clinical trial
One phenomenon that can be noted more frequently than any other in alternative medicine research is that studies arrive at wrong or misleading conclusions. This is more than a little disappointing, not least because it is the conclusion of a trial that is often picked up by health writers and others who in turn mislead the public. On this blog, we must have seen hundreds of examples of this irritating phenomenon. Here is yet another one. This study, a randomized, parallel, open-label exploratory trial, evaluated and compared the effects of systemic manual acupuncture, periauricular electroacupuncture and distal electroacupuncture for treating patients with tinnitus. It included patients who suffered from idiopathic tinnitus for more than two weeks were recruited. They were divided into three groups:
- systemic manual acupuncture group (MA),
- periauricular electroacupuncture group (PE),
- distal electroacupuncture group (DE).
Nine acupoints (TE 17, TE21, SI19, GB2, GB8, ST36, ST37, TE3 and TE9), two periauricular acupoints (TE17 and TE21), and four distal acupoints (TE3, TE9, ST36, and ST37) were selected. The treatment sessions were performed twice weekly for a total of 8 sessions over 4 weeks. Outcome measures were the tinnitus handicap inventory (THI) score and the loud and uncomfortable visual analogue scales (VAS). Demographic and clinical characteristics of all participants were compared between the groups upon admission using one-way analysis of variance (ANOVA). One-way ANOVA was used to evaluate the THI, VAS loud, and VAS uncomfortable scores. The least significant difference test was used as a post-hoc test. In total, 39 subjects were eligible for analysis. No differences in THI and VAS loudness scores were observed between groups. The VAS uncomfortable scores decreased significantly in MA and DE compared with those in PE. Within the group, all three treatments showed some effect on THI, VAS loudness scores and VAS uncomfortable scores after treatment except DE in THI. The authors concluded that there was no statistically significant difference between systemic manual acupuncture, periauricular electroacupuncture and distal electroacupuncture in tinnitus. However, all three treatments had some effect on tinnitus within the group before and after treatment. Systemic manual acupuncture and distal electroacupuncture have some effect on VAS. Neither of the three treatments tested in this study have been previously proven to work. Therefore, it is quite simply nonsensical to compare them. Comparative studies are indicated only with therapies that have a solid evidence-base. They are called ‘superiority trials’ and require a different statistical approach as well as much larger sample sizes. In other words, this study was an unethical waste of resources from the outset. With this in mind, there is only one conclusion that fits the data: there was no statistically significant difference between the three types of acupuncture. The data are therefore in keeping with the notion that all three are placebos. Alternatively one might conclude more clearly for those who are otherwise resistant to learning a lesson: POORLY DESIGNED CLINICAL TRIALS ARE UNETHICAL AND NEVER LEND THEMSELVES TO MEANINGFUL CONCLUSIONS.
Dana Ullman is an indefatigable promotor of bogus claims and an unwitting contributor of hilarity. Therefore he has become a regular feature of this blog (see for instance here, here and here). His latest laughable assertion is that lead and other poisonings can be successfully treated with homeopathy.
Just to make sure: lead poisoning is no joke. The greatest risk is to brain development in babies, where irreversible damage can occur. Higher levels can damage the kidneys and nervous system in both children and adults. Very high lead levels may cause seizures, unconsciousness and death.
In view of this, Ullman’s claim is surprising, to say the least. In order to persuade the unsuspecting public of his notion, Ullman first cites a review of basic research on homeopathy and toxins published in Human and Experimental Toxicology. “Of forty high-quality studies, 27 showed positive results from homeopathic treatment”, Ullman states.
Now, now, now Dana!
Has your mom not taught you that telling porkies is forbidden?
Or did you perhaps miss this line in the article’s abstract? “The quality of evidence in these studies was low with only 43% achieving one half of the maximum possible quality score and only 31% reported in a fashion that permitted re-evaluation of the data. Very few studies were independently replicated using comparable models.”
Hardly ‘high quality studies’, wouldn’t you agree?
But this review was of pre-clinical studies; what about the much more important clinical evidence?
Here Ullman cites one trial where a potentized homeopathic remedy, Arsenicum Album 30C, was administered to 55 people who were entered into a double-blind, placebo-controlled trial. According to Ullman, the homeopathically treated group “experienced higher excretion of arsenic in their urine for the first eleven days, compared to those given a placebo.”
Na, na, na, Dana, this is getting serious!!!
Another porky – and not even a little one.
The authors of this study clearly stated that, at the end of the 11-day RCT, there was no significant difference between the homeopathy and the placebo group: “The differences in the concentration between the two groups (drug versus placebo) were generally a little higher during the first week, but subsequently the differences were not so palpable, particularly at the 11th day.” And for those who are a bit slow on the uptake, they even included a graph that makes it abundantly clear.
The only other clinical study cited by Ullman in support of his surprising claim is a double-blind randomized trial which was conducted with 131 workers who suffered lead poisoning at the Ajax battery plant in Bauru, São Paulo State, Brazil. Subjects were prescribed homeopathic doses of lead (Plumbum metallicum 15C) or placebo which they took orally for 35 days. The results of this RCT show that homeopathy is not better than placebo.
So, we seem to have all of two RCTs on the subject (I did a quick Medline-search and also found no further RCTs), and both are negative.
