MD, PhD, FMedSci, FSB, FRCP, FRCPEd

guideline

One of the questions I hear frequently is ‘HOW CAN I BE SURE THIS STUDY IS SOUND’? Even though I have spent much of my professional life on this issue, I am invariably struggling to provide an answer. Firstly, because a comprehensive reply must inevitably have the size of a book, perhaps even several books. And secondly, to most lay people, the reply would be intensely boring, I am afraid.

Yet many readers of this blog evidently search for some guidance – so, let me try to provide a few indicators – indicators, not more!!! – as to what might signify a good and a poor clinical trial (other types of research would need different criteria).

INDICATORS SUGGESTIVE OF A GOOD CLINICAL TRIAL

  • Author from a respected institution.
  • Article published in a respected journal.
  • A clear research question.
  • Full description of the methods used such that an independent researcher could repeat the study.
  • Randomisation of study participants into experimental and control groups.
  • Use of a placebo in the control group where possible.
  • Blinding of patients.
  • Blinding of investigators, including clinicians administering the treatments.
  • Clear definition of a primary outcome measure.
  • Sufficiently large sample size demonstrated with a power calculation.
  • Adequate statistical analyses.
  • Clear presentation of the data such that an independent assessor can check them.
  • Understandable write-up of the entire study.
  • A discussion that puts the study into the context of all the important previous work in this area.
  • Self-critical analysis of the study design, conduct and interpretation of the results.
  • Cautious conclusion which are strictly based on the data presented.
  • Full disclosure of ethics approval and informed consent,
  • Full disclosure of funding sources.
  • Full disclosure of conflicts of interest.
  • List of references is up-to-date and includes also studies that contradict the authors’ findings.

I told you this would be boring! Not only that, but each bullet point is far too short to make real sense, and any full explanation would be even more boring to a lay person, I am sure.

What might be a little more fun is to list features of a clinical trial that might signify a poor study. So, let’s try that.

WARNIG SIGNALS INDICATING A POOR CLINICAL TRIAL

  • published in one of the many dodgy CAM journals (or in a book, blog or similar),
  • single author,
  • authors are known to be proponents of the treatment tested,
  • author has previously published only positive studies of the therapy in question (or member of my ‘ALT MED HALL OF FAME’),
  • lack of plausible rationale for the study,
  • lack of plausible rationale for the therapy that is being tested,
  • stated aim of the study is ‘to demonstrate the effectiveness of…’ (clinical trials are for testing, not demonstrating effectiveness or efficacy),
  • stated aim ‘to establish the effectiveness AND SAFETY of…’ (even large trials are usually far too small for establishing the safety of an intervention),
  • text full of mistakes, e. g. spelling, grammar, etc.
  • sample size is tiny,
  • pilot study reporting anything other than the feasibility of a definitive trial,
  • methods not described in sufficient detail,
  • mismatch between aim, method, and conclusions of the study,
  • results presented only as a graph (rather than figures which others can re-calculate),
  • statistical approach inadequate or not sufficiently detailed,
  • discussion without critical input,
  • lack of disclosures of ethics, funding or conflicts of interest,
  • conclusions which are not based on the results.

The problem here (as above) is that one would need to write at least an entire chapter on each point to render it comprehensible. Without further detailed explanations, the issues raised remain rather abstract or nebulous. Another problem is that both of the above lists are, of course, far from complete; they are merely an expression of my own experience in assessing clinical trials.

Despite these caveats, I hope that those readers who are not complete novices to the critical evaluation of clinical trials might be able to use my ‘warning signals’ as a form of check list that helps them to tell the chaff from the wheat.

On this blog, I have repeatedly pleaded for a change of the 2010 NICE guidelines for low back pain (LBP). My reason was that it had become quite clear that their recommendation to use spinal manipulation and acupuncture for recurrent LBP was no longer supported by sound evidence.

Two years ago, a systematic review (authored by a chiropractor and published in a chiro-journal) concluded that “there is no conclusive evidence that clearly favours spinal manipulation or exercise as more effective in treatment of CLBP.” A the time, I wrote a blog explaining that “whenever two treatments are equally effective (or, in this case, perhaps equally ineffective?), we must consider other important criteria such as safety and cost. Regular chiropractic care (chiropractors use spinal manipulation on almost every patient, while osteopaths and physiotherapists employ it less frequently)  is neither cheap nor free of serious adverse effects such as strokes; regular exercise has none of these disadvantages. In view of these undeniable facts, it is hard not to come up with anything other than the following recommendation: until new and compelling evidence becomes available, exercise ought to be preferred over spinal manipulation as a treatment of chronic LBP – and consequently consulting a chiropractor should not be the first choice for chronic LBP patients.”

