Updated Edition!
It seems that no ancient treatment is daft enough for some researchers of so-called alternative medicine (SCAM) to not pick it up. Even bloodletting is back, it seems!
The aim of this study was to investigate the effects of therapeutic phlebotomy on ambulatory blood pressure in patients with grade 1 hypertension. In this randomized-controlled intervention study, patients with unmedicated hypertension grade 1 were randomized into an intervention group (phlebotomy group; 500 mL bloodletting at baseline and after 6 weeks) and a control group (waiting list) and followed up for 8 weeks. The primary endpoint was the 24-h ambulatory mean arterial pressure between the intervention and control groups after 8 weeks. Secondary outcome parameters included ambulatory/resting systolic/diastolic blood pressure, heart rate, and selected laboratory parameters (e.g., hemoglobin, hematocrit, erythrocytes, and ferritin). Resting systolic/diastolic blood pressure/heart rate and blood count were also assessed at 6 weeks before the second phlebotomy to ensure safety. A per-protocol analysis was performed.
Fifty-three hypertension participants (56.7 ± 10.5 years) were included in the analysis (n = 25 intervention group, n = 28 control group). The ambulatory measured mean arterial pressure decreased by -1.12 ± 5.16 mmHg in the intervention group and increased by 0.43 ± 3.82 mmHg in the control group (between-group difference: -1.55 ± 4.46, p = 0.22). Hemoglobin, hematocrit, erythrocytes, and ferritin showed more pronounced reductions in the intervention group in comparison with the control group, with significant between-group differences. Subgroup analysis showed trends regarding the effects on different groups classified by serum ferritin concentration, body mass index, age, and sex. Two adverse events (AEs) (anemia and dizziness) occurred in association with the phlebotomy, but no serious AEs.
The authors concluded that therapeutic phlebotomy resulted in only minimal reductions of 24-h ambulatory blood pressure measurement values in patients with unmedicated grade 1 hypertension. Further high-quality clinical studies are warranted, as this finding contradicts the results of other studies.
This paper requires a few short comments:
- The effect on blood pressure was not ‘minimal’, as the authors pretend, it was non-existent (i.e. not significant and due to chance only).
- This lack of effect had to be expected considering human physiology.
- The fact that hemoglobin, hematocrit, erythrocytes, and ferritin all change after bloodletting is equally expected.
- Mild adverse effects are also no surprise.
- What is a surprise, however, that such a trial was ever conducted and passed by an ethics committee. Any medic who has not slept through his/her cardiovascular physiology lectures could have predicted the results quite accurately. And running a trial where the result is well-known before the study has started can hardly be called ethical.
In India, the homeopathic remedy, Arsenicum Album 30C (prepared from arsenic trioxide) is widely prescribed and publicly supplied to adults and children for preventing COVID infections. Inorganic arsenic, known as the “king of poisons” is a highly toxic substance with the potential to cause acute as well as chronic injury to multiple organ systems, mainly skin, lung, liver, and kidneys.
Indian researchers present three cases of acute liver injury, leading to the death of one patient with underlying non-alcoholic steatohepatitis (NASH) cirrhosis, after consumption of the homeopathic remedy AA30 for COVID-19 prevention.
Case one
A 70-year-old man with compensated non-alcoholic steatohepatitis (NASH)-related cirrhosis and diabetes mellitus consumed the homeopathic IB AA30 as prescribed for 12 weeks prior to the onset of symptoms. He presented with jaundice and abdominal distension within four weeks after the onset of loss of appetite and well-being. The patient was not on any other hepatotoxic agents, over-the-counter medications, or herbal and dietary supplements. Investigations revealed the presence of conjugated hyperbilirubinemia, ascites, and abnormal coagulation, suggestive of acute-on-chronic liver failure (ACLF). Further investigations to identify known causes of acute deterioration of underlying cirrhosis were performed, including a transjugular liver biopsy. All competing causes for acute liver injury were meticulously ruled out. These included infections-tests for immunoglobulin M (IgM) for viral hepatitis A and E; hepatitis B surface antigen and IgM antibody to hepatitis B core antigen; nucleic acid tests via polymerase chain reaction for hepatitis C; IgM for herpes zoster and herpes simplex, cytomegalovirus, parvovirus, Epstein-Barr virus. Complete auto-antibody testing for autoimmune hepatitis (AIH) was negative. The Roussel Uclaf Causality Assessment (RUCAM) demonstrated “probable” (score 7) drug-induced liver injury (DILI) and simplified AIH score was less than 5, revealing the cause of acute liver injury leading to ACLF as the homeopathic remedy, AA30. The liver biopsy revealed multiacinar hepatocyte necrosis, lymphocytic, neutrophilic, and eosinophilic inflammation in the absence of interface hepatitis, which were predominantly portal-based in the background of cirrhosis, suggestive of DILI. Analysis of drugs consumed could not be performed in view of inadequate sample availability. The patient and family consented to arsenic analysis in nail and hair samples which revealed extremely high levels of the heavy metal, supportive of arsenic toxicity and associated liver injury in the patient. Evaluation of hair and hair samples of two family members (below detection limits, method detection limit being 0.1 mg/kg), staying in the same household did not reveal levels signifying cluster arsenic poisoning from water or soil sources. The patient succumbed to complications related to ACLF, nine months after the initial diagnosis.
