The recent meta-analysis by Mathie et al for non-individualised homeopathy (recently discussed here) identified just 3 RCTs that were rated as ‘reliable evidence’. But just how rigorous are these ‘best’ studies? Let’s find out!
THE FIRST STUDY
The objective of the first trial was “to evaluate the efficacy of the non-hormonal treatment BRN-01 in reducing hot flashes in menopausal women.” Its design was that of a multicentre (35 centres in France), randomized, double-blind, placebo-controlled. One hundred and eight menopausal women, ≥50 years of age, were enrolled in the study. The eligibility criteria included menopause for <24 months and ≥5 hot flashes per day with a significant negative effect on the women’s professional and/or personal life. Treatment was either BRN-01 tablets, a registered homeopathic medicine [not registered in the UK] containing Actaea racemosa (4 centesimal dilutions [4CH]), Arnica montana (4CH), Glonoinum (4CH), Lachesis mutus (5CH), and Sanguinaria canadensis (4CH), or placebo tablets, prepared by Laboratoires Boiron according to European Pharmacopoeia standards [available OTC in France]. Oral treatment (2 to 4 tablets per day) was started on day 3 after study enrolment and was continued for 12 weeks. The main outcome measure was the hot flash score (HFS) compared before, during, and after treatment. Secondary outcome criteria were the quality of life (QoL) [measured using the Hot Flash Related Daily Interference Scale (HFRDIS)], severity of symptoms (measured using the Menopause Rating Scale), evolution of the mean dosage, and compliance. All adverse events (AEs) were recorded. One hundred and one women were included in the final analysis (intent-to-treat population: BRN-01, n = 50; placebo, n = 51). The global HFS over the 12 weeks, assessed as the area under the curve (AUC) adjusted for baseline values, was significantly lower in the BRN-01 group than in the placebo group (mean ± SD 88.2 ± 6.5 versus 107.2 ± 6.4; p = 0.0411). BRN-01 was well tolerated; the frequency of AEs was similar in the two treatment groups, and no serious AEs were attributable to BRN-01. The authors concluded that BRN-01 seemed to have a significant effect on the HFS, compared with placebo. According to the results of this clinical trial, BRN-01 may be considered a new therapeutic option with a safe profile for hot flashes in menopausal women who do not want or are not able to take hormone replacement therapy or other recognized treatments for this indication.
Laboratoires Boiron provided BRN-01, its matching placebo, and financial support for the study. Randomization and allocation were carried out centrally by Laboratoires Boiron. I would argue that the treatment time in this study was way too short for generating a therapeutic response. The evolution of the HFS in the two groups was assessed by analysis of the area under the curve (AUC) of the mean scores recorded weekly from each patient in each group over the duration of the study, including those at enrollment (before any treatment). I wonder whether this method was chosen only when the researchers noted that the HFS at the pre-defined time points did not yield a significant result or whether it was pre-determined (elsewhere in the methods section we are told that “The primary evaluation criterion was the effect of BRN-01 on the HFS, compared with placebo. The HFS was defined as the product of the daily frequency and intensity of all hot flashes experienced by the patient, graded by the women from 1 to 4 (1 = mild; 2 = moderate; 3 = strong; 4 = very strong). These data were recorded by the women on a self-administered questionnaire, assisted by a telephone call from a clinical research associate. Data were collected (i) during the first 2 days after enrolment and before any medication had been taken; (ii) then every Tuesday and Wednesday of each week until the 11th week of treatment, inclusive; and (iii) finally, every day of the 12th week of treatment.”). Two of the authors of this paper are employees of Boiron.
THE SECOND STUDY
The second trial was aimed at finding out “whether a well-known and frequently prescribed homeopathic preparation could mitigate post-operative pain.” It was a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of the homeopathic preparation Traumeel S® in minimizing post-operative pain and analgesic consumption following surgical correction of hallux valgus. Eighty consecutive patients were randomized to receive either Traumeel tablets or an indistinguishable placebo, and took primary and rescue oral analgesics as needed. Maximum numerical pain scores at rest and consumption of oral analgesics were recorded on day of surgery and for 13 days following surgery. Traumeel was not found superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial, however a transient reduction in the daily maximum post-operative pain score favoring the Traumeel arm was observed on the day of surgery, a finding supported by a treatment-time interaction test (p = 0.04). The authors concluded that Traumeel was not superior to placebo in minimizing pain or analgesic consumption over the 14 days of the trial. A transient reduction in the daily maximum post-operative pain score on the day of surgery is of questionable clinical importance.
