The question whether spinal manipulative therapy (SMT) has any specific therapeutic effects is still open. This fact must irritate ardent chiropractors, and they therefore try everything to dispel our doubts. One way would be to demonstrate a dose-effect relationship between SMT and the clinical outcome. But, for several reasons, this is not an easy task.
This RCT was aimed at identifying the dose-response relationship between visits for SMT and chronic cervicogenic headache (CGH) outcomes; to evaluate the efficacy of SMT by comparison with a light massage control.
The study included 256 adults with chronic CGH. The primary outcome was days with CGH in the prior 4 weeks evaluated at the 12- and 24-week primary endpoints. Secondary outcomes included CGH days at remaining endpoints, pain intensity, disability, perceived improvement, medication use, and patient satisfaction. Participants were randomized to 4 different dose levels of chiropractic SMT: 0, 6, 12, or 18 sessions. They were treated 3 times per week for 6 weeks and received a focused light-massage control at sessions when SMT was not assigned. Linear dose effects and comparisons to the no-manipulation control group were evaluated at 6, 12, 24, 39, and 52 weeks.
A linear dose-response was observed for all follow-ups, a reduction of approximately 1 CGH day/4 weeks per additional 6 SMT visits (p<.05); a maximal effective dose could not be determined. CGH days/4 weeks were reduced from about 16 to 8 for the highest and most effective dose of 18 SMT visits. Mean differences in CGH days/4 weeks between 18 SMT visits and control were -3.3 (p=.004) and -2.9 (p=.017) at the primary endpoints, and similar in magnitude at the remaining endpoints (p<.05). Differences between other SMT doses and control were smaller in magnitude (p > .05). CGH intensity showed no important improvement nor differed by dose. Other secondary outcomes were generally supportive of the primary.
The authors concluded that there was a linear dose-response relationship between SMT visits and days with CGH. For the highest and most effective dose of 18 SMT visits, CGH days were reduced by half, and about 3 more days per month than for the light-massage control.
This trial would make sense, if the effectiveness of SMT for CGH had been a well-documented fact, and if the study had rigorously controlled for placebo-effects.
But guess what?
Neither of these conditions were met.
A recent review concluded that there are few published randomized controlled trials analyzing the effectiveness of spinal manipulation and/or mobilization for TTH, CeH, and M in the last decade. In addition, the methodological quality of these papers is typically low. Clearly, there is a need for high-quality randomized controlled trials assessing the effectiveness of these interventions in these headache disorders. And this is by no means the only article making such statements; similar reviews arrive at similar conclusions. In turn, this means that the effects observed after SMT are not necessarily specific effects due to SMT but could easily be due to placebo or other non-specific effects. In order to avoid confusion, one would need a credible placebo – one that closely mimics SMT – and make sure that patients were ‘blinded’. But ‘light massage’ clearly does not mimic SMT, and patients obviously were aware of which interventions they received.
So, an alternative – and I think at least as plausible – conclusion of the data provided by this new RCT is this:
Chiropractic SMT is associated with a powerful placebo response which, of course, obeys a dose-effect relationship. Thus these findings are in keeping with the notion that SMT is a placebo.
And why would the researchers – who stress that they have no conflicts of interest – mislead us by making this alternative interpretation of their findings not abundantly clear?
I fear, the reason might be simple: they also seem to mislead us about their conflicts of interest: they are mostly chiropractors with a long track record of publishing promotional papers masquerading as research. What, I ask myself, could be a stronger conflict of interest?
(Pity that a high-impact journal like SPINE did not spot these [not so little] flaws)
We have repeatedly discussed the fact that alternative medicine (AM) is by no means free of risks. I find it helpful to divide them into two broad categories:
- direct risks of the intervention (such as stroke due to neck manipulation, or cardiac tamponade caused by acupuncture, or liver damage due to a herbal remedy) and
- indirect risks usually due to the advice given by AM practitioners.
The latter category is often more important than the former. It includes delay of effective treatment due to treatment with an ineffective or less effective form of AM. It is clear that this will cause patients to suffer unnecessarily.