Case two
A 68-year-old male with systemic hypertension controlled on telmisartan who ingested AA30 as prescribed for four weeks prior to the onset of symptoms. There was no associated jaundice or cholestatic symptoms, but liver tests revealed acute hepatitis with an elevation of liver enzymes. The patient was not on any other hepatotoxic agents, over-the-counter medications, or herbal and dietary supplements. Further investigations did not reveal the presence of underlying chronic liver disease or portal hypertension. All competing causes for acute liver injury were meticulously ruled out similar to the extensive workup that was done in case one. The RUCAM demonstrated “probable” (score 8) DILI and simplified AIH score was less than 5, revealing the cause of acute non-icteric hepatitis as the homeopathic remedy, AA30. The liver biopsy revealed perivenular hepatocyte necrosis, with predominantly portal-based mixed cellular inflammation consisting of plasma cells, eosinophils, lymphocytes, and scattered neutrophils. Additionally, ballooning of hepatocytes was marked with scattered rosettes and moderate interphase hepatitis in the presence of mild portal and sinusoidal fibrosis suggestive of DILI. Acute hepatitis resolved after drug withdrawal and finite course of steroids within three months, without any recurrence on follow-up.
Case three
A 48-year-old overweight woman consumed homeopathic AA30 pills as COVID-19 preventive for one week prior to the onset of her symptoms of cholestatic jaundice. Prior to the development of jaundice, she had nonspecific gastrointestinal symptoms such as nausea and progressive loss of appetite. Liver tests revealed conjugated hyperbilirubinemia with highly raised liver enzymes. The patient was not on any other hepatotoxic prescription drugs, over-the-counter medications, or herbal and dietary supplements. Further investigations did not reveal the presence of underlying chronic liver disease or portal hypertension. All competing causes for acute liver injury were meticulously ruled out similar to the extensive workup that was done in case one. The RUCAM demonstrated “probable” (score 7) DILI and simplified AIH score was less than 5, revealing the cause of acute cholestatic hepatitis as the homeopathic remedy, AA30. The liver biopsy revealed spotty, focal hepatocyte necrosis, with predominantly portal-based neutrophilic and eosinophil-rich inflammation, moderate steatosis, and mild interface hepatitis with underlying mild perisinusoidal fibrosis, suggestive of DILI. The acute cholestatic hepatitis resolved after drug withdrawal and a finite course of steroids within six months, without any recurrence on follow-up.
The chemical analysis and toxicology (inductively coupled optical emission spectroscopy and triple-quadrupole gas chromatography with tandem mass spectroscopy method) on two sets of AA30 samples retrieved from case three revealed D-mannose, melezitose, and arsenic respectively, demonstrating batch-to-batch variation due to poor manufacturing practices.
The authors draw the following conclusions: Health regulatory authorities, physicians, general and patient population must be aware of the potential harms associated with the large-scale promotion of untested, alternative medical systems during a medical emergency so as to prevent an “epidemic” of avoidable DILI within the ongoing pandemic. Even though ultra-diluted homeopathic remedies, found ineffective as shown in large-scale meta-analysis, are considered safe for use due to the absence of any active compound beyond 12C dilution. Nonetheless, poor manufacturing practices, use of concentrated tincture formulations, and adulteration and contamination of homeopathic remedies can still pose considerable toxicity in predisposed persons. From a scientific and evidence-based standpoint, it is imperative that the general population and at-risk persons understand that vaccination, and not untested, misleading IBs, remains the best available armamentarium against COVID-19 which helps in fighting back the pandemic.
If you have been following my blog for a while, you probably know the answer to this question. A recent article published in JAMA re-emphasizes it in an exemplary fashion:
According to National Health and Nutrition Examination Survey data, 52% of surveyed US adults reported using at least 1 dietary supplement in the prior 30 days and 31% reported using a multivitamin-mineral supplement. The most commonly cited reason for using supplements is for overall health and wellness and to fill nutrient gaps in the diet. Cardiovascular disease and cancer are the 2 leading causes of death and combined account for approximately half of all deaths in the US annually. Inflammation and oxidative stress have been shown to have a role in both cardiovascular disease and cancer, and dietary supplements may have anti-inflammatory and antioxidative effects.
