clinical trial
Patients with advanced non-small cell lung cancer (NSCLC) have limited treatment options. Alongside conventional anticancer treatment, additive homeopathy might help to alleviate side effects of conventional therapy. The aim of this study was to investigate whether additive homeopathy might influence quality of life (QoL) and survival in NSCLC patients.
In this prospective, randomized, placebo-controlled, double-blind, three-arm, multi-centre, phase III study, the researchers evaluated the possible effects of additive homeopathic treatment compared to placebo in patients with stage IV NSCLC, with respect to QoL in the two randomized groups and survival time in all three groups. Treated patients visited the university teaching hospital every 9 weeks: 150 patients with stage IV NSCLC were included in the study.
- 51 patients received individualized homeopathic remedies plus conventional treatments,
- 47 received placebo plus conventional treatments,
- 52 control patients without any homeopathic treatment were treated with conventional therapies and observed for survival only.
For groups 1 and 2, the study was double-blind. The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. The remedies were manufactured by stepwise dilution and succussion, thereby preparing stable GMP grade formulations.
QoL as well as functional and symptom scales showed significant improvement in the homeopathy group when compared with placebo after 9 and 18 weeks of homeopathic treatment (p < .001). Median survival time was significantly longer in the homeopathy group (435 days) versus placebo (257 days; p = .010) as well as versus control (228 days; p < .001). Survival rate in the homeopathy group differed significantly from placebo (p = .020) and from control (p < .001).
The authors concluded that QoL improved significantly in the homeopathy group compared with placebo. In addition, survival was significantly longer in the homeopathy group versus placebo and control. A higher QoL might have contributed to the prolonged survival. The study suggests that homeopathy positively influences not only QoL but also survival. Further studies including other tumour entities are warranted.
First of all, let me thank my friend Dana Ullman for alerting me to this new and interesting study. I have read what seems to be the full paper several times and have to admit that it puzzles me (and perhaps this version is just some type of pre-publication paper). Firstly, there seems to be no methods section (the abstract is followed by several tables and a discussion), and I am left guessing much of the details. Secondly, the paper raises several questions in my mind:
- What is the purpose of group 3? The authors call it a control group and state it allows assessing the real homeopathic effect on the homeopathic cohort as the real effect will be the natural historical effect minus the placebo effect and the homeopathic effect. Does that make sense?
- Was the study under-powered? From my reading of the text, the answer seems to be yes.
- What is the full list of conventional treatments the patients received, and did they differ between the 3 groups?
- If I understand it correctly, the study patients did not receive immuno-oncological therapy. Does that fact not render the study unethical?
- What homeopathic potencies were prescribed in group 1? The paper says: The constituents of the different homeopathic remedies were mainly of plant, mineral, or animal origin. This is unlikely, as most homeopathic remedies contain nothing.
- The authors seem to have used individualised homeopathy according to Hahnemann’s instructions. Did Hahnemann not strictly forbid combining his approach with other types of treatment?
- How well respected is THE ONCLOLOGIST, the journal that published the paper?
- Was the article peer-reviewed? If so, by whom?
- Was the placebo indistinguishable from the verum?
- Was the success of patient-blinding checked?
- Have similar findings regarding survival been reported previously? The authors call this finding ‘unexpected’; I find it more than that; it is baffling.
- Should we accept such surprising findings, or would it be more prudent to wait until independent replications are available?
- The first author of this trial is Prof Frass who has featured on this blog several times before (see for instance here, here, here, here and here). Frass has published several studies of homeopathy and invariably manages to produce positive results. Am I the only one to find this odd?
I would be most grateful, if the readers of this blog could assist me in finding answers to some of the above questions.
In my last post, I reported that there are no rigorous studies of homeopathy for diabetes. This was only partly true: there are no such trials to test homeopathy’s effects on the disease itself, but I did find a study of homeopathy for diabetic complications.
It comes from India and seems to be based on proper preliminary ground-work:
A prospective multi-centric clinical observational study was published in 2013 in the journal ‘HOMEOPATHY’. It was carried out from October 2005 to September 2009 by Central Council for Research in Homeopathy (CCRH) at its five institutes/units. Its authors were Patients suffering from diabetes mellitus (DM) and presenting with symptoms of diabetic polyneuropathy (DPN) were screened, investigated and were enrolled in the study after fulfilling the inclusion and exclusion criteria. Patients were evaluated by the diabetic distal symmetric polyneuropathy symptom score (DDSPSS) developed by the Council. A total of 15 homeopathic medicines were identified after repertorizing the nosological symptoms and signs of the disease. The appropriate constitutional medicine was selected and prescribed in 30, 200 and 1 M potency on an individualized basis. Patients were followed up regularly for 12 months.
Of 336 patients (167 males and 169 females) enrolled in the study, 247 patients (123 males and 124 females) were analysed. All patients who attended at least three follow-up appointments and baseline curve conduction studies were included in the analysis.). A statistically significant improvement in DDSPSS total score (p = 0.0001) was found at 12 months from baseline. Most objective measures did not show significant improvement. Lycopodium clavatum (n = 132), Phosphorus (n = 27) and Sulphur (n = 26) were the medicines most frequently prescribed. Adverse event of hypoglycaemia was observed in one patient only.
The authors concluded that this study suggests homeopathic medicines may be effective in managing the symptoms of DPN patients. Further studies should be controlled and include the quality of life (QOL) assessment.
As good as their word, they then conducted a more rigorous trial which was published this year:
This study (authored in 2020 by and published in ‘EXPLORE’, an even worse journal than ‘HOMEOPATHY’, in my view) assessed the efficacy of individualized homoeopathic medicines in management of diabetic distal symmetric polyneuropathy (DDSP). It was designed as a multi-centric double-blind, placebo controlled, randomised clinical trial and conducted by the Central Council for Research in Homoeopathy at 6 centres with a sample size of 84. Based on earlier observational studies and repertorial anamnesis of DDSP symptoms 15 homoeopathic medicines were shortlisted and validated scales were used for evaluating the outcomes post-intervention.
The primary outcome measure was change in Neuropathy Total Symptom Score-6 (NTSS-6) from baseline to 12 months. Secondary outcomes included changes in peripheral nerve conduction study (NCS), World Health Organization Quality of Life BREF (WHOQOL-BREF) and Diabetic Neuropathy Examination (DNE) Score at 12 months.
The data of 68 enrolled cases was considered for data analysis. Statistically significant difference (p<0.014) was found in NTSS-6 post intervention in the Verum group. Positive trend was noted for Verum group as per the graph plotted for DNE score and assessment done for NCS. No significant difference was found between the groups for WHOQOL-Bref. Out of 15 pre-identified homoeopathic medicines 11 medicines were prescribed in potencies in ascending order from 6C to 1M.