Traumeel is a mixture of 6 ingredients, 4 of which are in the D2 potency. Thus it neither is administered as a homeopathic remedy (no ‘like cures like’) nor is it highly diluted. In fact, it is not homeopathy at all but belongs to a weird offspring of homeopathy called ‘homotoxicology’ [this is an explanation from my book: Homotoxicology is a method inspired by homeopathy which was developed by Hans Heinrich Reckeweg (1905 – 1985). He believed that all or most illness is caused by an overload of toxins in the body. The toxins originate, according to Reckeweg, both from the environment and from the malfunction of physiological processes within the body. His treatment consists mainly in applying homeopathic remedies which usually consist of combinations of single remedies, because health cannot be achieved without ridding the body of toxins. The largest manufacturer and promoter of remedies used in homotoxicology is the German firm Heel.] The HEEL Company (Baden-Baden, Germany) provided funding for the performance and monitoring of this project, supplied the study medication and placebo, and prepared the randomization list. The positive outcome mentioned in the authors’ conclusion refers to a secondary endpoint. I would argue that the authors should not have noted it there and should have made it clear that the trial generated a negative result.
THE THIRD STUDY
Finally, the third of the 3 ‘rigorous’ studies “evaluated the effectiveness of the homeopathic preparation Plumbum Metallicum (PM) in reducing the blood lead levels of workers exposed to this metal.” The Brazilian researchers recruited 131 workers to this RCT who took PM in the CH15 potency or placebo for 35 days (10 drops twice daily). Thereafter, the percentage of workers whose lead level had fallen by at least 25% did not differ between the groups, both on intention to treat and per protocol analyses. The authors concluded that PM “had no effect in this study in terms of reducing serum lead in workers exposed to lead.”
This study lacks a power calculation, and arguably the period might have been too short to show an effect. The trial was published in the journal HOMEOPATHY which, some might argue, has not the most rigorous of peer-review procedures.
The third study seems the most rigorous by far, in my view. The other two trials are seriously under-whelming in several respects, primarily because we cannot be sure how much influence the commercial interests of the sponsor had on their findings. I am sure others will spot weaknesses in all three trials that I failed to see.
Mathie et al partly disagree with my assessment when they write in their paper: “We report separately our model validity assessments of these trials, evaluating consequently their overall quality based on a GRADE-like principle of ‘downgrading’ : two trials [23, 25] rated here as reliable evidence were downgraded to ‘low quality’ overall due to the inadequacy of their model validity; the remaining trial with reliable evidence  was judged to have adequate model validity. The latter study  thus comprises the sole RCT that can be designated ‘high quality’ overall by our approach, a stark finding that reveals further important aspects of the preponderantly low quality of the current body of evidence in non-individualised homeopathy.”
What Mathie et al seem to forget entirely is that none of the 3 RCTs is a trial of homeopathy as defined by treatment according to the ‘like cures like’ principle. The authors of the second study acknowledge this fact by stating: “Homeopathic purists may find fault in the administration of a standardized combination homeopathic formula to all patients, based upon clinical diagnosis – as opposed to the individualized manner dictated by standard homeopathic practice.”
So, which ever way we look upon this evidence, we cannot possibly deny that the evidence for non-individualised homeopathy is rubbish.
This new systematic review by proponents of homeopathy (and supported by a grant from the Manchester Homeopathic Clinic) tested the null hypothesis that “the main outcome of treatment using a non-individualised (standardised) homeopathic medicine is indistinguishable from that of placebo“. An additional aim was to quantify any condition-specific effects of non-individualised homeopathic treatment. In reporting this paper, I will stay very close to the published text hoping that this avoids both misunderstandings and accusations of bias on my side:
Literature search strategy, data extraction and statistical analysis followed the methods described in a pre-published protocol. A trial comprised ‘reliable evidence’ if its risk of bias was low or it was unclear in one specified domain of assessment. ‘Effect size’ was reported as standardised mean difference (SMD), with arithmetic transformation for dichotomous data carried out as required; a negative SMD indicated an effect favouring homeopathy.
The authors excluded the following types of trials: studies of crossover design; of radionically prepared homeopathic medicines; of homeopathic prophylaxis; of homeopathy combined with other (complementary or conventional) intervention; for other specified reasons. The final explicit exclusion criterion was that there was obviously no blinding of participants and practitioners to the assigned intervention.
Forty-eight different clinical conditions were represented in 75 eligible RCTs; 49 were classed as ‘high risk of bias’ and 23 as ‘uncertain risk of bias’; the remaining three trials displayed sufficiently low risk of bias to be designated reliable evidence. Fifty-four trials had extractable data: pooled SMD was -0.33 (95% confidence interval (CI) -0.44, -0.21), which was attenuated to -0.16 (95% CI -0.31, -0.02) after adjustment for publication bias. The three trials with reliable evidence yielded a non-significant pooled SMD: -0.18 (95% CI -0.46, 0.09). There was no single clinical condition for which meta-analysis produced reliable evidence.
A meta-regression was performed to test specifically for within-group differences for each sub-group. The results showed that there were no significant differences between studies that were and were not:
- included in previous meta-analyses (p = 0.447);
- pilot studies (p = 0.316);
- greater than the median sample (p = 0.298);
- potency ≥ 12C (p = 0.221);
- imputed for meta-analysis (p = 0.384);
- free from vested interest (p = 0.391);
- acute/chronic (p = 0.796);
- different types of homeopathy (p = 0.217).
