An abstract from the recent ‘2nd OFFICIAL SIPS CONFERENCE ON PLACEBO STUDIES’ caught my attention. It is not available on-line; therefore let me reproduce it here in full:
The role of placebo effects in mindfulness-based analgesia 1. Jonathan Davies. University of Sydney, Sydney, NSW, Australia. 2. Louise Sharpe. University of Sydney, Sydney, NSW, Australia. 3. Melissa Day. University of Queensland, Brisbane, QLD, Australia. 4. Ben Colagiuri. University of Sydney, Sydney, NSW, Australia.
Background: Mindfulness meditation can reduce pain both in experimental and clinical settings, though it is not known to what extent mindfulness-specific vs placebo-like expectancy effects account for these changes. This study aimed to: 1. establish whether placebo effects contribute to mindfulness-mediated analgesia; and 2. identify putative cognitive mechanisms responsible for placebo- vs mindfulness-mediated analgesia. Methods: We compared the effects of focussed-attention mindfulness training (6 x 20 min), sham mindfulness, and a no-treatment in a double-blind RCT for experimental heat pain. Sham mindfulness instructions lacked the ‘active ingredients’ of the real training but were matched on all other contextual factors. Results: Both real and sham mindfulness training led to greater pain tolerance relative to no treatment, but there was no difference between the real and sham training. This was accompanied by increased expectancy, beliefs, and pain-related cognitive processes in the two mindfulness groups relative to no treatment, but again there were no differences between real and sham training on these outcomes. There were no effects on pain intensity, pleasantness or threshold. Conclusion: These findings suggest that mindfulness training – at least those involving focused-attention – may lead to improved pain tolerance via the placebo effect rather than any specific mindfulness-related mechanisms. Potential mediators of these effects will be discussed.
I find this study remarkable in two ways:
- It shows that, with a bit of fantasy, ingenuity and will, one can design and use sham procedures even in clinical trials of mind/body therapies.
- Its results suggest that, if one does control for placebo effects, these treatments may not prove to be more than a placebo therapy.
What implications might this have for clinical practice?
Mindfulness is currently hugely popular. It would not be surprising, if the news that it might rely purely on placebo effects would calm down the enthusiasm about this treatment. Many might ask, does it matter? As long as patients benefit, the mechanism of action seems irrelevant. This, of course, is an interesting debate which we have had on this blog many times before.
What do you think?
The journal NATURE has just published an excellent article by Andrew D. Oxman and an alliance of 24 leading scientists outlining the importance and key concepts of critical thinking in healthcare and beyond. The authors state that the Key Concepts for Informed Choices is not a checklist. It is a starting point. Although we have organized the ideas into three groups (claims, comparisons and choices), they can be used to develop learning resources that include any combination of these, presented in any order. We hope that the concepts will prove useful to people who help others to think critically about what evidence to trust and what to do, including those who teach critical thinking and those responsible for communicating research findings.
Here I take the liberty of citing a short excerpt from this paper:
Claims about effects should be supported by evidence from fair comparisons. Other claims are not necessarily wrong, but there is an insufficient basis for believing them.
Claims should not assume that interventions are safe, effective or certain.
- Interventions can cause harm as well as benefits.
- Large, dramatic effects are rare.
- We can rarely, if ever, be certain about the effects of interventions.
Seemingly logical assumptions are not a sufficient basis for claims.
- Beliefs alone about how interventions work are not reliable predictors of the presence or size of effects.
- An outcome may be associated with an intervention but not caused by it.
- More data are not necessarily better data.
- The results of one study considered in isolation can be misleading.
- Widely used interventions or those that have been used for decades are not necessarily beneficial or safe.
- Interventions that are new or technologically impressive might not be better than available alternatives.
- Increasing the amount of an intervention does not necessarily increase its benefits and might cause harm.
Trust in a source alone is not a sufficient basis for believing a claim.
- Competing interests can result in misleading claims.
- Personal experiences or anecdotes alone are an unreliable basis for most claims.
- Opinions of experts, authorities, celebrities or other respected individuals are not solely a reliable basis for claims.
- Peer review and publication by a journal do not guarantee that comparisons have been fair.
Studies should make fair comparisons, designed to minimize the risk of systematic errors (biases) and random errors (the play of chance).