Several investigations have recently highlighted this important problem, including this study from Singapore which assessed the predictors of AM-use in patients with early inflammatory arthritis (EIA), and its impact on delay to initiation of disease-modifying anti-rheumatic drugs (DMARD). Data were collected prospectively from EIA patients aged ≥ 21 years. Current or prior AM-use was ascertained by face-to-face interviews. Predictors of AM-use and its effect on time to DMARD initiation were determined by multivariate logistic regression and Cox proportional hazards, respectively.
One hundred and eighty patients were included: 83.9% had rheumatoid arthritis, 57% were seropositive. Median (IQR). Chinese race, being non-English speaking, smoking and high DAS28 were independent predictors of AM-use. AM-users initiated DMARD later (median [IQR] 21.5 [13.1-30.4] vs. 15.6 [9.4-22.7] weeks in non-users, P = 0.005). AM-use and higher DAS28 were associated with a longer delay to DMARD initiation. Race, education level, being non-English speaking, smoking and sero-positivity were not associated.
The authors concluded that healthcare professionals should be aware of the unique challenges in treating patients with EIA in Asia. Healthcare beliefs regarding AM may need to be addressed to reduce treatment delay.
These findings are not dissimilar to results previously discussed, for instance:
- AM-use delays cancer diagnosis.
- The advice of non-medically qualified practitioners may delay cancer therapy.
- Chiropractic care may delay referral to effective treatment.
- Consultations with homeopaths can delay effective therapy.
The only solution to the problem I can think of would be to educate AM practitioners and the public such that they are aware of the issue and do everything possible to prevent such problems. But this is, of course, easier said than done, and it seems more than just optimistic to hope that such endeavours might be successful. The public is currently bombarded with misleading information and outright lies about AM (many of my previous post have addressed this problem). And practitioners would have to operate against their own financial interest to prevent these problems from occurring.
This means that treatment delays caused by AM-use and advice from AM practitioners are inevitable…
unless you have a better idea.
If so, please let me know.
This study tested chondroitin sulfate 800 mg/day (CS) pharmaceutical-grade in the management of symptomatic knee osteoarthritis. It was designed as a prospective, randomised, 6-month, 3-arm, double-blind, double-dummy, placebo and celecoxib (200 mg/day)-controlled trial. The primary endpoints were changes in pain on a Visual Analogue Scale (VAS) and in the Lequesne Index (LI). Minimal-Clinically Important Improvement (MCII), Patient-Acceptable Symptoms State (PASS) were used as secondary endpoints.
A total of 604 patients, diagnosed according to American College of Rheumalogy (ACR) criteria, were recruited in five European countries and followed for 182 days. CS and celecoxib showed a greater significant reduction in pain and LI than placebo. In the intention-to-treat (ITT) population, pain reduction in VAS at day 182 in the CS group (−42.6 mm) and in celecoxib group (−39.5 mm) was significantly greater than the placebo group (−33.3 mm) (p=0.001 for CS and p=0.009 for celecoxib). No difference observed between CS and celecoxib. Similar trend for the LI, as reduction in this metric in the CS group (−4.7) and celecoxib group (−4.6) was significantly greater than the placebo group (−3.7) (p=0.023 for CS and p=0.015 for celecoxib). Again, no difference was observed between CS and celecoxib. Both secondary endpoints (MCII and PASS) at day 182 improved significantly in the CS and celecoxib groups. All treatments demonstrated excellent safety profiles.
The authors concluded that a 800 mg/day pharmaceutical-grade CS is superior to placebo and similar to celecoxib in reducing pain and improving function over 6 months in symptomatic knee osteoarthritis (OA) patients. This formulation of CS should be considered a first-line treatment in the medical management of knee OA.
In my view, this is a good study with clear and useful results: CS seems to be efficacious and safe. Another recent study confirmed the superiority of CS over celecoxib at reducing cartilage volume loss in knee OA patients.
The current Cochrane review does not yet account for the new data; it concluded cautiously positive: A review of randomized trials of mostly low quality reveals that chondroitin (alone or in combination with glucosamine) was better than placebo in improving pain in participants with osteoarthritis in short-term studies. The benefit was small to moderate with an 8 point greater improvement in pain (range 0 to 100) and a 2 point greater improvement in Lequesne’s index (range 0 to 24), both seeming clinically meaningful. These differences persisted in some sensitivity analyses and not others. Chondroitin had a lower risk of serious adverse events compared with control. More high-quality studies are needed to explore the role of chondroitin in the treatment of osteoarthritis. The combination of some efficacy and low risk associated with chondroitin may explain its popularity among patients as an over-the-counter supplement.