The authors concluded that further studies must be taken up with larger sample size and defined parameters for NCS to assess the effectiveness of homoeopathy.
This looks to me as though the trial failed to produce a positive result on inter-group comparisons. The abstract is unfortunately not very clear, and I have no access to the full text (in case someone has, please send it to me). Judging from the abstract, the study has several important flaws. For instance, it was small and we don’t know why only 68 of 84 patients were considered for analysis. Normally, an intention to treat analysis would be needed for analysis of all 84 patients.
________________________________
So, does homeopathy have anything to offer to patients with diabetes?
As far as I can see, the answer is NO!
I’d be happy to change my mind, provided someone shows me convincing evidence.
Manual therapy is a commonly recommended treatment of low back pain (LBP), yet few studies have directly compared the effectiveness of thrust (spinal manipulation) vs non-thrust (spinal mobilization) techniques. This study evaluated the comparative effectiveness of spinal manipulation and spinal mobilization at reducing pain and disability compared with a placebo control group (sham cold laser) in a cohort of young adults with chronic LBP.
This single-blinded (investigator-blinded), placebo-controlled randomized clinical trial with 3 treatment groups was conducted at the Ohio Musculoskeletal and Neurological Institute at Ohio University from June 1, 2013, to August 31, 2017. Of 4903 adult patients assessed for eligibility, 4741 did not meet inclusion criteria, and 162 patients with chronic LBP qualified for randomization to 1 of 3 treatment groups. Participants received 6 treatment sessions of (1) spinal manipulation, (2) spinal mobilization, or (3) sham cold laser therapy (placebo) during a 3-week period. Licensed clinicians (either a doctor of osteopathic medicine or physical therapist), with at least 3 years of clinical experience using manipulative therapies provided all treatments.
Primary outcome measures were the change from baseline in Numerical Pain Rating Scale (NPRS) score over the last 7 days and the change in disability assessed with the Roland-Morris Disability Questionnaire (scores range from 0 to 24, with higher scores indicating greater disability) 48 to 72 hours after completion of the 6 treatments.
A total of 162 participants (mean [SD] age, 25.0 [6.2] years; 92 women [57%]) with chronic LBP (mean [SD] NPRS score, 4.3 [2.6] on a 1-10 scale, with higher scores indicating greater pain) were randomized.
- 54 participants were randomized to the spinal manipulation group,
- 54 to the spinal mobilization group,
- 54 to the placebo group.
There were no significant group differences for sex, age, body mass index, duration of LBP symptoms, depression, fear avoidance, current pain, average pain over the last 7 days, and self-reported disability. At the primary end point, there was no significant difference in change in pain scores between spinal manipulation and spinal mobilization (0.24 [95% CI, -0.38 to 0.86]; P = .45), spinal manipulation and placebo (-0.03 [95% CI, -0.65 to 0.59]; P = .92), or spinal mobilization and placebo (-0.26 [95% CI, -0.38 to 0.85]; P = .39). There was no significant difference in change in self-reported disability scores between spinal manipulation and spinal mobilization (-1.00 [95% CI, -2.27 to 0.36]; P = .14), spinal manipulation and placebo (-0.07 [95% CI, -1.43 to 1.29]; P = .92) or spinal mobilization and placebo (0.93 [95% CI, -0.41 to 2.29]; P = .17). A comparison of treatment credibility and expectancy ratings across groups was not statistically significant (F2,151 = 1.70, P = .19), indicating that, on average, participants in each group had similar expectations regarding the likely benefit of their assigned treatment.
The authors concluded that in this randomized clinical trial, neither spinal manipulation nor spinal mobilization appeared to be effective treatments for mild to moderate chronic LBP.
This is an exceptionally well-reported study. Yet, one might raise a few points of criticism:
- The comparison of two active treatments makes this an equivalence study, and much larger sample sizes are required or such trials (this does not mean that the comparisons are not valid, however).
- The patients had rather mild symptoms; one could argue that patients with severe pain might respond differently.
- Chiropractors could argue that the therapists were not as expert at spinal manipulation as they are; had they employed chiropractic therapists, the results might have been different.
- A placebo control group makes more sense, if it allows patients to be blinded; this was not possible in this instance, and a better placebo might have produced different findings.
Despite these limitations, this study certainly is a valuable addition to the evidence. It casts more doubt on spinal manipulation and mobilisation as an effective therapy for LBP and confirms my often-voiced view that these treatments are not the best we can offer to LBP-patients.
This randomized clinical trial tested the effects of laying on of hands (LooH) as a complementary therapy to kinesiotherapy, on pain, joint stiffness, and functional capacity of older women with knee osteoarthritis (KOA) compared to a control group.
Participants were assigned into 3 groups:
- LooH with a spiritual component (Group – SPG),
- LooH without a spiritual component (Group – LHG),
- a control group receiving no complementary intervention (Control Group – CG).
Patients were assessed at baseline, 8 weeks, and 16 weeks. Primary outcomes were joint stiffness and functional capacity (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC]), and pain (WOMAC and visual analogue scale). Secondary outcomes were anxiety, depression, mobility, and quality of life. Differences between groups were evaluated using an intention-to-treat approach.
A total of 120 women with KOA were randomized (40 participants per group). At 8 weeks, SPG differed significantly from the LHG for WOMAC Functional Status; Anxiety levels; and also from the CG for all outcomes with exception of WOMAC Stiffness. After 16 weeks, SPG differed significantly from the LHG only for WOMAC Functional Status and also from the CG for all outcomes with exception of WOMAC Stiffness and timed up-and-go.
The authors concluded that the results suggest that LooH with a “spiritual component” may promote better long-term functional outcomes than both LooH without a “spiritual component” and a control group without LooH.
This is an interesting study which seems well designed. Its findings are surprising and lack scientific plausibility. Therefore, sceptics will find it hard to accept the results and suspect some hidden bias or confounding to have caused it rather than the laying on of hands. SCAM enthusiasts would then probably claim that such an attitude exemplifies the bias of sceptics.
So, what can be done to find out who is right and who is wrong?
Whenever we are faced with a surprising finding based on a seemingly rigorous trial, it is wise to realise that there is a plethora of possible explanations and that speculations are usually not very helpful. There is always a danger of a clinical trial producing false or misleading findings. This could be due to a plethora of reasons such as error, undetected bias or confounding, fraud, etc.
What we really need is an independent replication – better two.
Chronic rhinosinusitis (CRS) is a common disorder. This trial tested the efficacy of individualized homeopathy (IH) in comparison with placebo in patients with CRS.