Anyone who is not given to compulsive porky-telling would, I guess, conclude from this evidence that people suffering from lead poisoning should urgently see conventional experts and avoid homeopaths at all costs – not so Dana Ullman who boldly concludes his article with these words:
“As an adjunct to conventional medical treatment, professional homeopathic care is recommended for people who have been exposed (or think they have been exposed) to toxic substances… Even if you do not have a professional homeopath in your town, many homeopathic practitioners “see” their patients via Skype or do consultations over the telephone. Unlike acupuncturists, who put needles in you, or chiropractors, who adjust your spine, homeopaths are not “hands-on”: they simply need to conduct a detailed interview… If your symptoms are serious or potentially serious, it is important to see a professional homeopath and/or physician. While a homeopath will commonly prescribe a safe homeopathic dose of the toxic substance to which one was exposed, the homeopath may instead decide that a different substance more closely matches the patient’s unique symptoms…”
It takes a lot these days to make me speechless but there, Dana, you almost succeeded!
A new study published in JAMA investigated the long-term effects of acupuncture compared with sham acupuncture and being placed in a waiting-list control group for migraine prophylaxis. The trial was a 24-week randomized clinical trial (4 weeks of treatment followed by 20 weeks of follow-up). Participants were randomly assigned to 1) true acupuncture, 2) sham acupuncture, or 3) a waiting-list control group. The trial was conducted from October 2012 to September 2014 in outpatient settings at three clinical sites in China. Participants 18 to 65 years old were enrolled with migraine without aura based on the criteria of the International Headache Society, with migraine occurring 2 to 8 times per month.
Participants in the true acupuncture and sham acupuncture groups received treatment 5 days per week for 4 weeks for a total of 20 sessions. Participants in the waiting-list group did not receive acupuncture but were informed that 20 sessions of acupuncture would be provided free of charge at the end of the trial. Participants used diaries to record migraine attacks. The primary outcome was the change in the frequency of migraine attacks from baseline to week 16. Secondary outcome measures included the migraine days, average headache severity, and medication intake every 4 weeks within 24 weeks.
A total of 249 participants 18 to 65 years old were enrolled, and 245 were included in the intention-to-treat analyses. Baseline characteristics were comparable across the 3 groups. The mean (SD) change in frequency of migraine attacks differed significantly among the 3 groups at 16 weeks after randomization; the mean (SD) frequency of attacks decreased in the true acupuncture group by 3.2 (2.1), in the sham acupuncture group by 2.1 (2.5), and the waiting-list group by 1.4 (2.5); a greater reduction was observed in the true acupuncture than in the sham acupuncture group (difference of 1.1 attacks; 95% CI, 0.4-1.9; P = .002) and in the true acupuncture vs waiting-list group (difference of 1.8 attacks; 95% CI, 1.1-2.5; P < .001). Sham acupuncture was not statistically different from the waiting-list group (difference of 0.7 attacks; 95% CI, −0.1 to 1.4; P = .07).
The authors concluded that among patients with migraine without aura, true acupuncture may be associated with long-term reduction in migraine recurrence compared with sham acupuncture or assigned to a waiting list.
Note the cautious phraseology: “… acupuncture may be associated with long-term reduction …”
The authors were, of course, well advised to be so atypically cautious:
- Comparisons to the waiting list group are meaningless for informing us about the specific effects of acupuncture, as they fail to control for placebo-effects.
- Comparisons between real and sham acupuncture must be taken with a sizable pinch of salt, as the study was not therapist-blind and the acupuncturists may easily have influenced their patients in various ways to report the desired result (the success of patient-blinding was not reported but would have gone some way to solving this problem).
- The effect size of the benefit is tiny and of doubtful clinical relevance.
My biggest concern, however, is the fact that the study originates from China, a country where virtually 100% of all acupuncture studies produce positive (or should that be ‘false-positive’?) findings and data fabrication has been reported to be rife. These facts do not inspire trustworthiness, in my view.
So, does acupuncture work for migraine? The current Cochrane review included 22 studies and its authors concluded that the available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking.
So, maybe acupuncture is effective. Personally, I am not convinced and certainly do not think that the new JAMA study significantly strengthened the evidence.
You may recall, we have dealt with the JCAM many times before; for instance here, here, here and here. Now they have come out with another remarkable paper. This study – no, the authors called it a ‘pilot study’ – was to compare the efficacy of Emotional Freedom Techniques (EFT) with that of Cognitive-Behavioral Therapy (CBT) in reducing adolescent anxiety. Sixty-three American high-ability students in grades 6–12, ages 10–18 years, who scored in the moderate to high ranges for anxiety on the Revised Children’s Manifest Anxiety Scale-2 (RCMAS-2) were randomly assigned to one of three groups:
- CBT (n = 21),
- EFT (n = 21),
- or waitlist control (n = 21).
EFT is an alternative therapy that incorporates acupoint stimulation. Students assigned to the CBT or EFT treatment groups received three individual sessions of the identified protocols from trained graduate counseling, psychology, or social work students enrolled at a large northeastern research university. The RCMAS-2 was used to assess preintervention and postintervention anxiety levels in participants.
EFT participants showed significant reduction in anxiety levels compared with the waitlist control group with a moderate to large effect size. CBT participants did not differ significantly from the EFT or control.
The authors concluded that EFT is an efficacious intervention to significantly reduce anxiety for high-ability adolescents.
They also state in their abstract that EFT is an evidence-based treatment for anxiety…
Are you happy with these conclusions?
Are you convinced that this trial lends itself to establish efficacy of anything?
Are you impressed with the trial design, the sample size, etc?
Are you sure that EFT is plausible, credible or evidence-based in any way?
No?
Me neither!