After removal of ‘C’-rated trials, the pooled SMD still favoured homeopathy for all sub-groups, but was statistically non-significant for 10 of the 18 (included in previous meta-analysis; pilot study; sample size > median; potency ≥12C; data imputed; free of vested interest; not free of vested interest; combination medicine; single medicine; chronic condition). There remained no significant differences between sub-groups—with the exception of the analysis for sample size > median (p = 0.028).
Meta-analyses were possible for eight clinical conditions, each analysis comprising two to 5 trials. A statistically significant pooled SMD, favouring homeopathy, was observed for influenza (N = 2), irritable bowel syndrome (N = 2), and seasonal allergic rhinitis (N = 5). Each of the other five clinical conditions (allergic asthma, arsenic toxicity, infertility due to amenorrhoea, muscle soreness, post-operative pain) showed non-significant findings. Removal of ‘C’-rated trials negated the statistically significant effect for seasonal allergic rhinitis and left the non-significant effect for post-operative pain unchanged; no higher-rated trials were available for additional analysis of arsenic toxicity, infertility due to amenorrhoea or irritable bowel syndrome. There were no ‘C’-rated trials to remove for allergic asthma, influenza, or muscle soreness. Thus, influenza was the only clinical condition for which higher-rated trials indicated a statistically significant effect; neither of its contributing trials, however, comprised reliable evidence.
The authors concluded that the quality of the body of evidence is low. A meta-analysis of all extractable data leads to rejection of our null hypothesis, but analysis of a small sub-group of reliable evidence does not support that rejection. Reliable evidence is lacking in condition-specific meta-analyses, precluding relevant conclusions. Better designed and more rigorous RCTs are needed in order to develop an evidence base that can decisively provide reliable effect estimates of non-individualised homeopathic treatment.
I am sure that this paper will lead to lively discussions in the comments section of this blog. I will therefore restrict my comments to a bare minimum.
In my view, this new meta-analysis essentially yield a negative result and confirms most previous, similar reviews.
- It confirms Linde’s conclusion that “insufficient evidence from these studies that homeopathy is clearly efficacious for any single clinical condition”.
- It confirms Linde’s conclusion that “there was clear evidence that studies with better methodological quality tended to yield less positive results”.
- It confirms Kleinjen’s conclusion that “most trials are of low methodological quality”.
- It also confirms the results of the meta-analysis by Shang et al (much-maligned by homeopaths) than “finding is compatible with the notion that the clinical effects of homoeopathy are placebo effects.”
- Finally, it confirms the conclusion of the analysis of the Australian National Health and Medical Research Council: “Homeopathy should not be used to treat health conditions that are chronic, serious, or could become serious. People who choose homeopathy may put their health at risk if they reject or delay treatments for which there is good evidence for safety and effectiveness. People who are considering whether to use homeopathy should first get advice from a registered health practitioner. Those who use homeopathy should tell their health practitioner and should keep taking any prescribed treatments.”
Another not entirely unimportant point that often gets missed in these discussions is this: even if we believe (which I do not) the most optimistic interpretation of these (and similar data) by homeopaths, we ought to point out that there is no evidence whatsoever that homeopathy cures anything. At the very best it provides marginal symptomatic relief. Yet, the claim of homeopaths that we hear constantly is that homeopathy is a causal and curative therapy.
The first author of the new meta-analysis is an employee of the Homeopathy Research Institute. We might therefore forgive him that he he repeatedly insists on dwelling on largely irrelevant (i. e. based on unreliable primary studies) findings. It seems obvious that firm conclusions can only be based on reliable data. I therefore disregard those analyses and conclusions that include such studies.
In the discussion, the authors of the new meta-analysis confirm my interpretation this by stating that they “reject the null hypothesis (non-individualised homeopathy is indistinguishable from placebo) on the basis of pooling all studies, but fail to reject the null hypothesis on the basis of the reliable evidence only.” And, in the long version of their conclusions, we find this remarkable statement: “Our meta-analysis of the current reliable evidence base therefore fails to reject the null hypothesis that the outcome of treatment using a non-individualised homeopathic medicine is not distinguishable from that using placebo.” A most torturous way of stating the obvious: the more reliable data show no difference between homeopathy and placebo.
Acupuncture is little more than a theatrical placebo! If we confront an acupuncture fan with this statement, he/she is bound to argue that there are some indications for which the evidence is soundly positive. One of these conditions, they would claim, is nausea and vomiting. But how strong are these data? A new study sheds some light on this question.
The objective of this RCT was to evaluate if consumption of antiemetics and eating capacity differed between patients receiving verum acupuncture, sham acupuncture, or standard care only during radiotherapy. Patients were randomized to verum (n = 100) or sham (n = 100) acupuncture (telescopic blunt sham needle) (12 sessions) and registered daily their consumption of antiemetics and eating capacity. A standard care group (n = 62) received standard care only.