Comparisons of interventions should be fair.
- Comparison groups and conditions should be as similar as possible.
- Indirect comparisons of interventions across different studies can be misleading.
- The people, groups or conditions being compared should be treated similarly, apart from the interventions being studied.
- Outcomes should be assessed in the same way in the groups or conditions being compared.
- Outcomes should be assessed using methods that have been shown to be reliable.
- It is important to assess outcomes in all (or nearly all) the people or subjects in a study.
- When random allocation is used, people’s or subjects’ outcomes should be counted in the group to which they were allocated.
Syntheses of studies should be reliable.
- Reviews of studies comparing interventions should use systematic methods.
- Failure to consider unpublished results of fair comparisons can bias estimates of effects.
- Comparisons of interventions might be sensitive to underlying assumptions.
Descriptions should reflect the size of effects and the risk of being misled by chance.
- Verbal descriptions of the size of effects alone can be misleading.
- Small studies might be misleading.
- Confidence intervals should be reported for estimates of effects.
- Deeming results to be ‘statistically significant’ or ‘non-significant’ can be misleading.
- Lack of evidence for a difference is not the same as evidence of no difference.
What to do depends on judgements about the problem, the relevance (applicability or transferability) of evidence available and the balance of expected benefits, harm and costs.
Problems, goals and options should be defined.
- The problem should be diagnosed or described correctly.
- The goals and options should be acceptable and feasible.
Available evidence should be relevant.
- Attention should focus on important, not surrogate, outcomes of interventions.
- There should not be important differences between the people in studies and those to whom the study results will be applied.
- The interventions compared should be similar to those of interest.
- The circumstances in which the interventions were compared should be similar to those of interest.
Expected pros should outweigh cons.
- Weigh the benefits and savings against the harm and costs of acting or not.
- Consider how these are valued, their certainty and how they are distributed.
- Important uncertainties about the effects of interventions should be reduced by further fair comparisons.
END OF QUOTE
I have nothing to add to this, except perhaps to point out how very relevant all of this, of course, is for SCAM and to warmly recommend you study the full text of this brilliant paper.
Japanese neurosurgeons reported the case of A 55-year-old man who presented with progressive pain and expanding swelling in his right neck. He had no history of trauma or infectious disease. The patient had undergone chiropractic manipulations once in a month and the last manipulation was done one day before the admission to hospital.
On examination by laryngeal endoscopy, a swelling was found on the posterior wall of the pharynx on the right side. The right piriform fossa was invisible. CT revealed hematoma in the posterior wall of the right oropharynx compressing the airway tract. Aneurysm-like enhanced lesion was also seen near the right common carotid artery. Ultrasound imaging revealed a fistula of approximately 1.2 mm at the posterior wall of the external carotid artery and inflow image of blood to the aneurysm of a diameter of approximately 12 mm. No dissection or stenosis of the artery was found. Jet inflow of blood into the aneurysm was confirmed by angiography. T1-weighted MR imaging revealed presence of hematoma on the posterior wall of the pharynx and the aneurysm was recognized by gadolinium-enhancement.
The neurosurgeons performed an emergency operation to remove the aneurysm while preserving the patency of the external carotid artery. The pin-hole fistula was sutured and the wall of the aneurysm was removed. Histopathological assessment of the tissue revealed a pseudoaneurysm (also called a false aneurism), a collection of blood that forms between the two outer layers of an artery.
The patient was discharged after 12 days without a neurological deficit. Progressively growing aneurysm of the external carotid artery is caused by various factors and early intervention is recommended. Although, currently, intravascular surgery is commonly indicated, direct surgery is also feasible and has advantages with regard to pathological diagnosis and complete repair of the parent artery.
The relationship between the pseudoaneurysm and the chiropractic manipulations seems unclear. The way I see it, there are the following three possibilities:
- The manipulations have causally contributed to the pseudo-aneurysm.
- They have exacerbated the condition and/or its symptoms.
- They are unrelated to the condition.
If someone is able to read the Japanese full text of this paper, please let us know what the neurosurgeons thought about this.
Cupping is a so-called alternative medicine (SCAM) that has existed in several ancient cultures. It recently became popular when US Olympic athletes displayed cupping marks on their bodies, and it was claimed that cupping is used for enhancing their physical performance. There are two distinct forms: dry and wet cupping.
