MD, PhD, FMedSci, FSB, FRCP, FRCPEd

causation

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A recently published study by Danish researchers aimed at comparing the effectiveness of a patient education (PEP) programme with or without the added effect of chiropractic manual therapy (MT) to a minimal control intervention (MCI). Its results seem to indicate that chiropractic MT is effective. Is this the result chiropractors have been waiting for?

To answer this question, we need to look at the trial and its methodology in more detail.

A total of 118 patients with clinical and radiographic unilateral hip osteoarthritis (OA) were randomized into one of three groups: PEP, PEP+ MT or MCI. The PEP was taught by a physiotherapist in 5 sessions. The MT was delivered by a chiropractor in 12 sessions, and the MCI included a home stretching programme. The primary outcome measure was the self-reported pain severity on an 11-box numeric rating scale immediately following the 6-week intervention period. Patients were subsequently followed for one year.

The primary analyses included 111 patients. In the PEP+MT group, a statistically and clinically significant reduction in pain severity of 1.9 points was noted compared to the MCI of 1.90. The number needed to treat for PEP+MT was 3. No difference was found between the PEP and the MCI groups. At 12 months, the difference favouring PEP+MT was maintained.

The authors conclude that for primary care patients with osteoarthritis of the hip, a combined intervention of manual therapy and patient education was more effective than a minimal control intervention. Patient education alone was not superior to the minimal control intervention.

This is an interesting, pragmatic trial with a result suggesting that chiropractic MT in combination with PEP is effective in reducing the pain of hip OA. One could easily argue about the small sample size, the need for independent replication etc. However, my main concern is the fact that the findings can be interpreted in not just one but in at least two very different ways.

The obvious explanation would be that chiropractic MT is effective. I am sure that chiropractors would be delighted with this conclusion. But how sure can we be that it would reflect the truth?

I think an alternative explanation is just as (possibly more) plausible: the added time, attention and encouragement provided by the chiropractor (who must have been aware what was at stake and hence highly motivated) was the effective element in the MT-intervention, while the MT per se made little or no difference. The PEP+MT group had no less than 12 sessions with the chiropractor. We can assume that this additional care, compassion, empathy, time, encouragement etc. was a crucial factor in making these patients feel better and in convincing them to adhere more closely to the instructions of the PEP. I speculate that these factors were more important than the actual MT itself in determining the outcome.

In my view, such critical considerations regarding the trial methodology are much more than an exercise in splitting hair. They are important in at least two ways.

Firstly, they remind us that clinical trials, whenever possible, should be designed such that they allow only one interpretation of their results. This can sometimes be a problem with pragmatic trials of this nature. It would be wise, I think, to conduct pragmatic trials only of interventions which have previously been proven to work.  To the best of my knowledge, chiropractic MT as a treatment for hip OA does not belong to this category.

Secondly, it seems crucial to be aware of such methodological issues and to consider them carefully before research findings are translated into clinical practice. If not, we might end up with  therapeutic decisions (or guidelines) which are quite simply not warranted.

I would not be in the least surprised, if chiropractic interest groups were to use the current findings for promoting chiropractic in hip-OA. But what, if the MT per se was ineffective, while the additional care, compassion and encouragement was? In this case, we would not need to recruit (and pay for) chiropractors and put up with the considerable risks chiropractic treatments can entail; we would merely need to modify the PE programme such that patients are better motivated to adhere to it.

As it stands, the new study does not tell us much that is of any practical use. In my view, it is a pragmatic trial which cannot readily be translated into evidence-based practice. It might get interpreted as good news for chiropractic but, in fact, it is not.

Some people will probably think that I am obsessed with writing about the risk of chiropractic. True, I have published quite a bit on this subject, both in the peer-reviewed literature as well as on this blog – but not because I am obsessed; on this blog, I will re-visit the topic every time a relevant new piece of evidence becomes available because it is indisputably such an important subject. Writing about it might prevent harm.

So far, we know for sure that mild to moderate as well as serious complications, including deaths, do occur after chiropractic spinal manipulations, particularly those of the upper spine.  What we cannot say with absolute certainty is whether they are caused by the treatment or whether they happened coincidentally. Our knowledge in this area relies mostly on case-reports and surveys which, by their very nature, do not allow causal inferences. Therefore chiropractors have, in the past, been able to argue that a causal link remains unproven.

