Proof of Principle or Concept studies are investigations usually for an early stage of clinical drug development when a compound has shown potential in animal models and early safety testing. This step often links between Phase-I and dose ranging Phase-II studies. These small-scale studies are designed to detect a signal that the drug is active on a patho-physiologically relevant mechanism, as well as preliminary evidence of efficacy in a clinically relevant endpoint.
For therapies that have been in use for many years, proof of concept studies are unusual to say the least. A proof of concept study of osteopathy has never been heard of. This is why I was fascinated by this new paper. The objective of this ‘proof of concept’ study was to evaluate the effect of osteopathic manipulative therapy (OMTh) on chronic symptoms of multiple sclerosis (MS).
Patients (n=22) with MS received 5 forty-minute MS health education sessions (control group) or 5 OMTh sessions (OMTh group). All participants completed a questionnaire that assessed their level of clinical disability, fatigue, depression, anxiety, and quality of life before the first session, one week after the final session, and 6 months after the final session. The Extended Disability Status Scale, a modified Fatigue Impact Scale, the Beck Depression Inventory-II, the Beck Anxiety Inventory, and the 12-item Short Form Health Survey were used to assess clinical disability, fatigue, depression, anxiety, and quality of life, respectively. In the OMTh group, statistically significant improvements in fatigue and depression were found one week after the final session. A non-significant increase in quality of life was also found in the OMTh group one week after the final session.
The authors concluded that the results demonstrate that OMTh should be considered in the treatment of patients with chronic symptoms of MS.
Who said that reading alternative medicine research papers is not funny? I for one laughed heartily when I read this (no need at all to go into the many obvious flaws of the study). Calling a pilot study ‘proof of concept’ is certainly not without hilarity. Drawing definitive conclusions about the effectiveness of OMTh is outright laughable. But issuing a far-reaching recommendation for use of OMTh in MS is just better than the best comedy. This had me in stiches!
I congratulate the Journal of the American Osteopathic Association and the international team of authors for providing us with such fun.
For every condition which is not curable by conventional medicine there are dozens of alternative treatments that offer a cure or at least symptomatic relief. Multiple sclerosis (MS) is such a disease. It is hard to find an alternative therapy that is not being promoted for MS.
Acupuncture is, of course, no exception. It is widely promoted for treating MS symptoms and many MS patients spend lots of money hoping that it does. The US ‘National MS Society’, For instance claim that acupuncture may provide relief for some MS-related symptoms, including pain, spasticity, numbness and tingling, bladder problems, and depression. There is no evidence, however, that acupuncture can reduce the frequency of MS exacerbations or slow the progression of disability. And the ‘British Acupuncture Council’ state that acupuncture may provide relief for some MS-related symptoms, including pain, spasticity, numbness and tingling, bladder problems, and depression.
Such claims seem a little over-optimistic; let’s have a look what the evidence really tells us.
The purpose of this brand-new review was to assess the literature on the effectiveness of acupuncture for treating MS. A literature search resulted in 12 peer-reviewed articles on the subject that examined the use of acupuncture to treat MS related quality of life, fatigue, spasticity, and pain. The majority of the studies were poorly designed-without control, randomization, or blinding. Description of the subjects, interventions, and outcome measures as well as statistical analysis were often lacking or minimal.
The authors concluded that although many of the studies suggested that acupuncture was successful in improving MS related symptoms, lack of statistical rigor and poor study design make it difficult to draw any conclusions about the true effectiveness of this intervention in the MS population. Further studies with more rigorous designs and analysis are needed before accurate claims can be made as to the effectiveness of acupuncture in this population.
And what about other alternative therapies? Our own systematic review of the subject included 12 randomized controlled trials: nutritional therapy (4), massage (1), Feldenkrais bodywork (1), reflexology (1), magnetic field therapy (2), neural therapy (1) and psychological counselling (2). But the evidence was not compelling for any of these therapies, with many trials suffering from significant methodological flaws. There is evidence to suggest some benefit of nutritional therapy for the physical symptoms of MS. Magnetic field therapy and neural therapy appear to have a short-term beneficial effect on the physical symptoms of MS. Massage/bodywork and psychological counselling seem to improve depression, anxiety and self-esteem.
