This systematic review was aimed at determining if there has been a change in the reporting of adverse events associated with spinal manipulation in randomized clinical trials (RCTs) since 2016.
Databases were searched from March 2016 to May 2022: MEDLINE (Ovid), Embase, CINAHL, ICL, PEDro, and Cochrane Library. The following search terms and their derivatives were adapted for each platform: spinal manipulation; chiropractic; osteopathy; physiotherapy; naprapathy; medical manipulation and clinical trial.
Domains of interest (pertaining to adverse events) included: completeness and location of reporting; nomenclature and description; spinal location and practitioner delivering manipulation; methodological quality of the studies and details of the publishing journal. Frequencies and proportions of studies reporting on each of these domains were calculated. Univariable and multivariable logistic regression models were fitted to examine the effect of potential predictors on the likelihood of studies reporting on adverse events.
There were 5399 records identified by the electronic searches, of which 154 (2.9%) were included in the analysis. Of these, 94 (61.0%) reported adverse events with only 23.4% providing an explicit description of what constituted an adverse event. Reporting of adverse events in the abstract had increased (n=29, 30.9%) while reporting in the results section had decreased (n=83, 88.3%) over the past 6 years. Spinal manipulation was delivered to 7518 participants in the included studies. No serious adverse events were reported in any of these studies.
The authors concluded that, while the current level of reporting of adverse events associated with spinal manipulation in RCTs has increased since our 2016 publication on the same topic, the level remains low and inconsistent with established standards. As such, it is imperative for authors, journal editors and administrators of clinical trial registries to ensure there is more balanced reporting of both benefits and harms in RCTs involving spinal manipulation.
In fact, it is an ethical imperative to accurately report adverse effects. Not reporting adverse effects amounts to a violation of medical research ethics. Adverse effects of spinal manipulation occur in about 50% of all patients. This means that investigators reporting significantly lower figures are likely guilty of under-reporting. And under-reporting of adverse events is also a breach of ethical standards.
My conclusion thus is that the vast majority of trials of spinal manipulation are unethical and should be discarded.
“The decline of homeopathy, the ‘medicine’ that doesn’t cure anything” is the title of a remarkable article in EL PAIS of which I take the liberty of showing you a few key passages:
In the more than 200 years that have passed since its invention, no one has been able to prove that homeopathy is actually capable of curing anything with its alleged medicines that have no active ingredients…
…EL PAÍS reached out to some of its main promoters, such as the pharmaceutical company Boiron, leader in the sector; the Spanish Association of Homeopathy Pharmacists and the Spanish Society of Homeopathic Doctors. In the absence of a response from all three, the explanations are given by experts who are more critical of the discipline.
Many people who used to consume homeopathy were not even aware that this was the case. Fernando Frías, one of the activists who worked to undermine the discipline’s remaining prestige, recalls that people did not believe them when they were told that compounds with diluted Berlin Wall were sold to overcome the feelings of oppression and anxiety. This was actually commercialized under the premise that “like cures like”: if the Berlin Wall oppressed, a piece of it diluted in water should remedy it. “Many were under the impression that it was just a natural therapy and that we were making things up to attack it,” says Frías…
… There has been a lot of debate about how to regulate an alleged drug whose only effect is, in truth, the placebo effect. In 2001, the European Parliament issued a directive that covered its use in countries with a homeopathic tradition; sources explain that this happened due to the pressure exerted by both the industries and the governments of countries where pseudoscience is deep-rooted, such as France (where Boiron is headquartered) or Germany, where its consumption is much higher than in others, such as Spain.
“Having regard to the particular characteristics of these homeopathic medicinal products, such as the very low level of active principles they contain and the difficulty of applying to them the conventional statistical methods relating to clinical trials, it is desirable to provide a special, simplified registration procedure for those homeopathic medicinal products which are placed on the market without therapeutic indications in a pharmaceutical form and dosage which do not present a risk for the patient,” states the directive.
