MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

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It has long been argued that chiropractic spinal manipulations are mere placebo interventions. Yet few controlled trials have assessed the efficacy of spinal manipulative therapy (SMT). No high quality trials have been performed to test the efficacy and effectiveness of Graston Technique® (GT), an instrument-assisted soft tissue therapy.

The objective of this trial was to determine the efficacy of SMT and GT compared to sham therapy for the treatment of non-specific thoracic spine pain.

People with non-specific thoracic pain were randomly allocated to one of three groups: SMT, GT, or a placebo (de-tuned ultrasound). GT is a popular soft-tissue technique in the United States and becoming more popular in other developed countries. GT is an instrument-assisted soft-tissue therapy involving the use of hand-held stainless steel instruments. The promoters of the GT claim that the instruments resonate in the clinician’s hands allowing the clinician to isolate soft-tissue “adhesions and restrictions”, and treat them precisely. Each participant received up to 10 supervised treatment sessions at Murdoch University chiropractic student clinic over a 4 week period.

The two outcome measures were self-administered instruments. Participants were given blank questionnaires in a package by a research assistant following their first treatment. Participants were instructed to complete the instruments at each assessment time point. After completion of the forms the participant posted them back to the Murdoch University Chiropractic Clinic. Research assistants remained blind to the outcome data for the entire study period. The participants and treatment providers were not blinded to the treatment allocation as it was clear that the groups were receiving different treatments. Participants in the placebo group were blinded to their placebo allocation until follow-up was complete at 12 months. Participants were surveyed for the adequacy of the placebo blinding at the end of the study.

Treatment outcomes were measured at baseline, 1 week, and at one, three, six and 12 months. Primary outcome measures included a modified Oswestry Disability Index, and the Visual Analogue Scale (VAS). Treatment effects were estimated with intention to treat analysis and linear mixed models.

One hundred and forty three participants were randomly allocated to the three groups (SMT = 36, GT = 63 and Placebo = 44). Baseline data for the three groups did not show any meaningful differences. Results of the intention to treat analyses revealed no time by group interactions, indicating no statistically significant between-group differences in pain or disability at 1 week, 1 month, 3 months, 6 months, or 12 months. There were significant main effects of time (p < 0.01) indicating improvements in pain and disability from baseline among all participants regardless of intervention. No significant adverse events were reported.

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The authors concluded that this study indicates that there is no difference in outcome at any time point for pain or disability when comparing SMT, Graston Technique® or sham therapy for thoracic spine pain, however all groups improved with time. These results constitute the first from a fully powered randomised controlled trial comparing SMT, Graston technique® and a placebo.

Some people claim that there is little wrong with placebo therapy, as long as it helps patients. This is not what I think, but even the proponents of this argument would agree that the placebo used in this way has to be safe. As SMT is by no means free of adverse effects, the argument cannot be applied here.

Other people will argue that this is about SMT and not chiropractic implying that I am conducting a vendetta against the poor chiropractors. I would disagree: we have just learnt that 93% of chiropractors consider SMT as their primary treatment. Yes, osteopaths and physiotherapists also use SMT but certainly not to this extent. Thus this discussion is mostly about chiropractic, and the onus is on chiropractors to demonstrate beyond doubt that SMT does more good than harm.

The true significance of this study is, I think, that the chiropractic profession now must convince us that spinal manipulation has any usefulness at all. They will have to conduct rigorous trials along the lines of this study to test for which condition these interventions generate outcomes that are significantly better than those achievable by sham.

Until such data are available, it would be wise, I think, to consider all therapeutic claims made for chiropractic unproven and bogus.

WATCH THIS SPACE!

While over on my post about the new NICE GUIDELINES on acupuncture for back pain, the acupuncturists’ assassination attempts of my character, competence, integrity and personality are in full swing, I have decided to employ my time more fruitfully and briefly comment on a new piece of acupuncture research.

This new Italian study was to determine the effectiveness of acupuncture for the management of hot flashes in women with breast cancer.

A total of 190 women with breast cancer were randomly assigned to two groups. Random assignment was performed with stratification for hormonal therapy; the allocation ratio was 1:1. Both groups received a booklet with information about climacteric syndrome and its management to be followed for at least 12 weeks. In addition, the acupuncture group received 10 traditional acupuncture treatment sessions involving needling of predefined acupoints.

The primary outcome was hot flash score at the end of treatment (week 12), calculated as the frequency multiplied by the average severity of hot flashes. The secondary outcomes were climacteric symptoms and quality of life, measured by the Greene Climacteric and Menopause Quality of Life scales. Health outcomes were measured for up to 6 months after treatment. Expectation and satisfaction of treatment effect and safety were also evaluated. We used intention-to-treat analyses.

Of the participants, 105 were randomly assigned to enhanced self-care and 85 to acupuncture plus enhanced self-care. Acupuncture plus enhanced self-care was associated with a significantly lower hot flash score than enhanced self-care at the end of treatment (P < .001) and at 3- and 6-month post-treatment follow-up visits (P = .0028 and .001, respectively). Acupuncture was also associated with fewer climacteric symptoms and higher quality of life in the vasomotor, physical, and psychosocial dimensions (P < .05).

