MD, PhD, FMedSci, FSB, FRCP, FRCPEd

clinical trial

Today is WORLD CANCER DAY.

Yesterday I prepared you for this event by alerting you to a disgusting cancer scam, and today I want to contrast this with more encouraging news from the strange world of alternative medicine. So I searched Medline for a fitting, recent publication showing at least some value of an alternative therapy. Believe me, such papers are few and far between.

But here is one:

The aim of this Cochrane review was to assess effects of yoga on health-related quality of life, mental health and cancer-related symptoms among women with a diagnosis of breast cancer who are receiving active treatment or have completed treatment. The authors conducted extensive literature searches and applied no language restrictions. RCTs were eligible, if they (1) compared yoga interventions to no therapy or to any other active therapy in women with a diagnosis of breast cancer, and (2) assessed at least one of the primary outcomes on patient-reported instruments, including health-related quality of life, depression, anxiety, fatigue or sleep disturbances.

Two review authors independently collected data on methods and results. The risk of publication bias was assessed through visual analysis of funnel plot symmetry and heterogeneity between studies. Subgroup analyses were conducted for current treatment status, time since diagnosis, stage of cancer and type of yoga intervention.

Twenty-four studies with a total of 2166 participants were included, 23 of which provided data for meta-analysis. Thirteen studies had low risk of selection bias, five studies reported adequate blinding of outcome assessment and 15 studies had low risk of attrition bias. Seventeen studies that compared yoga versus no therapy provided moderate-quality evidence showing that yoga improved health-related quality of life, reduced fatigue and reduced sleep disturbances in the short term. There was an overall low risk of publication bias.

Yoga did not appear to reduce depression or anxiety in the short term and had no medium-term effects on health-related quality of life or fatigue. Four studies that compared yoga versus psychosocial/educational interventions provided moderate-quality evidence indicating that yoga can reduce depression, anxiety and fatigue in the short term. Very low-quality evidence showed no short-term effects on health-related quality of life or sleep disturbances. Three studies that compared yoga to exercise presented very low-quality evidence showing no short-term effects on health-related quality of life or fatigue. No trial provided safety-related data.

The authors concluded that moderate-quality evidence supports the recommendation of yoga as a supportive intervention for improving health-related quality of life and reducing fatigue and sleep disturbances when compared with no therapy, as well as for reducing depression, anxiety and fatigue, when compared with psychosocial/educational interventions. Very low-quality evidence suggests that yoga might be as effective as other exercise interventions and might be used as an alternative to other exercise programmes.

As I said, this is most encouraging. Many women are attracted by yoga, and the news that it can improve their symptoms is clearly positive. I have said it often, but I say it again: in supportive and palliative cancer care there might be an important role for several forms of CAM. One has to make sure though that they do not interfere with conventional treatments, and – this is very important – cancer patients must not be misled to believe that they can be used to treat or cure cancer. Finally, patients should not pitch their hopes too high: the effect sizes of alternative treatments in cancer care are invariably small or modest which means that they can help to reduce symptoms but are unlikely to get rid of them completely.

On an even more sober note, I have to reiterate that none of the trials included in the above review reported safety data (yoga is not totally devoid of adverse-effects!). This is an almost stereotypical finding when assessing clinical trials of alternative therapies. It discloses a clear and unacceptable breach of publication ethics. How can we ever get a realistic impression of the risks of alternative medicine, if adverse effects remain unreported? It is high time that researchers, authors, journal editors and reviewers get this message and behave accordingly.

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

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

INDICATORS SUGGESTIVE OF A GOOD CLINICAL TRIAL

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

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

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

WARNIG SIGNALS INDICATING A POOR CLINICAL TRIAL

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

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

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

Hyperthyroidism is, so I am told, a frequent veterinary problem, particularly in elderly cats. Homeopathic treatment is sometimes used to treat this condition. One article even provided encouraging details based on 4 case-reports. All 4 cats showed resolution of clinical signs; three attained normal thyroid hormone levels.  The authors concluded that homeopathic and complementary therapies avoid the potential side effects of methimazole and surgical thyroidectomy, they are less costly than radioactive iodine treatment, and they provide an option for clients who decline conventional therapies.