Wet cupping involves scarring the skin with a sharp instrument and then applying a cup with a vacuum to suck blood from the wound. It can thus be seen (and was traditionally used) as a form of blood-letting. Wet cupping is being recommended by enthusiasts for a wide range of conditions. But does it work?
This study compared the effects of wet-cupping therapy with conventional therapy on persistent nonspecific low back pain (PNSLBP). In this randomized clinical trial, 180 participants with the mean age of 45±10 years old, who had been suffering from PNSLBP were randomly assigned to wet-cupping or conventional treatment. The wet-cupping group was treated with two separate sessions (4 weeks in total) on the inter-scapular and sacrum area. In the conventional treatment group, patients were conservatively treated using rest (6 weeks) and oral medications (3 weeks). The primary and the secondary outcome were the quantity of disability using Oswestry Disability Index (ODI), and pain intensity using Visual Analogue Scale (VAS), respectively.
The results show that there was no significant difference in demographic characteristics (age, gender, and body mass index) between the two groups. Therapeutic effect of wet-cupping therapy was comparable to conventional treatment in the 1st month follow-up visits. The functional outcomes of wet-cupping at the 3rd and 6th month visits were significantly superior compared to the conventional treatment group. The final ODI scores in the wet-cupping and conventional groups were 16.7 ± 5.7 and 22.3 ± 4.5, respectively (P<0.01).
The authors concluded that wet-cupping may be a proper method to decrease PNSLBP without any conventional treatment. The therapeutic effects of wet-cupping can be longer lasting than conventional therapy.
Perhaps the authors were joking? In any case, their conclusions cannot be taken seriously. Why? There are several reasons, but the most obvious ones are:
- There was no adequate control of the presumably substantial placebo effects of wet cupping.
- The control group received a treatment that is known to be ineffective or even detrimental.
For people with acute low back pain, advice to rest in bed is less effective than advice to stay active. Thus comparing wet cupping to a control group treated with bed rest is bound to generate a false-positive outcome for wet cupping.
My final point is perhaps the most important: wet cupping can lead to serious complication, and I therefore do not recommend it to anyone – other than masochists, perhaps.
Treating children is an important income stream for chiropractors and osteopaths. There is plenty of evidence to suspect that their spinal manipulations generate more harm than good; on this blog, we have discussed this problem more often than I care to remember (see for instance here, here, here, here and here). Yet, osteopaths and chiropractors carry on misleading parents to abuse their children with ineffective and dangerous spinal manipulations. A new and thorough assessment of the evidence seems to confirm this suspicion.
This systematic review evaluated the evidence for effectiveness and harms of specific SMT techniques for infants, children and adolescents. Controlled studies, describing primary SMT treatment in infants (<1 year) and children/adolescents (1-18 years), were included to determine effectiveness.
Of the 1,236 identified studies, 26 studies were eligible. Infants and children/adolescents were treated for various (non-)musculoskeletal indications, hypothesized to be related to spinal joint dysfunction. Studies examining the same population, indication and treatment comparison were scarce. The results showed that:
- Due to very low quality evidence, it is uncertain whether gentle, low-velocity mobilizations reduce complaints in infants with colic or torticollis, and whether high-velocity, low-amplitude manipulations reduce complaints in children/adolescents with autism, asthma, nocturnal enuresis, headache or idiopathic scoliosis.
- Five case reports described severe harms after HVLA manipulations in 4 infants and one child. Mild, transient harms were reported after gentle spinal mobilizations in infants and children, and could be interpreted as side effect of treatment.
The authors concluded that due to very low quality of the evidence, the effectiveness of gentle, low-velocity mobilizations in infants and HVLA manipulations in children and/or adolescents is uncertain. Assessments of intermediate outcomes are lacking in current pediatric SMT research. Therefore, the relationship between specific treatment and its effect on the hypothesized spinal dysfunction remains unclear. Gentle, low-velocity spinal mobilizations seem to be a safe treatment technique. Although scarcely reported, HVLA manipulations in infants and young children could lead to severe harms. Severe harms were likely to be associated with unexamined or missed underlying medical pathology. Nevertheless, there is a need for high quality research to increase certainty about effectiveness and safety of specific SMT techniques in infants, children and adolescents. We encourage conduction of controlled studies that focus on the effectiveness of specific SMT techniques on spinal dysfunction, instead of concluding about SMT as a general treatment approach. Large observational studies could be conducted to monitor the course of complaints/symptoms in children and to gain a greater understanding of potential harms.