A brand-new blinded parallel group RCT might fill this gap in our knowledge and might reject or establish the notion of causality once and for all. The authors’ objective was to establish the frequency and severity of adverse effects from short term usual chiropractic treatment of the spine when compared to a sham treatment group. They thus conducted the first ever RCT  with the specific aim to examine the occurrence of adverse events resulting from chiropractic treatment. It was conducted across 12 chiropractic clinics in Perth, Western Australia. The participants comprised 183 adults, aged 20-85, with spinal pain. Ninety two participants received individualized care consistent with the chiropractors’ usual treatment approach; 91 participants received a sham intervention. Each participant received two treatment sessions.

Completed adverse questionnaires were returned by 94.5% of the participants after the first appointment and 91.3% after the second appointment. Thirty three per cent of the sham group and 42% of the usual care group reported at least one adverse event. Common adverse events were increased pain (sham 29%; usual care 36%), muscle stiffness (sham 29%; usual care 37%), headache (sham 17%; usual care 9%). The relative risk was not significant for either adverse event occurrence (RR = 1.24 95% CI 0.85 to 1.81); occurrence of severe adverse events (RR = 1.9; 95% CI 0.98 to 3.99); adverse event onset (RR = 0.16; 95% CI 0.02 to 1.34); or adverse event duration (RR = 1.13; 95% CI 0.59 to 2.18). No serious adverse events were reported.

The authors concluded that a substantial proportion of adverse events following chiropractic treatment may result from natural history variation and non-specific effects.

If we want to assess causality of effects, we have no better option than to conduct an RCT. It is the study design that can give us certainty, or at least near certainty – that is, if the RCT is rigorous and well-made. So, does this study reject or confirm causality? The disappointing truth is that it does neither.

Adverse events were clearly more frequent with real as compared to sham-treatment. Yet the difference failed to be statistically significant. Why? There are at least two possibilities: either there was no true difference and the numerically different percentages are a mere fluke; or there was a true difference but the sample size was too small to prove it.

My money is on the second option. The number of patients was, in my view, way too small for demonstrating differences in frequencies of adverse effects. This applies to the adverse effects noted, but also, and more importantly, to the ones not noted.

The authors state that no serious adverse effects were observed. With less that 200 patients participating, it would have been most amazing to see a case of arterial dissection or stroke. From all we currently know, such events are quite rare and occur perhaps in one of 10 000 patients or even less often. This means that one would require a trial of several hundred thousand patients to note just a few of such events, and an RCT with several million patients to see a difference between real and sham treatment. It seems likely that such an undertaking will never be affordable.

So, what does this new study tell us? In my view, it is strong evidence to suggest a causal kink between chiropractic treatment and mild to moderate adverse effects. I dose not prove it, but merely suggests it – yet I am fairly sure that chiropractors, once again, will not agree with me.

On this blog, we have repeatedly discussed the serious adverse effects of Spinal Manipulative Therapies (SMT) as frequently administered by chiropractors, osteopaths and physiotherapists. These events mostly relate to vascular accidents involving vertebral or carotid arterial dissections after SMT of the upper spine. Lower down, the spine is anatomically far less vulnerable which, however, does not mean that injuries in this region after SMT are impossible. They have been reported repeatedly but, to the best of my knowledge, there is no up-to-date review of such events – that is until recently.

Australian researchers have just filled this gap by publishing a systematic review aimed at systematically reviewing all reports of serious adverse events following lumbo-pelvic SMT. They conducted electronic searches in MEDLINE, EMBASE, CINAHL, and The Cochrane Library up to January 12, 2012. Article-selection was performed by two independent reviewers using predefined criteria. Cases were included involving individuals 18 years or older who experienced a serious adverse event following SMT applied to the lumbar spine or pelvis by any type of provider (chiropractic, medical, physical therapy, osteopathic, layperson). A serious adverse event was defined as an untoward occurrence that resulted in death or was life threatening, required hospital admission, or resulted in significant or permanent disability. Reports published in English, German, Dutch, and Swedish were included.

The searches identified a total of 2046 papers, and 41 articles reporting a total of 77 cases were included in the review. Important case details were frequently missing in these reports, such as descriptions of SMT technique, the pre-SMT presentation of the patient, the specific details of the adverse event, time from SMT to the adverse event, factors contributing to the adverse event, and clinical outcome.