The authors concluded that acupuncture in association with enhanced self-care is an effective integrative intervention for managing hot flashes and improving quality of life in women with breast cancer.

This hardly needs a comment, as I have been going on about this study design many times before: the ‘A+B versus B’ design can only produce positive findings. Any such study concluding that ‘acupuncture (or whatever other intervention) is effective’ can therefore not be a legitimate test of a hypothesis and ought to be categorised as pseudo-science. Sadly, this problem seems more the rule than the exception in the realm of acupuncture research. That’s a pity really… because, if there is potential in acupuncture at all, this sort of thing can only distract from it.

I think the JOURNAL OF CLINICAL ONCOLOGY, its editors and reviewers, should be ashamed of having published such misleading rubbish.

My last post was about a researcher who manages to produce nothing but positive findings with the least promising alternative therapy, homeopathy. Some might think that this is an isolated case or an anomaly – but they would be wrong. I have previously published about researchers who have done very similar things with homeopathy or other unlikely therapies. Examples include:

Claudia Witt

George Lewith

John Licciardone

But there are many more, and I will carry on highlighting their remarkable work. For example, the research of a German group headed by Prof Gustav Dobos, one of the most prolific investigator in alternative medicine at present.

For my evaluation, I conducted a Medline search of the last 10 of Dobos’ published articles and excluded those not assessing the effectiveness of alternative therapies such as surveys, comments, etc. Here they are with their respective conclusions and publication dates:

SYSTEMATIC REVIEW COMPARING DIFFERENT YOGA STYLES (2016)

RCTs with different yoga styles do not differ in their odds of reaching positive conclusions. Given that most RCTs were positive, the choice of an individual yoga style can be based on personal preferences and availability.

SYSTEMATIC REVIEW OF YOGA FOR WEIGHT LOSS (2016)

Despite methodological drawbacks, yoga can be preliminarily considered a safe and effective intervention to reduce body mass index in overweight or obese individuals.

REVIEW OF INTEGRATIVE MEDICINE IN GYNAECOLOGICAL ONCOLOGY (2016)

…there is published, positive level I evidence for a number of CAM treatment forms.

SYSTEMATIC REVIEW OF MINDFULNESS FOR PSYCHOSES (2016)

Mindfulness- and acceptance-based interventions can be recommended as an additional treatment for patients with psychosis.

RCT OF CABBAGE LEAF WRAPS FOR OSTEOARTHOSIS (2016)

Cabbage leaf wraps are more effective for knee osteoarthritis than usual care, but not compared with diclofenac gel. Therefore, they might be recommended for patients with osteoarthritis of the knee.

SYSTEMATIC REVIEW OF HERBAL MEDICINES FOR COUGH (2015)

This review found strong evidence for A. paniculata and ivy/primrose/thyme-based preparations and moderate evidence for P. sidoides being significantly superior to placebo in alleviating the frequency and severity of patients’ cough symptoms. Additional research, including other herbal treatments, is needed in this area.

SYSTEMATIC REVIEW OF DIETARY APPROACHES FOR METABOLIC SYNDROME (2016)

Dietary approaches should mainly be tried to reduce macronutrients and enrich functional food components such as vitamins, flavonoids, and unsaturated fatty acids. People with Metabolic Syndrome will benefit most by combining weight loss and anti-inflammatory nutrients.

SYSTEMATIC REVIEW OF MIND BODY MEDICINE FOR CORONARY HEART DISEASE (2015)

In patients with CHD, MBM programs can lessen the occurrence of cardiac events, reduce atherosclerosis, and lower systolic blood pressure, but they do not reduce mortality. They can be used as a complement to conventional rehabilitation programs.

CRANIOSACRAL THERAPY (CST) FOR BACK PAIN (2016)

CST was both specifically effective and safe in reducing neck pain intensity and may improve functional disability and the quality of life up to 3 months after intervention.

REVIEW OF INTEGRATED MEDICINE FOR BREAST CANCER (2015)

Study data have shown that therapy- and disease-related side effects can be reduced using the methods of integrative medicine. Reported benefits include improving patients’ wellbeing and quality of life, reducing stress, and improving patients’ mood, sleeping patterns and capacity to cope with disease.

Amazed?

Dobos seems to be an ‘all-rounder’ whose research tackles a wide range of alternative treatments. That is perhaps unremarkable – but what I do find remarkable is the impression that, whatever he researches, the results turn out to be pretty positive. This might imply one of two things, in my view:

I let my readers chose which possibility they deem to be more likely.

Homeopathy is not blessed with many geniuses, it seems. Therefore, it is all the more noteworthy that there is one who seems to be so extraordinarily gifted that everything she touches turns to gold.

Her new and remarkable study intended to measure the efficacy of individualized homeopathic treatment for binge eating in adult males.