Objective To update its 2014 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a review of the evidence on the efficacy of supplementation with single nutrients, functionally related nutrient pairs, or multivitamins for reducing the risk of cardiovascular disease, cancer, and mortality in the general adult population, as well as the harms of supplementation.
Population Community-dwelling, nonpregnant adults.
Evidence Assessment The USPSTF concludes with moderate certainty that the harms of beta carotene supplementation outweigh the benefits for the prevention of cardiovascular disease or cancer. The USPSTF also concludes with moderate certainty that there is no net benefit of supplementation with vitamin E for the prevention of cardiovascular disease or cancer. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with multivitamins for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. The USPSTF concludes that the evidence is insufficient to determine the balance of benefits and harms of supplementation with single or paired nutrients (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined.
Recommendation The USPSTF recommends against the use of beta carotene or vitamin E supplements for the prevention of cardiovascular disease or cancer. (D recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of multivitamin supplements for the prevention of cardiovascular disease or cancer. (I statement) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the use of single- or paired-nutrient supplements (other than beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer. (I statement)
The report also elaborates on potential harms:
For many of the vitamins and nutrients reviewed, there was little evidence of serious harms. However, an important harm of increased lung cancer incidence was reported with the use of beta carotene by persons who smoke tobacco or have occupational exposure to asbestos.
Excessive doses of vitamin supplements can cause several known adverse effects; for example, moderate doses of vitamin A supplements may reduce bone mineral density, and high doses may be hepatotoxic or teratogenic. Vitamin D has potential harms, such as a risk of hypercalcemia and kidney stones, when given at high doses. The potential for harm from other supplements at high doses should be carefully considered.
There is nothing new here, of course. I (and others) have been trying to get these points across for many years. But it is nevertheless most gratifying to see the message repeated by a top journal such as JAMA. I hope JAMA is more successful than I was in changing the behavior of the often all too gullible public!
Nausea and vomiting are common symptoms of patients with advanced cancer. While there is some evidence for acupuncture point stimulation in the treatment of these symptoms for patients having anticancer treatment, there is little for when they are not related to such treatment.
This study aimed to determine whether acupressure at the pericardium 6 sites can help treat nausea and vomiting suffered by palliative care patients with advanced cancer. The researchers conducted a double-blind randomized controlled trial-active versus placebo acupressure wristbands. In-patients with advanced cancer in two specialist palliative care units who fitted either or both of the following criteria were approached: nausea that was at least of moderate severity; vomiting daily on average for the prior 3 days.
A total of 57 patients were randomized to have either active or placebo acupressure wristbands. There was no difference in any of the outcome measures between the two groups:
- change from the baseline number of vomits;
- Visual Analogue Scale for ‘did acupressure wristbands help you to feel better?’;
- the total number of doses of antiemetic medication;
- the need for escalation of antiemetics.
The authors concluded that, in contrast to a previously published feasibility study, active acupressure wristbands were no better than placebo for specialist palliative care in patients with advanced cancer and nausea and vomiting.
When the research into acupuncture for nausea and vomiting began some 20 years ago, the evidence turned out to be encouraging. Later, as the studies became more and more rigorous, many trials failed to confirm the initial findings. Today, the totality of the evidence is far less convincing than it seemed years ago.
This is a phenomenon that can be observed not just in acupuncture research but in many types of treatment:
- Initially, over-enthusiastic researchers become victims of their own optimism.
- These investigators are less into testing hypotheses than into confirming their own wishful thinking.
- Thus, several positive trials emerge.
- These, however, turn out to be methodologically flawed.
- Eventually, the subject might be picked up by real scientists who truly test hypotheses.
- More and more negative studies thus emerge.
- Depending on how many flawed studies were initially published and how critical the authors of systematic reviews are, it can take years until the totality of the evidence depicts the true picture which discloses the initial findings as false-positive.
The message is, I think, clear: poor quality studies have the potential to mislead us for many years. Eventually, however, the self-cleansing ability of science should generate the truth about the value of any treatment. In other words:
poor-quality science is not just useless, it causes long-term harm
and
critical thinking prevents harm
As promised, I would like to correct the errors in my previous assessment of this paper. To remind everyone:
This systematic review evaluated individualized homeopathy as a treatment for children with attention deficit and hyperactivity disorder (ADHD) when compared to placebo or usual care alone.
Thirty-seven online sources were searched up to March 2021. Studies investigating the effects of individualized homeopathy against any control in ADHD were eligible. Data were extracted to a predefined excel sheet independently by two reviewers.
