cost developments were not based on estimations, but resulted from methodical and statistical artifacts. Furthermore, the study suffered from several other weaknesses, like a 50% dropout rate, an inadequate description of statistical procedures, an extremely reduced statistical power, and a lack of clear distinction between experimental and retrospective analyses. Therefore, no valid conclusions can be drawn from this study.

Single-case causality assessment as a basis for clinical judgment.

Current methodology of therapeutic causality assessment can be traced back to four underlying paradigms: (1) empirical scientific judgment relies on experimentation (paradigm of experiment), (2) causality assessment requires repeated observations (paradigm of large numbers), (3) observed results must be compared with results of control observations (paradigm of comparison), and (4) observed objects or patients must be distributed to verum and control group by chance (paradigm of randomization). Problematic aspects of conventional methodology and the historical evolution of contemporary causality assessment illustrate the necessity and possibility of methodological alternatives. A fundamental alternative is offered by figural correspondence and figural experiments, which allow valid causality assessments in single-case situations without blinding, randomization, comparison, or large numbers of observations. The epistemological foundation of such single-case causality assessment is explained. Examples from clinical judgment are presented. Single-case causality assessment may be particularly appropriate for therapy judgment in complementary medicine.

The powerful placebo effect: fact or fiction?

In 1955, Henry K. Beecher published the classic work entitled "The Powerful Placebo." Since that time, 40 years ago, the placebo effect has been considered a scientific fact. Beecher was the first scientist to quantify the placebo effect. He claimed that in 15 trials with different diseases, 35% of 1082 patients were satisfactorily relieved by a placebo alone. This publication is still the most frequently cited placebo reference. Recently Beecher's article was reanalyzed with surprising results: In contrast to his claim, no evidence was found of any placebo effect in any of the studies cited by him. There were many other factors that could account for the reported improvements in patients in these trials, but most likely there was no placebo effect whatsoever. False impressions of placebo effects can be produced in various ways. Spontaneous improvement, fluctuation of symptoms, regression to the mean, additional treatment, conditional switching of placebo treatment, scaling bias, irrelevant response variables, answers of politeness, experimental subordination, conditioned answers, neurotic or psychotic misjudgment, psychosomatic phenomena, misquotation, etc. These factors are still prevalent in modern placebo literature. The placebo topic seems to invite sloppy methodological thinking. Therefore awareness of Beecher's mistakes and misinterpretations is essential for an appropriate interpretation of current placebo literature.

Placebo effect and placebo concept: a critical methodological and conceptual analysis of reports on the magnitude of the placebo effect.

Since 1955, when HK Beecher published his classic "The Powerful Placebo," it generally has been accepted that 35% of patients with any of a wide variety of disorders can be treated with placebos alone. In recent years, average cure rates of 70%, and up to 100%, also have been quoted. Like pharmacological preparations, placebos are credited with possessing time-effect curves; cumulation and carry-over effects; differentiated actions depending on color, size, or packaging; even toxic effects. It has been postulated that placebos can prolong life, that their effects occur in surgery as well as in medicine, and that they are mediated by endorphins. In this article source material that forms the scientific basis for such claims is examined. Analysis shows that the studies on which such ideas are based, except perhaps in bronchial asthma, do not in any way justify the conclusions drawn from them. The truth is that the placebo effect is counterfeited by a variety of factors including the natural history of the disease, regression to the mean, concomitant treatments, obliging reports, experimental subordination, severe methodological defects in the studies, misquotations, etc; even, on occasion, by the fact that the supposed placebo is actually not a placebo, but has to be acknowledged as having a specific action on the condition for which it is being given. A further reason for misjudgment is the lack of clarity of the placebo concept itself. Experimental subordination and conditioning are other areas of insufficient conceptual differentiation. The authors conclude that the literature relating to the magnitude and frequency of the placebo effect is unfounded and grossly overrated, if not entirely false. They pose the question whether the existence of the so-called placebo effect is itself not largely-or indeed totally-illusory.

A critique of the double-blind clinical trial. Part 2.

The randomized, double-blind study is generally regarded as the gold standard of clinical drug trials. Bias can occur as a result of the blinding procedure itself, but discussions of this type of bias have been few and far between. This article continues with a detailed discussion of such blinding errors, which can obscure genuine drug effects and be of a sufficient magnitude as to generate false-negative results. Uncritical blinding in clinical studies should therefore be questioned.

A critique of the double-blind clinical trial. Part 1.

The randomized, double-blind study is generally regarded as the gold standard of clinical drug trials. Bias can occur as a result of the blinding procedure itself, but discussions of this type of bias have been few and far between. This article presents a detailed discussion of such blinding errors, which can obscure genuine drug effects and be of a sufficient magnitude as to generate false-negative results. Uncritical blinding in clinical studies should therefore be questioned.