In its more than two centuries of history, this is not the first time that homeopathy loses ground. Still, Frías warns, it cannot be ruled out that at some point something will come up that will make it fashionable again. “Look at the example of chemtrails [the condensation trails left by airplanes that some conspiracy theorists believe are a way of poisoning the population from the air]. It seemed that no one remembered them anymore, but now they’re back,” he says. Frías cites the astrophysicist and disseminator Javier Armentia, who states that beliefs are like a rubber duck: no matter how much they sink, they always resurface. “Especially if there is money behind,” he adds.
As reported previously, homeopathy and other forms of so-called alternative medicine (SCAM) have come under fire in Spain. In 2017, ‘HOMEOPATHY PLUS‘ reported that “in a reversal of the 2015 Royal Legislative Decree, the Minister of Health has withdrawn homeopathic remedies and outlawed the practice in Spain’s national health services.” In 2018, more than 400 people signed an open letter triggered by the case of a cancer patient who died after preferring homeopathy to regular treatment. “Let’s be clear: pseudoscience kills,” begins the letter. Since then, the struggle of Spanish rational thinkers to stop misleading information about SCAM in general and homeopathy, in particular, has only intensified.
Spain is thus joining other European countries in opposing misinformation about homeopathy. Contrary to what some have claimed (for instance, in the comments section of this blog), most of the opponents do not want to restrict the public’s choice. People who wish to use homeopathy should be able to do so (but should pay for it themselves). However, the choice must be based on evidence-based information.
A team of French researchers assessed whether a conflict of interest (COI) might be associated with the direction of the results of meta-analyses of homoeopathy trials. Their analysis (published as a ‘letter to the editor) is complex, therefore, I present here only their main finding.
The team conducted a literature search until July 2022 on PubMed and Embase to identify meta-analyses of randomized clinical trials assessing the efficacy of homoeopathy. They then assessed the existence of potential COI, defined by the presence of at least one of the following criteria:
- affiliation of one or more authors to an academic homoeopathy research or care facility, or to the homoeopathy industry;
- research sponsored or funded by the homoeopathy industry;
- COI declared by the authors.
The researchers also evaluated and classified any spin in meta-analyses conclusions into three categories (misleading reporting, misleading interpretation and inappropriate extrapolation). Two reviewers assessed the quality of meta-analyses and the risk of bias based. Publication bias was evaluated by the funnel plot method. For all the studies included in these meta-analyses, the researchers checked whether they reported a statistically significant result in favour of homoeopathy. Further details about the methods are provided on OSF (https://osf.io/nqw7r/) and in the preregistered protocol (CRD42020206242).
Twenty meta-analyses were included in the analysis (list of references available at https://osf.io/nqw7r/).
- Among the 13 meta-analyses with COI, a significantly positive effect of homoeopathy emerged (OR=0.60 (95% CI 0.50 to 0.70)).
- There was no such effect for meta-analyses without COI (OR=0.96 (95% CI 0.75 to 1.23)).
The authors concluded that in the presence of COI, meta-analyses of homoeopathy trials are more likely
to have favourable results. This is consistent with recent research suggesting that systematic reviews with financial COI are associated with more positive outcomes.
Meta-analyses are systematic reviews (critical assessments of the totality of the available evidence) where the data from the included studies are pooled. For a range of reasons, this may not always be possible. Therefore the number of meta-analyses (20) is substantially lower than that of the existing systematic reviews (>50).
Both systematic reviews and meta-analyses are theoretically the most reliable evidence regarding the value of any intervention. I said ‘theoretically’ because, like any human endeavour, they need to be done in an unbiased fashion to produce reliable results. People with a conflict of interest by definition struggle to be free of bias. As we have seen many times, this would include homoeopaths.
This new analysis confirms what many of us have feared. If proponents of homeopathy with an overt conflict of interest conduct a meta-analysis of studies of homeopathy, the results tend to be more positive than when independent researchers do it. The question that emerges from this is the following:
Are the findings of those researchers who have an interest in producing a positive result closer to the truth than the findings of researchers who have no such conflict?
I let you decide.