Yes, you guessed correctly: such a paper can only be published in the journal ‘HOMEOPATHY‘, respectable journals would not allow such conclusions based on 4 case-reports. They don’t permit inferences as to cause and effect. We have no idea what would have happened to these animals without homeopathy – perhaps they would have fared even better!

What we need is a proper controlled trial. The good news is that such a study has just been published. This double-blinded, placebo-controlled randomised trial was aimed at testing the efficacy of individualised homeopathy in the treatment of feline hyperthyroidism. Cats were randomised into two treatment arms. Either a placebo or a homeopathic treatment was given to each cat blindly.

After 21 days, the T4 levels, weight (Wt) and heart rate (HR) were compared with pre-treatment values. There were no statistically significant differences in the changes seen between the two treatment arms following placebo or homeopathic treatment, or between the means of each parameter for either treatment arm before and after placebo or homeopathic treatment. In a second phase of the study, patients in both treatment arms were given methimazole treatment for 21 days and T4, Wt and HR determined again. Subsequently, statistically significant reductions were noted in T4 (P<0.0001) and HR (P=0.02), and a statistically significant increase was observed in Wt (P=0.004).

The authors concluded that the results of this study failed to provide any evidence of the efficacy of homeopathic treatment of feline hyperthyroidism.

So, homeopathy does not work – not in humans nor in animals. This statement, backed by solid facts, proves all those wrong who cannot resist uttering the notion that HOMEOPATHY CANNOT BE A PLACEBO BECAUSE IT WORKS IN ANIMALS.

It doesn’t!

And we have seen the evidence for the correctness of this fact so often (for instance here, here, here and here) that I feel embarrassed to say it again: highly diluted homeopathic remedies are placebos. As soon as we adequately control for placebo and other non-specific effects in properly controlled studies, the alleged effects, reported in anecdotes and other uncontrolled studies, simply disappear.

 

Mike Cummings recently stated on this blog “I’m not into blog banter.” Is he perhaps referring to some ‘alternative facts’? The truth seems to be that he blogs happily, regularly and – I am sad to say – disgracefully. This is a quote from his new post about the discussions regarding an acupuncture trial which was in the press a few days ago, (and also has been discussed on this blog):

START OF QUOTE

So there has been a big response to this paper press released by BMJ on behalf of the journal Acupuncture in Medicine. The response has been influenced by the usual characters – retired professors who are professional bloggers and vocal critics of anything in the realm of complementary medicine. They thrive on oiling up and flexing their EBM muscles for a baying mob of fellow sceptics (see my ‘stereotypical mental image’ here). Their target in this instant is a relatively small trial on acupuncture for infantile colic.[1] Deserving of being press released by virtue of being the largest to date in the field, but by no means because it gave a definitive answer to the question of the efficacy of acupuncture in the condition. We need to wait for an SR where the data from the 4 trials to date can be combined. On this occasion I had the pleasure of joining a short segment on the Today programme on BBC Radio 4 led by John Humphreys. My protagonist was the ever-amusing David Colquhoun (DC), who spent his short air-time complaining that the journal was even allowed to be published in the first place. You can learn all about DC care of Wikipedia – he seems to have a surprisingly long write up for someone whose profession career was devoted to single ion channels, perhaps because a significant section of the page is devoted to his activities as a quack-busting blogger. So why would BBC Radio 4 invite a retired basic scientist and professional sceptic blogger to be interviewed alongside one of the journal editors – a clinician with expertise in acupuncture (WMA)? At no point was it made manifest that only one of the two had ever been in a position to try to help parents with a baby that they think cries excessively. Of course there are a lot of potential causes of excessive crying, but I am sure DC would agree that it is unlikely to be attributable to a single ion channel…

END OF QUOTE

I encourage everyone to read Cummings post in full; it’s full of surprises. Here I just want to comment very briefly why I find his post disgraceful (the Cummings quotes are in bold followed by my comments):

….usual characters….. Disrespectful to the point of being derogatory, in my view

….retired professors….. Not true, non-retired professionals commented as well

….professional bloggers…. Meaning people who earn their income by blogging? Certainly not true!