This double-blind, randomized (1:1), placebo-controlled, preliminary trial (n = 62) was conducted at the National Institute of Homoeopathy, West Bengal, India. Primary outcome measure was the sino-nasal outcome test-20 (SNOT-20) questionnaire; secondary outcomes were the EQ-5D-5L questionnaire and EQ-5D-5L visual analogue scale scores, and five numeric rating scales (0-10) assessing intensity of sneezing, rhinorrhoea, post-nasal drip, facial pain/pressure, and disturbance in sense of smell, all measured at baseline and after the 2nd and 4th months of intervention. Group differences and effect sizes (Cohen’s d) were calculated on the intention-to-treat sample.
The two groups were comparable at baseline. Attrition rate was 6.5% (IH: 1, Placebo: 3). Although improvements in both primary and secondary outcome measures were higher in the IH group than placebo, with small to medium effect sizes, the group differences were statistically non-significant (all p > 0.05, unpaired t-tests). Calcarea carbonica, Lycopodium clavatum, Sulphur, Natrum muriaticum and Pulsatilla nigricans were the most frequently prescribed medicines. No harmful or unintended effects, homeopathic aggravations or any serious adverse events were reported from either group.
The authors who are affiliated with the following institutions:
- Department of Materia Medica, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Kolkata, West Bengal, India.
- Department of ENT, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Kolkata, West Bengal, India.
- Department of Paediatrics, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Kolkata, West Bengal, India.
- Department of Organon of Medicine and Homoeopathic Philosophy, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Kolkata, West Bengal, India.
- Department of Repertory, National Institute of Homoeopathy, Ministry of AYUSH, Govt. of India, Kolkata, West Bengal, India.
- Mahesh Bhattacharyya Homoeopathic Medical College and Hospital, Govt. of West Bengal, Howrah, West Bengal, India.
concluded that there was a small but non-significant direction of effect favoring homeopathy, which ultimately renders the trial as inconclusive. Rigorous trials and independent replications are recommended to arrive at a confirmatory conclusion.
Sorry, but this is the wrong conclusion. In the name of honesty and research integrity, it should read something like this:
Our study failed to show that IH has a significant effect on CRS.
But of course, this is no surprise. Why should IH work for CRS? The only remotely interesting finding here, in my view, is the fact that the authors noted not a single homeopathic aggravation (i. e. the occurrence of the ‘drug picture’ in a patient and thus a kind of homeopathic ‘proving’). Using IH, homeopaths would expect aggravations with some regularity. Could it be that homeopathic aggravations (and ‘provings’) are, like all effects of homeopathy, the result of misinterpretation, fantasy and wishful thinking? Investigating the issue systematically, we found already 17 years ago that this systematic review does not provide clear evidence that the phenomenon of homeopathic aggravations exists.
Dr Mathias Rath, the German born purveyor of multiple food supplements, and his organisation puzzle me a great deal. As previously reported, the ‘Dr Rath Foundation’ published an article about me. In it, the author got my name right, but not much more. Here is its opening passage [the numbers in square brackets refer to my comments below].
Professor Edzard Ernst: A Career Built On Discrediting Natural Health Science? [1]
Professor Edzard Ernst, a retired German [2] physician and academic, has recently [3] become a prominent advocate of plans that could potentially outlaw [4] the entire profession of naturopathic doctors [5] in Germany. Promoting the nonsensical idea that naturopathic medicine somehow poses a risk to public health, Ernst attacks its practitioners as supposedly having been educated in “nonsense” [6]. Tellingly, however, given that he himself has seemingly not published even so much as one completely original scientific trial of his own [7], Ernst’s apparent attempts to discredit natural healthcare approaches are largely reliant instead on his analysis or review of handpicked negative studies carried out by others [8].
- When I was appointed at Exeter to research alternative medicine in 1993, I had already been a full professor at Hannover, Germany and subsequently at Vienna, Austria. If anything, coming to Exeter was a big step down in terms of ‘career’, salary, number of co-workers etc. (full details in my memoir)
- I am German-born, became an Austrian citizen in 1990, and since 2000 I am a British national.
- I have been critical about the German ‘Heilpraktiker’ for more than 20 years.
- This refers to the recent ‘Muensteraner Memorandum’ which is the work of an entire team of multidisciplinary experts and advocates reforming this profession.
- ‘Heilpraktiker’ are certainly not doctors; they have no academic or medical background.
- This is correct, and I stand by my statement that educating people in vitalism and other long-obsolete concepts is pure nonsense.
- Since I am researching alternative medicine, I have conducted and published about 40 ‘scientific trials’, and before that time (1993) I have published about the same number again in various other fields.
- This refers to systematic reviews which, by definition, include all the studies available on a defines research question, regardless of their conclusion (their aim is to minimise random and selection biases) .
Rath states about himself that “Dr. Rath heads a research and development institute in nutritional and Cellular Medicine. His institute is conducting basic research and clinical studies to scientifically document the health benefits of micronutrients in fighting a multitude of diseases.”
But this is equally puzzling.
Firstly, because research does not aim ‘to scientifically document the health benefits of ‘ anything; it is for testing hypotheses; Rath surely must know that. Secondly, on Medline, I find dozens of publications by Rath. These refer mostly to mechanistic in-vitro or animal studies about the mode of action of vitamins and other natural compounds.
But ‘clinical studies‘?
None!
Hold on! My Medline searches did deliver one clinical trial – just one – (Rath himself lists more, but they seem to be meaningless observational studies without a control group). It was published as an abstract on his own website. Here is the abstract:
Healing of bone fractures is a prolonged process that can be affected by nutrition. Our objective was to critically evaluate the effect of supplementation with an essential nutrient complex, containing ascorbic acid, lysine, proline, and vitamin B6 on healing time of tibial fractures.
Design:
Random double-blind placebo-controlled study
Setting:
Dr. Jamdar Hospital, Jabalpur, India
Subjects and Intervention:
113 patients with unilateral displaced closed or grade I open tibial fractures were randomized to receive either standard care with placebo or with supplementation with an essential nutrient complex containing ascorbic acid, lysine, proline, and vitamin B6. Qualifying patients, on admission to the study, were clinically examined, radiographs of the affected limbs taken, fractures reduced under anesthesia, and above knee plaster casts applied. Radiographs were taken at each follow-up visit to confirm reduced alignment of fracture and proper callus formation.
Primary Outcome Measure:
The primary outcome measure was the number of weeks required for fracture to be healed. Healing was defined as absence of abnormal mobility at fracture site clinically, absence of pain elicited by stressing the fracture or by walking, and radiographic confirmation of callus formation.
Results:
Data analysis demonstrated reduced fracture-healing time associated with experimental supplementation. For PP analysis group, fracture healing time in 75% of the supplemented group of patients (N=21) was 17 weeks or less and 19 weeks or less in 75% of the placebo group patients (N=36). The percentage of patients with fractures healing in 10 weeks or less was 33.3% for the supplemented group and 11.1% for the placebo group. However, the difference in healing time between the two groups did not reach statistical significance.