Richard Rasker has been one of our most loyal commentators with hundreds of sensible contributions to his credit. And now he has published a book! “This book”, he writes in his introduction, “is perhaps best described as a kind of travel guide for exploring different worlds, some of which are probably familiar, while others may be completely alien to you. Some of those worlds only exist in the minds of people, while others are very real indeed, yet often go unnoticed or have unexpected things to offer. This journey is also my personal exploration, during which I try to look through the eyes of the inhabitants of worlds that are wildly different from my own, to try and understand why those people believe certain things, and why I myself believe different things.”
Richard is not a medic, he is a man who understands science and empathizes with the many people who try to make sense of the often confusing concepts of healthcare. In his book, he takes the reader by the hand and carefully guides him or her through some of the issues that are of concern to so many of us. The journey takes us to so-called alternative medicine (SCAM) and beyond. At its end, the reader is wiser, more knowledgeable, and has learned the art of critical thinking.
Most chapters start with a story or anecdote that enables the reader to identify with the subject at hand. This serves the purpose of focusing the reader’s mind on the issue at hand which is then explained in full detail. The fact that Richard is not a medic turns out to be a strength of this book. Richard is not even tempted (as medics invariably are) to use jargon or to assume that the reader has prior knowledge of the subject. Instead, he starts from first principles and makes it impossible to get lost on the journey. What may seem complicated and confusing thus becomes clear and straightforward; what might have appeared to be dry and off-putting thus becomes lively and fascinating.
The range of topics that this book tackles is vast. It covers much of SCAM, of course. But it also includes topics that are way beyond SCAM, such as radiation and vaccination. In essence, the book deals with most things that people concerned about their health tend to worry about. Because Richard is a gifted writer who can render things simple without making them unduly simplistic, the book is a joy to read.
In my view, this book is a MUST-READ for anyone who wants to find his/her way safely through the maze of seemingly complex problems in healthcare.
How often do we hear that chiropractic is safe because numerous trials reported no adverse events? This systematic review tested whether there has been a change in the reporting of adverse events associated with spinal manipulation in randomized clinical trials (RCTs) since 2016.
Databases were searched from March 2016 to May 2022: MEDLINE (Ovid), Embase, CINAHL, ICL, PEDro, and Cochrane Library. Domains of interest (pertaining to adverse events) included: completeness and location of reporting; nomenclature and description; spinal location and practitioner delivering manipulation; methodological quality of the studies and details of the publishing journal. Frequencies and proportions of studies reporting on each of these domains were calculated. Univariable and multivariable logistic regression models were fitted to examine the effect of potential predictors on the likelihood of studies reporting on adverse events.
5399 records were identified by the electronic searches, of which 154 (2.9%) were included in the analysis. Of these, 94 (61.0%) reported adverse events with only 23.4% providing an explicit description of what constituted an adverse event. Reporting of adverse events in the abstract has increased (n=29, 30.9%) while reporting in the results section has decreased (n=83, 88.3%) over the past 6 years. Spinal manipulation was delivered to 7518 participants in the included studies. No serious adverse events were reported in any of these studies.
The authors concluded as follows: while the current level of reporting of adverse events associated with spinal manipulation in RCTs has increased since our 2016 publication on the same topic, the level remains low and inconsistent with established standards. As such, it is imperative for authors, journal editors and administrators of clinical trial registries to ensure there is more balanced reporting of both benefits and harms in RCTs involving spinal manipulation.
This article is clearly relevant to our discussions about adverse events after spinal manipulation. However, I find it far too uncritical. This might be due to the affiliations of some of the authors:
- Integrative Spinal Research Group, Department of Chiropractic Medicine, University Hospital Balgrist and University of Zurich, Zurich, Switzerland.
- Department of Chiropractic, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, New South Wales, Australia.
Interestingly, the authors stated that they have no conflict of interest. Also interesting is the fact that they do not cite our paper from 2012. I, therefore, take the liberty of doing it:
Objective: To systematically review the reporting of adverse effects in clinical trials of chiropractic manipulation.