….vocal critics of anything in the realm of complementary medicine…. Critic not of ‘anything’ but merely of things that are false or misleading like the trial in question

….a baying mob of fellow sceptics…. Unquestionably meant to be insulting and arguably libelous

….Deserving of being press released by virtue of being the largest to date in the field…. Large is not necessarily a virtue that merits a press-release, particularly, if it is not matched with quality

….We need to wait for an SR where the data from the 4 trials to date can be combined…. More than doubtful that we ‘need to wait’. The 4 trials in question are all very weak and therefore cannot provide a firm answer via a systematic review

….the ever-amusing David Colquhoun…. Derogatory to the extreme

….why would BBC Radio 4 invite a retired basic scientist and professional sceptic blogger…. The answer could be because he understands science and has vast experience exposing false claims

….only one of the two had ever been in a position to try to help parents with a baby that they think cries excessively…. This does not necessarily mean that such a person understands science, and Cummings might even be an example for this

….is unlikely to be attributable to a single ion channel…. Even Cummings’ attempts at humour are quite appalling.

 

The comments of Dr Mike Cummings MB ChB Dip Med Ac, I am afraid, befit an ill-educated acupuncturist who feels personally hurt because his views have been challenged and who is not quite bright enough to have a rational discussion about his favourite subject, particularly with someone who has a superior grasp of the issues at hand (which are clearly not ‘how to stick a needle in a baby’). However, Cummings is not a simple acupuncturist; he happens to be a member of the medical profession, a medical director of the British Medical Acupuncture Society and (as he seems keen to point out) a journal editor. With these credentials, he should, in my view, be able to argue a bit more intelligently, truthfully and a lot more gracefully.

Sad, really!

One could almost think he wants to give acupuncture a bad name!!!

Acupuncture is often recommended as a treatment for shoulder pain, but its effectiveness is far from proven. A new study has just been published; but does it change this uncertainty?

A total of 227 patients with subacromial pain syndrome were recruited to this RCT. The patients were allocated to three groups who received either A) group exercise, B) group exercise plus acupuncture or C) group exercise plus electro-acupuncture. The primary outcome measure was the Oxford Shoulder Score. Follow-up was post treatment, and at 6 and 12 months. Data were analysed on intention-to-treat principles with imputation of missing values.

Treatment groups were similar at baseline. All treatment groups demonstrated improvements over time. Between-group estimates were, however, small and non-significant.

The authors concluded that neither acupuncture nor electro-acupuncture were found to be more beneficial than exercise alone in the treatment of subacromial pain syndrome. 

Well, that was to be expected!… I hear the rationalists amongst us exclaim.

Actually, I am not so sure.

One could easily have expected that the acupuncture groups (B and C) show a significant advantage over group A.

Why?

Because acupuncture is a ‘theatrical placebo’, a ritual that impresses patients and thus impacts on results, particularly on subjective outcomes like pain. If the results had shown a benefit for acupuncture + exercise (groups B and C) versus exercise alone (group A), what would we have made of it? Acupuncture fans would surely have claimed that it is evidence confirming acupuncture’s effectiveness. Sceptics, on the other hand, would have rightly insisted that it demonstrates nothing of the sort – it merely confirms that placebo effects can affect clinical outcomes such as pain.

As it turned out, however, this trial results happened to indicate that these placebo-effects can be so small that they fail to reach the level of statistical significance.