The situation regarding spinal manipulation for children might be summarised as follows:
- Spinal manipulations are not demonstrably effective for paediatric conditions.
- They can cause serious direct and indirect harm.
- Chiropractors and osteopaths are not usually competent to treat children.
- They nevertheless treat children regularly.
In my view, this is unethical and can amount to child abuse.
So-called alternative medicine (SCAM) is a seriously dangerous option for cancer patients who aim at curing their cancer with it. One cannot warn patients often and strongly enough, I believe. But when it comes to supportive cancer treatment (care that does not aim at changing the natural history of the disease), SCAM might have a place. I said ‘might’ because its exact role is far from clear.
The aim of this study was to investigate the effects of a complex, nurse-led, supportive care intervention using SCAM on patients’ quality of life (QoL) and associated patient-reported outcomes. In this prospective, pragmatic, bicentric, randomized controlled trial, women with breast or gynaecologic cancers undergoing a new regimen of chemotherapy (CHT) were randomly assigned to routine supportive care plus intervention (intervention group, IG) or routine care alone (control group, CG). The intervention consisted of SCAM applications and counseling for symptom management, as well as SCAM information material. The primary endpoint was global QoL measured with the EORTC-QLQ-C30 before and after SCAM.
In total, 126 patients were randomly assigned into the IG and 125 patients into the CG. The patients’ medical and socio-demographic characteristics were homogenous at baseline and at follow-up. No group effects on QoL were found upon completion of CHT, but there was a significant group difference in favour of the IG, 6 months later. IG patients did also experience significant better emotional functioning and less fatigue.
The authors concluded that the tested supportive intervention did not improve patients’ QoL outcomes directly after CHT (T3), but was associated with significant QoL improvements when considering the change from baseline to the time point T4, which could be assessed 6 months after patients’ completion of CHT. This delayed effect may have resulted due to a strengthening of patients’ self-management competencies.
A prospective, pragmatic, bicentric, randomized controlled trial! Doesn’t this sound rigorous? In fact, this term merely hides a trial that was destined to generate a positive result. As it followed the infamous A+B versus B design, it hardly had a chance to not come out positive.
The only thing I find amazing is that the short-term results failed to be statistically significant. Far too many SCAM researchers, it seems to me, view science as a tool for promoting their dubious ideas.
The use of SCAM with the aim of improving QoL might be helpful. But this assumption cannot be accepted on the basis of opinion; we need good science to find out which forms of SCAM are worth employing. Sadly, studies like the above are not in this category.
If you ask me, it is high time that this misleading nonsensical and unethical pseudo-research stops!
Spinal manipulation is an umbrella term for numerous manoeuvres chiropractors, osteopaths, physiotherapists and other clinicians apply to their patients’ vertebral columns. Spinal manipulations are said to be effective for a wide range of conditions. But how do they work? What is their mode of action? A new article tries to address these questions. here is its abstract:
Spinal manipulation has been an effective intervention for the management of various musculoskeletal disorders. However, the mechanisms underlying the pain modulatory effects of spinal manipulation remain elusive. Although both biomechanical and neurophysiological phenomena have been thought to play a role in the observed clinical effects of spinal manipulation, a growing number of recent studies have indicated peripheral, spinal and supraspinal mechanisms of manipulation and suggested that the improved clinical outcomes are largely of neurophysiological origin. In this article, we reviewed the relevance of various neurophysiological theories with respect to the findings of mechanistic studies that demonstrated neural responses following spinal manipulation. This article also discussed whether these neural responses are associated with the possible neurophysiological mechanisms of spinal manipulation. The body of literature reviewed herein suggested some clear neurophysiological changes following spinal manipulation, which include neural plastic changes, alteration in motor neuron excitability, increase in cortical drive and many more. However, the clinical relevance of these changes in relation to the mechanisms that underlie the effectiveness of spinal manipulation is still unclear. In addition, there were some major methodological flaws in many of the reviewed studies. Future mechanistic studies should have an appropriate study design and methodology and should plan for a long-term follow-up in order to determine the clinical significance of the neural responses evoked following spinal manipulation.