Data sources: Six databases were searched from 2000 to July 2011. Randomised clinical trials (RCTs) were considered, if they tested chiropractic manipulations against any control intervention in human patients suffering from any type of clinical condition. The selection of studies, data extraction, and validation were performed independently by two reviewers.
Results: Sixty RCTs had been published. Twenty-nine RCTs did not mention adverse effects at all. Sixteen RCTs reported that no adverse effects had occurred. Complete information on incidence, severity, duration, frequency and method of reporting of adverse effects was included in only one RCT. Conflicts of interests were not mentioned by the majority of authors.
Conclusions: Adverse effects are poorly reported in recent RCTs of chiropractic manipulations.
In percentage terms the results are similar. What is very different is that the authors of the new paper merely lament that the level remains low and inconsistent with established standards, while we make it clear in the abstract that adverse effect reporting is poor and in the paper identify this deficit as a violation against research ethics and thus as a form of scientific misconduct.
In view of all this, let me re-phrase the last sentence of the authors’ conclusion:
it is imperative for authors, journal editors, and administrators of clinical trial registries to ensure that researchers adhere to accepted ethical standards and that scientific misconduct no longer gets published.
Low back pain is the leading cause of years lived with disability globally, but most interventions have only short-lasting, small to moderate effects. Cognitive functional therapy (CFT) is an individualized approach that targets unhelpful pain-related cognitions, emotions, and behaviors that contribute to pain and disability. Movement sensor biofeedback might enhance treatment effects.
This study aimed to compare the effectiveness and economic efficiency of CFT, delivered with or without movement sensor biofeedback, with usual care for patients with chronic, disabling low back pain.
RESTORE was a randomized, three-arm, parallel-group, phase 3 trial, done in 20 primary care physiotherapy clinics in Australia. The researchers recruited adults (aged ≥18 years) with low back pain lasting more than 3 months with at least moderate pain-related physical activity limitation. Exclusion criteria were serious spinal pathology (eg, fracture, infection, or cancer), any medical condition that prevented being physically active, being pregnant or having given birth within the previous 3 months, inadequate English literacy for the study’s questionnaires and instructions, a skin allergy to hypoallergenic tape adhesives, surgery scheduled within 3 months, or an unwillingness to travel to trial sites. Participants were randomly assigned (1:1:1) via a centralized adaptive schedule to
- usual care,
- CFT only,
- CFT plus biofeedback.
The primary clinical outcome was activity limitation at 13 weeks, self-reported by participants using the 24-point Roland Morris Disability Questionnaire. The primary economic outcome was quality-adjusted life-years (QALYs). Participants in both interventions received up to seven treatment sessions over 12 weeks plus a booster session at 26 weeks. Physiotherapists and patients were not masked.
Between Oct 23, 2018, and Aug 3, 2020, the researchers assessed 1011 patients for eligibility. After excluding 519 (51·3%) ineligible patients, they randomly assigned 492 (48·7%) participants; 164 (33%) to CFT only, 163 (33%) to CFT plus biofeedback, and 165 (34%) to usual care. Both interventions were more effective than usual care (CFT only mean difference –4·6 [95% CI –5·9 to –3·4] and CFT plus biofeedback mean difference –4·6 [–5·8 to –3·3]) for activity limitation at 13 weeks (primary endpoint). Effect sizes were similar at 52 weeks. Both interventions were also more effective than usual care for QALYs, and much less costly in terms of societal costs (direct and indirect costs and productivity losses; –AU$5276 [–10 529 to –24) and –8211 (–12 923 to –3500).
The authors concluded that CFT can produce large and sustained improvements for people with chronic disabling low back pain at considerably lower societal cost than that of usual care.
This is a well-designed and well-reported study. It shows that CFT is better than usual care. The effect sizes are not huge and seem similar to many other treatments for chronic LBP, including the numerous so-called alternative medicine (SCAM) options that are available.
Faced with a situation where we have virtually dozens of therapies of similar effectiveness, what should we recommend to patients? I think this question is best and most ethically answered by accounting for two other important determinants of usefulness:
CFT is both low in risk and cost. So is therapeutic exercise. We would therefore need a direct comparison of the two to decide which is the optimal approach.