The results show that more patients in the verum and the sham acupuncture group did not need any antiemetic medications, as compared to the standard care group after receiving 27 Gray dose of radiotherapy. More patients in the verum and the sham acupuncture group were capable of eating as usual, compared to the standard care group. Patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture.
The authors concluded that patients receiving acupuncture had lower consumption of antiemetics and better eating capacity than patients receiving standard antiemetic care, plausible by nonspecific effects of the extra care during acupuncture.
I find these conclusions odd because they seem to state that acupuncture was more effective than standard care. Subsequently – almost as an afterthought – they mention that its effects are brought about by nonspecific effects. This is grossly misleading, in my view.
The study was designed as a comparison between real and sham acupuncture, and the standard care group was not a randomised comparison group. Therefore, the main result and conclusion has to focus on the comparison between verum and sham acupuncture. This comparison shows that the two did not produce different result. Therefore, the study shows that acupuncture was not effective.
A much more reasonable conclusion would have been: THIS STUDY FAILED TO FIND SIGNIFICANT EFFECTS OF ACUPUNCTURE BEYOND PLACEBO.
Tui Na is a massage technique that is based on the Taoist principles of TCM. It involves a range of manipulations usually performed by an operator’s finger, hand, elbow, knee, or foot applied to muscle or soft tissue at specific parts of the body. According to one website of TCM-proponents “Tui Na makes use of various hand techniques in combination with acupuncture and other manipulation techniques. To enhance the healing process, the practitioner may recommend the use of Chinese herbs. Many of the techniques used in this massage resemble that of a western massage like gliding, kneading, vibration, tapping, friction, pulling, rolling, pressing and shaking. In Tui Na massage, the muscles and tendons are massaged with the help of hands, and an acupressure technique is applied to directly affect the flow of Qi at different acupressure points of the body, thus facilitating the healing process. It removes the blockages and keeps the energy moving through the meridians as well as the muscles. A typical session of Tui Na massage may vary from thirty minutes to an hour. The session timings may vary depending on the patient’s needs and condition. The best part of the therapy is that it relaxes as well as energizes the person. The main benefit of Tui Na massage is that it focuses on the specific problem, whether it is an acute or a chronic pain associated with the joints, muscles or a skeletal system. This technique is very beneficial in reducing the pain of neck, shoulders, hips, back, arms, highs, legs and ankle disorders. It is a very effective therapy for arthritis, pain, sciatica and muscle spasms. Other benefits of this massage therapy include alleviation of the stress related disorders like insomnia, constipation, headaches and other disorders related to digestive, respiratory and reproductive systems. The greatest advantage of Tui Na is that it focuses on maintaining overall balance with both physical and mental health. Any one who wants to avoid the side effects of drugs or a chemical based treatment can adopt this effective massage technique to alleviate their pain. Tui Na massage therapy is now becoming a more common therapy method due to its focus on specific problems rather than providing a general treatment.”
This clearly begs the question IS IT EFFECTIVE?
This systematic review assessed the evidence of Tui Na for cervical radiculopathy. Seven databases were searched. Randomised controlled trials (RCTs) incorporating Tui Na alone or Tui Na combined with conventional treatment were included. Five studies involving 448 patients were found. The pooled analysis from the 3 trials indicated that Tui Na alone showed a significant lowering immediate effects on pain score with moderate heterogeneity compared to cervical traction. The meta-analysis from 2 trials revealed significant immediate effects of Tui Na plus cervical traction in improving pain score with no heterogeneity compared to cervical traction alone. None of the RCTs mentioned adverse effects. There was very low quality or low quality evidence to support the results.
The authors concluded that “Tui Na alone or Tui Na plus cervical traction may be helpful to cervical radiculopathy patients, but supportive evidence seems generally weak. Future clinical studies with low risk of bias and adequate follow-up design are recommended.”
In my view, this is a misleading conclusion. A correct one would have been: THE CURRENT EVIDENCE IS INSUFFICIENT TO DRAW ANY CONCLUSIONS ABOUT THE EFFECTIVENESS OF TUI NA.
Here are some of the most obvious reasons:
- there are far too few studies for a firm conclusion,
- the included RCTs lack scientific rigour,
- all trials originate from China where reliability seems to be a serious problem,
- traction is not a useful therapy for radiculopathy,
- the primary studies violate research ethics by not reporting adverse effects.
Personally, I am getting very tired of conclusions stating ‘…XY MAY BE EFFECTIVE/HELPFUL/USEFUL/WORTH A TRY…’ It is obvious that the therapy in question MAY be effective, otherwise one would surely not conduct a systematic review. If a review fails to produce good evidence, it is the authors’ ethical, moral and scientific obligation to state this clearly. If they don’t, they simply misuse science for promotion and mislead the public. Strictly speaking, this amounts to scientific misconduct.
