HRI Malta 2017-Cutting Edge Research in Homeopathy: HRI's Third International Research Conference in Malta.

The third international conference on "Cutting Edge Research in Homeopathy" organised by the Homeopathy Research Institute (HRI) was held on the inspiring and historic island of Malta from 9th to 11th of June, 2017. One hundred and two abstracts underwent peer review by the HRI Scientific Advisory Committee and external experts to produce the programme of 36 oral presentations and 37 posters, presented by researchers from 19 countries. The 2.5-day programme covered a diverse range of topics, including quantitative and qualitative clinical research, basic research, veterinary research, and provings. These intensive plenary and parallel sessions were interspersed with multiple opportunities for delegates to discuss and exchange ideas, in particular through interactive panel discussions and a pre-conference workshop. The continuing commitment of the homeopathy research community to generate high-quality studies in this rapidly evolving field was clear. In this conference report, we present highlights from this memorable event.

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.

Homeopathic Oscillococcinum® for preventing and treating influenza and influenza-like illness.

BACKGROUND: Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum® is a patented homeopathic medicine that is made from a 1% solution of wild duck heart and liver extract, which is then serially diluted 200 times with water and alcohol. OBJECTIVES: To determine whether homeopathic Oscillococcinum® is more effective than placebo in the prevention and/or treatment of influenza and influenza-like illness in adults or children. SEARCH METHODS: We searched CENTRAL (2014, Issue 8), MEDLINE (1966 to August week 4, 2014), MEDLINE In-Process & Other Non-Indexed Citations (4 September 2014), AMED (2006 to September 2014), Web of Science (1985 to September 2014), LILACS (1985 to September 2014) and EMBASE (1980 to September 2014). We contacted the manufacturers of Oscillococcinum® for information on further trials. SELECTION CRITERIA: Randomised, placebo-controlled trials of Oscillococcinum® in the prevention and/or treatment of influenza and influenza-like illness in adults or children. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed risk of bias in the eligible trials. MAIN RESULTS: No new trials were included in this 2014 update. We included six studies: two prophylaxis trials (327 young to middle-aged adults in Russia) and four treatment trials (1196 teenagers and adults in France and Germany). The overall standard of trial reporting was poor and hence many important methodological aspects of the trials had unclear risk of bias. There was no statistically significant difference between the effects of Oscillococcinum® and placebo in the prevention of influenza-like illness: risk ratio (RR) 0.48, 95% confidence interval (CI) 0.17 to 1.34, P value = 0.16. Two treatment trials (judged as 'low quality') reported sufficient information to allow full data extraction: 48 hours after commencing treatment, there was an absolute risk reduction of 7.7% in the frequency of symptom relief with Oscillococcinum® compared with that of placebo (risk difference (RD) 0.077, 95% CI 0.03 to 0.12); the RR was 1.86 (95% CI 1.27 to 2.73; P value = 0.001). A significant but lesser effect was observed at three days (RR 1.27, 95% CI 1.03 to 1.56; P value = 0.03), and no significant difference between the groups was noted at four days (RR 1.11, 95% CI 0.98 to 1.27; P value = 0.10) or at five days (RR 1.06, 95% CI 0.96 to 1.16; P value = 0.25). One of the six studies reported one patient who suffered an adverse effect (headache) from taking Oscillococcinum®. AUTHORS' CONCLUSIONS: There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum® in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum® could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum®.

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

BACKGROUND: Though potentially an important limitation in the literature of randomised controlled trials (RCTs) of homeopathy, the model validity of homeopathic treatment (MVHT) has not previously been systematically investigated. OBJECTIVE: As an integral part of a programme of systematic reviews, to assess MVHT of eligible RCTs of individualised homeopathic treatment. METHODS: From 46 previously identified papers in the category, 31 papers (reporting a total of 32 RCTs) were eligible for systematic review and were thus the subject of the study. For each of six domains of assessment per trial, MVHT was judged independently by three randomly allocated assessors from our group, who reached a final verdict by consensus discussion as necessary. RESULTS: Nineteen trials were judged overall as 'acceptable' MVHT, nine as 'uncertain' MVHT, and four as 'inadequate' MVHT. CONCLUSIONS: These results do not support concern that deficient MVHT has frequently undermined the published findings of RCTs of individualised homeopathy. However, the 13 trials with 'uncertain' or 'inadequate' MVHT will be a focus of attention in supplementary meta-analysis. New RCTs of individualised homeopathy must aim to maximise MVHT and to enable its assessment through clear reporting.