This case study was a 9-week pilot using an embedded, mixed-methods design. A 3-week baseline period was followed by a 6-week treatment period. The setting was the Homeopathic Health Clinic at the University of Johannesburg in Johannesburg, South Africa. Through purposive sampling, the research team recruited 15 Caucasian, male participants, aged 18-45 y, who were exhibiting binge eating. Individualized homeopathic remedies were prescribed to each participant. Participants were assessed by means of (1) a self-assessment calendar (SAC), recording the frequency and intensity of binging; (2) the Binge Eating Scale (BES), a psychometric evaluation of severity; and (3) case analysis evaluating changes with time.

Ten participants completed the study. The study found a statistically significant improvement with regard to the BES (P = .003) and the SAC (P = .006), with a large effect size, indicating that a decrease occurred in the severity and frequency of binging behaviour during the study period.

The authors concluded that this small study showed the potential benefits of individualized homeopathic treatment of binge eating in males, decreasing both the frequency and severity of binging episodes. Follow-up studies are recommended to explore this treatment modality as a complementary therapeutic option in eating disorders characterized by binge eating.

While two of the three authors have not ventured into trials of homeopathy before, the third and senior author (Janice Pellow from the Department of Homoeopathy, University of Johannesburg, South Africa) already has several homeopathic studies to her name. They seem all quite similar:

Number 1 was a clinical trial that concluded:

The study was too small to be conclusive, but results suggest the homeopathic complex, together with physiotherapy, can significantly improve symptoms associated with chronic low back pain due to osteoarthritis.

Number 2 was an RCT which concluded:

The homeopathic complex used in this study exhibited significant anti-inflammatory and pain-relieving qualities in children with acute viral tonsillitis.

Number 3 was a pilot study concluding:

Findings suggest that daily use of the homeopathic complex does have an effect over a 4-week period on physiological and cognitive arousal at bedtime as well as on sleep onset latency in psychophysiological onset insomnia sufferers.

Number 4 was an RCT that concluded:

The homeopathic medicine reduced the sensitivity reaction of cat allergic adults to cat allergen, according to the skin prick test.

See what I mean? Five studies and 5 positive results!

Considering that they were obtained with different types of homeopathy, with different patients suffering from different conditions, with different trial designs and with different sets of co-workers, this is an even more remarkable achievement. In the hands of Janice Pellow, homeopathy seems to work under all circumstances and for all conditions.

I feel a Noble Prize might be in the air.

Pity that she would not score all that highly on my (self-invented) TI.

 

Osteopathy is a confusing subject about which I have reported regularly on this blog (for instance here and here).

Recently, I came across a good article where someone had assessed 100 websites by UK osteopaths. The findings are impressive:

57% of websites in the survey published the ‘self-healing’ claim

70% publicised the fact they offered cranial therapy;

61% made a claim to treat one or more specific ailments not related to the musculoskeletal system;

48% of practitioners also personally offered another CAM therapy;

71% of all sites surveyed located in a setting where other CAM was immediately available.

In total, 93% of the randomly selected websites checked at least one, often more, of the criteria for pseudoscientific claims. The author concluded that quackery is far from existing only on the fringe of osteopathic practice.

In a previous article, the author had stated that “there’s some (not strong) evidence that manual therapy may have some benefit in the case of lower back pain.” This evidence for the assumption that osteopathy works for back pain seems to rely heavily on one researcher: Licciardone JC. He comes from ‘The Osteopathic Research Center, University of North Texas Health Science Center, Fort Worth‘. which also is the flag-ship of research into osteopathy with plenty of funds and a worldwide reputation.

In 2005, he and his team published a systematic review/meta-analysis of RCTs which concluded that “osteopathic manipulative therapy (OMT) significantly reduces low back pain. The level of pain reduction is greater than expected from placebo effects alone and persists for at least three months. Additional research is warranted to elucidate mechanistically how OMT exerts its effects, to determine if OMT benefits are long lasting, and to assess the cost-effectiveness of OMT as a complementary treatment for low back pain.”

This is the article cited regularly to support the statement that osteopathy is an effective therapy for back pain. As the paper is now over 10 years old, we clearly need a more up-to-date systematic review. Such an assessment of clinical research into osteopathic intervention for chronic non-specific low back pain (CNSLBP) was recently published by an Australian team. A thorough search of the literature in multiple electronic databases was undertaken, and all articles were included that reported clinical trials; had adult participants; tested the effectiveness and/or efficacy of osteopathic manual therapies applied by osteopaths, and had a study condition of CNSLBP. The quality of the trials was assessed using the Cochrane criteria. Initial searches located 809 papers, 772 of which were excluded on the basis of abstract alone. The remaining 37 papers were subjected to a detailed analysis of the full text, which resulted in 35 further articles being excluded. There were thus only two studies assessing the effectiveness of manual therapies applied by osteopaths in adult patients with CNSLBP. The results of one trial suggested that the osteopathic intervention was similar in effect to a sham intervention, and the other implies equivalence of effect between osteopathic intervention, exercise and physiotherapy.

In other words, there seems to be an overt contradiction between the conclusions of Licciardone JC and those of the Australian team. Why? we may well ask. Perhaps the Osteopathic Research Center is not in the best position to be impartial? In order to check them out, I decided to have a closer look at their publications.