Drug and alcohol dependencies are notoriously difficult to treat effectively. Patients and their families are often desperate and willing to try anything. This seems like an ideal ground for acupuncturists who are, in my experience, experts in putting up smokescreens hiding the true value of their treatment.
The best way to determine the value of any intervention is probably conducting a systematic review of the evidence from rigorous clinical trials. Today we are in the fortunate position to have not just one of those articles; but do they really tell us the truth?
This brand-new systematic review investigated the effects of acupuncture on alcohol-related symptoms and behaviors in patients with this disorder. The PubMed database was searched until 23 August 2016, and reference lists from review studies were also reviewed. The inclusion criteria were the following: (1) being published in a peer-reviewed English-language journal, (2) use of randomized controlled trials (RCTs), (3) assessing the effects of acupuncture on psychological variables in individuals with a primary alcohol problem, and (4) reporting statistics that could be converted to effect sizes.
Seventeen studies were identified for a full-text inspection, and seven (243 patients) of these met our inclusion criteria. The outcomes assessed at the last post-treatment point and any available follow-up data were extracted from each of the studies. Five studies treated patients by inserting a needle into several acupoints in each ear. Two studies stimulated body points with or without ear stimulation. Four studies treated control patients with a placebo needle or under a completely different type of intervention, such as relaxation or transdermal stimulation, whereas the remaining studies inserted needles into nonspecific points. The patients were treated for 2 weeks to 3 months, and the treatment duration per session was 15–45 min. The results of the meta-analysis demonstrated that an acupuncture intervention had a stronger effect on reducing alcohol-related symptoms and behaviours than did the control intervention. A beneficial but weak effect of acupuncture treatment was also found in the follow-up data.
The authors concluded that although our analysis showed a significant difference between acupuncture and the control intervention in patients with alcohol use disorder, this meta-analysis is limited by the small number of studies included. Thus, a larger cohort study is required to provide a firm conclusion.
I am used to reading poor research papers, but this one is like a new dimension. Here are just the most obvious flaws:
- by searching just one database, the likelihood of missing studies is huge,
- by excluding non-English papers, the review automatically becomes non-systematic,
- the included studies differed vastly in many respects and can therefore not be pooled.
As it happens, a further meta-analysis has just been published. Here is its abstract:
Acupuncture has been widely used as a treatment for alcohol dependence. An updated and rigorously conducted systematic review is needed to establish the extent and quality of the evidence on the effectiveness of acupuncture as an intervention for reducing alcohol dependence. This review aimed to ascertain the effectiveness of acupuncture for reducing alcohol dependence as assessed by changes in either craving or withdrawal symptoms.
In this systematic review, a search strategy was designed to identify randomised controlled trials (RCTs) published in either the English or Chinese literature, with a priori eligibility criteria. The following English language databases were searched from inception until June 2015: AMED, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and PubMed; and the following Chinese language databases were similarly searched: CNKI, Sino-med, VIP, and WanFang. Methodological quality of identified RCTs was assessed using the Jadad Scale and the Cochrane Risk of Bias tool.
Fifteen RCTs were included in this review, comprising 1378 participants. The majority of the RCTs were rated as having poor methodological rigour. A statistically significant effect was found in the two primary analyses: acupuncture reduced alcohol craving compared with all controls (SMD = −1.24, 95% CI = −1.96 to −0.51); and acupuncture reduced alcohol withdrawal symptoms compared with all controls (SMD = −0.50, 95% CI = −0.83 to −0.17). In secondary analyses: acupuncture reduced craving compared with sham acupuncture (SMD = −1.00, 95% CI = −1.79 to −0.21); acupuncture reduced craving compared with controls in RCTs conducted in Western countries (SMD = −1.15, 95% CI = −2.12 to −0.18); and acupuncture reduced craving compared with controls in RCTs with only male participants (SMD = −1.68, 95% CI = −2.62 to −0.75).
This study showed that acupuncture was potentially effective in reducing alcohol craving and withdrawal symptoms and could be considered as an additional treatment choice and/or referral option within national healthcare systems.
This Meta-analysis is only a little better than the first, I am afraid. What its conclusions do not sufficiently reflect, in my view, is the fact that the quality of the primary studies was mostly very poor – too poor to draw conclusions from (other than ‘acupuncture research is usually lousy’; see figure below). Therefore, I fail to see how the authors could draw the relatively firm and positive conclusions cited above. In my view, they should have stated something like this: DUE TO THE RISK OF BIAS IN MANY TRIALS, THE EFFECTIVENESS OF ACUPUNCTURE REMAINS UNPROVEN.
The authors of the first meta-analysis open the discussion by proudly declaring that “the present study is the first meta-analysis to examine the effect of acupuncture treatment on patients with alcohol use disorder and to provide data on the magnitude of this effect on alcohol-related clinical symptoms and behaviours.” They discretely overlook this meta-analysis from 2009 (and several others which even their rudimentary search would have identified):
Nineteen electronic databases, including English, Korean, Japanese, and Chinese databases, were systematically searched for RCTs of acupuncture for alcohol dependence up to June 2008 with no language restrictions. The methodological qualities of eligible studies were assessed using the criteria described in the Cochrane Handbook.