Until we have such a study, patients might just opt for one or both of them. What seems clear, meanwhile, is this: SCAM does not offer the best solution to chronic LBP. In particular, chiropractic, osteopathy, or acupuncture – which are neither low-cost nor risk-free – are, contrary to what some try so very hard to convince us of, sensible options.
The former Vice-Chancellor of Exeter University, Sir David Harrison, has died aged 92. He had a distinguished career including a 10-year tenure as Vice-Chancellor of the University, from 1984-1994. He also held numerous other prestigious roles in academia:
- Vice-Chancellor at Keele (1979-84),
- Chairman of the Committee of vice-Chancellors and Principals (1991-93),
- President of the Institution of Chemical Engineers (1991-92),
- Master of Selwyn College (1994-2000).
Sir David was educated at Bede School, Sunderland and Clacton County School, before becoming a 2nd Lieutenant in the Royal Electrical and Mechanical Engineers. He subsequently read Natural Sciences at Selwyn College, Cambridge, before receiving a PhD in Physical Chemistry. He then joined the newly formed Chemical Engineering Department doing research into Fluidisation which resulted in three books, all written with his close friend Prof John Davidson. He taught at Cambridge University until 1979, becoming a fellow of Selwyn in 1957 and its Senior Tutor.
Sir David also served as
- President of IChemE in 1991–2,
- Director of the Salters’ Institute of Industrial Chemistry from 1993–2015,
- Chair of the Committee of UK Vice-Chancellors and Principals from 1991–1993,
- Member of the Advisory Committee on the Safety of Nuclear Installations from 1993–1999.
He was also a member of the Ely Cathedral Council and the Royal School of Church Music, served on the Board of Management of the Northcott Theatre in Exeter, and received numerous honors including being knighted in 1997 “for services to education and nuclear safety”.
Sir David was VC when I was appointed in 1993. Apparently, the appointment committee suspected that I had no intention to leave my (secure for life and much better-paid) post in Vienna and only played a strategic game to improve my position there (as is often done by academics applying for jobs). David thus decided to phone my wife and ask her straight out: “Does your husband really want to come to Exeter?” Her answer was simple: “Yes.”
After I had been appointed, one of my first urgent needs was to separate my chair from the (unbelievably woolly) ‘Centre of Complementary Health Studies” of which I had become a director from the unit I planned to build – by no means an easy task. David easily understood the problem of mixing science with belief and was a great help to the success of this process. Next, I had to persuade all concerned that my task would not be teaching practitioners of complementary medicine (as had been foreseen in a feasibility study of my chair) but to conduct rigorous science. David made it clear that this was not merely a possible but a desirable option (full details about these developments here).
David was a wise VC, a true gentleman, and a most helpful superior. We got on very well thanks to his uncomplicated, direct approach. Whenever there was a significant problem with my job, he used to invite me for a cup of tea in his office, and 15 minutes later the problem was solved. He truly did pave the way for all the independent research we were able to conduct during the years that followed.
I was sad when he left Exeter in 1994 and things gradually became less and less agreeable for me. I owe David much gratitude and respect – RIP.
A “null field” is a scientific field where there is nothing to discover and where observed associations are thus expected to simply reflect the magnitude of bias.
This analysis aimed to characterize a null field using a known example, homeopathy (a pseudoscientific medical approach based on using highly diluted substances), as a prototype. The researchers identified 50 randomized placebo-controlled trials of homeopathy interventions from highly cited meta-analyses. The primary outcome variable was the observed effect size in the studies. Variables related to study quality or impact were also extracted.
The mean effect size for homeopathy was 0.36 standard deviations (Hedges’ g; 95% confidence interval: 0.21, 0.51) better than placebo, which corresponds to an odds ratio of 1.94 (95% CI: 1.69, 2.23) in favor of homeopathy. 80% of studies had positive effect sizes (favoring homeopathy). The effect size was significantly correlated with citation counts from journals in the directory of open-access journals and CiteWatch. We identified common statistical errors in 25 studies.