Three years ago, a systematic review of acupuncture for LBP (published in a TCM-journal) concluded that the effect of acupuncture “is likely to be produced by the nonspecific effects of manipulation.” At that time I concluded my blog-post with this question: Should NICE be recommending placebo-treatments and have the tax payer foot the bill? Now NICE have provided an answer.

The new draft guideline by NICE recommends various forms of exercise as the first step in managing low back pain. Massage and manipulation by a physiotherapist should only be used alongside exercise; there is not enough evidence to show they are of benefit when used alone. Moreover, patients should be encouraged to continue with normal activities as far as possible. Crucially, the draft guideline no longer recommends acupuncture for treating low back pain.

NICE concluded that the evidence shows that acupuncture is not better than sham treatment. Paracetamol on its own is no longer recommended either, instead non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or aspirin should be tried first. Talking therapies are recommended in combination with physical therapies for patients who had no improvement on previous treatments or who have significant psychological and social barriers to recovery.

Professor Mark Baker, clinical practice director for NICE, was quoted stating “Regrettably there is a lack of convincing evidence of effectiveness for some widely used treatments. For example acupuncture is no longer recommended for managing low back pain with or without sciatica. This is because there is not enough evidence to show that it is more effective than sham treatment.”

Good news for us all, I would say:

  • good news for patients who now hear from an accepted authority what to do when they suffer from LBP,
  • good news for society who does no longer need to spend vast amounts of money on questionable therapies,
  • good news for responsible clinicians who now have clear guidance which they can show and explain to their patients.

Not so good news, I admit, for acupuncturists, chiropractors and osteopaths who just had a major source of their income scrapped. I have tried to find some first reactions from these groups but, for the moment, they seemed to be stunned into silence – nobody seems to have yet objected to the new guideline. Instead, I found a very recent website where chiropractic is not just recommended for LBP therapy but where patients are instructed that, even in the absence of pain, they need to see their chiropractor regularly: “Maintenance chiropractic care is well supported in studies for controlling chronic LBP.”

NEVER LET THE TRUTH GET IN THE WAY OF YOUR CASH-FLOW…they seem to conclude.

Chiropractors are notorious for their overuse and misuse of x-rays for non-specific back and neck pain as well as other conditions. A recent study from the US has shown that the rate of spine radiographs within 5 days of an initial patient visit to a chiropractor is 204 per 1000 new patient examinations. Considering that X-rays are not usually necessary for patients with non-specific back pain, such rates are far too high. Therefore, a team of US/Canadian researchers conducted a study to evaluate the impact of web-based dissemination of a diagnostic imaging guideline discouraging the use of spine x-rays among chiropractors.

They disseminated an imaging guideline online in April 2008. Administrative claims data were extracted between January 2006 and December 2010. Segmented regression analysis with autoregressive error was used to estimate the impact of guideline recommendations on the rate of spine x-rays. Sensitivity analysis considered the effect of two additional quality improvement strategies, a policy change and an education intervention.

The results show a significant change in the level of spine x-ray ordering weeks after introduction of the guidelines (-0.01; 95% confidence interval=-0.01, -0.002; p=.01), but no change in trend of the regression lines. The monthly mean rate of spine x-rays within 5 days of initial visit per new patient exams decreased by 10 per 1000, a 5.26% relative decrease after guideline dissemination.

The authors concluded that Web-based guideline dissemination was associated with an immediate reduction in spine x-ray claims. Sensitivity analysis suggests our results are robust. This passive strategy is likely cost-effective in a chiropractic network setting.

These findings are encouraging because they suggest that at least some chiropractors are capable of learning, even if this means altering their practice against their financial interests – after all, there is money to be earned with x-ray investigations! At the same time, the results indicate that, despite sound evidence, chiropractors still order far too many x-rays for non-specific back pain. I am not aware of any recent UK data on chiropractic x-ray usage, but judging from old evidence, it might be very high.

It would be interesting to know why chiropractors order spinal x-rays for patients with non-specific back pain or other conditions. A likely answer is that they need them for the diagnosis of spinal ‘subluxations’. To cite just one of thousands of chiropractors with the same opinion: spinography is a necessary part of the chiropractic examination. Detailed analysis of spinographic film and motion x-ray studies helps facilitate a specific and timely correction of vertebral subluxation by the Doctor of Chiropractic. The correction of a vertebral subluxation is called: Adjustment.