I think there is one noteworthy message here: RCTs with such a design (no adequate control for placebo effects) can easily generate false-positive results (in this case, this did not happen, but it was nevertheless a possible outcome). Such studies are popular but utterly useless: they don’t advance our knowledge one single iota. If that is so, we should not waste our resources on them because, in the final analysis, this is not ethical. In other words, we must stop funding research that has little or no chance of advancing our knowledge.

This new RCT was embargoed until today; so, I had to wait until I was able to publish my comments. Here are the essentials of the study:

The Swedish investigators compared the effect of two types of acupuncture versus no acupuncture in infants with colic in public child health centres (CHCs). The study was designed as a multicentre, randomised controlled, single-blind, three-armed trial (ACU-COL) comparing two styles of acupuncture with no acupuncture, as an adjunct to standard care. Among 426 infants whose parents sought help for colic and registered their child’s fussing/crying in a diary, 157 fulfilled the criteria for colic and 147 started the intervention.

Parallel to usual care, study participants visited the study CHC twice a week for 2 weeks. Thus, all infants received usual care plus 4 extra visits to a CHC, during which parents met a nurse for 20–30 min and were able to discuss their infant’s symptoms. Together these were considered to represent gold standard care. The nurse listened, and gave evidence-based advice and calming reassurance. Breastfeeding mothers were encouraged to continue breastfeeding. At each visit, the study nurse carried the infant to a separate treatment room where they were left alone with the acupuncturist for 5 min.

The acupuncturist treated the baby according to group allocation and recorded the treatment procedures and any adverse events. Disposable stainless steel 0.20×13 mm Vinco needles (Helio, Jiangsu Province, China) were used. Infants allocated to group A received standardised MA at LI4. One needle was inserted to a depth of approximately 3 mm unilaterally for 2–5 s and then withdrawn without stimulation. Infants allocated to group B received semi-standardised individualised acupuncture, mimicking clinical TCM practice. Following a manual, the acupuncturists were able to choose one point, or any combination of Sifeng, LI4 and ST36, depending on the infant’s symptoms, as reported in the diary. A maximum of five insertions were allowed per treatment. Needling at Sifeng consisted of 4 insertions, each to a depth of approximately 1 mm for 1 s. At LI4 and ST36, needles were inserted to a depth of approximately 3 mm, uni- or bilaterally. Needles could be retained for 30 seconds. De qi was not sought, therefore stimulation was similarly minimal in groups A and B. Infants in group C spent 5 min alone with the acupuncturist without receiving acupuncture.

The effect of the two types of acupuncture was similar and both were superior to gold standard care alone. Relative to baseline, there was a greater relative reduction in time spent crying and colicky crying by the second intervention week (p=0.050) and follow-up period (p=0.031), respectively, in infants receiving either type of acupuncture. More infants receiving acupuncture cried <3 hours/day, and thereby no longer fulfilled criteria for colic, in the first (p=0.040) and second (p=0.006) intervention weeks. No serious adverse events were reported.

The authors concluded that acupuncture appears to reduce crying in infants with colic safely.

Notice that the investigators are cautious and state in the abstract that “acupuncture appears to reduce crying…” Their conclusions from the actual article are, however, quite different; here they state the following:

Among those initially experiencing excessive infant crying, the majority of parents reported normal values once the infant’s crying had been evaluated in a diary and a diet free of cow’s milk had been introduced. Therefore, objective measurement of crying and exclusion of cow’s milk protein are recommended as first steps, to avoid unnecessary treatment. For those infants that continue to cry >3 hours/day, acupuncture may be an effective treatment option. The two styles of MA tested in ACU-COL had similar effects; both reduced crying in infants with colic and had no serious side effects. However, there is a need for further research to find the optimal needling locations, stimulation and treatment intervals.

Such phraseology is much more assertive and seems to assume acupuncture caused specific therapeutic effects. Yet, I think, this assumption is not warranted.