Randomised controlled trials of homeopathy in humans: characterising the research journal literature for systematic review.

INTRODUCTION: A new programme of systematic reviews of randomised controlled trials (RCTs) in homeopathy will distinguish important attributes of RCT records, including: placebo controlled versus other-than-placebo (OTP) controlled; individualised versus non-individualised homeopathy; peer-reviewed (PR) versus non peer-reviewed (NPR) sources. AIMS: (a) To outline the methods used to search and categorise the RCT literature; (b) to report details of the records retrieved; (c) to compare our retrieved records with those reported in two previous systematic reviews (Linde et al., 1997; Shang et al., 2005). METHODS: Ten major electronic databases were searched for records published up to the end of 2011. A record was accepted for subsequent systematic review if it was a substantive report of a clinical trial of homeopathic treatment or prophylaxis in humans, randomised and controlled, and published in a PR or NPR journal. RESULTS: 489 records were potentially eligible: 226 were rejected as non-journal, minor or repeat publications, or lacking randomisation and/or controls and/or a 'homeopathic' intervention; 263 (164 PR, 99 NPR) were acceptable for systematic review. The 263 accepted records comprised 217 (137 PR, 80 NPR) placebo-controlled RCTs, of which 121 were included by, 66 were published after, and 30 were potentially eligible for, but not listed by, Linde or Shang. The 137 PR records of placebo-controlled RCTs comprise 41 on individualised homeopathy and 96 on non-individualised homeopathy. CONCLUSION: Our findings clarify the RCT literature in homeopathy. The 263 accepted journal papers will be the basis for our forthcoming programme of systematic reviews.

Homeopathic treatment of patients with influenza-like illness during the 2009 A/H1N1 influenza pandemic in India.

INTRODUCTION: We conducted a prospective, multi-centre, data collection survey of homeopathic practice in treatment of influenza-like illness in India during the 2009 pandemic of A/H1N1 influenza ('swine flu', SF). AIMS: To survey the practice of homeopathic practitioners in India in the management of SF, with respect to: (a) patients' symptoms at presentation and at follow-up (FU) consultation; (b) homeopathic medicines prescribed. METHODS: Data collection took place from October 2009 to February 2010, at the peak of the pandemic. All patients satisfying the minimum diagnostic symptoms of SF were eligible for inclusion. Data per appointment (in person or by telephone) were recorded by practitioners in spreadsheet format. All records were anonymised and included: whether patient was immunised against A/H1N1; influenza symptoms at consultation; the homeopathic medicine/s prescribed; whether antiviral medicine prescribed. RESULTS: Twenty-three homeopathic physicians contributed to data collection. At the first appointment, 1126 patients had valid SF symptoms. A total of 89 different combinations of SF symptoms was observed, the most common being temperature >38°C + cough + runny nose (n = 170; 15.1%). A total of 44 different remedies (or combinations of remedies) were used at these first appointments, the most frequently prescribed being Arsenicum album (n = 265; 23.5%). For a total of 99 FU appointments with valid SF symptoms, Arsenicum album was prescribed most frequently overall (n = 28; 28.0%). CONCLUSIONS: In our sample, the 2009 A/H1N1 influenza pandemic in India was characterised by several prominent symptoms and symptom/medicine associations, particularly temperature >38°C + cough + runny nose, associated with Arsenicum album. Future studies should collect additional keynote prescribing symptoms that influence the choice of homeopathic medicine.

Plausibility and evidence: the case of homeopathy.

Homeopathy is controversial and hotly debated. The conclusions of systematic reviews of randomised controlled trials of homeopathy vary from 'comparable to conventional medicine' to 'no evidence of effects beyond placebo'. It is claimed that homeopathy conflicts with scientific laws and that homoeopaths reject the naturalistic outlook, but no evidence has been cited. We are homeopathic physicians and researchers who do not reject the scientific outlook; we believe that examination of the prior beliefs underlying this enduring stand-off can advance the debate. We show that interpretations of the same set of evidence--for homeopathy and for conventional medicine--can diverge. Prior disbelief in homeopathy is rooted in the perceived implausibility of any conceivable mechanism of action. Using the 'crossword analogy', we demonstrate that plausibility bias impedes assessment of the clinical evidence. Sweeping statements about the scientific impossibility of homeopathy are themselves unscientific: scientific statements must be precise and testable. There is growing evidence that homeopathic preparations can exert biological effects; due consideration of such research would reduce the influence of prior beliefs on the assessment of systematic review evidence.