Conclusion:
Results showed encouraging trends that fracture-healing time is reduced by supplementation with an essential nutrient complex containing ascorbic acid, lysine, proline, and vitamin B6. In addition, the nutrient supplemented participants reported improved feeling of well-being with use of the supplement.
This is odd in several ways:
- Even though the conclusions hide it quite well, the trial was in fact negative, i. e. it failed to show a significant difference between the verum and the placebo in the primary outcome measure.
- The trial was never published as a peer-reviewed full paper. The website refers to its publication as a ‘letter to the editor’ (LTTE) in the notorious JACM (a LTTE is not normally peer-reviewed).
- Why was it never properly published?
- Could it be because there was no ethics approval [none was mentioned in the LTTE]?
- Could it be because there was no informed consent [none was mentioned in the LTTE]?
- The LTTE mentions that a larger study with 200 patients is planned. This was 16 years ago, and to date there is no trace of such a trial.
Rath’s latest contribution to the world of science is a paper implying that his supplements could play a role in the fight against the present pandemic; it is entitled ‘Effective and safe global public health strategy to fight the COVID-19 pandemic: Specific micronutrient composition inhibits Coronavirus cell-entry receptor (ACE2) expression’. Here is the abstract which clearly shows that Rath has not a jot of clinical evidence:
Optimum micronutrient intake is the only scientifically proven way to improve general immune resistance against infections, a fact documented in every leading textbook of biology. This study provides scientific evidence that, in addition, specific micronutrient compositions are powerful tools in the fight against the COVID-19 pandemic.
Both, SARS-CoV-2 – the virus that causes the current pandemic – and other coronaviruses enter body cells via a specific receptor, the Angiotensin-Converting-Enzyme 2 (ACE2). The ACE2 receptor is expressed by many cell types, including lung epithelial cells as well as endothelial cells of the vascular system.
Based on our earlier research that demonstrated that specific micronutrients can block several mechanisms of viral infections, we tested the efficacy of these natural compounds in suppressing the expression of the ACE2 receptor on human endothelial cells and small airway epithelial cells.
Our results show that a micronutrient composition comprising vitamin C as well as certain amino acids, polyphenols, and trace elements is able to suppress this viral ‘entry door’ into the body under both normal and inflammatory conditions, which are associated with infections.
Thus, vitamin-rich nutrition and micronutrient supplementation should be implemented as effective, safe and affordable public health strategies to fight the COVID-19 pandemic and help prevent future outbreaks. Optimizing the micronutrient status of the entire population should form the basis for any global strategy to help prevent future pandemics across the world, including the developing nations.
The Wiki-page on Rath lists 10 (!) legal cases in which he has been involved. This looks like he easily sues people who disagree with his often bizarre views and sales techniques. Considering this suspicion, I better be careful what I say here. Therefore let me conclude by meekly repeating the title of this post which comes from my friend Ben Goldacre who, together with THE GUARDIAN won a famous and expensive legal battle against Rath:
Rath is an example of the worst excesses of the alternative therapy industry.
PS
What I like best about the many supplements sold by Rath is the footnote in the patient leaflets:
THIS PRODUCT IS NOT INTENDED TO DIAGNOSE, TREAT, CURE OR PREVENT ANY DISEASE
Much of so-called alternative medicine (SCAM) is used in the management of osteoarthritis pain. Yet few of us ever seem to ask whether SCAMs are more or less effective and safe than conventional treatments.
This review determined how many patients with chronic osteoarthritis pain respond to various non-surgical treatments. Published systematic reviews of randomized controlled trials (RCTs) that included meta-analysis of responder outcomes for at least 1 of the following interventions were included: acetaminophen, oral nonsteroidal anti-inflammatory drugs (NSAIDs), topical NSAIDs, serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, cannabinoids, counselling, exercise, platelet-rich plasma, viscosupplementation (intra-articular injections usually with hyaluronic acid ), glucosamine, chondroitin, intra-articular corticosteroids, rubefacients, or opioids.
In total, 235 systematic reviews were included. Owing to limited reporting of responder meta-analyses, a post hoc decision was made to evaluate individual RCTs with responder analysis within the included systematic reviews. New meta-analyses were performed where possible. A total of 155 RCTs were included. Interventions that led to more patients attaining meaningful pain relief compared with control included:
- exercise (risk ratio [RR] of 2.36; 95% CI 1.79 to 3.12),
- intra-articular corticosteroids (RR = 1.74; 95% CI 1.15 to 2.62),
- SNRIs (RR = 1.53; 95% CI 1.25 to 1.87),
- oral NSAIDs (RR = 1.44; 95% CI 1.36 to 1.52),
- glucosamine (RR = 1.33; 95% CI 1.02 to 1.74),
- topical NSAIDs (RR = 1.27; 95% CI 1.16 to 1.38),
- chondroitin (RR = 1.26; 95% CI 1.13 to 1.41),
- viscosupplementation (RR = 1.22; 95% CI 1.12 to 1.33),
- opioids (RR = 1.16; 95% CI 1.02 to 1.32).
Pre-planned subgroup analysis demonstrated no effect with glucosamine, chondroitin, or viscosupplementation in studies that were only publicly funded. When trials longer than 4 weeks were analysed, the benefits of opioids were not statistically significant.
The authors concluded that interventions that provide meaningful relief for chronic osteoarthritis pain might include exercise, intra-articular corticosteroids, SNRIs, oral and topical NSAIDs, glucosamine, chondroitin, viscosupplementation, and opioids. However, funding of studies and length of treatment are important considerations in interpreting these data.
Exercise clearly is an effective intervention for chronic osteoarthritis pain. It has consistently been recommended by international guideline groups as the first-line treatment in osteoarthritis management. The type of exercise is likely not important.
Pharmacotherapies such as NSAIDs and duloxetine demonstrate smaller but statistically significant benefit that continues beyond 12 weeks. Opioids appear to have short-term benefits that attenuate after 4 weeks, and intra-articular steroids after 12 weeks. Limited data (based on 2 RCTs) suggest that acetaminophen is not helpful. These findings are consistent with recent Osteoarthritis Research Society International guideline recommendations that no longer recommend acetaminophen for osteoarthritis pain management and strongly recommend against the use of opioids.
Limited benefit was observed with other interventions including glucosamine, chondroitin, and viscosupplementation. When only publicly funded trials were examined for these interventions, the results were no longer statistically significant.
Adverse events were inconsistently reported. However, withdrawal due to adverse events was consistently reported and found to be greater in patients using opioids, SNRIs, topical NSAIDs, and viscosupplementation.
Few of the interventions assessed fall under the umbrella of so-called alternative medicine (SCAM):
- some forms of exercise,
- cannabinoids,
- counselling,
- chondroitin,
- glucosamine.