If you look up EFT, you will find that there is a surprising amount of papers on it. Most of them have one thing in common: they were published in highly dubious journals. The field does not inspire trust or competence. The authors of the study state that EFT is an easily implemented strategy that uses such techniques as awareness building, exposure, reframing of interpretation, and systematic desensitization, while teaching the participant to self-stimulate protocol-identified acupoints (i.e., acupuncture points) by tapping. The effectiveness of acupuncture for treating anxiety has been well documented. Rather than using acupuncture needles, EFT relies on the manual stimulation of the acupoints. A recent meta-analysis indicated that interventions using acupoint stimulation had a moderate effect size (Hedge’s g = −0.66 95% CI [−0.99, −0.33]) in reducing symptoms. In EFT, the client stimulates the protocol-identified acupoints by tapping on them. Preliminary studies have suggested that tapping and other alternative ways of stimulating acupuncture points to be as effective as acupuncture needling. The EFT protocol and identified acupoints that were used in this study are the ones recommended for research purposes by the Association for Comprehensive Energy Psychology…
Wikipedia tells us that “Emotional Freedom Techniques (EFT) is a form of counseling intervention that draws on various theories of alternative medicine including acupuncture, neuro-linguistic programming, energy medicine, and Thought Field Therapy (TFT). It is best known through Gary Craig’s EFT Handbook, published in the late 1990s, and related books and workshops by a variety of teachers. EFT and similar techniques are often discussed under the umbrella term “energy psychology”. Advocates claim that the technique may be used to treat a wide variety of physical and psychological disorders, and as a simple form of self-administered therapy.[1] The Skeptical Inquirer describes the foundations of EFT as “a hodgepodge of concepts derived from a variety of sources, [primarily] the ancient Chinese philosophy of chi, which is thought to be the ‘life force’ that flows throughout the body.” The existence of this life force is “not empirically supported”.[2] EFT has no benefit as a therapy beyond the placebo effect or any known-effective psychological techniques that may be provided in addition to the purported “energy” technique.[3] It is generally characterized as pseudoscience and it has not garnered significant support in clinical psychology.”
A recent systematic review of EFT concluded that “there were too few data available comparing EFT to standard-of-care treatments such as cognitive behavioral therapy, and further research is needed to establish the relative efficacy of EFT to established protocols.”
Notwithstanding these and many other verdicts on EFT, we now are asked to agree with the new study that EFT IS EFFICACIOUS.
Is this a joke?
They want us to believe this on the basis of a PILOT STUDY? Such studies are not even supposed to test efficacy! (Yet the authors of the trial state that this study was designed to meet the American Psychological Association (APA) Division 12 quality control criteria and the Consolidated Standards for Reporting Trials (CONSORT) criteria. I have to admit, they could have fooled me!)
No, it is not a joke, it is yet another nonsense from the ‘The Journal of Complementary and Alternative Medicine’ which, in my view, should henceforth be called THE JOURNAL OF ALTERNATIVE FACTS (JAF).
Although many conservative management options are being promoted for shoulder conditions, there is little evidence of their effectiveness. This review investigated one manual therapy approach, thrust manipulation, as a treatment option.
A systematic search was conducted of the electronic databases from inception to March 2016: PubMed, PEDro, ICL, CINAHL, and AMED. Two independent reviewers conducted the screening process to determine article eligibility. Inclusion criteria were manuscripts published in peer-reviewed journals with human participants of any age. The intervention included was thrust, or high-velocity low-amplitude, manipulative therapy directed to the shoulder and/or the regions of the cervical or thoracic spine. Studies investigating secondary shoulder pain or lacking diagnostic confirmation procedures were excluded. Methodological quality was assessed using the PEDro scale and the Cochrane risk-of-bias tool.
The initial search rendered 5041 articles. After screening titles and abstracts, 36 articles remained for full-text review. Six articles studying subacromial impingement syndrome met inclusion criteria. Four studies were randomized controlled trials (RCTs) and two were uncontrolled clinical studies. Five studies included one application of a thoracic spine thrust manipulation and one applied 8 treatments incorporating a shoulder joint thrust manipulation. Statistically significant improvements in pain scores were reported in all studies. Three of 4 RCTs compared a thrust manipulation to a sham, and statistical significance in pain reduction was found within the groups but not between them. Clinically meaningful changes in pain were inconsistent; three studies reported that scores met minimum clinically important difference, one reported scores did not, and two were unclear. Four studies found statistically significant improvements in disability; however, two were RCTs and did not find statistical significance between the active and sham groups.
The authors concluded that there is limited evidence to support or refute thrust manipulation as a solitary treatment for shoulder pain or disability associated with subacromial impingement syndrome. Studies consistently reported a reduction in pain and improvement in disability following thrust manipulation. In RCTs, active treatments were comparable to shams suggesting that addressing impingement issues by manipulation alone may not be effective. Thrust manipulative therapy appears not to be harmful, but AE reporting was not robust. Higher-quality studies with safety data, longer treatment periods and follow-up outcomes are needed to develop a stronger evidence-based foundation for thrust manipulation as a treatment for shoulder conditions.
This is yet another very odd conclusion from an otherwise almost acceptable analysis (but why include non-randomised studies on a subject where randomised trials are available?) . If pain reductions are found within groups but not between real and sham manipulation, the evidence is as clear as it can be: manipulations have no specific effects. In other words, they are a pure placebo therapy.
And what about this nonsense: there is limited evidence to support or refute thrust manipulation as a solitary treatment for shoulder pain? For responsible healthcare, we don’t need such weasel words, all we need is to stress loud and clear that there is no good positive evidence. This means the therapy is not evidence-based and we therefore should not recommend or use manipulation for shoulder pain.
But, in my view, the worst part in the conclusion section is this: thrust manipulative therapy appears not to be harmful, but AE reporting was not robust. Even if there had been adequate reporting of side-effects and even if this had not disclosed any problems, the safety of manipulation cannot be judged on the basis of such a small sample. Any responsible researcher should make it abundantly clear that the nasty habit by chiropractic pseudo-researchers of not reporting adverse effects is unethical and totally unacceptable.
My conclusion from all this: yet another attempt to white-wash a dodgy alternative therapy.