In fact, I believe, the study shows almost the opposite of what the authors conclude. Both minimal and TCM acupuncture seemed to reduce the symptoms of colic compared to no acupuncture at all. I think, this confirms previous research showing that acupuncture is a ‘theatrical placebo’. The study was designed without an adequate placebo group. It would have been easy to use some form of sham acupuncture in the control group. Why did the authors not do that? Heaven knows, but one might speculate that they were aiming for a positive result – and what better way to ensure it than with a ‘no treatment’ control group?

There are, of course, numerous other flaws. For instance, Prof David Colquhoun FRS, Professor of Pharmacology at University College London, criticised the study because of its lousy statistics:

START OF QUOTE

“It is truly astonishing that, in the 21st century, the BMJ still publishes a journal devoted to a form of pre-scientific medicine which after more than 3000 trials has still not been able to produce convincing evidence of efficacy1. Like most forms of alternative medicine, acupuncture has been advocated for a vast range of problems, and there is little evidence that it works for any of them. Colic has not been prominent in these claims. What parent would think that sticking needles into their baby would stop it crying? The idea sounds bizarre. It is. This paper certainly doesn’t show that it works.

“The statistical analysis in the paper is incompetent. This should have been detected by the referees, but wasn’t.  For a start, the opening statement, ‘A two-sided P value ≤0.05 was considered statistically significant’ is simply unacceptable in the light of all recent work about reproducibility.  Still worse, Table 1 uses the description ‘statistical tendency towards significance (p=0.051–0.1)’.

“Worst of all, Table 1 reports 24 different P values, of which three are (just) below 0.05. Yet no correction has been used for multiple comparisons. This is very bad practice. It’s highly unlikely that, if the proper correction had been done, any of the results would have given a type 1 error rate below 5%.

“Even were it not for this, most of the ‘significant’ P values are marginal (only slightly less than 0.05).  It is now well known that the type 1 error rate gives an optimistic view. What matters is the false positive rate – the chance that a ‘significant’ result is a false positive.  A p-value close to 0.05 implies that there is at least a 30% chance that they are false positives.  If one thought, a priori, that the chance of colic being cured by sticking needles into a baby was less than 50%, the false positive rate could easily be greater than 80%2.  It is now recognised that this misinterpretation of p-values is a major contributor to the crisis of reproducibility.

“Other problems concern the power calculation.  A priori calculations of power are well-known to be overoptimistic, because small trials usually overestimate the effect size.  In this case the initial estimated sample size was not attained, and a rather mysterious recalculation of power was used.

“Another small problem: the discussion points out that ‘the majority of infants in this cohort did not have colic’.

“The nature of the control group is not very clear. An appropriate control might have been to cuddle the baby – this was used in a study in which another implausible treatment, chiropractic, was shown not to work.  This appears not to have been done.

“Lastly, p-values are reported in the text without mention of effect sizes. This is contrary to all statistical advice.

“In conclusion, the design of the trial is reasonable (apart from the control group) but the statistical analysis is appalling.  It’s very likely that there aren’t any real effects of acupuncture at all. This paper serves more to muddy the waters than to add useful information. It’s a model for the sort of mistakes that have led to the crisis in reproducibility.  The BMJ should not be publishing this sort of stuff, and the referees seem to have no understanding of statistics.”

END OF QUOTE

Despite these rather obvious – some would say fatal – flaws, the editor of ACUPUNCTURE IN MEDICINE (AIM) thought this trial to be so impressively rigorous that he issued a press-release about it. This, I think, is particularly telling, perhaps even humorous: it shows what kind of a journal AIM is, and also provides an insight into the state of acupuncture research in general.

The long and short of it is that conclusions about specific therapeutic effects of acupuncture are not permissible. We know that colicky babies respond even to minimal attention, and this trial confirms that even a little additional TLC in the form of acupuncture will generate an effect. The observed outcome is most likely unrelated to acupuncture.

If you want to scientifically investigate this question, it might be a good idea NOT to start with the following sentence: “Auricular acupuncture (AA) is effective in the treatment of preoperative anxiety”. Yet, this is exactly what the authors did in their recent publication.