The 77 adverse events consisted of cauda equina syndrome (29 cases); lumbar disk herniation (23 cases); fracture (7 cases); haematoma or haemorrhagic cyst (6 cases); and12 cases of neurologic or vascular compromise, soft tissue trauma, muscle abscess formation, disrupted fracture healing, and oesophageal rupture.

The authors’ conclusion was that this systematic review describes case details from published articles that describe serious adverse events that have been reported to occur following SMT of the lumbo-pelvic region. The anecdotal nature of these cases does not allow for causal inferences between SMT and the events identified in this review.

This review is timely and sound. Yet several factors need consideration:

1) The search strategy was thorough but it is unlikely that all relevant articles were retrieved because these papers are often well-hidden in obscure and not electronically listed journals.

2) It is laudable that the authors included languages other than English but it would have been preferable to impose no language restrictions at all.

3) Under-reporting of adverse events is a huge problem, and it is anyone’s guess how large it really is [we have shown that, in our research it was precisely 100%]

4) This means that the 77 cases, which seem like a minute number, could in reality be 770 or 7700 or 77000; nobody can tell.

Cauda equina (horse tail) syndrome was the most frequent and most serious adverse event reported. This condition is caused by nerve injury at the lower end of the spinal canal. Symptoms can include leg pain along the sciatic nerve, severe back pain, altered or loss of sensation over the area around the genitals, anus and inner thighs as well as urine retention or incontinence and faecal incontinence. The condition must be treated as an emergency and usually requires surgical decompression of the injured nerves.

Disk herniation, the second most frequent adverse event, is an interesting complication of SMT. Most therapists using SMT would probably claim (no, I have no reference for that speculation!) that they can effectively treat herniated disks with SMT. The evidence for this claim is, as far as I know, non-existent. In view of the fact that SMT can actually cause a disk to herniate, I wonder whether SMT should not be contra-indicated for this condition. I am sure there will be some discussion about this question following this post.

The authors make a strong point about the fact that case reports never allow causal inference. One can only agree with this notion. However, the precautionary principle in medicine also means that, if case reports provide reasonable suspicion that an intervention might led to adverse-effects, we need to be careful and should warn patients of this possibility. It also means that it is up to the users of SMT to demonstrate beyond reasonable doubt that SMT is safe.

Neck pain is a common problem which is often far from easy to treat. Numerous therapies are being promoted but few are supported by good evidence. Could yoga be the solution?

The aim of a brand-new RCT was to evaluate the effectiveness of Iyengar yoga for chronic non-specific neck pain. Patients were randomly assigned to either yoga or exercise. The yoga group attended a 9-week yoga course, while the exercise group received a self-care manual on home-based exercises for neck pain. The primary outcome measure was neck pain. Secondary outcome measures included functional disability, pain at motion, health-related quality of life, cervical range of motion, proprioceptive acuity, and pressure pain threshold. Fifty-one patients participated in the study: yoga (n = 25), exercise (n = 26). At the end of the treatment phase, patients in the yoga group reported significantly less neck pain compared as well as less disability and better mental quality of life compared with the exercise group. Range of motion and proprioceptive acuity were improved and the pressure pain threshold was elevated in the yoga group.

The authors draw the following conclusion: “Yoga was more effective in relieving chronic nonspecific neck pain than a home-based exercise program. Yoga reduced neck pain intensity and disability and improved health-related quality of life. Moreover, yoga seems to influence the functional status of neck muscles, as indicated by improvement of physiological measures of neck pain.”

I’d love to agree with the authors and would be more than delighted, if an effective treatment for neck pain had been identified. Yoga is fairly safe and inexpensive; it promotes a generally healthy life-style, and is attractive to many patients; it has thus the potential to help thousands of suffering individuals. However, I fear that things might not be quite as rosy as the authors of this trial seem to believe.

The principle of an RCT essentially is that two groups of patients receive two different therapies and that any difference in outcome after the treatment phase is attributable to the therapy in question. Unfortunately, this is not the case here. One does not need to be an expert in critical thinking to realise that, in the present study, the positive outcome might be unrelated to yoga. For instance, it could be that the unsupervised home exercises were carried out wrongly and thus made the neck pain worse. In this case, the difference between the two treatment groups might not have been caused by yoga at all. A second possibility is that the yoga-group benefited not from the yoga itself but from the attention given to these patients which the exercise-group did not have. A third explanation could be that the yoga teachers were very kind to their patients, and that the patients returned their kindness by pretending to have less symptoms or exaggerating their improvements. In my view the most likely cause of the results seen in this study is a complex mixture of all the options just mentioned.

