Homeopathy Assessment-Contribution of the Human Sciences.

The recent questions about homeopathy raised by some sceptics have focused an awareness on this therapy and led different protagonists among the scientific community to seek a much-needed re-assessment. The inputs coming from external but benevolent experts will broaden the knowledge and the consciousness of the whole medical community, and more widely of the public, about the meaning and the value of homeopathy.Looking at this from the point of view of the human sciences gives a perspective on the universality of the philosophy that underlies homeopathic thinking, which is particularly visible in the methodological similarities between homeopathic provings and sociological or anthropological observations. It also explains how this view of health and care coincides with the expectations of the public, who no longer want a limited mechanical approach to the human body or more generally to the environment.The input to homeopathy of the human sciences, with their methodological tools and approaches, and highlighting the possibilities offered by mixed-methods research, could enable these notions to be heard and shared in the wider scientific community.

Five Years of Practical Experience Using the Revised Proving Guidelines of the Homœopathic Pharmacopœia Convention of the United States.

The Homœopathic Pharmacopœia of the United States (HPUS) is one of the three officially recognized compendia of medical drugs in the United States. A well-conducted homeopathic proving is one pathway to entry into the HPUS. In 2013, guidelines for homeopathic drug provings were updated to better assess the methodology of provings and improve the confidence in the outcomes generated. In addition, the team who developed the revised guidelines included a pragmatic approach to assess the quality of proving outcomes in terms of their usefulness in determining the therapeutic profile. The monograph review team, composed of homeopathic clinicians and researchers, has evaluated 25 new homeopathic medicines for monograph purposes. The team has noted that the guidelines have helped frame and standardize the monograph review process. The revised structure for monograph reporting has enhanced the reviewer's ability to ascertain the therapeutic profile for a new substance. Sponsors have stated that the new guidelines have helped increase their conformance with Good Clinical Practices, helped improve the reporting and transparency of their provings, and may help safeguard provings as a valid research method. Similar harmonized guidelines have been adopted by the European Committee for Homeopathy and the Liga Medicorum Homœopathica Internationalis.

Recommendations for Designing, Conducting and Reporting Observational Studies in Homeopathy.

BACKGROUND: Randomized placebo-controlled trials are considered to be the gold standard in clinical research and have the highest importance in the hierarchical system of evidence-based medicine. However, from the viewpoint of decision makers, due to lower external validity, practical results of efficacy research are often not in line with the huge investments made over decades. METHOD: We conducted a narrative review. With a special focus on homeopathy, we give an overview on cohort, comparative cohort, case-control and cross-sectional study designs and explain guidelines and tools that help to improve the quality of observational studies, such as the STROBE Statement, RECORD, GRACE and ENCePP Guide. RESULTS: Within the conventional medical research field, two types of arguments have been employed in favor of observational studies. First, observational studies allow for a more generalizable and robust estimation of effects in clinical practice, and if cohorts are large enough, there is no over-estimation of effect sizes, as is often feared. We argue that observational research is needed to balance the current over-emphasis on internal validity at the expense of external validity. Thus, observational research can be considered an important research tool to describe "real-world" care settings and can assist with the design and inform the results of randomised controlled trails. CONCLUSIONS: We present recommendations for designing, conducting and reporting observational studies in homeopathy and provide recommendations to complement the STROBE Statement for homeopathic observational studies.

Systematic Review and Meta-Analysis of Randomised, Other-than-Placebo Controlled, Trials of Individualised Homeopathic Treatment.