That was some time ago, and it is therefore reasonable to ask: has the evidence changed? Thankfully, the ‘American Academy of Neurology’ has just published the following guidelines entitles complementary and alternative medicine in multiple sclerosis:
Clinicians might offer oral cannabis extract for spasticity symptoms and pain (excluding central neuropathic pain) (Level A). Clinicians might offer tetrahydrocannabinol for spasticity symptoms and pain (excluding central neuropathic pain) (Level B). Clinicians should counsel patients that these agents are probably ineffective for objective spasticity (short-term)/tremor (Level B) and possibly effective for spasticity and pain (long-term) (Level C). Clinicians might offer Sativex oromucosal cannabinoid spray (nabiximols) for spasticity symptoms, pain, and urinary frequency (Level B). Clinicians should counsel patients that these agents are probably ineffective for objective spasticity/urinary incontinence (Level B). Clinicians might choose not to offer these agents for tremor (Level C). Clinicians might counsel patients that magnetic therapy is probably effective for fatigue and probably ineffective for depression (Level B); fish oil is probably ineffective for relapses, disability, fatigue, MRI lesions, and quality of life (QOL) (Level B); ginkgo biloba is ineffective for cognition (Level A) and possibly effective for fatigue (Level C); reflexology is possibly effective for paresthesia (Level C); Cari Loder regimen is possibly ineffective for disability, symptoms, depression, and fatigue (Level C); and bee sting therapy is possibly ineffective for relapses, disability, fatigue, lesion burden/volume, and health-related QOL (Level C). Cannabinoids may cause adverse effects. Clinicians should exercise caution regarding standardized vs nonstandardized cannabis extracts and overall CAM quality control/nonregulation. Safety/efficacy of other CAM/CAM interaction with MS disease-modifying therapies is unknown.
Interestingly, on yesterday it was announced that the NHS in Wales has just made available a cannabis-based spray for MS-sufferers (I should mention that most cannabis-based preparations are not full plant extracts and thus by definition not herbal but conventional medicines).
It would be wonderful, if other alternative therapies were of proven benefit to MS-sufferers. But sadly, this does not seem to be the case. I think it is better to be truthful about this than to raise false hopes of desperate patients.
Advocates of alternative medicine are incredibly fond of supporting their claims with anecdotes, or ‘case-reports’ as they are officially called. There is no question, case-reports can be informative and important, but we need to be aware of their limitations.
A recent case-report from the US might illustrated this nicely. It described a 65-year-old male patient who had had MS for 20 years when he decided to get treated with Chinese scalp acupuncture. The motor area, sensory area, foot motor and sensory area, balance area, hearing and dizziness area, and tremor area were stimulated once a week for 10 weeks, then once a month for 6 further sessions.
After the 16 treatments, the patient showed remarkable improvements. He was able to stand and walk without any problems. The numbness and tingling in his limbs did not bother him anymore. He had more energy and had not experienced incontinence of urine or dizziness after the first treatment. He was able to return to work full time. Now the patient has been in remission for 26 months.
The authors of this case-report conclude that Chinese scalp acupuncture can be a very effective treatment for patients with MS. Chinese scalp acupuncture holds the potential to expand treatment options for MS in both conventional and complementary or integrative therapies. It can not only relieve symptoms, increase the patient’s quality of life, and slow and reverse the progression of physical disability but also reduce the number of relapses and help patients.
There is absolutely nothing wrong with case-reports; on the contrary, they can provide extremely valuable pointers for further research. If they relate to adverse effects, they can give us crucial information about the risks associated with treatments. Nobody would ever argue that case-reports are useless, and that is why most medical journals regularly publish such papers. But they are valuable only, if one is aware of their limitations. Medicine finally started to make swift progress, ~150 years ago, when we gave up attributing undue importance to anecdotes, began to doubt established wisdom and started testing it scientifically.
Conclusions such as the ones drawn above are not just odd, they are misleading to the point of being dangerous. A reasonable conclusion might have been that this case of a MS-patient is interesting and should be followed-up through further observations. If these then seem to confirm the positive outcome, one might consider conducting a clinical trial. If this study proves to yield encouraging findings, one might eventually draw the conclusions which the present authors drew from their single case.