This team has published around 80 articles mostly in very low-impact osteopathic journals. They include several RCTs, and I decided to extract the conclusions of the last 10 papers reporting RCTs. Here they are:

RCT No 1 (2016)

Subgrouping according to baseline levels of chronic LBP intensity and back-specific functioning appears to be a simple strategy for identifying sizeable numbers of patients who achieve substantial improvement with OMT and may thereby be less likely to use more costly and invasive interventions.

RCT No 2 (2016)

The OMT regimen was associated with significant and clinically relevant measures for recovery from chronic LBP. A trial of OMT may be useful before progressing to other more costly or invasive interventions in the medical management of patients with chronic LBP.

RCT No 3 (2014)

Overall, 49 (52%) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 (25%) patients in the sham OMT group (RR, 2.04; 95% CI, 1.36-3.05). The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse.

RCT No 4 (2014)

These findings suggest that remission of psoas syndrome may be an important and previously unrecognized mechanism explaining clinical improvement in patients with chronic LBP following OMT.

RCT No 5 (2013)

The large effect size for OMT in providing substantial pain reduction in patients with chronic LBP of high severity was associated with clinically important improvement in back-specific functioning. Thus, OMT may be an attractive option in such patients before proceeding to more invasive and costly treatments.

RCT No 6 (2013)

The OMT regimen met or exceeded the Cochrane Back Review Group criterion for a medium effect size in relieving chronic low back pain. It was safe, parsimonious, and well accepted by patients.

RCT No 7 (2012)

This study found associations between IL-1β and IL-6 concentrations and the number of key osteopathic lesions and between IL-6 and LBP severity at baseline. However, only TNF-α concentration changed significantly after 12 weeks in response to OMT. These discordant findings indicate that additional research is needed to elucidate the underlying mechanisms of action of OMT in patients with nonspecific chronic LBP.

RCT No 8 (2010)

Osteopathic manipulative treatment slows or halts the deterioration of back-specific functioning during the third trimester of pregnancy.

RCT No 8 (2004)

The OMT protocol used does not appear to be efficacious in this hospital rehabilitation population.

RCT No 9 (2003)

Osteopathic manipulative treatment and sham manipulation both appear to provide some benefits when used in addition to usual care for the treatment of chronic nonspecific low back pain. It remains unclear whether the benefits of osteopathic manipulative treatment can be attributed to the manipulative techniques themselves or whether they are related to other aspects of osteopathic manipulative treatment, such as range of motion activities or time spent interacting with patients, which may represent placebo effects.

RCT No 10

Sorry, there is no 10th paper reporting an RCT.

Most of the remaining articles listed on Medline are comments and opinion papers. Crucially, it would be erroneous to assume that they conducted a total of 9 RCTs. Several of the above cited articles refer to the same RCT.

However, the most remarkable feature, in my view, is that the conclusions are almost invariably positive. Whenever I find a research team that manages to publish almost nothing but positive findings on one subject which most other experts are sceptical about, my alarm-bells start ringing.

In a previous blog, I have explained this in greater detail. Suffice to say that, according to my theory, the trustworthiness of the ‘Osteopathic Research Center’ is nothing to write home about.

What, I wonder, does that tell us about the reliability of the claim that osteopathy is effective for back pain?

TODAY IS ‘WORLD HOMEOPATHY DAY!!!

Let’s celebrate it by looking at the latest ‘cutting edge’ research on the world’s most commercially successful homeopathic remedy, Oscillococcinum®, a preparation of duck organs that are so highly diluted that not one molecule per universe is present in the end-product. It is therefore surprising to read that this new investigation finds it to be effective.

According to its authors, the goal of this controlled observational study was “to investigate the role of the homeopathic medicine in preventing respiratory tract infections (RTIs)”. The ‘study’ was not actually a study but a retrospective analysis of patients’ medical records. It examined 459 patients who were referred to a respiratory diseases specialist in Italy. Subjects who had taken any form of flu vaccine or any other type of vaccine (immuno-stimulants, bacterial lysates, or similar) were excluded from the study.  248 patients were treated with the homeopathic medicine, while 211 were, according to one statement by the authors, not treated. The latter group was deemed to be the control group. All patients were followed-up for at least 1 year, and up to a maximum of 10 years.

A significant reduction in the frequency of onset of RTIs was found in both the homeopathic medicine and untreated groups. The reduction in the mean number of RTI episodes during the period of observation vs. the year before inclusion in the study was significantly greater in the homeopathic-treated group than in untreated patients (-4.76 ± 1.45 vs. -3.36 ± 1.30; p = 0.001). The beneficial effect of the homeopathic medicine was not significantly related to gender, age, smoking habits or concomitant respiratory diseases when compared to the effect observed in untreated patients. The number of infections during the follow-up period is plotted in the graph.

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The authors concluded that these results suggest that homeopathic medicine may have a positive effect in preventing RTIs. However, randomized studies are needed before any firm conclusion can be reached.