Eleven studies, which comprised a total of 1,110 individual cases, were systematically reviewed. Only 2 of 11 trials reported satisfactorily all quality criteria. Four trials comparing acupuncture treatment and sham treatments reported data for alcohol craving. Three studies reported that there were no significant differences. Among 4 trials comparing acupuncture and no acupuncture with conventional therapies, 3 reported significant reductions. No differences between acupuncture and sham treatments were found for completion rates (Risk Ratio = 1.07, 95% confidence interval, CI = 0.91 to 1.25) or acupuncture and no acupuncture (Risk Ratio = 1.15, 95% CI = 0.79 to 1.67). Only 3 RCTs reported acupuncture-related adverse events, which were mostly minimal.
The results of the included studies were equivocal, and the poor methodological quality and the limited number of the trials do not allow any conclusion about the efficacy of acupuncture for treatment of alcohol dependence. More research and well-designed, rigorous, and large clinical trials are necessary to address these issues.
One does not need to be an expert in interpreting meta-analyses, I think, to see that this paper is more rigorous than the new ones (which incidentally were published in the very dubious journals). And this is why I trust the conclusions of this last-named meta-analysis more than those of the new one: the efficacy of acupuncture remains unproven. And this means that we should not employ or promote it for routine care.
Is spinal manipulative therapy (SMT) dangerous? This question has kept us on this blog busy for quite some time now. To me, there is little doubt that SMT can cause adverse effects some of which are serious. But many chiropractors seem totally unconvinced. Perhaps this new overview of reviews might help to clarify the issue. Its aim was to elucidate and quantify the risk of serious adverse events (SAEs) associated with SMT.
The authors searched five electronic databases from inception to December 8, 2015 and included reviews on any type of studies, patients, and SMT technique. The primary outcome was SAEs. The quality of the included reviews was assessed using a measurement tool to assess systematic reviews (AMSTAR). Since there were insufficient data for calculating incidence rates of SAEs, they used an alternative approach; the conclusions regarding safety of SMT were extracted for each review, and the communicated opinion were judged by two reviewers independently as safe, harmful, or neutral/unclear. Risk ratios (RRs) of a review communicating that SMT is safe and meeting the requirements for each AMSTAR item, were calculated.
A total of 283 eligible reviews were identified, but only 118 provided data for synthesis. The most frequently described adverse events (AEs) were stroke, headache, and vertebral artery dissection. Fifty-four reviews (46%) expressed that SMT is safe, 15 (13%) expressed that SMT is harmful, and 49 reviews (42%) were neutral or unclear. Thirteen reviews reported incidence estimates for SAEs, roughly ranging from 1 in 20,000 to 1 in 250,000,000 manipulations. Low methodological quality was present, with a median of 4 of 11 AMSTAR items met (interquartile range, 3 to 6). Reviews meeting the requirements for each of the AMSTAR items (i.e. good internal validity) had a higher chance of expressing that SMT is safe.
The authors concluded that it is currently not possible to provide an overall conclusion about the safety of SMT; however, the types of SAEs reported can indeed be significant, sustaining that some risk is present. High quality research and consistent reporting of AEs and SAEs are needed.
This article is valuable, if only for the wealth of information one can extract from it. There are, however, numerous problems. One is that the overview included mostly reviews of the effectiveness of SMT for various conditions. We know that studies of SMT often do not even mention AEs. If such studies are then pooled in a review, they inevitably generate an impression of safety. But this would, of course, be a false-positive result!
The authors of the overview are aware of this problem and address it in the following paragraph: “When only considering the subset of reviews, where the objective was to investigate AEs (37 reviews), then 8 reviews (22%) expressed that SMT is safe, 13 reviews (35%) expressed that SMT is harmful and 16 reviews (43%) were neutral or unclear regarding the safety of SMT. Hence, there is a tendency that a bigger proportion of these reviews are expressing that SMT is harmful compared to the full sample of reviews…”
To my surprise, I found several of my own reviews in the ‘neutral or unclear’ category. Here are the verbatim conclusions of three of them:
- It is concluded that serious cerebrovascular complications of spinal manipulation continue to be reported.
- The most common serious adverse events are vertebrobasilar accidents, disk herniation, and cauda equina syndrome.
- These data indicate that mild and transient adverse events seem to be frequent. Serious adverse events are probably rare but their incidence can only be estimated at present.
I find it puzzling how this could be classified as neutral or unclear. The solution of the puzzle might lie in the methodology used: “we appraised the communicated opinions of each review concerning the safety of SMT based on their conclusions regarding the AEs and SAEs. This was done by two reviewers independently (SMN, LK), who judged the communicated opinions as either ‘safe’, ‘neutral/unclear’ or ‘harmful’, based on the qualitative impression the reviewers had when reading the conclusions. The reviewers had no opinion about the safety/harmfulness of SMT before commencing the judgements. Cohen’s weighted Kappa was calculated for the agreement between the reviewers, with a value of 0.40–0.59 indicating ‘fair agreement’, 0.60–0.74 indicating ‘good agreement’ and ≥0.75 indicating ‘excellent agreement’. Disagreements were resolved by a third reviewer (MH).”