The call for more high quality trials was justified but has now been answered. In my view, CS can be considered an evidence-based option in the management of OA.
This double-blind RCT aimed to test the efficacy of self-administered acupressure for pain and physical function in adults with knee osteoarthritis (KOA).
150 patients with symptomatic KOA participated and were randomized to
- verum acupressure,
- sham acupressure,
- or usual care.
Verum and sham, but not usual care, participants were taught to self-apply acupressure once daily, five days/week for eight weeks. Assessments were collected at baseline, 4 and 8 weeks. The numeric rating scale (NRS) for pain was administered during weekly phone calls. Outcomes included the WOMAC pain subscale (primary), the NRS and physical function measures (secondary). Linear mixed regression was conducted to test between group differences in mean changes from baseline for the outcomes at eight weeks.
Compared with usual care, both verum and sham participants experienced significant improvements in WOMAC pain, NRS pain and WOMAC function at 8 weeks. There were no significant differences between verum and sham acupressure groups in any of the outcomes.
The authors concluded that self-administered acupressure is superior to usual care in pain and physical function improvement for older people with KOA. The reason for the benefits is unclear and placebo effects may have played a role.
Another very odd conclusion!
The authors’ stated aim was to TEST THE EFFICACY OF ACUPRESSURE. To achieve this aim, they rightly compared it to a placebo (sham) intervention. This comparison did not show any differences between the two. Ergo, the only correct conclusion is that acupressure is a placebo.
I know, the authors (sort of) try to say this in their conclusions: placebo effects may have played a role. But surely, this is more than a little confusing. Placebo effects were quite evidently the sole cause of the observed outcomes. Is it ethical to confuse the public in this way, I wonder.
The ACUPUNCTURE NOW FOUNDATION (ANF) has featured on this blog before. Today I want to re-introduce them because I just came across one of their articles which I found remarkable. In it, they define what many of us have often wondered about: the most important myth about acupuncture.
Is it acupuncture’s current popularity, its long history, its mode of action, its efficacy, its safety?
No, here is the answer directly from the ANF:
The most important myth that needs to be put to rest is the idea promoted by a small group of vocal critics that acupuncture is nothing more than a placebo. Many cite the fact that studies showing acupuncture to be highly effective were of low quality and that several higher quality studies show that, while acupuncture was clinically effective, it usually does not outperform “sham” acupuncture. But those studies are dominated by the first quality issue cited above; studies with higher methodological rigor where the “real” acupuncture was so poorly done as to not be a legitimate comparison. Yet despite the tendency toward poor quality acupuncture in studies with higher methodological standards, a benchmark study was done that showed “real” acupuncture clearly outperforming “sham” acupuncture in four different chronic pain conditions.3 When you add this study together with the fact veterinary acupuncture is used successfully in many different animals, the idea of acupuncture only being placebo must now be considered finally disproven. This is further supported by studies which show that the underlying physiological pathways activated by acupuncture sometimes overlap, but can be clearly differentiated from, those activated by placebo responses.
Yes, I was too.
The myth, according to the ANF, essentially is that sceptics do not understand the scientific evidence. And these blinkered sceptics even go as far as ignoring the findings from what the ANF consider to be a ‘benchmark study’! Ghosh, that’s nasty of them!!!
But, no – the benchmark study (actually, it was not a ‘study’ but a meta-analysis of studies) has been discussed fully on this blog (and in many other places too). Here is what I wrote in 2012 when it was first published:
An international team of acupuncture trialists published a meta-analysed of individual patient data to determine the analgesic effect of acupuncture compared to sham or non-acupuncture control for the following 4 chronic pain conditions: back and neck pain, osteoarthritis, headache, and shoulder pain. Data from 29 RCTs, with an impressive total of 17 922 patients, were included.
The results of this new evaluation suggest that acupuncture is superior to both sham and no-acupuncture controls for each of these conditions. Patients receiving acupuncture had less pain, with scores that were 0.23 (95% CI, 0.13-0.33), 0.16 (95% CI, 0.07-0.25), and 0.15 (95% CI, 0.07-0.24) SDs lower than those of sham controls for back and neck pain, osteoarthritis, and chronic headache, respectively; the effect sizes in comparison to no-acupuncture controls were 0.55 (95% CI, 0.51-0.58), 0.57 (95% CI, 0.50-0.64), and 0.42 (95% CI, 0.37-0.46) SDs.