This could well be the worst study of homeopathy, an area where there is no shortage of poor research, that I have seen for a long time. Here are some of its most obvious problems:

  • The aim was to investigate the role of homeopathic medicine – why then do the authors draw conclusions about its effectiveness?
  • The ‘control group’ was not ‘not treated’ as the authors claim, but these patients were prescribed the homeopathic remedy and did not comply. They were neither untreated – most would have self-medicated something else) nor a proper control group. This is what the authors state about it: “The physician initially instructed all 459 patients to take 1 dose of homeopathic medicine…A total of 211 patients were found to be non-compliant (i.e., they did not take the homeopathic medicine as recommended by the medical doctor), and these formed the control group.”
  • Why were vaccinated patients excluded? This would skew the sample towards anti-vaxers who tend to be homeopathy-fans.
  • A follow-up between 1 and 10 years? Are they serious? The authors tell us that “a total of 21 (4.6 %) patients ended the follow-up before 2012…” Did all the others die of homeopathic over-dose?
  • Before the start of the ‘study’, patients had more than 5 infections per year. This is way beyond the normal average of 1-2.
  • The authors inform us that “the primary outcome measure for assessing the effectiveness of the preventive treatment with homeopathic medicine was the reduction in the average number of RTI episodes per year versus the year before inclusion in the study.” This begs the question as to how the primary endpoint was assessed. The answer is by asking the patients or phoning them. This method is wide open to recall-bias and therefore not suited as a primary outcome measure.

My favourite alternative explanation for the reported findings – and there are many that have nothing to do with homeopathy – goes like this: some patients did not comply because their condition did not respond to homeopathy. These were the ones who were, on average, more severely ill. They needed something better than a homeopathic placebo and they therefore became the ‘control group’. As the differed systematically from the verum group, it would be most extraordinary, if they did not show different findings during follow-up.

So, is there nothing interesting here at all?

Not really…hold on, here is something: “The corresponding author thanks the Scientific Department of Laboratories Boiron S.r.l. (Milan, Italy) for funding the independent statistical analysis made at the Department of Medical and Surgical Sciences of the Alma Mater Studiorum-University of Bologna (Bologna, Italy).”

BOIRON SEEMS TO DECIDE ON FUNDING AFTER HOMEOPATHICALLY DILUTING SCIENTIFIC RIGOR AND COMMON SENSE.

Mindfulness-based stress reduction (MBSR) has not been rigorously evaluated as a treatment of chronic low back pain. According to its authors, this RCT was aimed at evaluating “the effectiveness for chronic low back pain of MBSR vs cognitive behavioural therapy (CBT) or usual care.”

The investigators randomly assigned patients to receive MBSR (n = 116), CBT (n = 113), or usual care (n = 113). CBT meant training to change pain-related thoughts and behaviours and MBSR meant training in mindfulness meditation and yoga. Both were delivered in 8 weekly 2-hour groups. Usual care included whatever care participants received.

Coprimary outcomes were the percentages of participants with clinically meaningful (≥30%) improvement from baseline in functional limitations (modified Roland Disability Questionnaire [RDQ]; range, 0-23) and in self-reported back pain bothersomeness (scale, 0-10) at 26 weeks. Outcomes were also assessed at 4, 8, and 52 weeks.

There were 342 randomized participants with a mean duration of back pain of 7.3 years. They attended 6 or more of the 8 sessions, 294 patients completed the study at 26 weeks, and 290 completed it at 52 weeks. In intent-to-treat analyses at 26 weeks, the percentage of participants with clinically meaningful improvement on the RDQ was higher for those who received MBSR (60.5%) and CBT (57.7%) than for usual care (44.1%), and RR for CBT vs usual care, 1.31 [95% CI, 1.01-1.69]). The percentage of participants with clinically meaningful improvement in pain bothersomeness at 26 weeks was 43.6% in the MBSR group and 44.9% in the CBT group, vs 26.6% in the usual care group, and RR for CBT vs usual care was 1.69 [95% CI, 1.18-2.41]). Findings for MBSR persisted with little change at 52 weeks for both primary outcomes.

The authors concluded that among adults with chronic low back pain, treatment with MBSR or CBT, compared with usual care, resulted in greater improvement in back pain and functional limitations at 26 weeks, with no significant differences in outcomes between MBSR and CBT. These findings suggest that MBSR may be an effective treatment option for patients with chronic low back pain.

At first glance, this seems like a well-conducted study. It was conducted by one of the leading back pain research team and was published in a top-journal. It will therefore have considerable impact. However, on closer examination, I have serious doubts about certain aspects of this trial. In my view, both the aims and the conclusions of this RCT are quite simply wrong.

The authors state that they aimed at evaluating “the effectiveness for chronic low back pain of MBSR vs cognitive behavioural therapy (CBT) or usual care.” This is not just misleading, it is wrong! The correct aim should have been to evaluate “the effectiveness for chronic low back pain of MBSR plus usual care vs cognitive behavioural therapy plus usual care or usual care alone.” One has to go into the method section to find the crucial statement: “All participants received any medical care they would normally receive.”