The authors concluded that a null field like homeopathy can exhibit large effect sizes, high rates of favorable results, and high citation impact in the published scientific literature. Null fields may represent a useful negative control for the scientific process.
The paper is perhaps not the easiest to comprehend but once you got the idea, you will agree with me that it is BRILLIANT. I warmly recommend it to all fans of homeopathy – in fact, if I could I’d offer it to King Charles as a present for the coronation.
Its authors are among the most prominent medical epidemiologist of our time with affiliations that speak for themselves:
- Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA.
- 2Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA.
- 3Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA; Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, CA, USA; Department of Medicine, Stanford University, Stanford, CA, USA; Department of Biomedical Data Science, Stanford University, Stanford, CA, USA; Department of Statistics, Stanford University, Stanford, CA, USA.
It is, of course, a pity that the article is behind a paywall – but fortunately, the senior author, John Ioannidis, published his email address together with the abstract: [email protected]. So, if you have trouble understanding the point of the analysis, I suggest you ask for a reprint to get your head around it. I promise it’s worth it.
I am pleased to announce that our regular contributors ‘DC‘ as well as ‘mimi‘ both correctly guessed the person responsible for the quote about informed consent that was the subject of yesterday’s post. Congratulations to both; that certainly wasn’t easy!
The quote is by Karl Brandt.
Who was Karl Brandt?
Brandt was a young and evidently gifted doctor when, during a series of coincidences, he became a member of Hitler’s ‘inner circle’ and acted as one of Hitler’s personal physicians (originally, he had wanted to join the team of Albert Schweitzer!). Hitler liked the good-looking, ambitious Brandt and thus gave him greater and greater responsibilities and power. Amongst other things, Brandt managed to become in charge of the German euthanasia program which killed about 70 000 patients who the Nazis considered to be ‘useless eaters’ and unworthy of their support. It had the cynical purpose of freeing up hospital beds for the war and cleansing the German gene pool. Brandt also was responsible for many of the unspeakably cruel and immoral medical experiments in the concentration camps.
After the war, Brandt was put on trial in Nuremberg. The trial became known as the ‘Doctors’ Trail‘. Twenty of the 23 defendants were medical doctors (Viktor Brack, Rudolf Brandt, and Wolfram Sievers were Nazi officials). They were accused of having been involved in Nazi human experimentation and mass murder under the guise of euthanasia. Brandt insisted that he had never done anything wrong, had followed orders, and had been guided by the highest morals, solid medical ethics, and his determination to do the very best for the German people.
During his interrogations, he stated the sentences that fascinated me when I first read it: ” On the one hand, there are experiments that are carried out for or with someone on a voluntary basis; on the other hand, there are those that take place against the will of the person concerned. A further subdivision indicates whether they are particularly dangerous or comparatively harmless and without any potential for danger. A further distinction must be made as to whether the result of the experiment is important or whether it is merely a ridiculous game played by a scientifically educated person. These six criteria form a kind of guideline that enables one to say YES or NO from a medical point of view.”
The quote is cited in the book by Ulf Schmidt which is extremely well-researched and worth reading for anyone with an interest in the subject. In my view, it gives a unique insight into the thinking of someone who clearly was bright yet power-hungry, scrupulous and deeply immoral:
- experiments “against the will of the person concerned” always were unlawful, immoral, and unethical according to the guidelines that existed at the time;
- “particularly dangerous” experiments should have never been considered;
- research that is merely a “ridiculous game played by a scientifically educated person” is pseudoscience and not ethical.