I have to admit, this made me laugh. Any article that starts with the claim spinal manipulation is an effective intervention and speaks about its observed clinical effects without critically assessing the evidence for it must be ridiculous. The truth is that, so far, it is unclear whether spinal manipulations cause any therapeutic effects at all. To take them as a given, therefore discloses a bias that can only be a hindrance to any objective evaluation.
Yet, perhaps unwittingly, the paper raises an important question: do we need to search for a mode of action of treatments that are unproven? It is a question, of course, that is relevant to all or at least much of SCAM.
Do we need to research the mode of action of acupuncture?
Do we need to research the mode of action of energy healing?
Do we need to research the mode of action of reflexology?
Do we need to research the mode of action of homeopathy?
Do we need to research the mode of action of Bach flower remedies?
Do we need to research the mode of action of cupping?
Do we need to research the mode of action of qigong?
In the absence of compelling evidence that a mode of action (other than the placebo response) exists, I would say: no, we don’t. Such research might turn out to be wasteful and carries the risk of attributing credibility to treatments that do not deserve it.
What do you think?
Many cancer patients use so-called alternative medicine (SCAM) such as Traditional Chinese Medicine (TCM). On this blog, we have repeatedly discussed whether this does more good than harm. This study sheds new light on the question. Specifically, it aims to explore the benefits of TCM therapy in the long-term survival of patients with hepatocellular carcinoma in China.
In total, 3483 patients with HCC admitted to the Beijing Ditan Hospital of Capital Medical University were enrolled. The researchers used 1:1 frequency matching by sex, age, diagnosis time, Barcelona Clinic Liver Cancer staging, and type of treatments to compare the TCM users (n = 526) and non-TCM users (n = 526). A Cox multivariate regression model was employed to evaluate the effects of TCM therapy on the HR value and Kaplan-Meier survival curve for mortality risk in HCC patients. A log-rank test was performed to analyse the effect of TCM therapy on the survival time of HCC patients.
The Cox multivariate analysis indicated that TCM therapy was an independent protective factor for 5-year survival in patients with HCC. The Kaplan-Meier curve also showed that after PS matching, TCM users had a higher overall survival rate and a higher progression-free survival rate than non-TCM users. TCM users, regardless of the classification of etiology, tumor stage, liver function level, or type of treatment, all benefited significantly from TCM therapy. The most commonly used Chinese patent medications used were Fufang Banmao Capsule, Huaier Granule, and Jinlong Capsule.
The authors concluded that using traditional Chinese medications as adjuvant therapy can probably prolong median survival time and improve the overall survival among patients with HCC. Further scientific studies and clinical trials are needed to examine the efficiency and safety.
I was unable to access the full article and therefore am unable to provide a detailed critique of it. From reading the abstract, I should point out, however, that this was not an RCT. To minimise bias, the researchers used a matching technique to generate two comparable groups. Such methods can be successful in matching for the named parameters, but they cannot match for the plethora of variables that might be relevant but were not measured. Therefore, the survival difference between the two groups might be due not to the therapies they received, but to the fact that the groups were not comparable in terms of factors that impact on survival.
Another important point about this paper is the obvious fact that it originates from China. We know from several independent investigations that such studies almost never report negative findings. We also know that TCM is a hugely important export item for China. Adding two and two together should therefore make us sceptical. I for one take the present findings with more than a pinch of salt.
Indian doctors have just published the case of a 38-year old man with cirrhosis of the liver due to compensated non-alcoholic fatty-liver-disease. He presented with acute worsening of his chronic liver disease. The acute event was not discernible even after extensive work up. Eventually, a transjugular liver biopsy revealed features suggestive of severe alcoholic hepatitis.
The patient and the family denied occult alcohol use when questioned over multiple times. According to the authors, the culprit ‘alcohol’ was found to be the homoeopathy medicines: the patient had been consuming a homeopathic remedy over a month for treatment of Gilbert’s syndrome. The researchers retrieved and tested the homoeopathy drug for alcohol content and found it contained 18% of ethanol. This, they felt, confirmed their diagnosis of alcoholic liver disease caused by the regular consumption of a homeopathic remedy.