BACKGROUND: This study focuses on randomised controlled trials (RCTs) of individualised homeopathic treatment (IHT) in which the control (comparator) group was other than placebo (OTP). AIMS: To determine the comparative effectiveness of IHT on health-related outcomes in adults and children for any clinical condition that has been the subject of at least one OTP-controlled trial. For each study, to assess the risk of bias and to determine whether its study attitude was predominantly 'pragmatic' or 'explanatory'. METHODS: Systematic review. For each eligible trial, published in the peer-reviewed literature up to the end of 2015, we assessed its risk of bias (internal validity) using the seven-domain Cochrane tool, and its relative pragmatic or explanatory attitude (external validity) using the 10-domain PRECIS tool. We grouped RCTs by whether they examined IHT as an alternative treatment (study design Ia), adjunctively with another intervention (design Ib), or compared with a no-intervention group (design II). For each RCT, we identified a 'main outcome measure' to use in meta-analysis: 'relative effect size' was reported as odds ratio (OR; values >1 favouring homeopathy) or standardised mean difference (SMD; values < 0 favouring homeopathy). RESULTS: Eleven RCTs, representing 11 different medical conditions, were eligible for study. Five of the RCTs (four of which in design Ib) were judged to have pragmatic study attitude, two were explanatory, and four were equally pragmatic and explanatory. Ten trials were rated 'high risk of bias' overall: one of these, a pragmatic study with design Ib, had high risk of bias solely regarding participant blinding (a bias that is intrinsic to such trials); the other trial was rated 'uncertain risk of bias' overall. Eight trials had data that were extractable for analysis: for four heterogeneous trials with design Ia, the pooled OR was statistically non-significant; collectively for three clinically heterogeneous trials with design Ib, there was a statistically significant SMD favouring adjunctive IHT; in the remaining trial of design 1a, IHT was non-inferior to fluoxetine in the treatment of depression. CONCLUSIONS: Due to the low quality, the small number and the heterogeneity of studies, the current data preclude a decisive conclusion about the comparative effectiveness of IHT. Generalisability of findings is limited by the variable external validity identified overall; the most pragmatic study attitude was associated with RCTs of adjunctive IHT. Future OTP-controlled trials in homeopathy should aim, as far as possible, to promote both internal validity and external validity.

The N-of-1 Clinical Trial: A Timely Research Opportunity in Homeopathy.

BACKGROUND: The randomised controlled trial (RCT) is considered the 'gold standard' for establishing treatment efficacy or effectiveness of an intervention, but its data do not infer response in an individual patient. Individualised clinical care, a fundamental principle in complementary and alternative medicine (CAM), including homeopathy, seems well disposed in principle to being researched by single-patient (N-of-1) study design. Guidelines for reporting N-of-1 trials have recently been developed. OBJECTIVE: To overview the current status in the literature of the N-of-1 method and its application in medicine, including CAM. To consider whether the N-of-1 trial design offers an opportunity for novel research in homeopathy. N-OF-1 TRIAL DESIGN: The N-of-1 trial applies the principles of the conventional crossover, blinded, RCT design. The treatment under study and the comparator are repeated in a randomised order, and with suitable washout time, over a defined period. N-of-1 design is constrained for use in chronic stable conditions, and for interventions that have quick onset and cessation of effect, with modest or negligible carryover. Outcome data can be aggregated and interpreted for the individual subject; they can also be pooled with data from several similar N-of-1 trials, enabling more generalisable conclusions. THE N-OF-1 TRIAL IN CAM: The typical individualisation of patient care can be accommodated in N-of-1 study design if the patient and the specific therapeutic intervention are selected within the constraints of the method. Application of the N-of-1 method in CAM has been advocated but has been mainly limited, in practice, to a small number of studies in herbal and traditional Chinese medicine. THE N-OF-1 TRIAL IN HOMEOPATHY: Individualised homeopathy can be accommodated for investigation within the same methodological constraints; less in-depth homeopathic approaches to prescribing are also amendable to investigation using the N-of-1 method. No such studies have been published. We identify three main targets in its ready applicability to homeopathy: (1) to optimise clinical care in an individual patient; (2) to investigate whether the outcomes of treatment using homeopathy differ from those of placebo; (3) to aggregate data from a series of N-of-1 trials to enable broader conclusions about a group of patients or intervention. CONCLUSION: The N-of-1 trial design offers important new investigative possibilities in homeopathy and should be explored as a means to optimise individualised health care or investigate effectiveness of the homeopathic intervention compared with placebo in individual subjects.

Model validity of randomised placebo-controlled trials of non-individualised homeopathic treatment.