Six studies were analyzed:
- 5 were RCTs
- 2 were controlled against standard treatments;
- 4 were placebo-controlled and double-blinded.
The meta-analysis revealed a significant effect size across studies of Hedges’ g = 0.542 (95% CI 0.311-0.772; z = 4,61; p < 0.001) against any control and of g = 0.605 (95% CI 0.05-1.16; z = 2.16, p = 0.03) against placebo. The effect estimations are based on studies with an average sample size of 52 participants.
The authors concluded that individualized homeopathy showed a clinically relevant and statistically robust effect in the treatment of ADHD.
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Now that I was able to access the full papers, I would like to offer a thorough analysis.
To get included in the review, primary studies had to be:
- Published after 1980,
- Investigating an individualized homeopathic intervention in childhood ADHD,
- Comparing the intervention to a control condition (placebo, standard care or treatment as usual, both of which are referred to as “active control”) in a randomized or non-randomized parallel-group study
design with one or more arms.
Six studies were included:
- Fibert, P., Peasgood, T. & Relton, C. Rethinking ADHD intervention trials: feasibility testing of two treatments and a methodology. Eur. J. Pediatr. 178, 983–993 (2019). – DOI
- Fibert, P., Relton, C., Heirs, M. & Bowden, D. A comparative consecutive case series of 20 children with a diagnosis of ADHD receiving homeopathic treatment, compared with 10 children receiving usual care. Homeopathy 105, 194–201 (2016). – DOI
- Jacobs, J., Williams, A. L., Girard, C., Njike, V. Y. & Katz, D. Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial. J. Altern. Complement. Med. 11, 799–806 (2005). – DOI
- Jones, M. The efficacy of homoeopathic simillimum in the treatment of attention-deficit/hyperactivity disorder (AD/HD) in schoolgoing children aged 6-11 years. https://openscholar.dut.ac.za/bitstream/10321/534/1/Jones_2009.pdf (2009).
- Frei, H. et al. Homeopathic treatment of children with attention deficit hyperactivity disorder: a randomised, double blind, placebo controlled crossover trial. Eur. J. Pediatr. 164, 758–767 (2005). – DOI
- Oberai, P. et al. Homoeopathic management of attention deficit hyperactivity disorder: a randomised placebo-controlled pilot trial. Indian J. Res. Homoeopathy 7, 158–167 (2013).
Exclusion criteria were:
- Homeopathic intervention not individualized,
- Serious methodological flaws, such as incidental unblinding, failure to report important data, or insufficient data for meta-analysis.
One study was excluded:
- Lamont, J. Homoeopathic treatment of attention deficit hyperactivity disorder. Br. Homeopathic J. 86, 196–200 (1997). – DOI
I will first make several points about Walach’s systematic review itself and then have a look at the primary studies that it included. Finally, I will try to draw some conclusions.
The review authors state in their introduction that “beneficial effects of this intervention [homeopathy] have been shown for various kinds of medical conditions, including child diarrhea, supportive care in cancer, fibromyalgia, or ADHD.” In other words, already in the introduction, they disclose their strong pro-homeopathy bias; it would, of course, not be difficult to find investigations that contradict their optimism.
Despite the stated inclusion/exclusion criteria, the authors did include the Frei-study that did not follow a parallel-group design (see also below).
The authors included two active-controlled studies both of which did not report the type of treatment received by the control group. In other words, these trials failed to report important data which was a stated exclusion criterium (see below).
In their discussion section, the authors state that “all included studies employed individualized homeopathy and were of comparable, solid quality, hence a lack of methodological rigor is unlikely the reason for the difference between homeopathy and controls…” This, I think, is grossly misleading; even according to the authors’ own assessments, one study was deemed to have a high risk of bias and in two studies the risk of bias was “unclear”.
The overall positive effect of homeopathy demonstrated by the review was determined almost exclusively by the study of Oberai et al (p-value = 0.000). In fact, the studies by Jones and by Jacobs were negative, and the one by Frei was borderline positive with a p-value of 0.46. The authors address this crucial issue repeatedly and claim that excluding Oberai et al would still generate an overall positive meta-analytic result. Yet, they do not mention that the overall result would no longer be clinically relevant.
Looking at the included primary studies, I should make the following points:
- The two Filbert studies, as mentioned, failed to report important data and should, according to the stated exclusion criteria, not have been included.
- The study by Jacobs was a pilot study and generated negative findings.
- The study by Jones is a non-peer-reviewed thesis. In my view, it should never have been included.
- The study by Frei was a cross-over trial. According to the exclusion/inclusion criteria of the authors, it should not have been included.
