MD, PhD, FMedSci, FSB, FRCP, FRCPEd

research

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One of the questions I hear frequently is ‘HOW CAN I BE SURE THIS STUDY IS SOUND’? Even though I have spent much of my professional life on this issue, I am invariably struggling to provide an answer. Firstly, because a comprehensive reply must inevitably have the size of a book, perhaps even several books. And secondly, to most lay people, the reply would be intensely boring, I am afraid.

Yet many readers of this blog evidently search for some guidance – so, let me try to provide a few indicators – indicators, not more!!! – as to what might signify a good and a poor clinical trial (other types of research would need different criteria).

INDICATORS SUGGESTIVE OF A GOOD CLINICAL TRIAL

  • Author from a respected institution.
  • Article published in a respected journal.
  • A clear research question.
  • Full description of the methods used such that an independent researcher could repeat the study.
  • Randomisation of study participants into experimental and control groups.
  • Use of a placebo in the control group where possible.
  • Blinding of patients.
  • Blinding of investigators, including clinicians administering the treatments.
  • Clear definition of a primary outcome measure.
  • Sufficiently large sample size demonstrated with a power calculation.
  • Adequate statistical analyses.
  • Clear presentation of the data such that an independent assessor can check them.
  • Understandable write-up of the entire study.
  • A discussion that puts the study into the context of all the important previous work in this area.
  • Self-critical analysis of the study design, conduct and interpretation of the results.
  • Cautious conclusion which are strictly based on the data presented.
  • Full disclosure of ethics approval and informed consent,
  • Full disclosure of funding sources.
  • Full disclosure of conflicts of interest.
  • List of references is up-to-date and includes also studies that contradict the authors’ findings.

I told you this would be boring! Not only that, but each bullet point is far too short to make real sense, and any full explanation would be even more boring to a lay person, I am sure.

What might be a little more fun is to list features of a clinical trial that might signify a poor study. So, let’s try that.

WARNIG SIGNALS INDICATING A POOR CLINICAL TRIAL

  • published in one of the many dodgy CAM journals (or in a book, blog or similar),
  • single author,
  • authors are known to be proponents of the treatment tested,
  • author has previously published only positive studies of the therapy in question (or member of my ‘ALT MED HALL OF FAME’),
  • lack of plausible rationale for the study,
  • lack of plausible rationale for the therapy that is being tested,
  • stated aim of the study is ‘to demonstrate the effectiveness of…’ (clinical trials are for testing, not demonstrating effectiveness or efficacy),
  • stated aim ‘to establish the effectiveness AND SAFETY of…’ (even large trials are usually far too small for establishing the safety of an intervention),
  • text full of mistakes, e. g. spelling, grammar, etc.
  • sample size is tiny,
  • pilot study reporting anything other than the feasibility of a definitive trial,
  • methods not described in sufficient detail,
  • mismatch between aim, method, and conclusions of the study,
  • results presented only as a graph (rather than figures which others can re-calculate),
  • statistical approach inadequate or not sufficiently detailed,
  • discussion without critical input,
  • lack of disclosures of ethics, funding or conflicts of interest,
  • conclusions which are not based on the results.

The problem here (as above) is that one would need to write at least an entire chapter on each point to render it comprehensible. Without further detailed explanations, the issues raised remain rather abstract or nebulous. Another problem is that both of the above lists are, of course, far from complete; they are merely an expression of my own experience in assessing clinical trials.

Despite these caveats, I hope that those readers who are not complete novices to the critical evaluation of clinical trials might be able to use my ‘warning signals’ as a form of check list that helps them to tell the chaff from the wheat.

The common cold is one of the indications for which homeopathy is deemed to be effective… by homeopaths that is! Non-homeopaths are understandably critical about this claim, not least because there is no good evidence for it. But, hold on, there is a new study which might change all this.

This study was recently published in COMPLEMENTARY THERAPIES IN MEDICINE which is supposed to be one of the better journals in this area. According to its authors, it was conducted “to determine if a homeopathic syrup was effective in treating cold symptoms in preschool children.” Children diagnosed with an upper respiratory tract infection were randomized to receive a commercial homeopathic cold syrup containing allium cepa 6X, hepar sulf calc 12X, natrum muriaticum 6X, phosphorous 12X, pulsatilla 6X, sulphur 12X, and hydrastasis 6X or placebo. Parents administered the study medication as needed for 3 days. The primary outcome was change in symptoms one hour after each dose. Parents also assessed the severity of each of the symptoms of runny nose, cough, congestion and sneezing at baseline and twice daily for 3 days, using a 4-point rating scale. A composite cold score was calculated by combining the values for each of the four symptoms. Among 261 eligible participants, data on 957 doses of study medication in 154 children were analyzed. There was no significant difference in improvement one hour after the dose for any symptom between the two groups. Analysis of twice daily data on the severity of cold symptoms compared to baseline values found that improvements in sneezing, cough and the composite cold score were significantly greater at both the first and second assessments among those receiving the cold syrup compared to placebo recipients.