BACKGROUND: The comprehensive systematic review of randomised placebo-controlled trials (RCTs) in homeopathy requires examination of a study's model validity of homeopathic treatment (MVHT) as well as its risk of bias (extent of reliable evidence). OBJECTIVE: To appraise MVHT in those RCTs of non-individualised homeopathy that an associated investigation had judged as 'not at high risk of bias'. DESIGN: Systematic review. METHODS: An assessment of MVHT was ascribed to each of 26 eligible RCTs. Another 49 RCTs were ineligible due to their high risk of bias. MAIN OUTCOME MEASURES: MVHT and the prior risk of bias rating per trial were merged to obtain a single overall quality designation ('high', 'moderate', 'low'), based on the GRADE principle of downgrading. RESULTS: The trials were rated as 'acceptable MVHT' (N = 9), 'uncertain MVHT' (N = 10) and 'inadequate MVHT' (N = 7); and, previously, as 'reliable evidence' (N = 3) and 'non-reliable evidence' (N = 23). The 26 trials were designated overall as: 'high quality' (N = 1); 'moderate quality' (N = 18); 'low quality' (N = 7). CONCLUSION: Of the 26 RCTs of non-individualised homeopathy that were judged 'not at high risk of bias', nine have been rated 'acceptable MVHT'. One of those nine studies was designated 'high quality' overall ('acceptable MVHT' and 'reliable evidence'), and is thus currently the only reported RCT that represents best therapeutic practice as well as unbiased evidence in non-individualised homeopathy. As well as minimising risk of bias, new RCTs in this area must aim to maximise MVHT and clarity of reporting.

Publications on experimental physical methods to investigate ultra high dilutions--an assessment on quality.

INTRODUCTION: Our first evaluation of fundamental research into the physics and physiology of Ultra High Dilution (UHD) was conducted in 1994. Since then, in 2003, Becker-Witt et al. conducted a more systematic evaluation of the literature and established the Score for Assessment of Physical Experiments on Homeopathy (SAPEH). While this evaluation focused on experimental methodologies, Stock-Schröer et al., in 2009, formulated a detailed guideline for authors on Reporting Experiments in Homeopathic Basic research (REHBaR) to promote a high standard in research as well as in its communication in scientific literature. METHOD: In this paper, we evaluate publications on basic research into the physics of UHD since the decade following the presentation of the SAPEH score (2004-2014), and present the state of progress in this field. RESULTS: Fundamental research into the physics of UHD has been reported at a steady rate over the past 60 years. Reported research of high quality as per SAPEH scoring appears to be still the exception rather than standard. CONCLUSION: Considering the importance of a fundamental understanding of what makes a UHD preparation, results of this study suggest that it may be beneficial to this field of fundamental research if grant challenges are approached in strategic way similar to other grant challenges in science.

When is lack of scientific integrity a reason for retracting a paper? A case study.

OBJECTIVE: The journal received a request to retract a paper reporting the results of a triple-blind randomized placebo-controlled trial. The present and immmediate past editors expand on the journal's decision not to retract this paper in spite of undisputable evidence of scientific misconduct on behalf of one of the investigators. METHODS: The editors present an ethical reflection on the request to retract this randomized clinical trial with consideration of relevant guidelines from the Committee on Publication Ethics (COPE) and the International Committee of Medical Journal Editors (ICMJE) applied to the unique contextual issues of this case. RESULTS: In this case, scientific misconduct by a blinded provider of a homeopathy intervention attempted to undermine the study blind. As part of the study, the integrity of the study blind was assessed. Neither participants nor homeopaths were able to identify whether the participant was assigned to homeopathic medicine or placebo. Central to the decision not to retract the paper was the fact that the rigorous scientific design provided evidence that the outcome of the study was not affected by the misconduct. The misconduct itself was thought to be insufficient reason to retract the paper. CONCLUSION: Retracting a paper of which the outcome is still valid was in itself considered unethical, as it takes away the opportunity to benefit from its results, rendering the whole study useless. In such cases, scientific misconduct is better handled through other professional channels.

New repertory, new considerations.