Consequently, the conclusions are equally wrong. They should have read as follows: Among adults with chronic low back pain, treatment with MBSR plus usual care or CBT plus usual care, compared with usual care alone, resulted in greater improvement in back pain and functional limitations at 26 weeks, with no significant differences in outcomes between MBSR and CBT.

In other words, this is yet another trial with the dreaded ‘A+B vs B’ design. Because A+B is always more than B (even if A is just a placebo), such a study will never generate a negative result (even if A is just a placebo). The results are therefore entirely compatible with the notion that the two tested treatments are pure placebos. Add to this the disappointment many patients in the ‘usual care group’ might have felt for not receiving an additional therapy for their pain, and you have a most plausible explanation for the observed outcomes.

I am totally puzzled why the authors failed to discuss these possibilities and limitations in full, and I am equally bewildered that JAMA published such questionable research.

 

Recently, I came across the ‘Clinical Practice Guidelines on the Use of Integrative Therapies as Supportive Care in Patients Treated for Breast Cancer’ published by the ‘Society for Integrative Oncology (SIO) Guidelines Working Group’. The mission of the SIO is to “advance evidence-based, comprehensive, integrative healthcare to improve the lives of people affected by cancer. The SIO has consistently encouraged rigorous scientific evaluation of both pre-clinical and clinical science, while advocating for the transformation of oncology care to integrate evidence-based complementary approaches. The vision of SIO is to have research inform the true integration of complementary modalities into oncology care, so that evidence-based complementary care is accessible and part of standard cancer care for all patients across the cancer continuum. As an interdisciplinary and inter-professional society, SIO is uniquely poised to lead the “bench to bedside” efforts in integrative cancer care.”

The aim of the ‘Clinical Practice Guidelines’ was to “inform clinicians and patients about the evidence supporting or discouraging the use of specific complementary and integrative therapies for defined outcomes during and beyond breast cancer treatment, including symptom management.”

This sounds like a most laudable aim. Therefore I studied the document carefully and was surprised to read their conclusions: “Specific integrative therapies can be recommended as evidence-based supportive care options during breast cancer treatment.”

How can this be? On this blog, we have repeatedly seen evidence to suggest that integrative medicine is little more than the admission of quackery into evidence-based healthcare. This got me wondering how their conclusion had been reached, and I checked the document even closer.

On the surface, it seemed well-made. A team of researchers first defined the treatments they wanted to look at, then they searched for RCTs, evaluated their quality, extracted their results, combined them into an overall verdict and wrote the whole thing up. In a word, they conducted what seems a proper systematic review.

Based on the findings of their review, they then issued recommendations which I thought were baffling in several respects. Let me just focus on three of the SIO’s recommendations dealing with acupuncture:

  1. “Acupuncture can be considered for treating anxiety concurrent with ongoing fatigue…” [only RCT (1) cited in support]
  2. “Acupuncture can be considered for improving depressive symptoms in women suffering from hot flashes…” [RCTs (1 and 2) cited in support] 
  3. “Acupuncture can be considered for treating anxiety concurrent with ongoing fatigue…” [only RCT (1) cited in support]
One or two studies as a basis for far-reaching guidelines? Yes, that would normally be a concern! But, at closer scrutiny, my worries about these recommendation turn out to be much more serious than this.

The actual RCT (1) cited in support of all three recommendations stated that the authors “randomly assigned 75 patients to usual care and 227 patients to acupuncture plus usual care…” As we have discussed often before on this blog and elsewhere, such a ‘A+B versus B study design’ will never generate a negative result, does not control for placebo-effects and is certainly not a valid test for the effectiveness of the treatment in question. Nevertheless, the authors of this study concluded that: “Acupuncture is an effective intervention for managing the symptom of cancer-related fatigue and improving patients’ quality of life.”

RCT (2) cited in support of recommendation number 2 seems to be a citation error; the study in question is not an acupuncture-trial and does not back the statement in question. I suspect they meant to cite their reference number 87 (instead of 88). This trial is an equivalence study where 50 patients were randomly assigned to receive 12 weeks of acupuncture (n = 25) or venlafaxine (n = 25) treatment for cancer-related hot flushes. Its results indicate that the two treatments generated the similar results. As the two therapies could also have been equally ineffective, it is impossible, in my view, to conclude that acupuncture is effective.

Finally, RCT (1) does in no way support recommendation number two. Yet RCT (1) and RCT (2) were both cited in support of this recommendation.

I have not systematically checked any other claims made in this document, but I get the impression that many other recommendations made here are based on similarly ‘liberal’ interpretations of the evidence. How can the ‘Society for Integrative Oncology’ use such dodgy pseudo-science for formulating potentially far-reaching guidelines?