The aim of this new study was to investigate whether AA can reduce exam anxiety as compared to placebo and no intervention. Forty-four medical students were randomized to receive AA, placebo, or no intervention in a crossover manner. Subsequently they completed three comparable oral anatomy exams with an interval of one month between the exams/interventions.

A licensed acupuncturist with more than five years of experience with this technique applied AA at the acupuncture points MA-IC1 (Lung), MA-TF1 (ear Shenmen), MA-SC (Kidney), MA-AT1 (Subcortex) and MA-TG (Adrenal gland) bilaterally. Indwelling fixed ‘New Pyonex’ needles embedded in a skin-coloured adhesive tape were used for AA. The participants were instructed by the acupuncturist to stimulate the auricular needles for 3–5 minutes, if they felt anxious. For the placebo procedure, ‘New Pyonex’ placebo needles were attached to five sites on the helix of the auricle bilaterally. ‘New Pyonex’ placebo needles have the same appearance as AA needles but consist of self-adhesive tape only. In order to avoid potential physiologic effects of acupressure, the participants were not instructed to stimulate the attached ‘New Pyonex’ placebo needles. AA and placebo needles were left in situ until the next day and were removed out of sight of the participants after the exam by the investigator, who was not involved in acupuncture procedure

Levels of anxiety were measured using a visual analogue scale before and after each intervention as well as before each exam. Additional measures included the State-Trait-Anxiety Inventory, duration of sleep at night, blood pressure, heart rate and the extent of participant blinding.

All included participants finished the study. Anxiety levels were reduced after AA and placebo intervention compared to baseline and the no intervention condition (p < 0.003). Moreover, AA was also better at reducing anxiety than placebo in the evening before the exam (p = 0.018). Participants were able to distinguish between AA and placebo intervention.

The authors concluded that both auricular acupuncture and placebo procedure were shown to be effective in reducing levels of exam anxiety in medical students. The superiority of verum AA over placebo AA and no intervention is considered to be due to stimulation of cranial nerves, but may have been increased in effect by insufficient participant blinding.

Here are just three of the major concerns I have about this study:

  • The trial design seems odd: a crossover study can only work well, if there is a stable baseline. This may not be the case with three consecutive exams; the anxiety experienced by students is bound to get less as time goes by. I think anyone who has passed a series of exams will confirm that there is a large degree of habituation.
  • It seems inadequate to employ just one acupuncturist; it means that the trial might end up testing not acupuncture per se but the skills of the therapist.
  • The placebo used for this study cannot possibly have fooled anyone into believing that it was real AA; volunteers were not even instructed to ‘stimulate’ the placebo devices. The difference to the ‘real thing’ must have been very clear to all involved. This means that the control for placebo-effects was woefully incomplete. In turn, this means that the observed outcomes are most likely due to residual bias.

In view of these concerns, allow me to re-phrase the authors’ conclusions:

THE RESULTS OF THIS POORLY-DESIGNED STUDY ARE DIFFICULT TO INTERPRET. MOST LIKELY THEY SHOW THAT ACUPUNCTURE IS NOT EFFECTIVE BUT MERELY WORKS THROUGH A PLACEBO-RESPONSE.

The WDDTY is not my favourite journal – far from it. The reason for my dislike is simple: far too many of its articles are utterly misleading and a danger to public health. Take this recent one entitled ‘Paleo-type diet reversing Crohn’s and ulcerative colitis’, for instance:

START OF QUOTE
Crohn’s disease and ulcerative colitis are being reversed solely by diet—essentially a Paleo diet. The non-drug approach has been successful in 80 per cent of children who’ve been put on the special diet.

The diet—called the specific carbohydrate diet (SCD)—has been pioneered by Dr David Suskind, a gastroenterologist at Seattle Children’s Hospital. The diet excludes grains, dairy, processed foods and sugars, other than honey, and promotes natural, nutrient-rich foods, including vegetables, fruits, meats and nuts.