The authors concluded that the homeopathic syrup appeared to be effective in reducing the severity of cold symptoms in the first day after beginning treatment.

Where to start? There are so many problems with this study that I find it difficult to chose the most crucial ones:

  • The study had a clearly defined primary endpoint; it was not affected by the homeopathic treatment which doubtlessly makes the study a negative trial. The only correct conclusion therefore is that THE HOMEOPATHIC SYRUP FAILED TO AFFECT THE PRIMARY OUTCOME MEASURE OF THIS STUDY. THEREFORE THE TRIAL DID NOT PRODUCE ANY EVIDENCE TO ASSUME THAT THE EXPERIMENTAL TREATMENT WAS EFFICACIOUS.
  • I don’t think that many of the primary or secondary outcome measures are validated or reliable.
  • All the positive results reported in the abstract and the article relate to secondary endpoints which are purely explanatory by nature. They should, in my view, not be mentioned in the conclusions at all.
  • The fact that some results turned out to be positive can be explained by the fact that the investigators ran dozens of tests for statistical significance which means that, by simple chance, some will turn out to produce a positive result.
  • A further explanation for the seemingly positive results might be the fact disclosed in the text of the article that the children in the homeopathy group received more conventional drugs than those in the placebo group.
  • Whatever the reason for these positive results, they certainly had nothing to do with the homeopathic syrup.
  • The study was funded by the company producing the syrup and for which one of the authors was employed as a consultant. This might be an explanation for the abominably poor science. In other words, this paper is not an exercise in testing a hypothesis but one in marketing.

While I might forgive the company for trying to maximise their sales figures, I do find it harder to forgive the authors, reviewers and editors for publishing such overtly false conclusions. In my view, they are all guilty of scientific misconduct.

Meniscus-injuries are common and there is no consensus as to how best treat them. Physiotherapists tend to advocate exercise, while surgeons tend to advise surgery.

Of course, exercise is not a typical alternative therapy but, as many alternative practitioners might disagree with this statement because they regularly recommend it to their patients, it makes sense to cover it on this blog. So, is exercise better than surgery for meniscus-problems?

The aim of this recent Norwegian study aimed to shed some light on this question. Specifically wanted to determine whether  exercise therapy is superior to arthroscopic partial meniscectomy for knee function in  patients with degenerative meniscal tears.

A total of 140 adults with degenerative medial meniscal tear verified by magnetic resonance imaging were randomised to either receiving 12 week supervised exercise therapy alone, or arthroscopic partial meniscectomy alone. Intention to treat analysis of between group difference in change in knee injury and osteoarthritis outcome score (KOOS4), defined a priori as the mean score for four of five KOOS subscale scores (pain, other symptoms, function in sport and recreation, and knee related quality of life) from baseline to two-year follow-up and change in thigh muscle strength from baseline to three months.

The results showed no clinically relevant difference between the two groups in change in KOOS4 at two years (0.9 points, 95% confidence interval −4.3 to 6.1; P=0.72). At three months, muscle strength had improved in the exercise group (P≤0.004). No serious adverse events occurred in either group during the two-year follow-up. 19% of the participants allocated to exercise therapy crossed over to surgery during the two-year follow-up, with no additional benefit.

The authors concluded that the observed difference in treatment effect was minute after two years of follow-up, and the trial’s inferential uncertainty was sufficiently small to exclude clinically relevant differences. Exercise therapy showed positive effects over surgery in improving thigh muscle strength, at least in the short-term. Our results should encourage clinicians and middle-aged patients with degenerative meniscal tear and no definitive radiographic evidence of osteoarthritis to consider supervised exercise therapy as a treatment option.

As I stated above, I mention this trial because exercise might be considered by some as an alternative therapy. The main reason for including it is, however, that it is in many ways an exemplary good study from which researchers in alternative medicine could learn.