Based on these findings, the authors reached the conclusion that “acupuncture is effective for the treatment of chronic pain and is therefore a reasonable referral option. Significant differences between true and sham acupuncture indicate that acupuncture is more than a placebo. However, these differences are relatively modest, suggesting that factors in addition to the specific effects of needling are important contributors to the therapeutic effects of acupuncture”.
… even the enthusiastic authors of this article admit that, when compared to sham, the effect size of real acupuncture is too small to be clinically relevant. Therefore one might argue that this meta-analysis confirms what critics have suggested all along: acupuncture is not a useful treatment for clinical routine.
Unsurprisingly, the authors of the meta-analysis do their very best to play down this aspect. They reason that, for clinical routine, the comparison between acupuncture and non-acupuncture controls is more relevant than the one between acupuncture and sham. But this comparison, of course, includes placebo- and other non-specific effects masquerading as effects of acupuncture – and with this little trick (which, by the way is very popular in alternative medicine), we can, of course, show that even sugar pills are effective.
I do not doubt that context effects are important in patient care; yet I do doubt that we need a placebo treatment for generating such benefit in our patients. If we administer treatments which are effective beyond placebo with kindness, time, compassion and empathy, our patients will benefit from both specific and non-specific effects. In other words, purely generating non-specific effects with acupuncture is far from optimal and certainly not in the interest of our patients. In my view, it cannot be regarded as not good medicine, and the authors’ conclusion referring to a “reasonable referral option” is more than a little surprising in my view.
Acupuncture-fans might argue that, at the very minimum, the new meta-analysis does demonstrate acupuncture to be statistically significantly better than a placebo. Yet I am not convinced that this notion holds water: the small residual effect-size in the comparison of acupuncture with sham might not be the result of a specific effect of acupuncture; it could be (and most likely is) due to residual bias in the analysed studies.
The meta-analysis is strongly driven by the large German trials which, for good reasons, were heavily and frequently criticised when first published. One of the most important potential drawbacks was that many participating patients were almost certainly de-blinded through the significant media coverage of the study while it was being conducted. Moreover, in none of these trials was the therapist blinded (the often-voiced notion that therapist-blinding is impossible is demonstrably false). Thus it is likely that patient-unblinding and the absence of therapist-blinding importantly influenced the clinical outcome of these trials thus generating false positive findings. As the German studies constitute by far the largest volume of patients in the meta-analysis, any of their flaws would strongly impact on the overall result of the meta-analysis.
So, has this new meta-analysis finally solved the decades-old question about the effectiveness of acupuncture? It might not have solved it, but we have certainly moved closer to a solution, particularly if we employ our faculties of critical thinking. In my view, this meta-analysis is the most compelling evidence yet to demonstrate the ineffectiveness of acupuncture for chronic pain.
END OF QUOTE
The ANF-text then goes from bad to worse. First they cite the evidence from veterinary acupuncture as further proof of the efficacy of their therapy. Well, the only systematic review in this are is, I think, by my team; and it concluded that there is no compelling evidence to recommend or reject acupuncture for any condition in domestic animals. Some encouraging data do exist that warrant further investigation in independent rigorous trials.
Lastly, the ANF mentions acupuncture’s mode of action which they seem to understand clearly and fully. Congratulations ANF! In this case, you are much better than the many experts in basic science or neurology who almost unanimously view these ‘explanations’ of how acupuncture might work as highly adventurous hypotheses or speculations.
So, what IS the most important myth about acupuncture? I am not sure and – unlike the ANF – I do not feel that I can speak for the rest of the world, but one of the biggest myths FOR ME is how acupuncture fans constantly manage to mislead the public.