The criteria for entering medicines in repertory rubrics are unclear and partly incorrect. A new repertory should be based on clear and objective criteria. Retrospective and prospective assessment of medicines and symptoms by the Dutch Committee for Methods and Validation gives an indication of the validity of existing repertory entries. Reliance on the experience of one expert is the cause of part of the shortcomings of the repertory. This experience is highly influenced by chance. Another part is due to the use of absolute rather than relative occurrence of symptoms. Yet another part is caused by not comparing prevalence in the population 'cured' by a medicine with the remainder of the population. In many cases we need better definitions of symptoms. A clear protocol and prospective research could overcome many shortcomings of the repertory. Statistics help to get more objective criteria, but we still need to reach consensus about how to handle probabilities of outcomes of our assessments.

Transparently reporting adverse effects of traditional Chinese medicine interventions in randomized controlled trials.

Although all Chinese materia medica (CMM) come from nature, CMM interventions have both therapeutic effects and adverse effects (AEs). Normally, AEs in randomized controlled trial (RCT) with traditional Chinese medicine (TCM) could be divided into five types as follows: 1) AEs under proper TCM principles and guidelines, such as the toxicity (acute and chronic) and allergy; 2) AEs due to improper usage without following TCM principles, involving without following the TCM therapeutic principles, over-dosage, improper processing and preparation methods, improper formula strategy, etc; 3) AEs due to contamination in CMM, such as heavy metal and pesticides contaminations in Chinese herbal medicine interventions, and intentional or unintentional contamination with drug(s); 4) AEs due to replacement of CMMs; 5) AEs due to drug-herb interaction. AEs of TCM should be treated properly. Overestimation or underestimation about AEs of TCM intervention will bring a wrong message to patients and health care providers. In order to give readers a more comprehensive understanding about the safety issue of study intervention, Consolidated Standards of Reporting Trials (CONSORT) for TCM should involve the background information on side effects of each CMM constituents and/or the study intervention, specific outcome assessment on AEs, the details of reported AEs and the interpretation of the AEs occurrence in a structural RCT report.

Does potentized HgCl2 (Mercurius corrosivus) affect the activity of diastase and alpha-amylase?

BACKGROUND: Homeopathic drugs even with dilutions beyond 10(23) (high potencies) are frequently used, although their working mechanism is still unknown. Curative information preserved in solvent structure is postulated to exert biologic effects. OBJECTIVE: The objective was to test for a stimulating or inhibiting effect of high potencies of the homeopathic remedy HgCl2 (Mercurius corrosivus) on two sugar hydrolases. METHODS: High potencies were produced using stepwise dilution plus shaking. Controls included potentized solvent (aqua bidestillata), equimolar dilutions without shaking, and enzyme-free references. Tested were potencies with dilution factors 1:200 (CC) on diastase extract from winter barley, and 1:100 (C) on alpha-amylase from hog pancreas. Enzyme activity was colorimetrically determined by Lugol's iodine-starch reaction. RESULTS: An inhibiting effect of HgCl2 on enzyme activities was observed only in low potencies and dilutions. Statistically significant differences between potencies and controls were not found in randomized and blinded experiments. CONCLUSIONS: This experimental design provided independent reproducible results of cell-free in vitro assays. However, it did not indicate an effect of potentized HgCl2 on hydrolases. Demonstrating potency effects may require additional experimental features.

Bioelectrographic correlates of the direct vision phenomenon.

OBJECTIVES: A method for training children and adults to perceive visual information without using the eyes has been developed. A study was conducted to investigate the correlation of this perceptual capacity, known as direct vision (DV), with bioelectrographic measurements. DESIGN: Using the technique of dynamic digital gas-discharge visualization (GDV) bioelectrography, seven subjects were tested on three occasions over a 7-month period while they were in the process of reading information from a computer screen and reading printed text; this testing was repeated after an interval of 2 years. RESULTS: In multiple trials it was found that with the perception of information by DV, curves of GDV versus time exhibited specific dynamics, confirming the phenomenon of DV. At least three types of GDV characteristics can be distinguished in this state. This study also identified improvements in the psychosomatic state of children during the 7-month course of training in DV. CONCLUSIONS: The phenomenon of DV presents a newly recognized type of human information processing. It is based on a specific type of mental training that is statistically reproducible and has been assimilated by hundreds of children in Russia who are blind or have poor vision. The discovery of DV opens new perspectives in the study of the mechanisms of consciousness. The GDV characteristics that were observed during the perception of information by DV support the hypothesis that DV occurs through signals within the visible range of the electromagnetic spectrum. These results allow the proposal of a hypothesis for the way in which the brain, as well as the human system as a whole, registers information.