Like so many alternative therapies, exercise is a treatment for which placebo-controlled studies are difficult, if not impossible. But that does not mean that rigorous tests of its value are impossible. The present study shows the way how it can be done.

Meaningful clinical research is no rocket science; it merely needs well-trained scientists who are willing to test the (rather than promote) their hypotheses. Sadly such individuals are as rare as gold dust in the realm of alternative medicine.

Dietary and herbal supplements (DHS) are currently popular. They are being promoted as being natural and therefore safe – an assumption that is clearly wrong: some DHS can contain toxic substances or they might cause interactions with drugs or other DHS.

This study explored whether adverse events were actually associated with such interactions and examined specific characteristics among inpatient DHS users prone to such adverse events. It was designed as a cross-sectional survey of 947 patients hospitalized in 12 departments of a tertiary academic medical centre in Haifa, Israel. It evaluated the rate of DHS use among inpatients, the potential for interactions, and actual adverse events during hospitalization associated with DHS use. It also assessed whether DHS consumption was documented in patients’ medical files. Statistical analysis was used to delineate DHS users at risk for adverse events associated with interactions with conventional drugs or other DHS.

The results show that about half of all patients took DHS. In 17 (3.7%) of the 458 DHS users, an adverse event may have been caused by DHS-drug-DHS interactions. According to the Drug Interaction Probability Scale, 14 interactions “probably” caused the adverse events, and 11 “possibly” caused them. Interactions occurred more frequently in older patients (p = 0.025, 95% CI: 2.26-19.7), patients born outside Israel (p = 0.025, 95% CI: 0.03-0.42), those with ophthalmologic (p = 0.032, 95% CI: 0.02-0.37) or gastrointestinal (p = 0.008, 95% CI: 0.05-0.46) comorbidities, and those using higher numbers of DHS (p < 0.0001, 95% CI: 0.52-2.48) or drugs (p = 0.027, 95% CI: 0.23-3.77).

The authors concluded that approximately one in 55 hospitalizations in this study may have been caused by adverse events associated with DHS-drug-DHS interactions. To minimize the actual occurrence of adverse events, medical staff education regarding DHS should be improved.

This seems to be a good study and it generated interesting findings on an important topic.

Why do I have nevertheless a problem with it?

The answer is simple but not pleasant: very similar results have been published almost simultaneously in more than one journal. The link above is to an article in the BR J CLIN PHARMACOL of October this year. The following text is from the abstract of an article in INTERN EMERG MED also of October this year:

Of 927 patients who agreed to answer the questionnaire, 458 (49.4 %) reported the use of 89 different DHS. Potential DHS-DHS interactions were identified in 12.9 % of DHS users. Three interactions were associated with the actual occurrence of adverse events. Patients at risk of DHS-DHS interactions included females (p = 0.026) and patients with greater numbers of concomitant medications (p < 0.0001) and of consumed DHS (p < 0.0001). In 88.9 % of DHS users, DHS use was not reported in medical files and only 18 % of the DHS involved in interactions were documented. Potential DHS-DHS interactions are common in inpatients, and may lead to hospitalization or worsen existing medical conditions. The causal relationship between potential interactions and actual adverse events requires further study.

END OF QUOTE

And to my surprise, I also found a third article also from the October issue of INTERN EMERG MED reporting on this survey. Here is part of its abstract:

DHS users were determined via a questionnaire. The Natural Medicine database was used to search for potential DHS-drug interactions for identified DHS, and the clinical significance was evaluated using Lexi-interact online interaction analysis. Medical files were assessed for documentation of DHS use. Univariate and multivariate logistic regression analyses were used to characterize potential risk factors for DHS-drug interactions. Of 927 patients consenting to answer the questionnaire, 458 (49 %) reported DHS use. Of these, 215 (47 %) had at least one potential interaction during hospitalization (759 interactions). Of these interactions, 116 (15 %) were potentially clinically significant. Older age [OR = 1.02 (1.01-1.04), p = 0.002], males [OR = 2.11 (1.35-3.29), p = 0.001] and increased number of used DHS [OR = 4.28 (2.28-8.03), p < 0.001] or drugs [OR = 1.95 (1.17-3.26), p = 0.011] were associated with potential interactions in DHS users. Physicians documented only 16.5 % of DHS involved in these interactions in patients’ medical files. In conclusion, a substantial number of inpatients use DHS with potential interactions with concomitant medications. Medical staff should be aware of this, question patients on DHS usage and check for such interactions.