The British Homeopathic Association (BHA) is a registered charity founded in 1902. Their objectives are “to promote and develop the study and practice of homeopathy and to advance education and research in the theory and practice of homeopathy…” and their priority is “to ensure that homeopathy is available to all…” The BHA believes that “homeopathy should be fully integrated into the healthcare system and available as a treatment choice for everyone…”
This does not bode well, in my view. Specifically, it does not seem as though we can expect unbiased information from the BHA. Yet, from a charity we certainly do not expect a packet of outright lies – so, let’s have a look.
The BHA have a website (thank you Greg for reminding me of this source; I have long known about it and used it often for lectures when wanting to highlight the state of homeopathic thinking) where they provide “THE EVIDENCE FOR HOMEOPATHY“. I find the data presented there truly remarkable, so much so that I present a crucial section from it below:
START OF QUOTE
The widely accepted method of proving whether or not a medical intervention works is called a randomised controlled trial (RCT). One group of patients, the control group, receive placebo (a “dummy” pill) or standard treatment, and another group of patients receive the medicine being tested. The trial becomes double-blinded when neither the patient nor the practitioner knows which treatment the patient is getting. RCTs are often referred to as the “gold standard” of clinical research.
Up to the end of 2014, a total of 104 papers reporting good-quality placebo-controlled RCTs in homeopathy (on 61 different medical conditions) have been published in peer-reviewed journals. 41% of these RCTs have reported a balance of positive evidence, 5% a balance of negative evidence, and 54% have not been conclusively positive or negative. For full details of all these RCTs and more in-depth information on the research in general, visit the research section of the Faculty of Homeopathy’s website. Also, see 2-page evidence summary with full references.
END OF QUOTE
Impressive!
But is it true?
Let’s have a closer look at the percentage figures: according to the BHA
- 41% of all RCT are positive,
- 5% are negative,
- 54% are inconclusive.
These numbers are hugely important because they are being cited regularly across the globe as one of the most convincing bit of evidence to date in support of homeopathy. If they were true, many more RCT would be positive than negative. They would, in fact, constitute a strong indicator suggesting that homeopathic remedies are more than placebos.
One does not need to look far to find that these figures are clearly not correct! To disclose the ‘mistake’, we do not even need to study any of the 104 RCTs in question, we only need to straighten out the BHA’s ‘accounting error’ and ask: what on earth is an ‘inconclusive’ RCT?
A positive RCT obviously is one where homeopathy generated better outcomes than the placebo; similarly a negative RCT is one where the opposite was the case; in other words, where the placebo generated better outcomes than homeopathy. But what is an ‘inconclusive’ RCT? It turns out that, according to the BHA, it is one where there was no significant difference between the results obtained with placebo and homeopathy.
WHAT???
Yes, you understood correctly!
Outside homeopathy such RCTs are categorised as negative studies – they fail to show that homeopathy out-performs placebo and therefore confirm the null-hypothesis. An RCT is a test of the null-hypothesis (the experimental treatment is not better than the control) and can only confirm or reject this hypothesis. Certainly finding that the experimental treatment is not better than the control is not inconclusive bit a confirmation of the null-hypothesis. In other words it is a negative result.
So, let’s look at the little BHA – statistic again, and this time let’s do the accounting properly:
- 41% of all RCTs are positive,
- 59% are negative.
This means that, according to this very simplistic method, the majority of RCTs is negative. I say ‘very simplistic’ because, for a proper analysis of the trial evidence, we need to account, of course, for the quality of each trial. If the quality of the positive RCTs is, on average, less rigorous than that of the negative RCTs, the overall result would become yet more clearly negative. Most assessments of homeopathy that consider this essential factor do, in fact, confirm that this is the case.
Once all this has been analysed properly, we still have to account for factors like publication bias. Negative trials get often not published and therefore the overall picture gets easily distorted and generates a false-positive image. At the end of a sound evaluation along these lines, the result would fail to show that homeopathy differs from placebo.
Regardless of all these necessary and important considerations, the BHA website then tells us that the RCT method is problematic when it comes to testing homeopathy: “The RCT model of measuring efficacy of a drug poses some challenges for homeopathic research. In homeopathy, treatment is usually tailored to the individual. A homeopathic prescription is based not only on the symptoms of disease in the patient but also on a host of other factors that are particular to that patient, including lifestyle, emotional health, personality, eating habits and medical history. The “efficacy” of an individualised homeopathic intervention is thus a complex blend of the prescribed medicine together with the other facets of the in-depth consultation and integrated health advice provided by the practitioner; under these circumstances, the specific effect of the homeopathic medicine itself may be difficult to quantify with precision in RCTs.”
What are they trying to say here?
I am not sure.
Are they perhaps claiming that, even if an independent scientist disclosed their ‘accounting error’ and demonstrated that, in fact, the RCT evidence fails to support homeopathy, the BHA would still argue that homeopathy works?
I think so!
It looks to me that the BHA is engaged in the currently popular British past-time: THEY WANT THE CAKE AND EAT IT.
All this is more than a little disturbing, and I think it begs several questions:
- Is this type of behaviour in keeping with the charitable status of the BHA?
- Does it really ‘promote and develop the study and practice of homeopathy and to advance education and research’?
- Is it not rather unethical to mislead the public in such a gross and dishonest fashion?
- Is it not fraudulent to insist on false accounting?
I would be interested to get your views on this.
Yes, homeopaths are incredibly fond of the notion that homeopathy has been proven to work in numerous population studies of outbreaks of infectious diseases. The argument is bound to come up in any discussion with a ‘well-informed’ homeopathy fan. Therefore, it might be worth addressing it once and for all.
This website offers a fairly good summary of what homeopaths consider to be convincing evidence. It also provides links to the original articles which is valuable for all who want to study them in full detail. I will therefore present the crucial passage here unchanged.