A randomized, double-blind, placebo-controlled study of classical homeopathy in generalized anxiety disorder.

BACKGROUND: Homeopathy is commonly used for the treatment of medical and psychological conditions. Such prevalent use, however, is not supported by robust, methodologically sound research. This study evaluates the effect of homeopathic treatment in generalized anxiety disorder, a prevalent mental disorder characterized by an enduring pattern of excessive apprehension and distress and by mental and bodily complaints. METHOD: Forty-four patients with DSM-IV generalized anxiety disorder participated in a randomized, double-blind, placebo-controlled 10-week trial of individually tailored homeopathic remedy. Homeopathic therapy was administered by an expert who followed the traditional routines of homeopathic diagnosis and prescription. Thirty-nine subjects completed the study (20 in the active treatment group and 19 in the placebo group). Subjects' symptoms were rated before treatment and after 5 and 10 weeks of treatment, with the Hamilton Rating Scale for Anxiety (HAM-A) as main outcome measure. Additional measures of outcome included the Brief Symptom Inventory, the Psychological General Well-Being Index, the Hamilton Rating Scale for Depression, the Beck Depression Inventory, Spielberger's State-Trait Anxiety Inventory, and a Visual Analogue Scale of subjective distress. RESULTS: Significant (p <.05) improvement in most measures, including the HAM-A, was observed in both the active treatment and placebo groups, yet no group effect was observed. CONCLUSION: The effect of homeopathic treatment on mental symptoms of patients with generalized anxiety disorder did not differ from that of placebo. The improvement in both conditions was substantial. Improvement of such magnitude may account for the current belief in the efficacy of homeopathy and the current increase in the use of this practice.

The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture.

BACKGROUND: To investigate the methodological quality of randomized controlled trials in three areas of complementary medicine. METHODS: The methodological quality of 207 randomized trials collected for five previously published systematic reviews on homeopathy, herbal medicine (Hypericum for depression, Echinacea for common cold), and acupuncture (for asthma and chronic headache) was assessed using a validated scale (the Jadad scale) and single quality items. RESULTS: While the methodological quality of the trials was highly variable, the majority had important shortcomings in reporting and/or methodology. Major problems in most trials were the description of allocation concealment and the reporting of drop-outs and withdrawals. There were relevant differences in single quality components between the different complementary therapies: For example, acupuncture trials reported adequate allocation concealment less often (6% versus 32% of homeopathy and 26% of herb trials), and trials on herbal extracts had better summary scores (mean score 3.12 versus 2.33 for homeopathy and 2.19 for acupuncture trials). Larger trials published more recently in journals listed in Medline and in English language scored significantly higher than trials not meeting these criteria. CONCLUSION: Trials of complementary therapies often have relevant methodological weaknesses. The type of weaknesses varies considerably across interventions.

Efficacy of homeopathic arnica: a systematic review of placebo-controlled clinical trials.

BACKGROUND: The efficacy of homeopathic remedies has remained controversial. The homeopathic remedy most frequently studied in placebo-controlled clinical trials is Arnica montana. OBJECTIVE: To systematically review the clinical efficacy of homeopathic arnica. MATERIALS AND METHODS: Computerized literature searches were performed to retrieve all placebo-controlled studies on the subject. The following databases were searched: MEDLINE, EMBASE, CISCOM, and the Cochrane Library. Data were extracted in a predefined, standardized fashion independently by both authors. There were no restrictions on the language of publications. RESULTS: Eight trials fulfilled all inclusion criteria. Most related to conditions associated with tissue trauma. Most of these studies were burdened with severe methodological flaws. On balance, they do not suggest that homeopathic arnica is more efficacious than placebo. CONCLUSION: The claim that homeopathic arnica is efficacious beyond a placebo effect is not supported by rigorous clinical trials.