END OF QUOTE

What is the difference between the three articles? The first one in INTERN EMERG MED authored by Levy I, Attias S, Ben Arye E, Goldstein L, Schiff E evaluated “potential DHS-DHS interactions among inpatients”. The second one in INTERN EMERG MED also authored by Levy I, Attias S, Ben Arye E, Goldstein L, Schiff E evaluated “potentially dangerous interactions of DHS with prescribed medications among inpatients”. Finally the one in BR J CLIN PHARMACOL also authored by Levy I, Attias S, Ben-Arye E, Goldstein L, Schiff E  assessed in addition the interactions between DHS and prescription drugs.

Dual publications are usually considered to be a violation of research ethics. Publication of different aspects of one single data-set in multiple articles is called ‘salami-slicing’ and is often considered to be poor form.

My question to you, the reader of this post, is: What type of scientific misconduct do we have here?

I have warned you before to be sceptical about Chinese studies. This is what I posted on this blog more than 2 years ago, for instance:

Imagine an area of therapeutics where 100% of all findings of hypothesis-testing research are positive, i.e. come to the conclusion that the treatment in question is effective. Theoretically, this could mean that the therapy is a miracle cure which is useful for every single condition in every single setting. But sadly, there are no miracle cures. Therefore something must be badly and worryingly amiss with the research in an area that generates 100% positive results.

Acupuncture is such an area; we and others have shown that Chinese trials of acupuncture hardly ever produce a negative finding. In other words, one does not need to read the paper, one already knows that it is positive – even more extreme: one does not need to conduct the study, one already knows the result before the research has started. But you might not believe my research nor that of others. We might be chauvinist bastards who want to discredit Chinese science. In this case, you might perhaps believe Chinese researchers.

In this systematic review, all randomized controlled trials (RCTs) of acupuncture published in Chinese journals were identified by a team of Chinese scientists. A total of 840 RCTs were found, including 727 RCTs comparing acupuncture with conventional treatment, 51 RCTs with no treatment controls, and 62 RCTs with sham-acupuncture controls. Among theses 840 RCTs, 838 studies (99.8%) reported positive results from primary outcomes and two trials (0.2%) reported negative results. The percentages of RCTs concealment of the information on withdraws or sample size calculations were 43.7%, 5.9%, 4.9%, 9.9%, and 1.7% respectively.

The authors concluded that publication bias might be major issue in RCTs on acupuncture published in Chinese journals reported, which is related to high risk of bias. We suggest that all trials should be prospectively registered in international trial registry in future.

END OF QUOTE

Now an even more compelling reason emerged for taking evidence from China with a pinch of salt:

A recent survey of clinical trials in China has revealed fraudulent practice on a massive scale. China’s food and drug regulator carried out a one-year review of clinical trials. They concluded that more than 80 percent of clinical data is “fabricated“. The review evaluated data from 1,622 clinical trial programs of new pharmaceutical drugs awaiting regulator approval for mass production. Officials are now warning that further evidence malpractice could still emerge in the scandal.
According to the report, much of the data gathered in clinical trials are incomplete, failed to meet analysis requirements or were untraceable. Some companies were suspected of deliberately hiding or deleting records of adverse effects, and tampering with data that did not meet expectations.

“Clinical data fabrication was an open secret even before the inspection,” the paper quoted an unnamed hospital chief as saying. Contract research organizations seem have become “accomplices in data fabrication due to cutthroat competition and economic motivation.”

A doctor at a top hospital in the northern city of Xian said the problem doesn’t lie with insufficient regulations governing clinical trials data, but with the failure to implement them. “There are national standards for clinical trials in the development of Western pharmaceuticals,” he said. “Clinical trials must be carried out in three phases, and they must be assessed at the very least for safety,” he said. “But I don’t know what happened here.”

Public safety problems in China aren’t limited to the pharmaceutical industry and the figure of 80 percent is unlikely to surprise many in a country where citizens routinely engage in the bulk-buying of overseas-made goods like infant formula powder. Guangdong-based rights activist Mai Ke said there is an all-pervasive culture of fakery across all products made in the country. “It’s not just the medicines,” Mai said. “In China, everything is fake, and if there’s a profit in pharmaceuticals, then someone’s going to fake them too.” He said the problem also extends to traditional Chinese medicines, which are widely used in conjunction with Western pharmaceuticals across the healthcare system.
“It’s just harder to regulate the fakes with traditional medicines than it is with Western pharmaceuticals, which have strict manufacturing guidelines,” he said.