In a recent PJ article, Michael Marshall from the ‘Good Thinking Society’ asked “WHY ON EARTH IS THE NHS SPENDING EVEN A SINGLE PENNY ON HOMEOPATHY?”. A jolly good question, given the overwhelmingly negative evidence, I thought – but one that must be uncomfortable to homeopaths. Sure enough, a proponent of homeopathy, Jeanette Lindsay from Glasgow, has objected to Marshall’s arguments in a short comment which is a fairly typical defence of homeopathy; I therefore take the liberty of reproducing it here (the 12 references in her text were added by me and refer to my footnotes below):
I wonder if people such as Michael Marshall (The Pharmaceutical Journal 2016;297:101), who would refuse  patients the option of NHS homeopathic treatment, have considered the plight of people failed by evidence-based medicine ?  Where are those with chronic, disabling conditions to turn when the medicines available on the NHS do not work, or worse, are positively harmful? 
Take the instance of a woman with multiple drug allergies who has no means of treating her severe inflammatory arthritis and no suitable analgesia.  It has been demonstrated that disease states with immune system involvement are particularly susceptible to the placebo effect but how does one induce this? Current thinking precludes treatment with placebo medicines but it so happens that homeopathic remedies would appear, from the results of clinical trials , to be a good substitute.  Used properly, there is a good chance that in this case homeopathic treatment may achieve a real therapeutic effect. 
Patients who cannot tolerate allopathic  treatment do not just go away because they cannot take the prescribed medicine.  They suffer and surely deserve a better range of options  than those provided by the current obsession with evidence-based medicine.  The availability of homeopathic treatment is important and should not be denied until better alternatives become commonplace.  Michael Marshall does not ‘refuse’ homeopathy on the NHS; that is not in his power. He merely questions whether NHS funds should not be spent on treatments that demonstrably do more good than harm.  I am sure he as carefully considered such patients.  Depending on the exact circumstances, such patients have many options: for instance, they could change their physician, have their diagnosis re-considered, or try a non-drug treatment.  An allergy to one drug is rarely (I would even say never) associated with allergies to all drugs for any given condition. Even if this were the case, there are several non-drug treatments for arthritis or other diseases.  I think this is fantasy; there is no good evidence from clinical trials to show that homeopathy is efficacious for either inflammatory or degenerative arthritis.  Is this an admission that homeopathic remedies are placebos?  I am not aware of sound evidence to support this statement.  ‘Allopathic’ is a derogatory term introduced by Hahnemann to defame conventional medicine.  I have never seen a patient who could not tolerate any prescription medicine. I suspect this is fantasy again.  Patients deserve the optimal therapy available for their conditions – that is a therapy that demonstrably generates more good than harm. Homeopathy is clearly not in this category.  An obsession? Yes, perhaps it is an obsession for some dedicated healthcare professionals to provide the best possible treatments for their patients. But the way it is put here, it sounds as though this was something despicable. I would argue that such an ‘obsession’ would be most commendable.  For practically all conditions, symptoms, illesses and diseases that afflict mankind, better alternatives than homeopathy have been available since about 150 years.
It seems to me that Jeanette Lindsay has been harshly disappointed by conventional medicine. Perhaps this is why, one day, she consulted a homeopath and received the empathy, understanding and compassion that she needed to get better. Many homeopaths excel at these qualities; and this is the main reason why their patients swear by them, even though their remedies are pure placebos.
My advice to such patients is: find a physician who has time, empathy and compassion. They do exist! Once you have found such a doctor, you can benefit from the compassion and empathy just as you may have benefitted from the homeopath’s compassion and empathy. But in addition to these benefits (and contrary to what you got from your homeopath), you will also be able to profit from the efficacy of the treatments prescribed.
To put it simply: homeopaths can help patients via non-specific therapeutic effects; responsible physicians can help patients via non-specific therapeutic effects plus the specific effects of the treatments they prescribe.
In alternative medicine, good evidence is like gold dust and good evidence showing that alternative therapies are efficacious is even rarer. Therefore, I was delighted to come across a brand-new article from an institution that should stand for reliable information: the NIH, no less.
According to its authors, this new article “examines the clinical trial evidence for the efficacy and safety of several specific approaches—acupuncture, manipulation, massage therapy, relaxation techniques including meditation, selected natural product supplements (chondroitin, glucosamine, methylsulfonylmethane, S-adenosylmethionine), tai chi, and yoga—as used to manage chronic pain and related disability associated with back pain, fibromyalgia, osteoarthritis, neck pain, and severe headaches or migraines.”