Method for appraising model validity of randomised controlled trials of homeopathic treatment: multi-rater concordance study.

BACKGROUND: A method for assessing the model validity of randomised controlled trials of homeopathy is needed. To date, only conventional standards for assessing intrinsic bias (internal validity) of trials have been invoked, with little recognition of the special characteristics of homeopathy. We aimed to identify relevant judgmental domains to use in assessing the model validity of homeopathic treatment (MVHT). We define MVHT as the extent to which a homeopathic intervention and the main measure of its outcome, as implemented in a randomised controlled trial (RCT), reflect 'state-of-the-art' homeopathic practice. METHODS: Using an iterative process, an international group of experts developed a set of six judgmental domains, with associated descriptive criteria. The domains address: (I) the rationale for the choice of the particular homeopathic intervention; (II) the homeopathic principles reflected in the intervention; (III) the extent of homeopathic practitioner input; (IV) the nature of the main outcome measure; (V) the capability of the main outcome measure to detect change; (VI) the length of follow-up to the endpoint of the study. Six papers reporting RCTs of homeopathy of varying design were randomly selected from the literature. A standard form was used to record each assessor's independent response per domain, using the optional verdicts 'Yes', 'Unclear', 'No'. Concordance among the eight verdicts per domain, across all six papers, was evaluated using the kappa (κ) statistic. RESULTS: The six judgmental domains enabled MVHT to be assessed with 'fair' to 'almost perfect' concordance in each case. For the six RCTs examined, the method allowed MVHT to be classified overall as 'acceptable' in three, 'unclear' in two, and 'inadequate' in one. CONCLUSION: Future systematic reviews of RCTs in homeopathy should adopt the MVHT method as part of a complete appraisal of trial validity.

Homeopathic Oscillococcinum(®) for preventing and treating influenza and influenza-like illness.

BACKGROUND: Influenza is a highly infectious viral disease that is particularly common in the winter months. Oscillococcinum(®) is a patented homeopathic medicine that is made from a 1% solution of wild duck heart and liver extract, which is then serially diluted 200 times with water and alcohol. OBJECTIVES: To determine whether homeopathic Oscillococcinum(®) is more effective than placebo in the prevention and/or treatment of influenza and influenza-like illness in adults or children. SEARCH METHODS: We searched CENTRAL (2012, Issue 7), MEDLINE (1966 to July week 4, 2012), MEDLINE In-Process & Other Non-Indexed Citations (6 August 2012), AMED (2006 to August 2012), Web of Science (1985 to August 2012), LILACS (1985 to August 2012) and EMBASE (1980 to August 2012). We contacted the manufacturers of Oscillococcinum(®) for information of more trials. SELECTION CRITERIA: Randomised, placebo-controlled trials of Oscillococcinum(®) in the prevention and/or treatment of influenza and influenza-like illness in adults or children. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data and assessed risk of bias in the eligible trials. MAIN RESULTS: We included six studies: two prophylaxis trials (327 young to middle-aged adults in Russia) and four treatment trials (1196 teenagers and adults in France and Germany). The overall standard of trial reporting was poor and hence many important methodological aspects of the trials had unclear risk of bias. There was no statistically significant difference between the effects of Oscillococcinum(®) and placebo in the prevention of influenza-like illness: risk ratio (RR) 0.48, 95% confidence interval (CI) 0.17 to 1.34, P = 0.16. Two treatment trials (judged as 'low quality') reported sufficient information to allow full data extraction: 48 hours after commencing treatment, there was an absolute risk reduction of 7.7% in the frequency of symptom relief with Oscillococcinum(®) compared with that of placebo (risk difference (RD) 0.077; 95% CI 0.03 to 0.12); the RR was 1.86 (95% CI 1.27 to 2.73; P = 0.001). A significant but lesser effect was observed at three days (RR 1.27, 95% CI 1.03 to 1.56; P = 0.03), and no significant difference between the groups was noted at four days (RR 1.11, 95% CI 0.98 to 1.27; P = 0.10) or at five days (RR 1.06; 95% CI 0.96 to 1.16; P = 0.25). One of the six studies reported one patient who suffered an adverse effect (headache) from taking Oscillococcinum(®). AUTHORS' CONCLUSIONS: There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum(®) in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum(®) could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum(®).