Complementary and alternative medicine in asthma: do they work?

OBJECTIVE: An increasing number of patients with asthma are attracted by complementary and alternative medicine (CAM). Therefore, it is of importance that scientific evidence about the efficacy of this type of therapy is regarded. METHOD: We searched the electronic databases Medline, Embase and the Cochrane Library for controlled trials and systematic reviews to evaluate the evidence of the most popular alternative therapies, i.e. acupuncture, homeopathy, breathing techniques, herbal and nutritional therapies. RESULTS: Claims that acupuncture is effective for the treatment of asthma are not based on well-performed clinical trials. The role of homeopathy in the treatment of asthma needs further evaluation. Breathing techniques, e.g. improved control of breathing by yoga, may contribute to the control of asthma symptoms, but due to the small number of controlled trials and due to the small number of patients it is not possible to make firm judgments. Herbal remedies cannot be recommended based on the available evidence. Recommendations for a diet high in vitamin C and marine fatty acids are not harmful, but evidence for clinically meaningful effects are scant. CONCLUSION: Up to now evidence is lacking that alternative forms of medicine are more effective than placebo in asthma. However, lack of evidence does not always mean that treatment is ineffective, but it could mean that effectiveness has not been adequately investigated. High quality research as in conventional therapy should be fostered in complementary medicine.

Clinical trials of classical homeopathy: reflections on appropriate research designs.

The growing popularity of complementary medicine has been accompanied by a call for controlled clinical studies to examine the efficacy and validity of its various methods. The difficulties encountered in applying the evaluation methods of conventional medicine to complementary medicine are the result of the different paradigms underlying these two methods of medicine, and the differences in the healing process. This paper attempts to bridge the gap between these two approaches and to suggest a possibility to use conventional research methodology in clinical studies of classical homeopathy. Two methods are described. One is the randomization into a placebo or a treatment group after an individual remedy is chosen for each patient. This method requires an experienced homeopath and is reproducible only by the same homeopath in the same population. On the other hand, the expected success rate will be high. Another method is prescribing and treating according to so-called keynotes, a set of symptoms known to respond to a particular remedy that must be present in a patient in order to elicit a reaction from the remedy. This method is more suitable to a conventional design of a clinical study and is reproducible by anyone. Yet the expected success rate is much lower. Some general design issues that may have a particular impact on clinical trials of classical homeopathy are discussed, including the need for sufficiently powered trials to detect relatively small effects, strategies to deal with patient preference and embracing the use of "active-control" pragmatic trial designs.

Clinical trials of homeopathy and placebo: analysis of a scientific debate.

OBJECTIVE: Homeopathy is controversial, primarily because of the use of medicines diluted beyond the Avogadro limit. This article examines the scientific debate on whether homeopathy can have effects greater than placebo in humans. METHODS: Five rigorous English-language clinical studies published in high-impact journals that favored homeopathy were identified. Letters and other articles written in response to these articles were then retrieved and analyzed. RESULTS: Much of the content of responses to positive homeopathic research was rhetorical in nature and antagonistic in tone: homeopathic researchers were accused of bias and of being in the pocket of homeopathic manufacturers; arguments were raised that are demonstrably inaccurate or irrelevant to the interpretation of research; words such as "magic" or "potion" were used to paint homeopathic research as inherently unscientific. Other commentators argued that based on theoretical grounds homeopathy could not possibly be effective, any positive trial result must be due to bias. Surprisingly few responses raised substantive methodologic or statistical issues. Many of these are clearly inaccurate or irrelevant. The possibility of publication bias-selective publication of positive results-was raised by some commentators and remains an important criticism of the apparently positive nature of the clinical trial evidence. The most persuasive argument against accepting differences between homeopathy and placebo on the basis of current evidence is that homeopathy is scientifically implausible and so requires more evidence than normal. CONCLUSIONS: Investigators undertaking clinical research in homeopathy need to be responsive both to the dangers of publication bias and to the requirement for stronger than usual levels of evidence.