START OF QUOTE
By the end of year 2014, there have been 19 papers published on Epidemiological studies on 7 epidemic diseases (scarlet fever, typhus fever, Cholera, Dengue, meningococcal, influenza and Leptospirosis) in 11 peer-reviewed (beyond year 1893) journals in evidence of Homeopathy including 2 Randomised Controlled Trials.
1. Samuel Hahnemann, “The Cure and prevention of scarlet fever”, Zeitschrift für Praktischen Medizin (Journal of Practical Medicine), 1801, Republished in Lesser Writings. B.Jain Publishing, New Delhi
Preventive use of homeopathy was first applied in 1799 during an epidemic of scarlet fever in Königslütter, Germany, when Dr. Hahnemann prescribed a single dose of Belladonna, as the remedy of the genus epidemicus to susceptible children in the town with more than 95% success rate. In this paper, he also specified how the Belladonna has to be potentised to 1/24,000,000 dilution. His recommended dose of Belladonna was 0.0416 nanograms to be repeated every 72 hrs. This is the first recorded nano dose of medicine used in treatment of any disease [6]. It was another 125 years before Gladys Henry and George Frederick developed a vaccine for scarlet fever in 1924.
2. Samuel Hahnemann, “Scarlet fever and Purpura miliaris, two different diseases”, Zeitschrift für Praktischen Medizin, vol. 24, part. 1, 1806
3. Samuel Hahnemann, “Observations on scarlet fever”, Allgemeine Reichanzeiger (General Reich Gazette), No. 160, Germany, 1808
4. Samuel Hahnemann, “Reply to a question about the prophylactic for scarlet fever”, Zeitschrift für Praktischen Medizin, vol. 27, part. 4, p. 152-156, 1808
5. Samuel Hahnemann, “Treatment of typhus & fever at present prevailing”, Allgemeine Reichanzeiger, No. 6, Jan. 1814.
6. Hufeland, Prophylactic powers of Belladonna against Scarlet Fever , The Lancet, 1829
The proper use of belladonna has, in most cases, prevented infection. Numerous observations have shown that, by the general use of belladonna, epidemics of scarlet fever have actually been arrested. In those few instances where the use of belladonna was insufficient to prevent infection, the disease has been invariably slight. The Prussian (German Empire) Government ordered the use of the prophylactic during all scarlet fever epidemics
7. Samuel Hahnemann, “Cure and prevention of Asiatic cholera”, Archiv für die homöopathische Heilkunst (Archives for the Homoeopathic Healing Art), Vol. 11, part 1, 1831.
Cuprum 30c once every week as preventive medicine
8. Samuel Hahnemann, “On the contagiousness of cholera”. British Homoeopathic Journal, Vol. 7, 1849
9. Samuel Hahnemann, “Appeal to Thinking Philanthropists Respecting the Mode of Propagation of the Asiatic Cholera”, 20 pages, 1831. Republished in British Homoeopathic Journal, Oct 1849.
He said, “On board ships – in those confined spaces, filled with mouldy watery vapours, the cholera-miasm finds a favourable element for its multiplication, and grows into an enormously increased brood of those excessively minute, invisible, living creatures, so inimical to human life, of which the contagious matter of the cholera most probably consists millions of those miasmatic animated beings, which, at first developed on the broad marshy banks or the tepid Ganges– on board these ships, I say, this concentrated aggravated miasm kills several of the crew …” [7].
It was another 59 years (1890) before Koch saw these organisms, and later on orthodox medicine gave them the name ‘germs’
10. Charles Woodhull Eaton, The Facts about Variolinum, Transactions of the American Institute of Homoeopathy, 1907
2806 patients were treated prophylactically with Variolinum 30 (a nosode) for prevention of smallpox in Iowa. Of the 547 patients definitely exposed, only 14 developed the disease. Efficacy rate of 97.5%
11. Taylor Smith A, Poliomyelitis and prophylaxis British Homoeopathic Journal, 1950
In 1950 during an epidemic of poliomyelitis, Dr Taylor Smith of Johannesburg, South Africa protected 82 people with homoeopathic Lathyrus sativus. Of the 82 so immunised, 12 came into direct contact with disease. None were infected.
12. Oscillococcinum 200c in the treatment of influenza during epidemic in France from 1984-1987, British Journal of Clinical Pharmacology (1989)
A DBRPCT, Oscillococcinum 200c taken twice daily for 5 days significantly increased the rate of cure within two days (n=487, 237 treated and 241 on placebo), absence of symptoms at 48 hours, relative risk estimate significantly favour homeopathy (p=0.048), no pain and no fever (p=0.048), recovery rate (headache, stiffness, articular pain, shivering reduction) at 48 hours better in homeopathy group (p=0.032)
13. Bernard Leary, Cholera 1854 Update, British Homoeopathic Journal, 1994
Sir William Wilde, the well-known allopathic doctor of Dublin, which in his work entitled “Austria and its Institutions”, wrote: “Upon comparing the report of the treatment of Cholera in the Homeopathic hospital testified to by two allopathic medical inspectors appointed by Government with that of the treatment of the same disease in the other hospitals of Vienna during the same period the epidemic of 1836, it appeared that while two-thirds of the cases treated by Dr. Fleischmann the physician of the Homeopathic hospital, recovered, two-thirds of those treated by the ordinary methods in the other hospitals died.”