Children are going into complete remission after just 12 weeks on the diet, a new study has discovered. Ten children with inflammatory bowel disease (IBD)—an umbrella term for Crohn’s and ulcerative colitis—were put on the diet, and eight were completely symptom-free by the end of the study. Suskind started exploring a dietary approach to IBD because he became convinced that the standard medical treatment of steroids or other medication was inadequate. “For decades, medicine has said diet doesn’t matter, that it doesn’t impact disease. Now we know that diet does have an impact, a strong impact. It works, and now there’s evidence,” he said.

END OF QUOTE

“For decades, medicine has said diet doesn’t matter, that it doesn’t impact disease”.

Really?

In this case, I must have studied an entirely different subject all these years ago at university – I had been told it was medicine but perhaps…???…!!!

It took me some time to find the original paper – they cited a wrong reference (2017 instead of 2016). But eventually I located it. Here is its abstract:

GOAL:

To determine the effect of the specific carbohydrate diet (SCD) on active inflammatory bowel disease (IBD).

BACKGROUND:

IBD is a chronic idiopathic inflammatory intestinal disorder associated with fecal dysbiosis. Diet is a potential therapeutic option for IBD based on the hypothesis that changing the fecal dysbiosis could decrease intestinal inflammation.

STUDY:

Pediatric patients with mild to moderate IBD defined by pediatric Crohn’s disease activity index (PCDAI 10-45) or pediatric ulcerative colitis activity index (PUCAI 10-65) were enrolled into a prospective study of the SCD. Patients started SCD with follow-up evaluations at 2, 4, 8, and 12 weeks. PCDAI/PUCAI, laboratory studies were assessed.

RESULTS:

Twelve patients, ages 10 to 17 years, were enrolled. Mean PCDAI decreased from 28.1±8.8 to 4.6±10.3 at 12 weeks. Mean PUCAI decreased from 28.3±23.1 to 6.7±11.6 at 12 weeks. Dietary therapy was ineffective for 2 patients while 2 individuals were unable to maintain the diet. Mean C-reactive protein decreased from 24.1±22.3 to 7.1±0.4 mg/L at 12 weeks in Seattle Cohort (nL<8.0 mg/L) and decreased from 20.7±10.9 to 4.8±4.5 mg/L at 12 weeks in Atlanta Cohort (nL<4.9 mg/L). Stool microbiome analysis showed a distinctive dysbiosis for each individual in most prediet microbiomes with significant changes in microbial composition after dietary change.

CONCLUSIONS:

SCD therapy in IBD is associated with clinical and laboratory improvements as well as concomitant changes in the fecal microbiome. Further prospective studies are required to fully assess the safety and efficacy of dietary therapy in patients with IBD.

What does this mean?

The WDDTY report bears very little resemblance to the journal article (let alone with the title of their article or any other published research by David Suskind).

How come?

I cannot be sure, but I would not be surprised to hear that the latter was ‘egged up’ to make the former appear more interesting.

If that is so, WDDTY are (once again) guilty of misleading the public to the point of endangering lives of vulnerable patients.

SHAME ON EVERY OUTLET THAT SELLS WDDTY, I’d say.

Can intercessory prayer improve the symptoms of sick people?

Why should it? It’s utterly implausible!

Because the clinical evidence says so?

No, the current Cochrane review concluded that [the] findings are equivocal and, although some of the results of individual studies suggest a positive effect of intercessory prayer, the majority do not and the evidence does not support a recommendation either in favour or against the use of intercessory prayer. We are not convinced that further trials of this intervention should be undertaken and would prefer to see any resources available for such a trial used to investigate other questions in health care.

Yet, not all seem to agree with this; and some even continue to investigate prayer as a medical therpy.

For this new study (published in EBCAM), the Iranian investigators randomly assigned 92 patients in 2 groups to receive either 40 mg of propranolol twice a day for 2 month (group “A”) or 40 mg of propranolol twice a day for 2 months with prayer (group “B”). At the beginning of study and 3 months after intervention, patients’ pain was measured using the visual analogue scale.