I know none of the authors (Heather Greenlee, Lynda G. Balneaves, Linda E. Carlson, Misha Cohen, Gary Deng, Dawn Hershman, Matthew Mumber, Jane Perlmutter, Dugald Seely, Ananda Sen, Suzanna M. Zick, Debu Tripathy) of the document personally. They made the following collective statement about their conflicts of interest: “There are no financial conflicts of interest to disclose. We note that some authors have conducted/authored some of the studies included in the review.” I am a little puzzled to hear that they have no financial conflicts of interest (do not most of them earn their living by practising integrative medicine? Yes they do! The article informs us that: “A multidisciplinary panel of experts in oncology and integrative medicine was assembled to prepare these clinical practice guidelines. Panel members have expertise in medical oncology, radiation oncology, nursing, psychology, naturopathic medicine, traditional Chinese medicine, acupuncture, epidemiology, biostatistics, and patient advocacy.”). I also suspect they have other, potentially much stronger conflicts of interest. They belong to a group of people who seem to religiously believe in the largely nonsensical concept of integrative medicine. Integrating unproven treatments into healthcare must affect its quality in much the same way as the integration of cow pie into apple pie would affect the taste of the latter.

After considering all this carefully, I cannot help wondering whether these ‘Clinical Practice Guidelines’ by the ‘Society for Integrative Oncology’ are just full of honest errors or whether they amount to fraud and scientific misconduct.

WHATEVER THE ANSWER, THE GUIDELINES MUST BE RETRACTED, IF THIS SOCIETY WANTS TO AVOID LOSING ALL CREDIBILITY.

In recent blogs, I have written much about acupuncture and particularly about the unscientific notions of traditional acupuncturists. I was therefore surprised to see that a UK charity is teaming up with traditional acupuncturists in an exercise that looks as though it is designed to mislead the public.

The website of ‘Anxiety UK’ informs us that this charity and the British Acupuncture Council (BAcC) have launched a ‘pilot project’ which will see members of Anxiety UK being able to access traditional acupuncture through this new partnership. Throughout the pilot project, they proudly proclaim, data will be collected to “determine the effectiveness of traditional acupuncture for treating those living with anxiety and anxiety based depression.”

This, they believe, will enable both parties to continue to build a body of evidence to measure the success rate of this type of treatment. Anxiety UK’s Chief Executive Nicky Lidbetter said: “This is an exciting project and will provide us with valuable data and outcomes for those members who take part in the pilot and allow us to assess the benefits of extending the pilot to a regular service for those living with anxiety. “We know anecdotally that many people find complementary therapies used to support conventional care can provide enormous benefit, although it should be remembered they are used in addition to and not instead of seeking medical advice from a doctor or taking prescribed medication. This supports our strategic aim to ensure that we continue to make therapies and services that are of benefit to those with anxiety and anxiety based depression, accessible.”

And what is wrong with that, you might ask.

What is NOT wrong with it, would be my response.

To start with, traditional acupuncture relies of obsolete assumptions like yin and yang, meridians, energy flow, acupuncture points etc. They have one thing in common: they fly in the face of science and evidence. But this might just be a triviality. More important is, I believe, the fact that a pilot project cannot determine the effectiveness of a therapy. Therefore the whole exercise smells very much like a promotional activity for pure quackery.

And what about the hint in the direction of anecdotal evidence in support of the study? Are they not able to do a simple Medline search? Because, if they had done one, they would have found a plethora of articles on the subject. Most of them show that there are plenty of studies but their majority is too flawed to draw firm conclusions.

A review by someone who certainly cannot be accused of being biased against alternative medicine, for instance, informs us that “trials in depression, anxiety disorders and short-term acute anxiety have been conducted but acupuncture interventions employed in trials vary as do the controls against which these are compared. Many trials also suffer from small sample sizes. Consequently, it has not proved possible to accurately assess the effectiveness of acupuncture for these conditions or the relative effectiveness of different treatment regimens. The results of studies showing similar effects of needling at specific and non-specific points have further complicated the interpretation of results. In addition to measuring clinical response, several clinical studies have assessed changes in levels of neurotransmitters and other biological response modifiers in an attempt to elucidate the specific biological actions of acupuncture. The findings offer some preliminary data requiring further investigation.”

Elsewhere, the same author, together with other pro-acupuncture researchers, wrote this: “Positive findings are reported for acupuncture in the treatment of generalised anxiety disorder or anxiety neurosis but there is currently insufficient research evidence for firm conclusions to be drawn. No trials of acupuncture for other anxiety disorders were located. There is some limited evidence in favour of auricular acupuncture in perioperative anxiety. Overall, the promising findings indicate that further research is warranted in the form of well designed, adequately powered studies.”

What does this mean in the context of the charity’s project?

I think, it tells us that acupuncture for anxiety is not exactly the most promising approach to further investigate. Even in the realm of alternative medicine, there are several interventions which are supported by more encouraging evidence. And even if one disagrees with this statement, one cannot possibly disagree with the fact that more flimsy research is not required. If we do need more studies, they must be rigorous and not promotion thinly disguised as science.

I guess the ultimate question here is one of ethics. Do charities not have an ethical and moral duty to spend our donations wisely and productively? When does such ill-conceived pseudo-research cross the line to become offensive or even fraudulent?

Yes, we discussed this study on a previous blog post. But, as it is ‘ACUPUNCTURE AWARENESS WEEK’ in the UK, and because of another reason (which will become clear in a minute) I decided to revisit the trial.