- The study by Oberai et al is the trial that has by far the largest effect size and thus is the driver of the overall result of the review. It is therefore important to have a closer look at it.
Here is the abstract:
Objective: To evaluate the usefulness of individualised homoeopathic medicines in treatment of Attention Deficit Hyperactivity Disorder (ADHD).
Design: Randomised placebo-controlled single-blind pilot trial.
Setting: Central Research Institute (Homoeopathy), Kottayam, Kerala, India from June 2009 to November 2011.
Participants: Children aged 6-15 years meeting the Diagnostic Statistical Manual of mental disorders (DSM-IV) criteria for ADHD.
Interventions: A total of 61 patients (Homoeopathy = 30, placebo = 31) were randomised to receive either individualised homoeopathic medicine in fifty millesimal (LM) potency or placebo for a period of one year.
Outcome measures: Conner’s Parent Rating Scale-Revised: Short (CPRS-R (S)), Clinical Global Impression-Severity Scale (CGI-SS), Clinical Global Impression- Improvement Scale (CGI-IS) and Academic performance.
Results: A total of 54 patients (homoeopathy = 27, placebo = 27) were analysed under modified intention to treat (ITT). All patients in homoeopathy group showed better outcome in baseline adjusted General Linear Model (GLM) repeated measures ANCOVA for oppositional, cognition problems, hyperactivity and ADHD Index (domains of CPRS-R (S)) and CGI-IS at T3, T6, T9 and T12 (P = 0.0001). The mean baseline-adjusted treatment difference between groups at month 12 from baseline for all individual outcome measures favoured homoeopathy group; Oppositional (−16.4, 95% CI – 20.5 to − 12.2, P = 0.0001), Cognition problems (−15.5, 95% CI − 19.2 to − 11.8, P = 0.0001), Hyperactivity (−20.6, 95% CI − 25.6 to − 15.4, P = 0.0001), ADHD I (−15.6, 95% CI − 19.5 to − 11.6, P = 0.0001), Academic performance 14.4%, 95% CI 8.3 to 20.5, P = 0.0001), CGISS (−1.6, 95% CI − 1.9 to − 1.2, P = 0.0001), CGIIS (−1.6, 95% CI − 2.3 to -0.9, P = 0.0001).
Conclusion: This pilot study provides evidence to support the therapeutic effects of individualised homoeopathic medicines in ADHD children. However, the results need to be validated in multi-center randomised double-blind placebo-controlled clinical trial.
Here are a few points of concern related to the Oberai et al:
- The trial was a mere pilot study.
- Despite the fact that it is now 9 years old, the authors never published a definitive trial.
- The study was published in an obscure journal that is not Medline-listed.
- The study is very poorly reported.
- It is unclear how the diagnosis of ADHD for including the patients was verified.
- The control patients were treated for one year with a placebo and no other therapies. In my view, this is not ethical.
- The method of randomization is unclear.
- The authors state that acute symptoms were treated throughout the study period with homeopathy, even in the control group. This seems odd and defies the principle of a placebo-controlled trial.
- The authors state that only the patients were blind, not the investigators. This opens the door wide for all sorts of biases. It is, for example, likely that it also de-blinded the patients (the verum could be adjusted and changed, while the placebo remained constant).
All in all, this paper is of poor quality, Its findings are far from trustworthy and were not meant to be definitive. According to the following exclusion criteria, it should have been excluded:
- It had several serious methodological flaws.
- It did not blind the investigators.
- It is likely that patients were de-blinded.
- It failed to report important data.
So, why did Walach and his co-authors include it?
Could it be because, without the Oberai-study, the overall findings of the review would at best have turned out to be borderline significant and not clinically relevant?
In a previous post, I reported about the ‘biggest ever’, ‘history-making’ conference on integrative medicine. It turns out that it was opened by none other than Prince Charles. Here is what the EXPRESS reported about his opening speech:
Opening the conference, Charles said:
“I know a few people have seen this integrated approach as being in some way opposed to modern medicine. It isn’t. But we need to combine this with a personal approach that also takes account of our beliefs, hopes, culture and history. It builds upon the abilities of our minds and bodies to heal, and to live healthy lives by improving diet and lifestyle.”
Dr. Michael Dixon, Chair of the College of Medicine, said:
“Medicine, as we know it, is no longer affordable or sustainable. Nor is it able to curb the increase in obesity, mental health problems and most long-term diseases. A new medical mindset is needed, which goes to the heart of true healthcare. The advantages and possibilities of social prescription are limitless. An adjustment to the system now will provide a long-term, sustainable solution for the NHS to meet the ever-increasing demand for funding and healthcare professionals.”