It is unclear why the authors did not include SCAMs such as chiropractic, osteopathy, massage therapy, acupuncture, herbal medicines, neural therapy, etc. in their review. All of these SCAMs are frequently used for osteoarthritis pain. If they had included these treatments, how do you think they would have fared?
Excessive eccentric exercise of inadequately conditioned skeletal muscle results in focal sites of injury within the muscle fibres. 
These injuries cause pain which usually is greatest about 72 hours after the exercise. This type of pain is called delayed-onset muscle soreness (DOMS) and provides an accessible model for studying the effects of various treatments that are said to have anaesthetic activities; it can easily be reproducibly generated without lasting harm or ethical concerns.
In so-called alternative medicine (SCAM) DOMS is employed regularly to test treatments which are promoted for pain management. Thus several acupuncture trials using this method have become available. Yet, the evidence for the effects of acupuncture on DOMS is inconsistent which begs the question whether across all trials an effects emerges.
The aim of this systematic review therefore was to explore the effects of acupuncture on DOMS. Studies investigating the effect of acupuncture on DOMS in humans that were published before March 2020 were obtained from 8 electronic databases. The affected muscles, groups, acupuncture points, treatment sessions, assessments, assessment times, and outcomes of the included articles were reviewed. The data were extracted and analysed via a meta-analysis.
A total of 15 articles were included, and relief of DOMS-related pain was the primary outcome. The meta-analysis showed that there were no significant differences between acupuncture and sham/control groups, except for acupuncture for DOMS on day 1 (total SMD = -0.62; 95% CI = -1.12∼0.11, P < 0.05) by comparing with control groups.
The authors concluded that acupuncture for DOMS exhibited very-small-to-small and small-to-moderate effects on pain relief for the sham and no acupuncture conditions, respectively. Evidence indicating the effects of acupuncture on DOMS was little because the outcome data during the follow-up were insufficient to perform an effective meta-analysis.
A mere glance at the Forrest plot reveals that acupuncture is unlikely to have any effect on DOMS at all. The very small average effect that does emerge originates mainly from one outlier, the 2008 study by Itoh et al. This trial was published by three acupuncturists from the Department of Clinical Acupuncture and Moxibustion, Meiji University of Integrative Medicine, Kyoto, Japan. It has numerous weaknesses, for instance there are just 10 volunteers in each group, and can therefore be safely discarded.
In essence, this means that there is no good evidence that acupuncture is effective at reducing pain caused by DOMS.
This Cochrane review assessed the efficacy and safety of aromatherapy for people with dementia. The researchers included randomised controlled trials which compared fragrance from plants in an intervention defined as aromatherapy for people with dementia with placebo aromatherapy or with treatment as usual. All doses, frequencies and fragrances of aromatherapy were considered. Participants in the included studies had a diagnosis of dementia of any subtype and severity.
The investigators included 13 studies with 708 participants. All participants had dementia and in the 12 trials which described the setting, all were resident in institutional care facilities. Nine trials recruited participants because they had significant agitation or other behavioural and psychological symptoms in dementia (BPSD) at baseline. The fragrances used were:
- lavender (eight studies);
- lemon balm (four studies);
- lavender and lemon balm,
- lavender and orange,
- cedar extracts (one study each).
For six trials, assessment of risk of bias and extraction of results was hampered by poor reporting. Four of the other seven trials were at low risk of bias in all domains, but all were small (range 18 to 186 participants; median 66). The primary outcomes were:
- agitation,
- overall behavioural,
- psychological symptoms,
- adverse effects.
Ten trials assessed agitation using various scales. Among the 5 trials for which the confidence in the results was moderate or low, 4 trials reported no significant effect on agitation and one trial reported a significant benefit of aromatherapy. The other 5 trials either reported no useable data or the confidence in the results was very low. Eight trials assessed overall BPSD using the Neuropsychiatric Inventory and there was moderate or low confidence in the results of 5 of them. Of these, 4 reported significant benefit from aromatherapy and one reported no significant effect.
Adverse events were poorly reported or not reported at all in most trials. No more than two trials assessed each of our secondary outcomes of quality of life, mood, sleep, activities of daily living, caregiver burden. There was no evidence of benefit on these outcomes. Three trials assessed cognition: one did not report any data and the other two trials reported no significant effect of aromatherapy on cognition. The confidence in the results of these studies was low.
The authors reached the following conclusions: We have not found any convincing evidence that aromatherapy (or exposure to fragrant plant oils) is beneficial for people with dementia although there are many limitations to the data. Conduct or reporting problems in half of the included studies meant that they could not contribute to the conclusions. Results from the other studies were inconsistent. Harms were very poorly reported in the included studies. In order for clear conclusions to be drawn, better design and reporting and consistency of outcome measurement in future trials would be needed.
This is a thorough review. It makes many of the points that I so often make regarding SCAM research:
- too many of the primary studies are badly designed;
- too many of the primary studies are too small;
- too many of the primary studies are poorly reported;
- too many of the primary studies fail to mention adverse effects thus violating research ethics;
- too many of the primary studies are done by pseudo-scientists who use research for promotion rather than testing hypotheses.
It is time that SCAM researchers, ethic review boards, funders, editors and journal reviewers take these points into serious consideration – if only to avoid clinical research getting a bad reputation and losing the support of patients without which it cannot exist.
About one in three individuals have elevated blood pressure. This is bad news because hypertension is one of the most important risk factors for cardiovascular events like strokes and heart attacks. Luckily, there are many highly effective approaches for treating elevated blood pressure (diet, life-style, medication, etc.), and the drug management of hypertension has improved over the last few decades.
But unfortunately all anti-hypertensive drugs have side-effects and some patients look towards so-called alternative medicine (SCAM) to normalise their blood pressure. Therefore, we have to ask: are SCAMs effective treatments for hypertension? Because of the prevalence of hypertension, this is a question of great importance for public health.
In 2005, I addressed the issue by publishing a review entitled ‘Complementary/alternative medicine for hypertension: a mini-review‘. Here is its abstract:
Many hypertensive patients try complementary/alternative medicine for blood pressure control. Based on extensive electronic literature searches, the evidence from clinical trials is summarised. Numerous herbal remedies, non-herbal remedies and other approaches have been tested and some seem to have antihypertensive effects. The effect size is usually modest, and independent replications are frequently missing. The most encouraging data pertain to garlic, autogenic training, biofeedback and yoga. More research is required before firm recommendations can be offered.
Since the publication of this paper, more systematic reviews have become available. In order to get an overview of this evidence, I conducted a few simple Medline searches for systematic reviews (SRs) of SCAM published between 2005 and today. I included only SRs that were focussed on just one specific therapy as a treatment of just one specific condition, namely hypertension (omitting SRs with titles such as ‘Alternative treatments for cardiovascular conditions’). Reviews on prevention were also excluded. Here is what I found (the conclusions of each SR is quoted verbatim):
- A 2020 SR of auricular acupressure including 18 RCTs: The results demonstrated a favorable effect of auricular acupressure to reduce blood pressure and improve sleep in patients with hypertension and insomnia. Further studies to better understand the acupoints and intervention times of auricular acupressure are warranted.