According to Luo, academic ethics is an underdeveloped field in China, leading to an academic culture that is accepting of manipulation of data. “I don’t think that the 80 percent figure is overstated,” Luo said.

And what should we conclude from all this?

I find it very difficult to reach a verdict that does not sound hopelessly chauvinistic but feel that we have little choice but to distrust the evidence that originates from China. At the very minimum, I think, we must scrutinise it thoroughly; whenever it looks too good to be true, we ought to discard it as unreliable and await independent replications.

For some time now, the research activity in and around alternative medicine has been seemingly buoyant. In each of the last 4 years, Medline listed around 2 000 articles is the category of ‘complementary alternative medicine’. This will surely look impressive to many!

Why then did I write ‘seemingly’? To comprehend this a little better, we should have some comparisons. Here are numbers of Medline-listed articles published in 2015 for a few other areas:

  • Surgery: 176 277
  • Psychology: 65 679
  • Internal medicine: 36 998
  • Obstetrics/gynaecology: 13 818
  • Pharmacology: 194 322
  • Paediatrics: 30 646

Now you see, I hope, why the 2 049 Medline-listed articles in the category of ‘complementary alternative medicine’ are only seemingly impressive. But what about specific alternative therapies? Here are numbers of Medline-listed articles published in 2015 for some major alternative treatments:

  • Homeopathy: 181
  • Herbal medicine: 1 572
  • Chiropractic: 314
  • Acupuncture: 1 784
  • Naturopathy: 45
  • Dietary supplements: 5 199

These figures are perhaps interesting but not easy to interpret. They might indicate that certain sections of alternative medicine are more open to scientific scrutiny than others. Or do they show that for some areas there are more research funds and expertise than others? I am not sure I know the answer.

If we look a little closer at the research activity in defined alternative therapies, we are bound to get disappointed. I have recently done this for homeopathy and for acupuncture and reached rather gloomy conclusions.

In the case of homeopathy the were:

  1. The research activity into homeopathy is currently very subdued.
  2. Arguably the main research question of efficacy does not seem to concern researchers of homeopathy all that much.
  3. There is an almost irritating abundance of papers that are data-free and thrive on opinion (my category of ‘other papers’).
  4. Given all this, I find it hard to imagine that this area of investigation is going to generate much relevant new knowledge or clinical progress.

And in the case of acupuncture, I stated:

  • Too little research is focussed on the two big questions: efficacy and safety.
  • In relation to the meagre output in RCTs, there are too many systematic reviews.
  • As long as we cannot be sure that acupuncture is more than a placebo, all these pre-clinical studies seem a bit out of place.
  • The vast majority of the articles were in low or very low impact journals.
  • There was only one paper that I would consider outstanding.

And what about the quality of the research into alternative medicine?

Well, this is a sad and depressing tale! If you doubt it, read my previous post or indeed any of the other ~500 which I have written on this particular subject in the past.

This is a post that I wanted to write for a while (I had done something similar on acupuncture moths ago); but I had to wait, and wait, and wait…until finally there were the awaited 100 Medline listed articles on homeopathy with a publication date of 2016. It took until the beginning of August to reach the 100 mark. To put this into perspective with other areas of alternative medicine, let me give you the figures for 3 other therapies:

  • there are currently  1 413 articles from 2016 on herbal medicine;
  • 875 on acupuncture;
  • and 256 on chiropractic.

And to give you a flavour of the research activity in some areas of conventional medicine:

  • there are currently almost 100 000 articles from 2016 on surgery;
  • 1 410 on statins;
  • and 33 033 on psychotherapy.

This suggests quite strongly, I think, that the research activity in homeopathy is relatively low (to put it mildly).

So, what do the first 100 Medline articles on homeopathy cover? Here are some of the findings of my mini-survey:

  • there were 4 RCTs;
  • 3 systematic reviews;
  • 8 papers on observational-type data (case series, observational studies etc.);
  • 9 animal studies;
  • 14 other pre-clinical or basic research studies;
  • 1 pilot study;
  • 14 investigations of the quality of homeopathic preparations;
  • 15 surveys;
  • 2 investigations into the adverse effects of homeopathic treatments;
  • 49 other papers (e. g. comments, opinion pieces, letters, perspective articles, editorials).

I should mention that, because I assessed 100 papers, the above numbers can be read both as absolute as well as percentage figures.

How should we interpret my findings?