All patients who participate in present study were Muslim. At the beginning of study and before intervention, the mean score of pain in patients in groups A and B were 5.7 ± 1.6 and 6.5 ± 1.9, respectively. According to results of independent t test, mean score of pain intensity at the beginning of study were similar between patients in 2 groups (P > .05). Three month after intervention, mean score of pain intensity decreased in patients in both groups. At this time, the mean scores of pain intensity were 5.4 ± 1.1 and 4.2 ± 2.3 in patients in groups A and B, respectively. This difference between groups was statistically significant (P < .001).

figure

The above figure shows the pain score in patients before and after the intervention.

The authors concluded that the present study revealed that prayer can be used as a nonpharmacologic pain coping strategy in addition to pharmacologic intervention for this group of patients.

Extraordinary claims require extraordinary proof. This study is, in fact, extraordinary – but only in the sense of being extraordinarily poor, or at least it is extraordinary in its quality of reporting. For instance, all we learn in the full text article about the two treatments applied to the patient groups is this: “The prayer group participated in an 8-week, weekly, intercessory prayer program with each session lasting 45 minutes. Pain reduction was measured at baseline and after 3 months, by registered nurses who were specialist in pain management and did not know which patients were in which groups (control or intervention), using a visual analogue scale.”

Intercessory prayer is the act of praying on behalf of others. This mans that the patients receiving prayer might have been unaware of being ‘treated’. In this case, the patients could have been adequately blinded. But this is not made clear in the article.

More importantly perhaps, the authors fail to provide any numeric results. All that we are given is the above figure. It is not possible therefore to run any type of check on the data. We are simply asked to believe what the authors have written. I for one have great difficulties in doing so. All I do believe in relation to this article is that

  • the journal EBCAM is utter trash,
  • constantly publishing rubbish is unethical and a disservice to everyone,
  • prayer does not need further research of this nature,
  • and poor studies often generate false-positive findings.

Perhaps I have a weak spot for fish oil; more likely, however, I just like positive news – and, in alternative medicine, there is not much of it. That’s why I have written about the potential benefits of fish-oil again and again and again and again.

Reduced intake of fish oil, i.e. n−3 long-chain polyunsaturated fatty acids (LCPUFAs), may be a contributing factor to the increasing prevalence of asthma and other wheezing disorders. Yet the evidence is neither clear nor strong. This study was aimed at shedding more light on the issue; specifically, it tested the effect of supplementation with n−3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring.

The investigators randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n−3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children’s lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n−3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there were no statistically significant associations between supplementation and asthma exacerbations, eczema, or allergic sensitization.

The authors concluded that supplementation with n−3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third.

The authors must be congratulated. This trial is stunning in many ways: it was carefully designed and executed; its results are clear and important; its write-up is excellent. The research was supported by private and public research funds, all of which are listed at www.copsac.com. The Lundbeck Foundation, the Danish Ministry of Health, the Danish Council for Strategic Research, the Danish Council for Independent Research, and the Capital Region Research Foundation provided core support.

It is debatable whether the intake of fish oil falls under the umbrella of alternative medicine. In a way, it reminds me of the famous saying: what do we call alternative medicine that works? We call it medicine. It also holds an important reminder for all who make claims about the benefit of alternative therapies: extraordinary claims require extraordinary evidence.

Can these findings be translated into practical advice to consumers? The NEJM discussed this question in an accompanying article in which the case of a fictional pregnant woman (Ms. Franklin) was considered. Here is what they concluded: …there is benefit and little risk associated with n−3 LCPUFA supplementation. Even though we do not know Ms. Franklin’s EPA and DHA levels, there is likely to be a benefit for her child, at little risk, cost, or inconvenience. She should start taking n−3 LCPUFA supplements.

Despite my soft spot for fish oil, I might add that, while we give advice of this nature, we nevertheless need to insist on independent replications to have certainty.

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