In case you have forgotten, here is its abstract once again:

Background: Hot flashes (HFs) affect up to 75% of menopausal women and pose a considerable health and financial burden. Evidence of acupuncture efficacy as an HF treatment is conflicting.

Objective: To assess the efficacy of Chinese medicine acupuncture against sham acupuncture for menopausal HFs.

Design: Stratified, blind (participants, outcome assessors, and investigators, but not treating acupuncturists), parallel, randomized, sham-controlled trial with equal allocation. (Australia New Zealand Clinical Trials Registry: ACTRN12611000393954)

Setting: Community in Australia.

Participants: Women older than 40 years in the late menopausal transition or postmenopause with at least 7 moderate HFs daily, meeting criteria for Chinese medicine diagnosis of kidney yin deficiency.

Interventions: 10 treatments over 8 weeks of either standardized Chinese medicine needle acupuncture designed to treat kidney yin deficiency or noninsertive sham acupuncture.

Measurements: The primary outcome was HF score at the end of treatment. Secondary outcomes included quality of life, anxiety, depression, and adverse events. Participants were assessed at 4 weeks, the end of treatment, and then 3 and 6 months after the end of treatment. Intention-to-treat analysis was conducted with linear mixed-effects models.

Results: 327 women were randomly assigned to acupuncture (n = 163) or sham acupuncture (n = 164). At the end of treatment, 16% of participants in the acupuncture group and 13% in the sham group were lost to follow-up. Mean HF scores at the end of treatment were 15.36 in the acupuncture group and 15.04 in the sham group (mean difference, 0.33 [95% CI, −1.87 to 2.52]; P = 0.77). No serious adverse events were reported.

Limitation: Participants were predominantly Caucasian and did not have breast cancer or surgical menopause.

Conclusion: Chinese medicine acupuncture was not superior to noninsertive sham acupuncture for women with moderately severe menopausal HFs.

When I first discussed this trial, I commented that the trial has several strengths: it includes a large sample size and the patients were adequately blinded to eliminate the effects of expectations. It was published in a top journal, and we can therefore assume that it was properly peer-reviewed. Combined with the evidence from our previous systematic review, this indicates that acupuncture has no effect beyond placebo.

The reason for bringing it up again is that a comment about the study has recently appeared, not just any old comment but one from the British Medical Acupuncture Society. It is, in my view, gratifying and interesting. It was published on ‘facebook’ and is therefore in danger of getting forgotten. I hope to preserve it by citing it in full.

Here it is:

A large rigorous trial published in a prestigious general medical journal, and the usual mantra rings out – acupuncture is no better than sham. In this case there was not a fraction of difference from a non-penetrating sham in a two-armed trial with over 300 women. Ok,…so we have known for some time that we really need 400 in each arm to demonstrate the usual difference over sham seen in meta-analysis in pain conditions, but there really was not even a sniff of a difference here. So is that it for acupuncture in hot flushes? Well, we have a 40% symptom reduction in both groups, and a strong conviction from some practitioners that it really seems to work. Is 40% enough for a strong conviction? I have heard some dramatic stories from medical acupuncturist colleagues that really would be hard to dismiss as non-specific effects, and from others I have heard relative ambivalence about the effects in hot flushes.

Personally I always try to consider mechanisms, and I wish researchers in the field would do the same before embarking on their trials. That is not intended as a criticism of this trial, but some consideration of mechanisms might allow us to explain all our data, including the contribution of this trial.

Acupuncture has recognised effects that are local to the needle, in the spinal cord (mainly in the segments stimulated) and in the brain (as well as humoral effects in CSF and blood). The latter are probably the mildest of the three categories, and require the best group of patient responders for them to be observable in clinical practice.

Menopausal hot flushes are explained by the effects of reduced oestrogens on the thermoregulatory centre in the anterior hypothalamus. It is certainly plausible that the neuro-inhibitory effects of endogenous opioids such as beta-endorphin, which we know can be released by acupuncture stimulation in experimental settings, could stablise neurones in the anterior hypothalamus that have become irritable due to a sudden drop in oestrogens.

So are endogenous opioids always released by acupuncture? Well, they and their effects seem to be measurable in experiments that use what I call proper acupuncture. That is, strong stimulation to deep somatic tissue. In the laboratory, and indeed in my clinic, this is only usually achieved in a palatable manner by electroacupuncture to muscle, although repeated manual stimulation every few minutes may have similar effects.

Ee et al used a relatively gentle acupuncture protocol, so they may have only generated measurable effects, based on mechanistic speculation, in the most responsive patients, perhaps less than 10%.

What does all this tell us? Well this trial clearly demonstrates that gentle acupuncture protocols generate effects in women with hot flushes via context rather than penetrating needling. In conditions that rely on central effects, I think we still need to consider stronger stimulation protocols and enriched enrollment in trials, ie preselecting responders before randomisation.

In my original comment I also predicted: “One does not need to be a clairvoyant to predict that acupuncturists will now find what they perceive as a flaw in the new study and claim that its results were false-negative.”

I am so glad Mike Cummings and the BMAS rushed to prove me right.

It’s so nice to know one can rely on someone in these uncertain times!

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