The results of this huge undertaking are complex, of course, but in a nutshell they are at least partly positive for alternative medicine. Specifically, the authors state that “based on a preponderance of positive trials vs negative trials, current evidence suggests that the following complementary approaches may help some patients manage their painful health conditions: acupuncture and yoga for back pain; acupuncture and tai chi for OA of the knee; massage therapy for neck pain with adequate doses and for short-term benefit; and relaxation techniques for severe headaches and migraine. Weaker evidence suggests that massage therapy, SM, and osteopathic manipulation might also be of some benefit to those with back pain, and relaxation approaches and tai chi might help those with fibromyalgia.”
This is excellent news! Finally, we have data from an authoritative source showing that some alternative treatments can be recommended for common pain conditions.
Hold on, not so fast! Yes, the NIH is a most respectable organisation, but we must not blindly accept anything of importance just because it appears to come form a reputable source. Let’s look a bit closer at the actual evidence provided by the authors of this paper.
Reading the article carefully, it is impossible not to get troubled. Here are a few points that concern me most:
- the safety of a therapy cannot be evaluated on the basis of data from RCTs (particularly as it has been shown repeatedly that trials of alternative therapies often fail to report adverse effects); much larger samples are needed for that; any statements about safety in the aims of the paper are therefore misplaced;
- the authors talk about efficacy but seem to mean effectiveness;
- the authors only included RCTs from the US which must result in a skewed and incomplete picture;
- the article is from the National Center for Complementary and Integrative Health which is part of the NIH but which has been criticised repeatedly for being biased in favour of alternative medicine;
- not all of the authors seem to be NIH staff, and I cannot find a declaration of conflicts of interest;
- the discussion of the paper totally lacks any critical thinking;
- there is no assessment of the quality of the trials included in this review.
My last point is by far the most important. A summary of this nature that fails to take into account the numerous limitations of the primary data is, I think, as good as worthless. As I know most of the RCTs included in the analyses, I predict that the overall picture generated by this review would have changed substantially, if the risks of bias in the primary studies had been accounted for.
Personally, I find it lamentable that such a potentially worthy exercise ended up employing such lousy methodology. Perhaps even more lamentable is the fact that the NIH (or one of its Centers) can descend that low; to mislead the public in this way borders on scientific misconduct and is, in my view, unethical and unacceptable.
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?
The two dietary supplements chondroitin and glucosamine have been around for some time. They are being promoted mostly for osteoarthritis; some claim that they reduce pain, others even believe that they restore the damaged cartilage and thus reverse the disease process. But neither for a symptomatic nor causal therapy has the evidence so far been truly convincing. A new trial might change this situation.
This study compared the efficacy and safety of chondroitin sulfate plus glucosamine hydrochloride (CS+GH) versus celecoxib in patients with knee osteoarthritis and severe pain.
The ‘Double-blind Multicentre Osteoarthritis interVEntion trial with SYSADOA’ (MOVES) was conducted in France, Germany, Poland and Spain and evaluated treatment with CS+GH versus celecoxib in 606 patients with Kellgren and Lawrence grades 2–3 knee osteoarthritis and moderate-to-severe pain (Western Ontario and McMaster osteoarthritis index (WOMAC) score ≥301; 0–500 scale). Patients were randomised to receive 400 mg CS plus 500 mg GH three times a day or 200 mg celecoxib every day for 6 months. The primary outcome was the mean decrease in WOMAC pain from baseline to 6 months. Secondary outcomes included WOMAC function and stiffness, visual analogue scale for pain, presence of joint swelling/effusion, rescue medication consumption, Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria and EuroQoL-5D.
The results show that the adjusted mean change (95% CI) in WOMAC pain was −185.7 (−200.3 to −171.1) (50.1% decrease) with CS+GH and −186.8 (−201.7 to −171.9) (50.2% decrease) with celecoxib, meeting the non-inferiority margin of −40: −1.11 (−22.0 to 19.8; p=0.92). All sensitivity analyses were consistent with that result. At 6 months, 79.7% of patients in the combination group and 79.2% in the celecoxib group fulfilled OMERACT-OARSI criteria. Both groups elicited a reduction >50% in the presence of joint swelling; a similar reduction was seen for effusion. No differences were observed for the other secondary outcomes. Adverse events were rare and similarly distributed between groups.
The authors concluded that CS+GH has comparable efficacy to celecoxib in reducing pain, stiffness, functional limitation and joint swelling/effusion after 6 months in patients with painful knee osteoarthritis, with a good safety profile.