14. Meningococcinum – its protective effect against meningococcal disease, Homeopathy Links, 2001 (2001)
A total of 65,826 people between the ages of 0–20 were immunised homeopathically to protect against meningococcal disease while 23,532 were not. Over a year period, 4 out of 65,826 protected homeopathically developed meningococcal infection. 20 out of 23,532 not protected developed meningococcal infection. Based on the infection rate in the unprotected group, 58 cases of infection could have been expected in the homeopathically protected group. Instead, there were only four cases of meningococcal infection. Statistical analysis showed that homeopathic immunisation offered 95% protection in the first six months and 91% protection over the year against meningococcal disease. [8]
15. Contribution of homeopathy to the control of an outbreak of dengue epidemic in Macaé, Rio de Janeiro, Brazil in 2007-8 , International Journal of High Dilution Research, 2008
In a campaign ‘Homeopathy campaign against dengue’ by Brazilian Govt, “156,000 doses of homeopathic remedy were freely distributed in April and May 2007 to asymptomatic patients and 129 doses to symptomatic patients treated in outpatient clinics, according to the notion of genus epidemicus . The remedy used was a homeopathic complex against dengue containing Phosphorus 30c, Crotalus horridus 30c and Eupatorium perfoliatum 30c. The incidence of the disease in the first three months of 2008 fell 93% by comparison to the corresponding period in 2007, whereas in the rest of the State of Rio de Janeiro there was an increase of 128%.”
16. Marino R. Eupatorium perfoliatum 30c for the Dengue Epidemics in Brazil in 2007. International Journal of High Dilution Research, 2008
In May 2001, prophylactic use of Eupatorium perfoliatum 30c single dose was given during a dengue outbreak to 40% of residents in the most highly affected neighbourhood which resulted in significant decrease in dengue incidence by 81.5% (p<0.0001) when compared with those neighbourhoods that did not receive homeopathic prophylaxis.
17. Bracho et. al. Application of 200C potency of bacteria for Leptospirosis epidemic control in Cuba 2007-8 (2010)
Conducted by the Finlay Institute, a vaccines producer in Cuba gave 2.308562 million (70% of the target population above the age of 1 year) people in Cuba given two doses (1 dose=5 drops) of 200C potency of a nosode prepared from Leptospirosis bacteria, each (7-9 days apart), for protection against Leptospirosis (fever+jaundice+ inflammation in kidney+enlargement of spleen) with 84% decrease in disease incidence and only 10 reported cases. Dramatic decrease in morbidity within two weeks and zero morbidity of hospitalised patients, non-treated (8.8 millions) area saw an increase in number of cases from 309 cases in 2007 to 376 in 2008 representing a 21% increase. The cost of homeopathic immunization =1/15th of conventional vaccine.
18. Effect of individualized homoeopathic treatment in influenza like illness, Indian Journal of Research in Homeopathy (2013)
A multicenter, single blind, randomized, placebo controlled study to evaluate the effect of homoeopathic medicines in the treatment of Influenza like illness and to compare the efficacy of LM (50 millisimal) potency vis-à-vis centesimal (C) potency. In LM group (n=152), C group (n=147) or placebo (n=148) group. The study revealed the significant effect of individualized homoeopathic treatment in the patients suffering from ILI with no marked difference between LM and Centesimal groups. The medicines which were commonly prescribed were: Arsenic album, Bryonia alba, Rhus tox., Belladonna, Nux vomica, Sepia, Phosphorus, Gelsemium, Sulphur, Natrum mur. and Aconitum napellus. [9]
19. Reevaluation of the Effectiveness of Homoeoprophylaxis Against Leptospirosis in Cuba in 2007-8, Journal of Evidence-based Complementary & Alternative Medicine (2014)
The results support the previous conclusions that homoeoprophylaxis can be used to effectively immunize people against targeted infectious diseases such as leptospirosis.
References
[1] Iman Navab, Lives saved by Homeopathy in Epidemics and Pandemics, https://drnancymalik.wordpress.com/2013/01/23/epidemics-and-pandemics/
[2] Reshu Agarwal, Natural History of Disease and Homeopathy at different levels of Intervention, http://www.homeorizon.com/homeopathic-articles/homeopathic-philosophy/disease-history
[3] Homoeopathy- Science of Gentle Healing, Deptt. of AYUSH, Ministry of Health & Family Welfare, Govt, of India, 2013, http://www.ccrhindia.org/Dossier/content/page22.html
[4] Conversation with David Little, http://hpathy.com/homeopathy-papers/conversations-with-david-little/
[5] Nancy Malik, Principles of Homeopathy Explained, 2015, https://drnancymalik.wordpress.com/article/homeopathy-explained/
[6] Nancy Malik, Recent Advances in Nanoparticle Research in Homeopathy, Homeopathy 4 Everyone, Vol.12, Issue 6, 18 June 2015, http://hpathy.com/scientific-research/recent-advances-in-nanoparticle-research-in-homeopathy/
[7] Samuel Hahnemann, “Appeal to Thinking Philanthropists Respecting the Mode of Propagation of the Asiatic Cholera”, 20 pages, 1831, Translated by R E Dudgeon, M.D. in The Lesser Writings of Samuel Hahnemann, 1851, B Jain Publishers, reproduced edition, 2002, p. 758
[8] Fran Sheffield, Homeoprophylaxis: Human Records, Studies and Trials, 2014, http://homeopathyplus.com/Homeoprophylaxis-Human-Records-Studies-Trials.pdf
[9] Homoeopathy in Flu-like Illness- Factsheet, Central Council for Research in Homoeopathy, Deptt. of AYUSH, Ministry of Health & Family Welfare, Govt, of India, 2015, http://ccrhindia.org/pdf/swineflu.pdf
END OF QUOTE
Whenever I read articles of this nature, I get a little embarrassed. It seems obvious to me that the authors of such reviews have done some ‘research’ and believe strongly in the correctness in what they write. It embarrasses me to see how such people, full of good will, can be so naïve, ignorant and wrong. They clearly fail to understand several crucial issues. To me. this seems like someone such as me lecturing others about car mechanics, quantum physics or kite flying. I have no idea about these subjects, and therefore it would be idiotic to lecture others about them. But homeopaths tend to be different! And this is when my embarrassment quickly turns into anger: articles like the above spread nonsense and misguide people about important issues. THEY ARE DANGEROUS! There is little room for embarrassment and plenty of room for criticism. So, let’s criticise the notions advanced above.