As with my previous evaluation, I must caution not to draw generalizable conclusions from them. What follows should therefore be taken with a pinch of salt (or two):

  1. The research activity into homeopathy is currently very subdued.
  2. Arguably the main research question of efficacy does not seem to concern researchers of homeopathy all that much.
  3. There is an almost irritating abundance of papers that are data-free and thrive on opinion (my category of ‘other papers’).
  4. Given all this, I find it hard to imagine that this area of investigation is going to generate much relevant new knowledge or clinical progress.

On a good day, I get several emails from complete strangers; some are complimentary, others are critical, and others again are just strange. Few are stranger than the exchange I am about to disclose.

The author asked me twice to treat his/her emails with ‘trust and confidence’; after the second email, I nevertheless felt that I should not respect this wish but needed to share this brief exchange with my readers. I have, however, erased all the details that would allow an identification of the author.

 

INITIAL EMAIL of 18/7/2016

I am responding to you latest post regarding “Informed Consent”. I have decided to do so because my instincts suggest that we may in fact have an empathy in our individual objective to establish an evidence base for complementary medicine. However, I do not have any empathy with many of the contributors to your blog and especially with those that have a desire to “grind homeopathic vets and feed them to the pigs” Given that you moderate the site, I am surprised that you allowed such a post.

As you are aware, I obtained a copy of your book “A Scientist in Wonderland” which I have read with considerable interest and as you know, I have posted extracts on your blog. In this respect I make the following observations:

1. Your early experiences of homeopathy were positive and on this basis I find great difficulty in accepting that you are as anti-homeopathy as you publically state. From my own experience, this is not logical.

2. I am of the opinion that the sad loss of your Hungarian friend and colleague is an influencing factor, particularly as you avoided any mention of him receiving any form of alternative medicine.

3. I can empathise with your frustration at the lack of support from the alternative medicine community, as I have experienced this in my own efforts.

4. I am inclined to accept the possibility that you are using the blog to deliberately provoke the homeopathic community into action from a long standing but understandable state of complacency. (If you know that something works, then why is there a need to prove it).

5. I find difficulty to believe that you are at home surrounded by such closed minded individuals, because, historically, you have always moved on from such situations. However, I am not sure that you know how you can escape from the trap that you now find yourself in. Is this what you want for the rest of your life?

For a variety of reasons, I embarked on this … venture as a means of finding evidence that these therapies do work and have found that the homeopathy community is somewhat less than supportive in my efforts, so I do understand your potential frustration.

I appreciate that my observations are assumption based and may be wishful thinking on my part; however, if my assumptions have validity, please contact me, otherwise ignore this message.

If you do choose to pursue this conversation, then it must take place under the strict condition of TRUST & CONFIDENCE.

 

MY REPLY of 18/7/2016

thank you for your email. you say you read my memoir; may I suggest you read it again – because the answers to your questions seem to be all in there. your assumptions about me are quite wrong, and I think my book explains why.

best regards
e ernst

 

THE RESPONSE of 21/7/2016

In Britain we have a saying “Don’t mention the war when speaking to a German”, so out of respect I refrained from mentioning the Nazi regime in my last message; however, as you have made an implied reference to it, I will now comment.

I have some six years of close working experience with a large German organisation … so that I am fully aware of the significant differences between the German and British mentality and approach to life. I am therefore able to appreciate many of the difficulties that you will have encountered when arriving in this country to take up the Exeter post, which by definition was designed to advise the UK alternative therapy community how to do things properly!

The Anglo/Germanic axis is a significant challenge under normal circumstances but for you to arrive in this country and make direct comparisons between alternative medicine and the Third Reich in a country that spearheaded the fight against the Nazi’s at a cost of nearly half a million British lives was a fatal mistake on your part.

Having spent some forty years in and around the alternative health world here in Britain, India and the USA I don’t think your view point can be further from the truth. What amazes me is that you do not moderate Nazi type comments such as “grinding homeopaths and feeding them to pigs” from your blog which is a complete contradiction to your reasoning.

Your blog purports to provide cautionary advice to would be patients choosing alternative health options but your band of followers seem to have no understanding whatsoever as to the importance of respect for others. They seem to believe that from the offset, respect has to be earned, which implies judgement. Any doctor or therapist that starts from this view point when dealing with a patient, should not be treating patients at all. Empathy and respect are key factors in the healing process and those that automatically practice this naturally operate under and accept a moral code of ethics which forms part of all training within the main alternative treatments. The fundamental ethic behind all medicine is “first do no harm”. How can this be achieved if you do not respect the patient, regardless of his views?