To jump at conclusions in the way the authors did, is neither justified nor responsible. It is unjustified because case-reports never lend themselves to such generalisations. And it is irresponsible because desperate patients, who often fail to understand the limitations of case-reports and tend to believe things that have been published in medical journals, might act on these words. This, in turn, would raise false hopes or might even lead to patients forfeiting those treatments that are evidence-based.
It is high time, I think, that proponents of alternative medicine give up their love-affair with anecdotes and join the rest of the health care professions in the 21st century.
Reflexology is one of the most popular of all alternative therapies. Anyone who has ever had a session knows why: it is a strangely pleasant and oddly agreeable experience. Reflexologists massage your feet which can be mildly painful but usually is quite relaxing. They look for and subsequently focus on areas of tenderness believing they correspond to specific organs or whole organ systems. Even though few reflexologists would admit to it, they tend to make vague and unreliable diagnoses: if they feel something unusual at a certain point of the sole of your foot, they assume that a certain inner organ is in trouble. Reflexologists even have maps where the sole of a foot is depicted showing which area corresponds to which organ.
The treatment might be enjoyable but the assumptions that underpin it are nonsensical for at least two reasons: firstly, there are no nerve or other connections between a specific area on the sole of a foot and a certain organ. Secondly, the maps which reflexologists employ differ and fail to agree which area corresponds to which organ. Thus there are inconsistencies within the realm of reflexology and there are inconsistencies in relation to the known facts regarding physiology, anatomy etc.
Proponents of reflexology are quite undisturbed by these problems and seem to believe that not their assumptions but science must be wrong. After all, reflexology does work! That is to say that patients perceive benefit from it, pay out of their own pocket for the experience and tend to come back for more.
Several years ago, we asked 8 UK professional organisations of reflexology which conditions they thought could be treated effectively with reflexology. We gave them a list of 25 conditions to chose from, many of which were serious, e.g. cancer and AIDS. Collectively, the organisations felt that 22 of these illnesses would respond to reflexology.
But this is opinion, not evidence! What do the trial data tell us? Is reflexology more than a placebo?
As with many other areas of alternative medicine, controlled clinical trials are scarce; but this is not to say that none at all are available. Our own trial of reflexology for menopausal symptoms failed to show that this therapy has any effects beyond placebo. More recently, we published a systematic review to evaluate all of the 23 studies that had been published at that stage. They related to a wide range of medical conditions and their methodological quality was often poor. Nine high quality randomised clinical trials (RCTs) generated negative findings. Eight RCTs suggested that reflexology is effective for the following conditions: diabetes, premenstrual syndrome, cancer patients, multiple sclerosis, symptomatic idiopathic detrusor over-activity and dementia. These studies, however, were wide open to bias. Therefore, our conclusions had to be cautious: the best clinical evidence does not demonstrate convincingly reflexology to be an effective treatment for any medical condition.
For you and me, this simply means that there is currently no good evidence to suggest that reflexology works. But the story does not end here. There will be more studies and enthusiasts are most likely to concede that our conclusions were incorrect. In fact, a further trial has just become available.
This new single-blind, randomized and placebo controlled study included 20 moderately to severely affected multiple sclerosis patients. Each participant received for 8 weeks, 1 hour per week of either reflexology or sham reflexology. The primary outcome measure was the Multiple Sclerosis Impact Scale at baseline, 8 weeks and 16 weeks. The results revealed improvements in both groups but no statistically significant differences between the two groups at either 8 or 16 weeks. The conclusions of the investigators were clear: The results do not support the use of reflexology for symptom relief in a more disabled multiple sclerosis population and are strongly suggestive of a placebo response.
There is, of course, nothing wrong with a relaxing foot-massage; it is agreeable, no doubt, and if someone wants to pay for the luxury, why not? By contrast, there is a lot wrong with reflexology, I think. A foot-massage is not administered under the pretence of generating any specific therapeutic effects. Reflexologists, however, claim they can exert highly specific effects on inner organs, influence the natural history of a wide range of diseases, and provide reliable diagnoses. They thus mislead their clients. This is not just wrong, it also has the potential to do serious harm. I believe it is time to end this nonsense.