In other words, the categorisation was done on the basis of subjective judgements of two researchers. It seems obvious that, if their attitude was favourable towards SMT, their judgements would be influenced. The three examples from my own work cited above indicates to me that their verdicts were indeed far from objective.
So what is the main message here? In my view, it can be summarized in the following quote from the overview: “a bigger proportion of these reviews are expressing that SMT is harmful …”
Yes, yes, yes – I know that, if you are a chiropractor (or other practitioner using mostly SMT), you are unlikely to agree with this!
Perhaps you can agree with this statement then:
As long as there is reasonable doubt about the safety of SMT, and as long as we cannot be sure that SMT generates more good than harm, we should be very cautious using it for routine healthcare and do rigorous research to determine the truth (it’s called the precautionary principle and applies to all types of healthcare).
Therapeutic Touch is a therapy mostly popular with nurses. We have discussed it before, for instance here, here, here and here. To call it implausible would be an understatement. But what does the clinical evidence tell us? Does it work?
This literature review by Iranian authors was aimed at critically evaluating the data from clinical trials examining the clinical efficacy of therapeutic touch as a supportive care modality in adult patients with cancer.
Four electronic databases were searched from the year 1990 to 2015 to locate potentially relevant peer-reviewed articles using the key words therapeutic touch, touch therapy, neoplasm, cancer, and CAM. Additionally, relevant journals and references of all the located articles were manually searched for other potentially relevant studies.
The number of 334 articles was found on the basis of the key words, of which 17 articles related to the clinical trial were examined in accordance with the objectives of the study. A total of 6 articles were in the final dataset in which several examples of the positive effects of healing touch on pain, nausea, anxiety and fatigue, and life quality and also on biochemical parameters were observed.
The authors concluded that, based on the results of this study, an affirmation can be made regarding the use of TT, as a non-invasive intervention for improving the health status in patients with cancer. Moreover, therapeutic touch was proved to be a useful strategy for adult patients with cancer.
This review is badly designed and poorly reported. Crucially, its conclusions are not credible. Contrary to what the authors stated when formulating their aims, the methods lack any attempt of critically evaluating the primary data.
A systematic review is more than a process of ‘pea counting’. It requires a rigorous assessment of the risk of bias of the included studies. If that crucial step is absent, the article is next to worthless and the review degenerates into a promotional excercise. Sadly, this is the case with the present review.
You may think that this is relatively trivial (“Who cares what a few feeble-minded nurses do?”), but I would disagree: if the medical literature continues to be polluted by such irresponsible trash, many people (nurses, journalists, healthcare decision makers, researchers) who may not be in a position to see the fatal flaws of such pseudo-reviews will arrive at the wrong conclusions and make wrong decisions. This will inevitably contribute to a hindrance of progress and, in certain circumstances, must endanger the well-being or even the life of vulnerable patients.
The aim of this paper was to systematically review effectiveness, safety, and robustness of evidence for complementary and alternative medicine in managing premature ejaculation (PE). Nine databases were searched through September 2015. Randomized controlled trials (RCTs) evaluating complementary and alternative medicine for PE were included. Studies were included if they reported on intravaginal ejaculatory latency time (IELT) and/or another validated PE measurement. Adverse effects were summarized.
Ten RCTs were included. Two assessed acupuncture, five assessed Chinese herbal medicine, one assessed Ayurvedic herbal medicine, and two assessed topical “severance secret” cream. Risk of bias was unclear in all studies because of unclear allocation concealment or blinding, and only five studies reported stopwatch-measured IELT. Acupuncture slightly increased IELT over placebo in one study (mean difference [MD] = 0.55 minute, P = .001). In another study, Ayurvedic herbal medicine slightly increased IELT over placebo (MD = 0.80 minute, P = .001). Topical severance secret cream increased IELT over placebo in two studies (MD = 8.60 minutes, P < .001), although inclusion criteria were broad (IELT < 3 minutes). Three studies comparing Chinese herbal medicine with selective serotonin reuptake inhibitors (SSRIs) favored SSRIs (MD = 1.01 minutes, P = .02). However, combination treatment with Chinese medicine plus SSRIs improved IELT over SSRIs alone (two studies; MD = 1.92 minutes, P < .00001) and over Chinese medicine alone (two studies; MD = 2.52 minutes, P < .00001). Adverse effects were not consistently assessed but where reported were generally mild.
The authors concluded that there is preliminary evidence for the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical severance secret cream in improving IELT and other outcomes. However, results are based on clinically heterogeneous studies of unclear quality. There are sparse data on adverse effects or potential for drug interactions. Further well-conducted randomized controlled trials would be valuable.