- A 2020 SR of Chinese herbal medicines (CHM) including 30 studies: CHM combined with conventional Western medicine may be effective in lowering blood pressure and improving vascular endothelial function in patients with hypertension.
- A 2020 SR of Tai chi including 28 RCTs: Tai Chi could be recommended as an adjuvant treatment for hypertension, especially for patients less than 50 years old.
- A 2020 SR of Tai chi including 13 trials: Tai chi is an effective physical exercise in treating essential hypertension compared with control interventions.
- A 2020 SR of Tai chi including 31 controlled clinical trials: Tai Ji Quan is a viable antihypertensive lifestyle therapy that produces clinically meaningful BP reductions (i.e., 10.4 mmHg and 4.0 mmHg of SBP and DBP reductions, respectively) among individuals with hypertension.
- A 2020 SR of pycnogenol including 7 trials: the present meta-analysis does not suggest any significant effect of pycnogenol on BP.
- A 2019 SR of Policosanol including 19 studies: Policosanol could lower SBP and DBP significantly; future long term studies are required to confirm these findings in the general population.
- A 2019 SR of dietary phosphorus including 14 studies: We found no consistent association between total dietary phosphorus intake and BP in adults in the published literature nor any randomized trials designed to examine this association.
- A 2019 SR of ginger including 6 RCTs: ginger supplementation has favorable effects on BP.
- A 2019 SR of corn silk tea (CST) including 5 RCTs: limited evidence showed that CST plus antihypertensive drugs might be more effective in lowering blood pressure compared with antihypertensive drugs alone.
- A 2019 SR of blood letting including 7 RCTs: no definite conclusions regarding the efficacy and safety of BLT as complementary and alternative approach for treatment of hypertension could be drew due to the generally poor methodological design, significant heterogeneity, and insufficient clinical data.
- A 2019 SR of Xiao Yao San (XYS) including 17 trials: XYS adjuvant to antihypertensive drugs maybe beneficial for hypertensive patients in lowering BP, improving depression, regulating blood lipids, and inhibiting inflammation.
- A 2019 SR of Chinese herbal medicines including 9 RCTs: Chinese herbal medicine as complementary therapy maybe beneficial for postmenopausal hypertension.
- A 2019 Cochrane review of guided imagery including 2 trials: There is insufficient evidence to inform practice about the use of guided imagery for hypertension in pregnancy.
- A 2019 Cochrane review of acupuncture including 22 RCTs: At present, there is no evidence for the sustained BP lowering effect of acupuncture that is required for the management of chronically elevated BP.
- A 2019 SR of wet cupping including 7 RCTs: no firm conclusions can be drawn and no clinical recommendations made.
- A 2019 SR of transcendental meditation (TM) including 9 studies: TM was associated with within-group (but not between-groups) improvements in BP.
- A 2019 SR of yoga including 49 trials: yoga is a viable antihypertensive lifestyle therapy that produces the greatest BP benefits when breathing techniques and meditation/mental relaxation are included.
- A 2018 SR of mindfulness-based stress reduction (MBSR) including 5 studies: The MBSR program is a promising behavioral complementary therapy to help people with hypertension lower their blood pressure
- A 2018 SR of beetroot juice (BRJ) including 11 studies: BRJ supplementation should be promoted as a key component of a healthy lifestyle to control blood pressure in healthy and hypertensive individuals.
- A 2018 SR of taurine including 7 studies: ingestion of taurine at the stated doses and supplementation periods can reduce blood pressure to a clinically relevant magnitude, without any adverse side effects.
- A 2018 SR of acupuncture including 30 RCTs: there is inadequate high quality evidence that acupuncture therapy is useful in treating hypertension.
- A 2018 SR of co-enzyme Q10 including 17 RCTs: CoQ10 supplementation may result in reduction in SBP levels, but did not affect DBP levels among patients with metabolic diseases.
- A 2018 SR of a traditional Chinese formula Longdanxiegan decoction (LDXGD) including 9 trials: Due to poor methodological quality of the included trials, as well as potential reporting bias, our review found no conclusive evidence for the effectiveness of LDXGD in treating hypertension.
- A 2018 SR of viscous fibre including 22 RCTs: Viscous soluble fiber has an overall lowering effect on SBP and DBP.
- A 2017 SR of yoga breathing exercise (pranayama) including 13 studies: The pranayama’s effect on BP were not robust against selection bias due to the low quality of studies. But, the lowering BP effect of pranayama is encouraging.
- A 2017 SR of dietary nitrate supplementation including 13 trials: Positive effects of medium-term dietary nitrate supplementation on BP were only observed in clinical settings, which were not corroborated by more accurate methods such as 24-h ambulatory and daily home monitorings.
- A 2017 SR of Vitamin D supplementation including 8 RCTs: vitamin D is not an antihypertensive agent although it has a moderate SBP lowering effect.
- A 2017 SR of pomegranate including 8 RCTs: The limited evidence from clinical trials to date fails to convincingly show a beneficial effect of pomegranate on blood pressure
- A 2017 SR of ‘forest bathing’ including 20 trials: This systematic review shows a significant effect of Shinrin-yoku on reduction of blood pressure.
- A 2017 SR of Niuhuang Jiangya Preparation (NHJYP) including 12 RCTs: Our review indicated that NHJYP has some beneficial effects in EH patients with liver-yang hyperactivity and abundant phlegm-heat syndrome.
- A 2017 SR of Chinese medicines (CM) including 24 studies: CM might be a promising approach for the elderly with isolated systolic hypertension, while the evidence for CM employed alone was insufficient.
- A 2017 SR of beetroot juice including 22 RCTs: Our results demonstrate the blood pressure-lowering effects of beetroot juice and highlight its potential NO3-independent effects.
- A 2017 SR of blueberry including 6 RCTs: the results from this meta-analysis do not favor any clinical efficacy of blueberry supplementation in improving BP
- A 2016 Cochrane review of co-enzyme Q10 including 3 RCTs: This review provides moderate-quality evidence that coenzyme Q10 does not have a clinically significant effect on blood pressure.
- A 2016 SR of Nigella sativa including 11 RCTs: short-term treatment with N. sativa powder can significantly reduce SBP and DBP levels.
- A 2016 SR of vitamin D3 supplementation including 30 RCTs: Supplementation may be beneficial at daily doses >800 IU/day for <6 months in subjects ≥50 years old.
- A 2016 SR of anthocyanin supplementation including 6 studies: results from this meta-analysis do not favor any clinical efficacy of supplementation with anthocyanins in improving blood pressure.