At a personal level, I am concerned that your early experiences have distorted your views and unfortunately you have managed to alienate yourself from the very form of healthcare that would best resolve these issues without the need for suppressive drugs.

I suggest that you re-read your book and honestly ask yourself if the “peaceful vantage point” referred to on page 170, in any way measures up to the “peaceful, happy time” you mention on page 36.

I again extend my offer of an exploratory conversation in an atmosphere of “trust and confidence”.

END OF QUOTE

I do not feel like adding any comments just now… perhaps just a few questions:

How is it possible that someone who has obviously read quite a bit of what I have published misunderstands so much of it? Deluded? Demented? Or worse?

What a silly question! At least this is what most sceptics would say: if we are not sure that it works, we do not need to spend any thoughts on a potential mechanism!

However, in the realm of acupuncture, the potential mode of action remains a hotly debated and fundamentally relevant issue.

The TCM folks, of course, ‘knew’ all along how acupuncture works: it re-balances the life-forces yin and yang. This is a nice theory – it has but one disadvantage: it has no bearing whatsoever on reality. Vitalistic ideas such as this one have long been proven to be nothing but fantasy.

Meanwhile, several more plausible hypotheses have been developed, and hundreds of papers have been published on the subject. One recent article, for instance, suggests a range of mechanisms including microinjury, increased local blood flow, facilitated healing, and analgesia. Acupuncture may trigger a somatic autonomic reflex, thereby affecting the gastric and cardiovascular functions. Acupuncture may also change the levels of neurotransmitters such as serotonin and dopamine, thereby affecting the emotional state and craving… By affecting other pain-modulating neurotransmitters such as met-enkephalin and substance P along the nociceptive pathway, acupuncture may relieve headache. Acupuncture may affect the hypothalamus pituitary axis and reduce the release of the luteinizing hormone…

Another article states that the Western explanation for acupuncture effectiveness is based upon more than half a century of basic and clinical research, which identified the activation of sensory system and the subsequent activity-dependent regulation of neurotransmitters, neurohormones, and several classes of neuromodulators as plausible mechanism for the acupuncture‘s therapeutic properties. The regulation of neurotrophins’ expression and activity is one of the possible neurophysiological mechanisms underlying acupuncture‘s effects on neuropathic pain, nerve injury, neurodegeneration, and even in the regulation of gonadal functions…

Recently Burnstock proposed that mechanical deformation of the skin by needles and application of heat or electrical current leads to release of large amounts of ATP from keratinocytes, fibroblasts and other cells in skin; the ATP then occupies specific receptor subtypes expressed on sensory nerve endings in the skin and tongue; the sensory nerves send impulses through ganglia to the spinal cord, the brain stem, hypothalamus and higher centres; the brain stem and hypothalamus contain neurons that control autonomic functions, including cardiovascular, gastrointestinal, respiratory, urinogenital and musculo-skeletal activity. Impulses generated in sensory fibres in the skin connect with interneurons to modulate (either inhibition or facilitation) the activities of the motoneurons in the brain stem and hypothalamus to change autonomic functions; specifically activated sensory nerves, via interneurons, also inhibit the neural pathways to the pain centres in the cortex.

A brand-new article in the journal SCIENTIFIC AMERICAN puts the hypothesis in perspective:

…scientists have been studying a roster of potential biological pathways by which needling might relieve pain. The most successful of these efforts has centered on adenosine, a chemical believed to ease pain by reducing inflammation. A 2010 mouse study found that acupuncture needles triggered a release of adenosine from the surrounding cells into the extracellular fluid that diminished the amount of pain the rodents experienced. The mice had been injected with a chemical that made them especially sensitive to heat and touch. The researchers reported a 24-fold increase in adenosine concentration in the blood of the animals after acupuncture, which corresponded to a two-thirds reduction in discomfort, as revealed by how quickly they recoiled from heat and touch. Injecting the mice with compounds similar to adenosine had the same effect as acupuncture needling. And injecting compounds that slowed the removal of adenosine from the body boosted the effects of acupuncture by making more adenosine available to the surrounding tissue for longer periods. Two years later a different group of researchers went on to show that an injection of PAP, an enzyme that breaks other compounds in the body down into adenosine, could relieve pain for an extended chunk of time by increasing the amount of adenosine in the surrounding tissue. They dubbed that experimental procedure “PAPupuncture.”