In my recent book, I briefly touched upon epidemics in relation to homeopathy:
Epidemics are outbreaks of disease occurring at the same time in one geographical area and affecting large number of people. In homeopathy, epidemics are important because, in its early days, they seemed to provide evidence for the notion that homeopathy is effective. The results of homeopathic treatment seemed often better than those obtained by conventional means. Today we know that this was not necessarily due to the effects of homeopathy per se, but might have been a false impression caused by bias and confounding.
This tells us the main reason why the much-treasured epidemiological evidence of homeopaths is far from compelling. The review above does not mention these caveats at all. But it is lousy also for a whole host of other reasons, for instance:
- The text contains several errors (which I find too petty to correct here).
- The list of studies is the result of cherry-picking the evidence.
- It confuses what epidemiological studies are; RCTs are certainly not epidemiological studies, for instance.
- It also omits some of the most important epidemiological studies suggesting homeopathy works.
- It cites texts that are clearly not epidemiological studies.
- Several studies are on prevention of illness rather than on treatment.
- Some studies do not even employ homeopathy at all.
In the typical epidemiological case/control study, one large group of patients [A] is retrospectively compared to another group [B]. By large, I mean with a sample size of thousands of patients. In our case, group A has been treated homeopathically, while group B received the treatments available at the time. It is true that several of such reports seemed to suggest that homeopathy works. But this does by no means prove anything; the result might have been due to a range of circumstances, for instance:
- group A might have been less ill than group B,
- group A might have been richer and therefore better nourished,
- group A might have benefitted from better hygiene in the homeopathic hospital,
- group A might have received better care, e. g. hydration,
- group B might have received treatments that made the situation not better but worse.
Because these are RETROSPECTIVE studies, there is no way to account for these and many other factors that might have influenced the outcome. This means that epidemiological studies of this nature can generate interesting results which, in turn, need testing in properly controlled studies where these confounding factors are adequately controlled for. Without such tests, they are next to worthless for recommendations regarding clinical practice.
As it happens, the above author also included two RCT in the review (these are NOT epidemiological studies, as I already mentioned). Let’s have a quick look at them.
The first RCT is flawed for a range of reasons and has been criticised many times before. Even its authors state that “the result cannot be explained given our present state of knowledge, but it calls for further rigorously designed clinical studies.” More importantly, the current Cochrane review of Oscillococcinum, the remedy used in this study, concluded: “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.”
The second RCT is equally flawed; for instance, its results could be due to the concomitant use of paracetamol, and it seems as though the study was not double blind. The findings of this RCT have so far not been confirmed by an independent replication.
What puzzles me most with these regularly voiced notions about the ‘epidemiological evidence’ for homeopathy is not the deplorable ineptitude of those who promote them, but it is this: do homeopaths really believe that conventional medics and scientists would ignore such evidence, if it were sound or even just encouraging? This assumes that all healthcare professionals (except homeopaths) are corrupt and cynical enough not to follow up leads with the potential to change medicine for ever. It assumes that we would supress knowledge that could save the lives of millions for the sole reason that we are against homeopathy or bribed by ‘BIG PHARMA’.
Surely, this shows more clearly than anything else how deluded homeopaths really are!!!
Today is WORLD CANCER DAY.
Yesterday I prepared you for this event by alerting you to a disgusting cancer scam, and today I want to contrast this with more encouraging news from the strange world of alternative medicine. So I searched Medline for a fitting, recent publication showing at least some value of an alternative therapy. Believe me, such papers are few and far between.
But here is one:
The aim of this Cochrane review was to assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment. The authors conducted extensive literature searches and applied no language restrictions. RCTs were eligible, if they (1) compared yoga interventions to no therapy or to any other active therapy in women with a diagnosis of breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances.
Two review authors independently collected data on methods and results. The risk of publication bias was assessed through visual analysis of funnel plot symmetry and heterogeneity between studies. Subgroup analyses were conducted for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention.
Twenty-four studies with a total of 2166 participants were included, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias. Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life, reduced fatigue and reduced sleep disturbances in the short term. There was an overall low risk of publication bias.
Yoga did not appear to reduce depression or anxiety in the short term and had no medium-term effects on health-related quality of life or fatigue. Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression, anxiety and fatigue in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life or sleep disturbances. Three studies that compared yoga to exercise presented very low-quality evidence showing no short-term effects on health-related quality of life or fatigue. No trial provided safety-related data.
The authors concluded that moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.
As I said, this is most encouraging. Many women are attracted by yoga, and the news that it can improve their symptoms is clearly positive. I have said it often, but I say it again: in supportive and palliative cancer care there might be an important role for several forms of CAM. One has to make sure though that they do not interfere with conventional treatments, and – this is very important – cancer patients must not be misled to believe that they can be used to treat or cure cancer. Finally, patients should not pitch their hopes too high: the effect sizes of alternative treatments in cancer care are invariably small or modest which means that they can help to reduce symptoms but are unlikely to get rid of them completely.
On an even more sober note, I have to reiterate that none of the trials included in the above review reported safety data (yoga is not totally devoid of adverse-effects!). This is an almost stereotypical finding when assessing clinical trials of alternative therapies. It discloses a clear and unacceptable breach of publication ethics. How can we ever get a realistic impression of the risks of alternative medicine, if adverse effects remain unreported? It is high time that researchers, authors, journal editors and reviewers get this message and behave accordingly.