One has to be an optimist to agree that this constitutes ‘preliminary evidence for the effectiveness of acupuncture, Chinese herbal medicine, Ayurvedic herbal medicine, and topical severance secret cream in improving IELT and other outcomes.’ In the discussion section, the authors stress that “…all 10 studies were classed as having an overall unclear risk of bias because of unclear reporting of allocation concealment (all 10 studies) and unclear blinding of participants and personnel (five studies).” This hardly allows even a preliminary conclusion, in my view.
So, what DOES this review show? I think it demonstrates that
- alternative therapies are being touted and occasionally tested for even the most unlikely conditions,
- the quality of the studies is generally too poor to justify the research (particularly in an area as intrusive as PE),
- clinical trials often seem to be used not for finding answers but for promotion,
- in alternative medicine, trialists regularly violate research ethics by failing to report adverse effects.
The title of the press-release was impressive: ‘Columbia and Harvard Researchers Find Yoga and Controlled Breathing Reduce Depressive Symptoms’. It certainly awoke my interest and I looked up the original article. Sadly, it also awoke the interest of many journalists, and the study was reported widely – and, as we shall see, mostly wrongly.
According to its authors, the aims of this study were “to assess the effects of an intervention of Iyengar yoga and coherent breathing at five breaths per minute on depressive symptoms and to determine optimal intervention yoga dosing for future studies in individuals with major depressive disorder (MDD)”.
Thirty two subjects were randomized to either the high-dose group (HDG) or low-dose group (LDG) for a 12-week intervention of three or two intervention classes per week, respectively. Eligible subjects were 18–64 years old with MDD, had baseline Beck Depression Inventory-II (BDI-II) scores ≥14, and were either on no antidepressant medications or on a stable dose of antidepressants for ≥3 months. The intervention included 90-min classes plus homework. Outcome measures were BDI-II scores and intervention compliance.
Fifteen HDG and 15 LDG subjects completed the intervention. BDI-II scores at screening and compliance did not differ between groups. BDI-II scores declined significantly from screening (24.6 ± 1.7) to week 12 (6.0 ± 3.8) for the HDG (–18.6 ± 6.6; p < 0.001), and from screening (27.7 ± 2.1) to week 12 (10.1 ± 7.9) in the LDG. There were no significant differences between groups, based on response (i.e., >50% decrease in BDI-II scores; p = 0.65) for the HDG (13/15 subjects) and LDG (11/15 subjects) or remission (i.e., number of subjects with BDI-II scores <14; p = 1.00) for the HDG (14/15 subjects) and LDG (13/15 subjects) after the 12-week intervention, although a greater number of subjects in the HDG had 12-week BDI-II scores ≤10 (p = 0.04).
The authors concluded that this dosing study provides evidence that participation in an intervention composed of Iyengar yoga and coherent breathing is associated with a significant reduction in depressive symptoms for individuals with MDD, both on and off antidepressant medications. The HDG and LDG showed no significant differences in compliance or in rates of response or remission. Although the HDG had significantly more subjects with BDI-II scores ≤10 at week 12, twice weekly classes (plus home practice) may rates of response or remission. Although the HDG, thrice weekly classes (plus home practice) had significantly more subjects with BDI-II scores ≤10 at week 12, the LDG, twice weekly classes (plus home practice) may constitute a less burdensome but still effective way to gain the mood benefits from the intervention. This study supports the use of an Iyengar yoga and coherent breathing intervention as a treatment to alleviate depressive symptoms in MDD.
The authors also warn that this study must be interpreted with caution and point out several limitations:
- the small sample size,
- the lack of an active non-yoga control (both groups received Iyengar yoga plus coherent breathing),
- the supportive group environment and multiple subject interactions with research staff each week could have contributed to the reduction in depressive symptoms,
- the results cannot be generalized to MDD with more acute suicidality or more severe symptoms.
In the press-release, we are told that “The practical findings for this integrative health intervention are that it worked for participants who were both on and off antidepressant medications, and for those time-pressed, the two times per week dose also performed well,” says The Journal of Alternative and Complementary Medicine Editor-in-Chief John Weeks
At the end of the paper, we learn that the authors, Dr. Brown and Dr. Gerbarg, teach and have published Breath∼Body∼Mind©, a technique that uses coherent breathing. Dr. Streeter is certified to teach Breath∼Body∼Mind©. No competing financial interests exist for the remaining authors.
Taking all of these issues into account, my take on this study is different and a little more critical:
- The observed effects might have nothing at all to do with the specific intervention tested.
- The trial was poorly designed.
- The aims of the study are not within reach of its methodology.
- The trial lacked a proper control group.
- It was published in a journal that has no credibility.
- The limitations outlined by the authors are merely the tip of an entire iceberg of fatal flaws.
- The press-release is irresponsibly exaggerated.
- The authors have little incentive to truly test their therapy and seem to use research as a means of promoting their business.
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.