- A 2016 SR of flaxseed including 15 trials: This meta-analysis of RCTs showed significant reductions in both SBP and DBP following supplementation with various flaxseed products.
- A 2016 SR of massage therapy including 9 RCTs: This systematic review found a medium effect of massage on SBP and a small effect on DBP in patients with hypertension or prehypertension.
- A 2015 SR of massage therapy including 24 studies: There is some encouraging evidence of massage for essential hypertension.
- A 2015 SR of transcendental meditation (TM) including 12 studies: an approximate reduction of systolic and diastolic BP of -4.26 mm Hg (95% CI=-6.06, -2.23) and -2.33 mm Hg (95% CI=-3.70, -0.97), respectively, in TM groups compared with control groups.
- A 2015 SR of Zhen Wu Decoction (ZWD) including 7 trials: This systematic review revealed no definite conclusion about the application of ZWD for hypertension due to the poor methodological quality, high risk of bias, and inadequate reporting on clinical data.
- A 2015 SR of acupuncture including 23 RCTs: Our review provided evidence of acupuncture as an adjunctive therapy to medication for treating hypertension, while the evidence for acupuncture alone lowing BP is insufficient.
- A 2015 SR of xuefu zhuyu decoction (XZD) including 15 studies: This meta-analysis provides evidence that XZD is beneficial for hypertension.
- A 2015 SR of Shenqi pill including 4 RCTs: This systematic review firstly provided no definite evidence for the efficacy and safety of Shenqi pill for hypertension based on the insufficient data.
- A 2015 SR of Jian Ling Decoction (JLD) including 10 trials: Owing to insufficient clinical data, it is difficult to draw a definite conclusion regarding the effectiveness and safety of JLD for essential hypertension.
- A 2015 SR of Chinese herbal medicines (CHM) including 5 trials: No definite conclusions about the effectiveness and safety of CHM for resistant hypertension could be drawn.
- A 2015 SR of Chinese medicines (CM) including 27 RCTs: When combined with Western medines, CM as a complementary treatment approach has certain effects for the control of hypertension and protection of target organs.
- A 2015 SR of berberine including 17 RCTs: This study indicates that berberine has comparable therapeutic effect on type 2 DM, hyperlipidemia and hypertension with no serious side effect.
- A 2015 SR of garlic including 9 double-blind trials: Although evidence from this review suggests that garlic preparations may lower BP in hypertensive individuals, the evidence is not strong.
- A 2015 SR of chlorogenic acids (CGAs) including 5 studies: CGA intake causes statistically significant reductions in systolic and diastolic blood pressures.
- A 2014 SR of omega-3 fatty acid supplementation including 70 RCTs: provision of EPA+DHA reduces systolic blood pressure, while provision of ≥2 grams reduces diastolic blood pressure.
- A 2014 SR of green tea including 20 RCTs: Green tea intake results in significant reductions in systolic blood pressure
- A 2014 SR of probiotics including 9 studies: consuming probiotics may improve BP by a modest degree, with a potentially greater effect when baseline BP is elevated, multiple species of probiotics are consumed, the duration of intervention is ≥8 weeks, or daily consumption dose is ≥10(11) colony-forming units.
- A 2014 SR of yoga including 17 trials: The evidence for the effectiveness of yoga as a treatment of hypertension is encouraging but inconclusive.
- A 2014 SR of yoga including 7 RCTs: very low-quality evidence was found for effects of yoga on systolic and diastolic blood pressure.
- A 2014 SR of yoga including 120 studies: yoga is an effective adjunct therapy for HPT and worthy of inclusion in clinical guidelines.
- A 2014 SR of moxibustion: a beneficial effect of using moxibustion interventions on KI 1 to lower blood pressure compared to antihypertensive drugs.
- A 2014 SR of acupuncture including 4 sham-controlled RCTs: acupuncture significantly lowers blood pressure in patients taking antihypertensive medications.
- A 2014 SR of Tuina including 7 RCTs: The findings from our review suggest that Tuina might be a beneficial adjuvant for patients with EH
- A 2014 SR of ‘kidney tonifying’ (KT) Chinese herbal mixture including 6 studies: Compared with antihypertensive drugs alone, KT formula combined with antihypertensive drugs may provide more benefits for patients with SH.
- A 2014 SR of Tongxinluo capsule including 25 studies : There is some but weak evidence about the effectiveness of TXL in treating patients with hypertension.
- A 2014 SR of moxibustion including 5 RCTs: no confirm conclusion about the effectiveness and safety of moxibustion as adjunctive treatment for essential hypertension could be made
- A 2013 SR of Qi Ju Di Huang Wan (QJDHW) including 10 RCTs: QJDHW combined with antihypertensive drugs might be an effective treatment for lowering blood pressure and improving symptoms in patients with essential hypertension.
- A 2013 SR of yoga including 17 studies: Yoga can be preliminarily recommended as an effective intervention for reducing blood pressure.
- A 2013 SR of Tianma Gouteng Yin (TGY) including 22 RCTs: No confirmed conclusion about the effectiveness and safety of TGY as adjunctive treatment for essential hypertension … could be made.
- A 2013 SR of Zhen Gan Xi Feng Decoction (ZGXFD) including 6 RCTs: ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH
- A 2013 SR of Tianmagouteng decoction including 9 RCTs: Tianmagouteng decoction can decrease both systolic and diastolic blood pressure.
- A 2013 SR of fish oil including 17 RCTs: The small but statistically significant effects of fish-oil supplements in hypertensive participants in this review have important implications for population health and lowering the risk of stroke and ischaemic heart disease.
- A 2013 SR of acupuncture including 35 RCTs: While there are some evidences that suggest potential effectiveness of acupuncture for hypertension, the results were limited by the methodological flaws of the studies.
- A 2013 SR of yoga including 6 studies: There is some encouraging evidence of yoga for lowering SBP and DBP.
- A 2012 SR of spinal manipulation therapy (SMT) including 10 studies: There is currently a lack of low bias evidence to support the use of SMT as a therapy for the treatment of
- A 2012 SR of vitamin C including 29 trials: In short-term trials, vitamin C supplementation reduced SBP and DBP.
- A 2012 SR of magnesium supplementation including 22 trials: magnesium supplementation appears to achieve a small but clinically significant reduction in BP, an effect worthy of future prospective large randomised trials using solid methodology.
- A 2012 SR of Banxia Baizhu Tianma Decoction (BBTD) including 16 RCTs: There is encouraging evidence of BBTD for lowering SBP, but evidence remains weak.
- A 2012 SR of Liu Wei Di Huang Wan (LWDHW) including 6 RCTs: LWDHW combined with antihypertensive drugs appears to be effective in improving blood pressure and symptoms in patients with essential hypertension.