This study thus teaches us two valuable lessons: 1) whenever possible, RCTs should be designed such that a clear attribution of cause and effect is possible, once the results are on the table; 2) if cause and effect cannot be clearly defined, it is unwise to draw conclusions that are definite and have the potential to mislead the public.

In the UK, we have about 150000 practitioners of Spiritual Healing (SH). They treat all sorts of conditions claiming to channel ‘healing energy’ into the patient’s body which enables him/her to heal itself. The plausibility of SH is very close to zero and, despite numerous trials, its clinical effectiveness remains unproven. A new and, in my view, remarkable study of SH was aimed at investigating whether “SH could support patients with breast cancer”.

Spiritual Healing was provided by 4 healers registered with the National Federation of Spiritual Healers. Twelve patients with breast cancer undergoing long-term hormone treatment and experiencing its adverse-effects as onerous, self-referred themselves and were given ten weekly sessions of approximately 40 minutes each. Data collected included participant’s daily records, direct observations noted by the healers, the researcher’s field diary and a one-to-one semi-structured interview.

The alleged positive effects of SH included alleviation of the physical adverse-effects of their treatment, increased energy levels, enhanced well-being, emotional relaxation, and re-engagement with pre-cancer activities. Although one participant admitted considering a drug holiday prior to joining the study, none of the participants felt tempted to stop their hormonal treatments while receiving SH. The authors concluded that “these qualitative findings indicate that SH has the potential to support patients with breast cancer in the maintenance of their long-term orthodox treatments. Further research is needed to test SH as a cost-effective complementary therapy, for those undergoing long-term cancer treatments.”

As I already mentioned, I think this study is remarkable. Having done quite a bit of research into SH myself, I know how bizarre this intervention truly is. A typical treatment session might be with the patient lying on a couch in a relaxing atmosphere, often accompanied by soothing background music; the healer would talk gently but very little to enable the patient to be comfortable and relax; the SH itself might be performed by the healer moving his/her hands at a distance over the body of the patient; the healer would explain that this may cause the sensation of warmth as the ‘healing energy’ enters the body. Altogether, the experience is exotic to say the least.

It is therefore not surprising that SH generates a host of non-specific effects, including the most enormous placebo-response I have ever witnessed in any clinical trial which I have been involved in. I am mentioning this, of course, to point out that the above-noted effects are entirely compatible with those of placebo. As the study has no control group, there is no way of knowing what the effects of SH per se might have been. The fact that patients self-referred themselves to SH would only amplify this placebo-response. In the discussion of the paper, we find a further interesting pointer regarding patients’ prior experience with conventional health care professionals: “participants felt they were left to cope alone as their side-effects were trivialized.”  This seems to suggest that the group of patients were indeed highly selected and all had suffered badly from previous experiences of poorly administered heath care. Thus their expectations of SH were probably high which, in turn, would exaggerate the placebo-response even further.

All of these phenomena might well be fascinating and could provide ample material for relevant research. They deserve to be analysed carefully and discussed openly and critically. Unfortunately none of this happened in the present study. The authors do not even consider the possibility that the observed effects could be related to anything else than their SH. Their stated aim to investigate whether SH supports cancer patients is not even approached; the authors simply assume a cause-effect relationship without demonstrating one. I find this is more than just a missed opportunity; in my view, it is pseudo-science. And this is the reason why I find this study remarkable.

Many cancer patients use some form of complementary and alternative medicine (CAM), mostly as an adjunct to conventional cancer therapies to improve the symptoms of the disease or to alleviate the side-effects of the often harsh cancer-therapy. The hope is that this approach leads to less suffering and perhaps even longer survival – but is this really so?

In a recently published study, Korean researchers evaluated whether CAM-use influenced the survival and health-related quality of life (HRQOL) of terminal cancer patients. From July 2005 to October 2006, they prospectively studied a cohort study of 481 cancer patients. During a follow-up of 163.8 person-years, they identified 466 deceased patients. Their multivariate analyses of these data showed that, compared with non-users, CAM-users did not have better survival. Using mind-body interventions or prayer was even associated with significantly worse survival. CAM users reported significantly worse cognitive functioning and more fatigue than nonusers. In sub-group analyses, users of alternative medical treatments, prayer, vitamin supplements, mushrooms, or rice and cereal reported significantly worse HRQOL. The authors conclude that “CAM did not provide any definite survival benefit, CAM users reported clinically significant worse HRQOLs.”