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Charles very kindly acknowledges that not everyone is convinced about his concept of integrated/integrative medicine. Good point your royal highness! But I fear Charles did not quite understand our objections. In a nutshell: it is not possible to cure the many ills of conventional medicine by adding unproven and disproven therapies to it. In fact, it distracts from our duty to constantly improve conventional medicine. And pretending it is all about diet and lifestyle is simply not true (see below). Moreover, it is disingenuous to pretend that diet and lifestyle do not belong to conventional healthcare.
Dr. Dixon’s concern about the affordability of medicine is, of course, justified. But the notion that “the advantages and possibilities of social prescription are limitless” is a case of severe proctophasia, and so is Dixon’s platitude about ‘adjusting the system’. His promotion of treatments like Acupuncture, Alexander Technique, Aromatherapy, Herbal Medicine, Homeopathy, Hypnotherapy, Massage, Naturopathy, Reflexology, Reiki, Tai Chi, Yoga Therapy will not adjust anything, it will only make healthcare less efficient.
I do not doubt for a minute that doctors are prescribing too many drugs and that we could save huge amounts by reminding patients that they are responsible for their own health while teaching them how to improve it without pills. This is what we learn in medical school! All we need to do is remind everyone concerned. In fact, Charles and his advisor, Michael, could be most helpful in achieving this – but not by promoting a weird branch of healthcare (integrative/integrated medicine or whatever other names they choose to give it) that can only distract from the important task at hand.
Alan Gaby, the assistant editor of the journal Integr Med has written an interesting commentary about widespread fraud in natural health products research. Here is an excerpt of his article:
During the past 49 years, I have reviewed and analyzed more than 50 000 papers from the biomedical literature, most of which were related to the field of nutritional medicine. Doing this work has given me some understanding of how to assess the reliability of a study. Over the past 10 to 15 years, an uncomfortably large and growing number of published papers related to my area of expertise have left me wondering whether the research was fabricated; that is, whether people were writing papers about research that had not actually been conducted. If the studies were not actually conducted, the publishing of this research is an affront to all who value integrity in science, and it has the potential to harm practitioners and patients who rely on its findings.
The studies that have raised concerns have come primarily from Iran and to a lesser extent from Egypt, China, India, Japan, and a few other countries. Characteristics of these concerning studies typically include one or more of the following:
- The study comes from an investigator or research group that has published an enormous number of randomized clinical trials in a relatively short period of time.
- The number of participants in the trial is unusually large, when considering the resources that appear to be available to the researchers.
- The recruitment period for the trial is unusually short.
- The paper is submitted to a journal unusually rapidly after the study is completed, or in some cases before it would have been possible to have completed the trial.
- A randomized double-blind trial is conducted before there is any preliminary evidence of efficacy in humans (such as case reports or uncontrolled trials). Because double-blind trials are expensive to conduct, such trials are generally reserved for treatments for which there is some evidence of efficacy.
- The magnitude of the reported improvement is much larger than is typically seen in trials using just one or two nutrients.
- No funding source is listed or the study is listed as self-funded. This is of particular concern when the sample size or study design suggests that the study was expensive.
- The design of the study raises ethical issues, such as participants not being permitted to use treatments that are known to be effective.
- One or more baseline characteristics of the study group appear to be implausible.
- The research was conducted by a student as part of a graduate school thesis, and the magnitude of the project seems to have been beyond the capabilities and resources of a student.
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What Gaby alludes to is a problem indeed. I have previously posted about the Chinese aspect of this story. What Gaby does not mention is the fact that even many studies of so-called alternative medicine (SCAM) which seem to be not overtly fraudulent are nevertheless highly suspect. I am referring to trials that are fatally flawed and/or studies that draw unwarranted conclusions. These are, of course, the types of studies that are the main target of this blog. Because they are so numerous, I feel that the damage they do is much bigger than that of the more overtly fraudulent papers.
This systematic review evaluated individualized homeopathy as a treatment for children with attention deficit and hyperactivity disorder (ADHD) when compared to placebo or usual care alone.
Thirty-seven online sources were searched up to March 2021. Studies investigating the effects of individualized homeopathy against any control in ADHD were eligible. Data were extracted to a predefined excel sheet independently by two reviewers.
Six studies were analyzed:
- 5 were RCTs
- 2 were controlled against standard treatments;
- 4 were placebo-controlled and double-blinded.
The meta-analysis revealed a significant effect size across studies of Hedges’ g = 0.542 (95% CI 0.311-0.772; z = 4,61; p < 0.001) against any control and of g = 0.605 (95% CI 0.05-1.16; z = 2.16, p = 0.03) against placebo. The effect estimations are based on studies with an average sample size of 52 participants.