This is a rigorous trial, and I do trust its findings. However, I am not entirely sure what they actually mean: is CS+GH as effective or as ineffective as the COX-2-inhibitor celecoxib? The most recent meta-analysis on the subject found that diclofenac (150 mg/day) was likely to be more effective in alleviating pain than celecoxib (200 mg/day). But that does, of course, not necessarily imply that celecoxib is ineffective.
The other big issue here is safety. COX-2-inhibitors had a bad press because of the risk of cardiovascular side-effects. In comparison, the CS+GH supplement is an almost risk-free alternative. Bearing in mind that we are dealing with long-term treatments here, I think the results of this study might persuade me, had I to choose between these two treatments, to opt for the dietary supplement.
Twenty years ago, I published a short article in the British Journal of Rheumatology. Its title was ALTERNATIVE MEDICINE, THE BABY AND THE BATH WATER. Reading it again today – especially in the light of the recent debate (with over 700 comments) on acupuncture – indicates to me that very little has since changed in the discussions about alternative medicine (AM). Does that mean we are going around in circles? Here is the (slightly abbreviated) article from 1995 for you to judge for yourself:
“Proponents of alternative medicine (AM) criticize the attempt of conducting RCTs because they view this is in analogy to ‘throwing out the baby with the bath water’. The argument usually goes as follows: the growing popularity of AM shows that individuals like it and, in some way, they benefit through using it. Therefore it is best to let them have it regardless of its objective effectiveness. Attempts to prove or disprove effectiveness may even be counterproductive. Should RCTs prove that a given intervention is not superior to a placebo, one might stop using it. This, in turn, would be to the disadvantage of the patient who, previous to rigorous research, has unquestionably been helped by the very remedy. Similar criticism merely states that AM is ‘so different, so subjective, so sensitive that it cannot be investigated in the same way as mainstream medicine’. Others see reasons to change the scientific (‘reductionist’) research paradigm into a broad ‘philosophical’ approach. Yet others reject the RCTs because they think that ‘this method assumes that every person has the same problems and there are similar causative factors’.
The example of acupuncture as a (popular) treatment for osteoarthritis, demonstrates the validity of such arguments and counter-arguments. A search of the world literature identified only two RCTs on the subject. When acupuncture was tested against no treatment, the experimental group of osteoarthritis sufferers reported a 23% decrease of pain, while the controls suffered a 12% increase. On the basis of this result, it might seem highly unethical to withhold acupuncture from pain-stricken patients—’if a patient feels better for whatever reason and there are no toxic side effects, then the patient should have the right to get help’.
But what about the placebo effect? It is notoriously difficult to find a placebo indistinguishable to acupuncture which would allow patient-blinded studies. Needling non-acupuncture points may be as close as one can get to an acceptable placebo. When patients with osteoarthritis were randomized into receiving either ‘real acupuncture or this type of sham acupuncture both sub-groups showed the same pain relief.
These findings (similar results have been published for other AMs) are compatible only with two explanations. Firstly acupuncture might be a powerful placebo. If this were true, we need to establish how safe acupuncture is (clearly it is not without potential harm); if the risk/benefit ratio is favourable and no specific, effective form of therapy exists one might still consider employing this form as a ‘placebo therapy’ for easing the pain of osteoarthritis sufferers. One would also feel motivated to research this powerful placebo and identify its characteristics or modalities with the aim of using the knowledge thus generated to help future patients.
Secondly, it could be the needling, regardless of acupuncture points and philosophy, that decreases pain. If this were true, we could henceforward use needling for pain relief—no special training in or equipment for acupuncture would be required, and costs would therefore be markedly reduced. In addition, this knowledge would lead us to further our understanding of basic mechanisms of pain reduction which, one day, might evolve into more effective analgesia. In any case the published research data, confusing as they often are, do not call for a change of paradigm; they only require more RCTs to solve the unanswered problems.
Conducting rigorous research is therefore by no means likely to ‘throw out the baby with the bath water’. The concept that such research could harm the patient is wrong and anti-scientific. To follow its implications would mean neglecting the ‘baby in the bath water’ until it suffers serious damage. To conduct proper research means attending the ‘baby’ and making sure that it is safe and well.