Most proponents of CAM would find this result counter-intuitive and might think it is a one-off coincidental result or a fluke. But, in fact, it is not; similar data have been reported before. For instance, a Norwegian study from 2003 examined the association between CAM-use and cancer survival. Survival data were obtained with a follow-up of 8 years for 515 cancer patients. A total of 112 patients used CAM. During the follow-up period, 350 patients died. Death rates were higher in CAM-users (79%) than in those who did not use CAM (65%). The hazard ratio of death for CAM-use compared with no use was 1.30. The authors of this paper concluded that “use of CAM seems to predict a shorter survival from cancer.”

I imagine that, had the results been the opposite (i.e. showing that CAM-users live longer and have a better quality of life), most CAM-enthusiasts would not have hesitated in claiming a cause effect relationship (i.e. that the result was due to the use of alternative medicine). Critical thinkers, however, are more careful, after all, correlation is not causation! So, how can these findings be explained?

There are, of course, several possibilities, for example:

1) Some patients might use ineffective alternative therapies instead of effective cancer treatments thus shortening their life and reducing their quality of life.

2) Other patients might employ alternative treatments which cause direct harm; for this, there are numerous options; for instance, if they self-medicate St John’s Wort, they would decrease the effectiveness of many mainstream medications, including some cancer drugs.

3) Patients who elect to use alternative medicine as an adjunct to their conventional cancer treatment might, on average, be more sick than those who stay clear of alternative medicine.

The available data do not allow us to say which explanation applies. But things are rarely black or white, and I would not be surprised, if a complex combination of all three possibilities came closest to the truth.

Whenever I have the occasion to discuss with  practitioners of alternative medicine the pros and cons of their methods, I hear sooner or later the argument “WE TREAT THE ROOT CAUSES OF DISEASE !!!” This remark emerges regularly regardless of the type of treatment the practitioner uses, and regardless of what disease we might have been talking about.

The statement is regularly pronounced with such deep conviction (and almost audible exclamation marks) that I am inclined to conclude these practitioners fully and wholeheartedly believe it. The implication usually is that, in conventional medicine, we only treat the symptoms of our patients. Quite often, this latter notion is not just gently implied but also forcefully expressed.

I have often wondered where this assumption and the fierce conviction with which it is expressed come from. The answer, I have come to conclude after many years of having such debates, is quite simple: it is being taught over and over again during the practitioners’ training, and it constitutes a central message of most ‘textbooks’ for the aspiring alternative practitioner.

It is not difficult to find the actual origin of all this. The notion that alternative practitioners treat the root causes is clearly based on the practitioners’ understanding of aetiology. If a traditional acupuncturist, for instance, becomes convinced that all disease is the expression of an imbalance of life-forces, and that needling acupuncture points will re-balance these forces thus restoring health, he must automatically assume that he is treating the root causes of any condition. If a chiropractor believes that all diseases  are due to ‘subluxations’ of the spine, it must seem logical to him that spinal ‘adjustment’ is synonymous with treating the root cause of whatever complaint his patient is suffering from. If a Bowen therapist is convinced that “the Bowen Technique aims to balance the whole person, not just the symptoms“, he is bound to be equally sure that “practically any problem can potentially be addressed” by this intervention.

Let us assume for a minute that all these practitioners are correct in believing that their interventions are causal treatments, i.e. therapies directed against the cause of a disease. Successful treatment of any root cause can only mean that the therapy in question completely  heals the problem at hand. If we abolish the cause of a disease, we would expect the disease to disappear for good.

This, I think, begs a crucial question: ARE THERE ANY DISEASES WHICH ARE REPRODUCIBLY CURED BY AN ALTERNATIVE THERAPY?

I have contemplated it frequently and discussed it often with practitioners but, so far, I have not identified a single one.  I have no problem naming diseases which conventional medicine can cure – but, in alternative medicine, I only draw blanks. Even those alternative therapies which might be effective are not causal but symptomatic by nature. Honestly, I have not yet come across a single alternative treatment for which there is compelling evidence proving that it can produce more than symptom-relief.

But, of course, I might be wrong, over-critical, blind, bought by the pharmaeutical industry, dishonest or stupid. So, the purpose of this post is to clarify this issue once and for all. I herewith invite practitioners to name a disease for which there is sound evidence proving that it can be cured by their therapy.

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