The authors concluded that individualized homeopathy showed a clinically relevant and statistically robust effect in the treatment of ADHD.
This is a counter-intuitive result (to put it mildly), and it is, therefore, wise to have a look at the 6 included studies:
1.Frei, H. et al. Homeopathic treatment of children with attention deficit hyperactivity disorder: a randomised, double blind, placebo controlled crossover trial. Eur. J. Pediatr. 164, 758–767 (2005).
This was a trial with just 62 patients who had previously responded to homeopathy. The study was conducted by known proponents of homeopathy and had a highly unusual design. The results suggested that homeopathy was better than placebo.
2. Oberai, P. et al. Homoeopathic management of attention deficit hyperactivity disorder: a randomised placebo-controlled pilot trial. Indian J. Res. Homoeopathy 7, 158–167 (2013).
This one was published in an obscure journal that I could not access.
3. Jacobs, J., Williams, A. L., Girard, C., Njike, V. Y. & Katz, D. Homeopathy for attention-deficit/hyperactivity disorder: a pilot randomized-controlled trial. J. Altern. Complement. Med. 11, 799–806 (2005)
This study showed that there were no statistically significant differences between homeopathic remedy and placebo groups on the primary or secondary outcome variables.
4. Jones, M. The efficacy of homoeopathic simillimum in the treatment of attention-deficit/hyperactivity disorder (AD/HD) in schoolgoing children aged 6-11 years (2009).
This was a small unpublished (and not peer-reviewed) thesis. Its results showed no statistically significant effect of treatment.
5. Lamont, J. Homoeopathic treatment of attention deficit hyperactivity disorder. Br. Homeopathic J. 86, 196–200 (1997)
This was a small (n=46) trial with an unusual design. Its results suggested that homeopathy was better than placebo.
6. von Ammon, K. et al. Homeopathic RCT embedded in a long-term observational study of children with ADHD—a successful model of whole systems CAM research. Eur. J. Integr. Med. 1, 27 (2008).
Even though the journal is Medline-listed, I was unable to find this paper. I did, however, find a paper by the same authors with the same title. It turned out to be a duplication of the paper by Frei et al listed above.
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All in all, this brief analysis of the available abstracts (most full papers are behind paywalls) leaves many questions as to the trustworthiness of this systematic review unanswered. The fact that H. Walach (and other apologists of homeopathy) is its senior author does not inspire me with overwhelming confidence. In any case, I very much doubt that the authors’ conclusion is correct. I therefore would encourage someone with access to all full papers to initiate a more thorough analysis; the abstracts obviously leave many questions unanswered. For instance, it would be crucial to know how many of the trials followed an A+B versus B design (I suspect most studies did, and this would completely invalidate the review’s conclusion). I am more than happy to co-operate with such an evaluation.
Today, a 3-day conference is starting on ‘INTEGRATIVE MEDICINE’ (IM) in London. Dr. Michael Dixon, claims that it is going to be the biggest such conference ever and said that it ‘will make history’. Dixon is an advisor to Prince Charles, chair of the College of Medicine and Integrated Health (CoMIH, of which Charles is a patron), and joint-chair of the congress. The other co-chair is Elizabeth Thompson. Both have been the subject of several previous posts on this blog.
Dixon advertised the conference by commenting: “I am seeing amongst by younger colleagues, the newly trained GPs, that they have a new attitude towards healthcare. They are not interested in whether something is viewed as conventional, complementary, functional or lifestyle, they are just looking at what works for their patients. Through this conference, we aim to capture that sense of hope, open-mindedness, and patient-centred care”. I believe that this ‘history-making’ event is a good occasion to yet again review the concept of IM.
The term IM sounds appealing, yet it is also confusing and misleading. The confusion starts with the fact that our American friends call it integrative medicine, while we in the UK normally call it integrated medicine, and it ends with different people understanding different things by IM. In conventional healthcare, for instance, people use the term to mean the integration of social and medical care. In the bizarre world of alternative medicine, IM is currently used to signify the parallel use of alternative and conventional therapies on an equal footing.
Today, there are many different definitions of the latter version of IM. Prince Charles, one of the world’s most ardent supporter of IM, used to simply call it ‘the best of both worlds’. A recent, more detailed definition is a ‘healing-oriented medicine that takes account of the whole person, including all aspects of lifestyle. It emphasizes the therapeutic relationship between practitioner and patient, is informed by evidence, and makes use of all appropriate therapies’. This seems to imply that conventional medicine is not healing-orientated, does not account for the whole person, excludes aspects of lifestyle, neglects the therapeutic relationship, is not informed by evidence, and does not employ all appropriate therapies. This, I would argue is a bonanza of strawman fallacies, i.e. the misrepresentation of an opponent’s qualities with a view of defeating him more easily and making one’s own position look superior. Perhaps this is unsurprising – after all, Dixon has been once named ‘a pyromaniac in a field of (integrative) strawmen’.