Brandt tried to present himself as the ‘honest’, upright Nazi who did what he did because of a deep conviction and because he wanted the best. He seemed to have fooled others and possibly even himself. Several influential personalities rallied to his support. Yet, the judges at Nuremberg did neither believe his version of events nor were they inclined to pardon his behavior. Brandt was found guilty of:
- War crimes: performing medical experiments, without the subjects’ consent, on prisoners of war and civilians of occupied countries, in the course of which experiments the defendants committed murders, brutalities, cruelties, tortures, atrocities, and other inhuman acts. Also planning and performing the mass murder of prisoners of war and civilians of occupied countries, stigmatized as aged, insane, incurably ill, deformed, and so on, by gas, lethal injections, and diverse other means in nursing homes, hospitals, and asylums during the Euthanasia Program and participating in the mass murder of concentration camp inmates;
- Crimes against humanity: committing crimes also on German nationals;
- Membership in a criminal organization, the SS. The charges against him included special responsibility for, and participation in, Freezing, Malaria, LOST Gas, Sulfanilamide, Bone, Muscle and Nerve Regeneration and Bone Transplantation, Sea-Water, Epidemic Jaundice, Sterilization, and Typhus Experiments.
Brandt was executed on 2 June 1948.
The discussions around informed consent at the Nuremberg ‘doctors trial’ brought this subject into a renewed focus and eventually led to the formulation of the now famous ‘Nuremberg Code‘.
Low back pain (LBP) affects almost all of us at some stage. It is so common that it has become one of the most important indications for most forms of so-called alternative medicine (SCAM). In the discussions about the value (or otherwise) of SCAMs for LBP, we sometimes forget that there are many conventional medical options to treat LBP. It is therefore highly relevant to ask how effective they are. This overview aimed to summarise the evidence from Cochrane Reviews of the efficacy, effectiveness, and safety of systemic pharmacological interventions for adults with non‐specific LBP.
The Cochrane Database of Systematic Reviews was searched from inception to 3 June 2021, to identify reviews of randomised controlled trials (RCTs) that investigated systemic pharmacological interventions for adults with non‐specific LBP. Two authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools. The review focused on placebo comparisons and the main outcomes were pain intensity, function, and safety.
Seven Cochrane Reviews that included 103 studies (22,238 participants) were included. There was high confidence in the findings of five reviews, moderate confidence in one, and low confidence in the findings of another. The reviews reported data on six medicines or medicine classes: paracetamol, non‐steroidal anti‐inflammatory drugs (NSAIDs), muscle relaxants, benzodiazepines, opioids, and antidepressants. Three reviews included participants with acute or sub‐acute LBP and five reviews included participants with chronic LBP.
There was high‐certainty evidence for no evidence of difference between paracetamol and placebo for reducing pain intensity (MD 0.49 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI ‐1.99 to 2.97), reducing disability (MD 0.05 on a 0 to 24 scale (higher scores indicate worse disability), 95% CI ‐0.50 to 0.60), and increasing the risk of adverse events (RR 1.07, 95% CI 0.86 to 1.33).
There was moderate‐certainty evidence for a small between‐group difference favouring NSAIDs compared to placebo at reducing pain intensity (MD ‐7.29 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI ‐10.98 to ‐3.61), high‐certainty evidence for a small between‐group difference for reducing disability (MD ‐2.02 on a 0‐24 scale (higher scores indicate worse disability), 95% CI ‐2.89 to ‐1.15), and very low‐certainty evidence for no evidence of an increased risk of adverse events (RR 0.86, 95% CI 0. 63 to 1.18).
Muscle relaxants and benzodiazepines
There was moderate‐certainty evidence for a small between‐group difference favouring muscle relaxants compared to placebo for a higher chance of pain relief (RR 0.58, 95% CI 0.45 to 0.76), and higher chance of improving physical function (RR 0.55, 95% CI 0.40 to 0.77), and increased risk of adverse events (RR 1.50, 95% CI 1. 14 to 1.98).
None of the included Cochrane Reviews aimed to identify evidence for acute LBP.
No evidence was identified by the included reviews for acute LBP.
No evidence was identified by the included reviews for chronic LBP.
There was low‐certainty evidence for a small between‐group difference favouring NSAIDs compared to placebo for reducing pain intensity (MD ‐6.97 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI ‐10.74 to ‐3.19), reducing disability (MD ‐0.85 on a 0‐24 scale (higher scores indicate worse disability), 95% CI ‐1.30 to ‐0.40), and no evidence of an increased risk of adverse events (RR 1.04, 95% CI ‐0.92 to 1.17), all at intermediate‐term follow‐up (> 3 months and ≤ 12 months postintervention).