Why did the patient help from a homeopath? Gilbert’s syndrome doesn’t usually require any treatment at all. Two weeks into his new treatment, the patient claimed he was feeling drowsy and slurring his speech, as if intoxicated. The liquid homeopathic formulation was therefore reduced at this stage. A further two weeks passed when his eyes yellowed, his urine darkened, and his legs began to swell. A liver tests confirmed a spike in his bilirubin 10 times above normal, with liver enzymes also elevated. All signs were thus pointing to an acute form of hepatitis commonly associated with alcohol binges. With the patient adamant he hadn’t touched alcohol, the doctors looked for other causes of hepatitis. None were found. When the patient admitted using homeopathy, his doctors thought to have found an explanation for the problem.
Despite starting the patient on a range of treatments and referring him to a liver transplant centre for further management, the damage to the patient’s liver proved to be irreversible. One month and 12 days later, the patient developed multiple organ failure and passed away. The authors of this case report point out “at risk patients and the general population need to be educated regarding the fact that complementary and alternative medications are not without side-effects.”
I do agree with their comment, but I very much doubt that their diagnosis of homeopathy-induced liver disease was correct. If the alcohol in the homeopathic remedy truly had been the cause, the patient would have needed to consume well in excess of one litre of it per day. The authors do not tell us about the volume of consumption, but I doubt that a patient would be able to afford such an orgy in homeopathy.
Highly diluted homeopathic remedies contain nothing, it is often said. This is not entirely true. In the case of solid preparations (globuli), they do contain sugar, and in the case of liquid remedies, they contain alcohol. Yet, as a source of either ingredient, they are neither practical nor economical. I fear therefore that the medical team of the diseased man are mistaken when accusing homeopathy of being the cause of their patient’s death.
Kampo, the traditional Japanese herbal medicine, developed out of traditional Chinese herbal medicine after it was introduced into Japan in the 7th century. In the early 20th century, Kampo was further influenced by modern Western medicine and science. The Kampo system is a pragmatic and simplified version of Chinese herbal medicine. Kampo medicines are standardised and not normally individualised as in Chinese herbal medicine. They are based on the symptoms of the patient, interpreted in the tradition of Kampo. Kampo diagnostic criteria consider hypofunction and hyperfunction, heat and cold, superficies and interior, and yin and yang.
Today, Kampō is fully integrated into the Japanese national health care system, and numerous Kampo preparations are registered in Japan and reimbursable from public funds. In Japan, Kampo is thus not a so-called alternative medicine (SCAM), but outside this country it clearly is.
Standardised Kampo formulas contain mixtures of herbal ingredients. They are manufactured under proper quality control. The most commonly used plants include liquorice, ginger and Chinese peony root. Most Japanese doctors routinely prescribe Kampo medicines, and most patients combine Kampo with Western medicine. Since 2002, the teaching of Kampo has been included in Japanese curricula of medical and pharmacy education. The efficacy of Kampo medicines is often less solidly documented than one would hope or expect. There is a remarkable shortage of high-quality clinical trials.
As Kampo medicines contain pharmacologically active ingredients, they can also cause adverse effects and might interact with synthetic drugs. Yet, the risks of Kampo are currently woefully under-investigated. And this is why an analysis of adverse events associated with Kampo formulations that was just published is particularly important.
The researchers obtained reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analysed.
There were 4,232 reported adverse events associated with Kampo. They related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix.
The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba.
The authors concluded that Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety.
While this paper presents invaluable data, its authors offer little by way of critical discussion. There is hardly any good evidence to show that any of the Kampo formulas are effective. Thus a discussion needs to be had about the question whether they generate more good than harm. The authors are completely silent on this important issue, and I suspect the reason might be that Kampo is a bit of a ‘holy cow’ in Japan that must not be questioned.
The numbers of adverse events are impressively high, but we do not know how they compare to adverse events in other areas of healthcare. For instance, it would be valuable to have comparative data indicating how many adverse events occurred with Kampo compared to synthetic drugs per 1 000 patients using them.
Thus we are left with the conclusion that, once proper post-marketing methods are employed to monitor SCAM, we are likely to realise that adverse events do occur more frequently than SCAM enthusiasts might have predicted. In my view, it is high time that we have effective adverse event monitoring in all areas of SCAM.