Perhaps definitions are too theoretical and it is more productive to look at what IM stands for in real life. If you surf the Internet, you can find thousands of clinics that carry the name IM. It will take you just minutes to discover that there is not a single alternative therapy, however ridiculous, that they don’t offer. What is more, there is evidence to show that doctors who are into IM are also often against public health measures such as vaccinations.
The UK ‘Integrated Medicine Alliance’, a grouping within the CoMIH, offers information sheets on all of the following treatments: Acupuncture, Alexander Technique, Aromatherapy, Herbal Medicine, Homeopathy, Hypnotherapy, Massage, ,Naturopathy, Reflexology, Reiki, Tai Chi, Yoga Therapy. The one on homeopathy, for example, tells us that “homeopathy … can be used for almost any condition either alone or in a complementary manner.” Compare this to what the NHS says about it: “homeopathic remedies perform no better than placebos (dummy treatments)”.
This evidently grates with the politically correct definition above: IM is not well-informed about the evidence, and it does use inappropriate treatments. In fact, it is little more than a clumsy attempt to smuggle unproven and disproven alternative therapies into the mainstream of healthcare. It does render medicine not better but will inevitably make it worse, and this is surely not in the best interest of vulnerable patients who, I would argue, have a right to be treated with the most effective therapies currently available.
The conference can perhaps be characterized best by having a look at its sponsors. ‘Gold sponsor’ is WELEDA, and amongst the many further funders of the meeting are several other manufacturers of mistletoe medications for cancer. I just hope that the speakers at this meeting – Dixon has managed to persuade several reputable UK contributors – do not feel too embarrassed when they pass their exhibitions.
I came across an interesting case report recently published in an Austrian magazine. Here is my translation for non-German speakers:
A 42-year-old woman from Vienna has suffered from endometriosis since the age of 13. But it was only 8 years later that she found out what made the first two days of her menstruation so unbearable. She was not allowed to take painkillers to help herself during all that time. Her parents listened to medical “gurus” who distrusted conventional medicine.
“I grew up in a household where almost all illnesses were treated with homeopathy,” she wrote on Twitter. That’s exactly what became the IT expert’s undoing. In a recent interview, she looked back bitterly: “All infections and illnesses were treated with Bach flower remedies or homeopathics. Only in case of accidents or broken bones did my parents drive me to the hospital.” Her father suffered from an auto-immune disease. Because conventional medicine could not help him, he tried alternative approaches. “My parents slowly drifted more and more into this scene. At some point, they stopped listening to ‘normal’ doctors. It went downhill from there.”
As a girl, the Viennese had little chance of standing up to her parents’ “whisperers,” as she calls their esoteric advice. “When I got my period, I was in the worst pain. I fainted every month, even falling off my chair when I did it, once even at school. I vomited until I was so exhausted that I fell asleep.”
She begged her family to finally be allowed to consult a gynecologist. But he didn’t take the teenager seriously at the time and simply wanted to prescribe her the pill without a thorough examination. “I then went to my parents’ homeopathic ‘pill pusher’, who gave me homeopathics against my complaints. I wasn’t allowed to take painkillers because they ‘damage the liver’.” The guru persuaded the young woman that her health problems were her fault. “He said I just didn’t accept myself as a woman and that’s why I was in pain. I thought for a long time that I was just not strong and good enough.”
It wasn’t until she was already in her early 20s that her then-boyfriend took her to a gynecologist who finally took her condition seriously. “The ultrasound showed that I had quite a few cysts in my abdomen.” The diagnosis was also finally certain: she was now officially suffering from endometriosis. She was given the right medicine, and most of the endometriotic growths regressed. But a cyst had wrapped itself tightly around her right ovary, damaging it irrevocably over the years. It had died. “Homeopathy cost me my ovary,” the Viennese woman laments.
The fact that she nevertheless was able to become the mother of two children is thanks to her other ovary, which fortunately remained intact. But the feeling of having been treated wrongly, or not treated at all, for such a long time makes her angry. “I don’t blame my parents today. They have apologized and found their own way out of the gurus’ world of thought and out of the scene,” she emphasizes. “But I blame the people who pretend to be able to cure the majority of all diseases with homeopathy. Yet most of the time they can’t even find the right diagnosis and just give patients some stuff that has no side effects.” She now calls for an end to homeopathy.
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How many times have I said it?
His remedy might be risk-free, but the homeopath certainly isn’t!