Muscle relaxants and benzodiazepines
There was low‐certainty evidence for a small between‐group difference favouring benzodiazepines compared to placebo for a higher chance of pain relief (RR 0.71, 95% CI 0.54 to 0.93), and low‐certainty evidence for no evidence of difference between muscle relaxants and placebo in the risk of adverse events (RR 1.02, 95% CI 0.67 to 1.57).
There was high‐certainty evidence for a small between‐group difference favouring tapentadol compared to placebo at reducing pain intensity (MD ‐8.00 on a 0 to 100 scale (higher scores indicate worse pain), 95% CI ‐1.22 to ‐0.38), moderate‐certainty evidence for a small between‐group difference favouring strong opioids for reducing pain intensity (SMD ‐0.43, 95% CI ‐0.52 to ‐0.33), low‐certainty evidence for a medium between‐group difference favouring tramadol for reducing pain intensity (SMD ‐0.55, 95% CI ‐0.66 to ‐0.44) and very low‐certainty evidence for a small between‐group difference favouring buprenorphine for reducing pain intensity (SMD ‐0.41, 95% CI ‐0.57 to ‐0.26).
There was moderate‐certainty evidence for a small between‐group difference favouring strong opioids compared to placebo for reducing disability (SMD ‐0.26, 95% CI ‐0.37 to ‐0.15), moderate‐certainty evidence for a small between‐group difference favouring tramadol for reducing disability (SMD ‐0.18, 95% CI ‐0.29 to ‐0.07), and low‐certainty evidence for a small between‐group difference favouring buprenorphine for reducing disability (SMD ‐0.14, 95% CI ‐0.53 to ‐0.25).
There was low‐certainty evidence for a small between‐group difference for an increased risk of adverse events for opioids (all types) compared to placebo; nausea (RD 0.10, 95% CI 0.07 to 0.14), headaches (RD 0.03, 95% CI 0.01 to 0.05), constipation (RD 0.07, 95% CI 0.04 to 0.11), and dizziness (RD 0.08, 95% CI 0.05 to 0.11).
There was low‐certainty evidence for no evidence of difference for antidepressants (all types) compared to placebo for reducing pain intensity (SMD ‐0.04, 95% CI ‐0.25 to 0.17) and reducing disability (SMD ‐0.06, 95% CI ‐0.40 to 0.29).
The authors concluded as follows: we found no high‐ or moderate‐certainty evidence that any investigated pharmacological intervention provided a large or medium effect on pain intensity for acute or chronic LBP compared to placebo. For acute LBP, we found moderate‐certainty evidence that NSAIDs and muscle relaxants may provide a small effect on pain, and high‐certainty evidence for no evidence of difference between paracetamol and placebo. For safety, we found very low‐ and high‐certainty evidence for no evidence of difference with NSAIDs and paracetamol compared to placebo for the risk of adverse events, and moderate‐certainty evidence that muscle relaxants may increase the risk of adverse events. For chronic LBP, we found low‐certainty evidence that NSAIDs and very low‐ to high‐certainty evidence that opioids may provide a small effect on pain. For safety, we found low‐certainty evidence for no evidence of difference between NSAIDs and placebo for the risk of adverse events, and low‐certainty evidence that opioids may increase the risk of adverse events.
This is an important overview, in my opinion. It confirms what I and others have been stating for decades: WE CURRENTLY HAVE NO IDEAL SOLUTION TO LBP.
This is regrettable but true. It begs the question of what one should recommend to LBP sufferers. Here too, I have to repeat myself: (apart from staying as active as possible) the optimal therapy is the one that has the most favourable risk/benefit profile (and does not cost a fortune). And this option is not drugs, chiropractic, osteopathy, acupuncture, or any other SCAM – it is (physio)therapeutic exercise which is cheap, safe, and (mildly) effective.