One of the questions I hear frequently is ‘HOW CAN I BE SURE THIS STUDY IS SOUND’? Even though I have spent much of my professional life on this issue, I am invariably struggling to provide an answer. Firstly, because a comprehensive reply must inevitably have the size of a book, perhaps even several books. And secondly, to most lay people, the reply would be intensely boring, I am afraid.
Yet many readers of this blog evidently search for some guidance – so, let me try to provide a few indicators – indicators, not more!!! – as to what might signify a good and a poor clinical trial (other types of research would need different criteria).
INDICATORS SUGGESTIVE OF A GOOD CLINICAL TRIAL
- Author from a respected institution.
- Article published in a respected journal.
- A clear research question.
- Full description of the methods used such that an independent researcher could repeat the study.
- Randomisation of study participants into experimental and control groups.
- Use of a placebo in the control group where possible.
- Blinding of patients.
- Blinding of investigators, including clinicians administering the treatments.
- Clear definition of a primary outcome measure.
- Sufficiently large sample size demonstrated with a power calculation.
- Adequate statistical analyses.
- Clear presentation of the data such that an independent assessor can check them.
- Understandable write-up of the entire study.
- A discussion that puts the study into the context of all the important previous work in this area.
- Self-critical analysis of the study design, conduct and interpretation of the results.
- Cautious conclusion which are strictly based on the data presented.
- Full disclosure of ethics approval and informed consent,
- Full disclosure of funding sources.
- Full disclosure of conflicts of interest.
- List of references is up-to-date and includes also studies that contradict the authors’ findings.
I told you this would be boring! Not only that, but each bullet point is far too short to make real sense, and any full explanation would be even more boring to a lay person, I am sure.
What might be a little more fun is to list features of a clinical trial that might signify a poor study. So, let’s try that.
WARNIG SIGNALS INDICATING A POOR CLINICAL TRIAL
- published in one of the many dodgy CAM journals (or in a book, blog or similar),
- single author,
- authors are known to be proponents of the treatment tested,
- author has previously published only positive studies of the therapy in question (or member of my ‘ALT MED HALL OF FAME’),
- lack of plausible rationale for the study,
- lack of plausible rationale for the therapy that is being tested,
- stated aim of the study is ‘to demonstrate the effectiveness of…’ (clinical trials are for testing, not demonstrating effectiveness or efficacy),
- stated aim ‘to establish the effectiveness AND SAFETY of…’ (even large trials are usually far too small for establishing the safety of an intervention),
- text full of mistakes, e. g. spelling, grammar, etc.
- sample size is tiny,
- pilot study reporting anything other than the feasibility of a definitive trial,
- methods not described in sufficient detail,
- mismatch between aim, method, and conclusions of the study,
- results presented only as a graph (rather than figures which others can re-calculate),
- statistical approach inadequate or not sufficiently detailed,
- discussion without critical input,
- lack of disclosures of ethics, funding or conflicts of interest,
- conclusions which are not based on the results.
The problem here (as above) is that one would need to write at least an entire chapter on each point to render it comprehensible. Without further detailed explanations, the issues raised remain rather abstract or nebulous. Another problem is that both of the above lists are, of course, far from complete; they are merely an expression of my own experience in assessing clinical trials.
Despite these caveats, I hope that those readers who are not complete novices to the critical evaluation of clinical trials might be able to use my ‘warning signals’ as a form of check list that helps them to tell the chaff from the wheat.
Hyperthyroidism is, so I am told, a frequent veterinary problem, particularly in elderly cats. Homeopathic treatment is sometimes used to treat this condition. One article even provided encouraging details based on 4 case-reports. All 4 cats showed resolution of clinical signs; three attained normal thyroid hormone levels. The authors concluded that homeopathic and complementary therapies avoid the potential side effects of methimazole and surgical thyroidectomy, they are less costly than radioactive iodine treatment, and they provide an option for clients who decline conventional therapies.
Yes, you guessed correctly: such a paper can only be published in the journal ‘HOMEOPATHY‘, respectable journals would not allow such conclusions based on 4 case-reports. They don’t permit inferences as to cause and effect. We have no idea what would have happened to these animals without homeopathy – perhaps they would have fared even better!
What we need is a proper controlled trial. The good news is that such a study has just been published. This double-blinded, placebo-controlled randomised trial was aimed at testing the efficacy of individualised homeopathy in the treatment of feline hyperthyroidism. Cats were randomised into two treatment arms. Either a placebo or a homeopathic treatment was given to each cat blindly.
After 21 days, the T4 levels, weight (Wt) and heart rate (HR) were compared with pre-treatment values. There were no statistically significant differences in the changes seen between the two treatment arms following placebo or homeopathic treatment, or between the means of each parameter for either treatment arm before and after placebo or homeopathic treatment. In a second phase of the study, patients in both treatment arms were given methimazole treatment for 21 days and T4, Wt and HR determined again. Subsequently, statistically significant reductions were noted in T4 (P<0.0001) and HR (P=0.02), and a statistically significant increase was observed in Wt (P=0.004).
The authors concluded that the results of this study failed to provide any evidence of the efficacy of homeopathic treatment of feline hyperthyroidism.
So, homeopathy does not work – not in humans nor in animals. This statement, backed by solid facts, proves all those wrong who cannot resist uttering the notion that HOMEOPATHY CANNOT BE A PLACEBO BECAUSE IT WORKS IN ANIMALS.
It doesn’t!
And we have seen the evidence for the correctness of this fact so often (for instance here, here, here and here) that I feel embarrassed to say it again: highly diluted homeopathic remedies are placebos. As soon as we adequately control for placebo and other non-specific effects in properly controlled studies, the alleged effects, reported in anecdotes and other uncontrolled studies, simply disappear.