- A 2012 SR of aromatherapy including 5 studies: The existing trial evidence does not show convincingly that aromatherapy is effective for hypertension.
- A 2012 empty Cochrane review: As no trials could be identified, no conclusions can be made about the role of TGYF in the treatment of primary hypertension.
- A 2012 SR of yoga including 10 studies: Not only does yoga reduce high BP but it has also been demonstrated to effectively reduce blood glucose level, cholesterol level, and body weight, major problems affecting the American society.
- A 2011 SR of L-arginine including 11 RCTs: This meta-analysis provides further evidence that oral L-arginine supplementation significantly lowers both systolic and diastolic BP.
- A 2011 SR of soy isoflavones including 14 RCTs: Soy isoflavone extracts significantly decreased SBP but not DBP in adult humans, and no dose-response relationship was observed.
- A 2010 SR of moxibustion including 4 RCTs: There is insufficient evidence to suggest that moxibustion is an effective treatment for hypertension.
- A 2010 SR of acupunctures including 20 studies: Because of the paucity of rigorous trials and the mixed results, these findings result in limited conclusions. More rigorously designed and powered studies are needed.
- A 2010 SR of cupping including 3 trials: the evidence is not significantly convincing to suggest cupping is effective for treating hypertension.
- A 2010 empty Cochrane review: There is insufficient evidence to support the benefit of Roselle for either controlling or lowering blood pressure in patients with hypertension.
- A 2009 SR of acupuncture including 11 RCTs: the notion that acupuncture may lower high BP is inconclusive.
- A 2008 SR of transcendental meditation including 9 studies: The regular practice of Transcendental Meditation may have the potential to reduce systolic and diastolic blood pressure by approximately 4.7 and 3.2 mm Hg, respectively.
- A 2008 SR of relaxation therapies including 25 trials: the evidence in favour of a causal association between relaxation and blood pressure reduction is weak.
- A 2007 SR of qigong including 12 RCTs: There is some encouraging evidence of qigong for lowering SBP, but the conclusiveness of these findings is limited.
- A 2007 SR of co-enzyme Q10 including 12 trials: coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects.
- A 2007 SR of stress reduction programs including 106 studies: Available evidence indicates that among stress reduction approaches, the Transcendental Meditation program is associated with significant reductions in BP.
- A 2006 Cochrance review of magnesium supplementation including 12 RCTs: the evidence in favour of a causal association between magnesium supplementation and blood pressure reduction is weak and is probably due to bias.
- A 2006 Cochrane review of calcium supplementation including 13 RCTs: evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias.
ALMOST 100 NEW SRs!
To be honest, if I had known the volume of the material, I would probably not have tackled this task. Since the publication of my mini-review in 2005, there has been an explosion of similar papers:
- 1 in 2005
- 2 in 2006
- 3 in 2007
- 2 in 2008
- 1 in 2009
- 4 in 2010
- 2 in 2011
- 8 in 2012
- 8 in 2013
- 12 in 2014
- 12 in 2015
- 6 in 2016
- 9 in 2017
- 7 in 2018
- 12 in 2019
As this is based on very simple Medline searches, the list is certainly not complete. Despite this fact, several conclusions seem to emerge:
- There is no shortage of SCAMs that have been tested for hypertension.
- Most seem to have positive effects; in many cases, they seem too good to be true.
- Many of the SRs are of poor methodological quality, based on poor quality primary studies, published in less than reputable journals. Some SRs, for instance, include studies without a control group which is likely to lead to false-positive overall conclusions about the effectiveness of the SCAM in question.
- In recent years, there are more and more SRs by Chinese authors focussed on Chinese herbal mixtures that are unknown and unobtainable outside China. These SRs are invariably based on studies published in Chinese language in journals that are inaccessible. This means it is almost impossible for the reader, reviewer or editor to check their accuracy. The reliability of the conclusions of these SRs must therefore be doubted.
- Most of the primary studies included in the SRs lack long-term data. Thus the usefulness of the SCAM in question is questionable.
- With several of the SCAMs, the dose of the treatment and treatment schedule is less than clear. For instance, one might ask how frequently a patient should have acupuncture to control her hypertension.
- Some of the SCAMs assessed in these SRs seem of doubtful practicality. For instance, it might not be feasible nor economical for patients to receive regular acupuncture to manage their blood pressure.
- Several contradictions emerge from some of the SRs of the same modality. This is particularly confusing because SRs are supposed to be the most reliable type of evidence. In most instances, however, the explanation can easily be found by looking at the quality of the SRs. If SRs are based on uncontrolled studies, or if they fail to critically evaluate the reliability of the included primary trials, they are likely to arrive at conclusions that are too positive. Examples for such confusion are the multiple SRs of co-enzyme Q10 or the three yoga SRs of 2014.
- Because of this confusion, SCAM advocates are able to select false-positive SRs to support their opinion that SCAM is effective.
- Despite a substantial amount of positive evidence, none of the SCAMs have become part of the routine in the management of hypertension. A 2013 statement by the American Heart Association entitled Beyond medications and diet: alternative approaches to lowering blood pressure: a scientific statement from the american heart association concluded that it is reasonable for all individuals with blood pressure levels >120/80 mm Hg to consider trials of alternative approaches as adjuvant methods to help lower blood pressure when clinically appropriate. A suggested management algorithm is provided, along with recommendations for prioritizing the use of the individual approaches in clinical practice based on their level of evidence for blood pressure lowering, risk-to-benefit ratio, potential ancillary health benefits, and practicality in a real-world setting.
What lessons might this brief overview of SRs teach us? I think the following points are worth considering:
- Systematic reviews are the best type of evidence we have for estimating the effectiveness of treatments. But it is essential that they include a strong element of CRITICAL evaluation of the primary studies. Without it, a SR is incomplete and potentially counter-productive.
- The primary studies of SCAM are far too often of poor quality. This means that researchers should thrive to improve the rigour of their investigations.
- Both poor-quality primary studies and uncritically conducted SRs are prone to yielding findings that are too good to be true.
- Editors and reviewers have a responsibility to prevent the publication of trials and SRs that are of poor quality and thus likely to mislead us.
- Those SCAMs that have shown promising effects on hypertension (for instance Tai chi) should now be submitted to further independent scrutiny to find out whether their efficacy and usefulness can be confirmed, for instance, by 24-h ambulatory and daily home blood pressure monitoring and studies testing their acceptability in real life settings. Subsequently, we ought to determine whether the SCAM in question can be reasonably integrated in routine blood pressure management.
- The adjunctive use of a SCAM that has been proven to be effective and practical seems a reasonable approach. Yet, it requires proper scientific scrutiny.
- There is a paucity of cost-effectiveness studies and investigations of the risks of SCAM which needs to be addressed before any SCAM is considered for routine care.