Both sets of findings have excited researchers—and for good reason. The current options for treating pain are limited and rely mostly on manipulating the body’s natural pain-management system, known as the opioid system. Opioid-based painkillers are problematic for several reasons. Not only does their efficacy tend to wane over time, but they have been linked to an epidemic of addiction and overdose deaths across the U.S.—so much so that the Centers for Disease Control and Prevention has recently advised doctors to seriously restrict their use. The available nonopioid pain treatments are few; many of them require multiple injections or catheterization to work; and they often come with side effects, such as impaired movement. Adenosine offers an entirely new mechanism to exploit for potential treatments—one that may come with fewer side effects and less potential for addiction. What is more, adenosine can be made to circulate in the body for prolonged stretches. Pharmaceutical companies are actively investigating adenosine-related compounds as potential drugs.

But however promising adenosine may be as a treatment, the findings from this research do not prove that acupuncture itself “works.” For one thing, the researchers did not show that the release of adenosine was specific to acupuncture. Acupuncture needles might cause adenosine to flood the surrounding tissue, but so might a hard pinch, or applied pressure, or any number of other physical insults. In fact, both of the studies found that when adenosine was turned on in mouse tissue by other mechanisms, the pain response was equal to or better than the response generated by acupuncture. For another thing, the study results offered no support for the use of acupuncture to treat any of the other conditions for which the procedure is often advertised. A localized adenosine response may mitigate localized pain. That does not mean it can also cure insomnia or infertility.

It may well be that the reams of research scientists have done on acupuncture have lit the path toward improved understanding of—and eventually better treatments for—intractable pain. But it may also be time to take whatever bread crumbs have been laid out by that work and move on.

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As we see, there is no shortage of potential explanations as to HOW acupuncture works. The most plausible theory still is that it works largely or even exclusively via a placebo effect.

Due to this type of mechanistic research, acupuncture has gained much credibility. The question is, does it deserve it? In my view, it would be much more fruitful to first make sure THAT acupuncture works (beyond a placebo response) and, if so, for what conditions. The question HOW it works is unquestionably interesting but in the final analysis it probably is secondary.

Yesterday, a press-release reached me announcing that a Chinese herbal medicine, ‘Phynova Joint and Muscle Relief Tablets’, containing the active ingredient Sigesbeckia, is now on sale in the UK for the first time in Boots The Chemist: 

Sigesbeckia is the first traditional Chinese treatment granted a traditional herbal registration (THR) under the traditional herbal medicines product directive in the UK, by drug safety watchdog the Medicines and Healthcare Products Regulatory Agency (MHRA).  Oxford based Phynova which manufactures the product was granted the UK licence last year. 

Containing 500mg of the active ingredient, Phynova Joint and Muscle Relief Tablets are specially formulated for the relief of backache, arthritis, minor sports injuries, rheumatic or muscular pains and general aches and pains in muscles or joints.  Two tablets are taken each day, one in the morning and one in the evening. They have no known side effects and are non-addictive. .. 

The product, which retails at £19.99 for one month’s supply of 60 tablets, is available in 950 UK Boots outlets and online via Click and Collect from all stores.  It will be sold both Over the Counter (OTC) by pharmacist staff and off the shelf as part of Boots’ pain relief fixture… 

END OF QUOTE

What on earth is a ‘joint and muscle relief’? Personally I do not want to be relieved of my joints and muscles!!!

Yes, I know, they probably mean ‘joint and muscle pain relief’ but were not allowed to say so because this is a medical indication.

And what about the claim of ‘no side-effects’; is it possible that a pharmacological treatment has positive effects without any risks at all? This is not what they told me during my pharmacology course, if I remember correctly. And anyway, even placebos have side-effects!

I admit, I was puzzled.

The covering letter of the press-release provided more amazement: it informed me that “Phynova joint and muscle relief contains the active ingredient Sigesbeckia which has been through clinical trials and has been used for pain relief in China for hundreds of years…” It was the remark about clinical trials (PLURAL!!!) that caught my interest most.

So, I looked up ‘Sigesbeckia’ on Medline and found as good as nothing. This is mainly because the plant is spelled correctly ‘Siegesbeckia’ in honour of the famous botanist Siegesbeck.

Looking up ‘Siegesbeckia’, I found many pre-clinical studies but no clinical trials.

Next I searched for a comment from the MHRA and discovered that their account makes it very clear that a licence has been granted to this product “exclusively upon long standing use… and not upon data from clinical trials.”

So, who is right?

Are there clinical trials of this product or not? And, if there are any, where are they?

Perhaps someone from Phynova can enlighten us?

 

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