This, of course, merely highlights the futility of this practice: despite the fact that the concept is still deeply engrained in the teaching of chiropractic, ‘subluxation’ is a mystical entity or dogma which “is similar to the Santa Claus construct”, characterised by a “significant lack of evidence to fulfil the basic criteria of causation”. But even if chiropractic ‘subluxation’ were real, it would not be diagnosable with spinal x-ray investigations.

The inescapable conclusion from all this, I believe, is that the sooner chiropractors abandon their over-use of x-ray studies, the better for us all.

One of the questions I hear regularly is ‘HOW DO THE EFFECTS OF THIS ALTERNATIVE TREATMENT COMPARE TO THOSE OF CONVENTIONAL OPTIONS’? Take acupuncture in the management of osteoarthritis, for instance. There is some encouraging evidence suggesting it might help. The most recent systematic review that I know of concluded that “acupuncture provided significantly better relief from knee osteoarthritis pain and a larger improvement in function than sham acupuncture, standard care treatment, or waiting for further treatment.” However, in order to estimate its value in practice, we ought to know whether it is as good as or perhaps even better than standard treatments. In other words, what we really want to know is its relative effectiveness.

Data to evaluate the relative effectiveness of acupuncture or other alternative therapies are hard to come by. Ideally, one would require clinical trials which provide direct comparisons between the alternative and the conventional therapy. Sadly, such studies are scarce or even non-existent. Therefore we might have to rely on more indirect evidence. A new paper could be a step in the right direction.

The aim of this systematic review was to critically evaluate existing osteoarthritis (OA) management guidelines to better understand potential issues and barriers.

A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, two authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality; three generated summary recommendations based on the extracted guideline data.

Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol for first line treatment and oral or topical NSAIDs for second line therapy. Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin.

I think that this tells us fairly clearly that, compared to other options, acupuncture is not considered to be an overwhelmingly effective treatment for osteoarthritis by those who understand that condition best. Several other therapies seem to be preferable because the evidence is clearer and stronger and their effect sizes is larger. This, I think begs the question whether it is in the best interest of patients or indeed ethical to ignore this knowledge and recommend acupuncture as a treatment of osteoarthritis.

More generally speaking, we should always bear in mind that it is not enough proving a therapy to be effective; we usually also need to consider what else is on offer. And if you think that this is rather complex, you are, of course, correct – but wait until someone mentions issues such as safety and cost of all the relevant therapeutic options.

Some national and international guidelines advise physicians to use spinal manipulation for patients suffering from acute (and chronic) low back pain. Many experts have been concerned about the validity of this advice. Now an up-date of the Cochrane review on this subject seems to provide clarity on this rather important matter.

Its aim was to assess the effectiveness of spinal manipulative therapy (SMT) as a treatment of acute low back pain. Randomized controlled trials (RCTs) testing manipulation/mobilization in adults with  low back pain of less than 6-weeks duration were included. The primary outcome measures were pain, functional status and perceived recovery. Secondary endpoints were return-to-work and quality of life. Two authors independently conducted the study selection, risk of bias assessment and data extraction. The effects were examined for SMT versus  inert interventions, sham SMT,  other interventions, and for SMT as an adjunct to other forms of treatment.

The researchers identified 20 RCTs with a total number of 2674 participants, 12 (60%) RCTs had not been included in the previous version of this review. Only 6 of the 20 studies had a low risk of bias. For pain and functional status, there was low- to very low-quality evidence suggesting no difference in effectiveness of SMT compared with inert interventions, sham SMT or as adjunct therapy. There was varying quality of evidence suggesting no difference in effectiveness of SMT compared with other interventions. Data were sparse for recovery, return-to-work, quality of life, and costs of care.

The authors draw the following conclusion: “SMT is no more effective for acute low back pain than inert interventions, sham SMT or as adjunct therapy. SMT also seems to be no better than other recommended therapies. Our evaluation is limited by the few numbers of studies; therefore, future research is likely to have an important impact on these estimates. Future RCTs should examine specific subgroups and include an economic evaluation.”

In other words, guidelines that recommend SMT for acute low back pain are not based on the current best evidence. But perhaps the situation is different for chronic low back pain? The current Cochrane review of 26 RCTs is equally negative: “High quality evidence suggests that there is no clinically relevant difference between SMT and other interventions for reducing pain and improving function in patients with chronic low-back pain. Determining cost-effectiveness of care has high priority. Further research is likely to have an important impact on our confidence in the estimate of effect in relation to inert interventions and sham SMT, and data related to recovery.”

This clearly begs the question why many of the current guidelines seem to mislead us. I am not sure I know the answer to this one; however I suspect that the panels writing the guidelines might have been dominated by chiropractors and osteopaths or their supporters who have not exactly made a name for themselves for being impartial. Whatever the reason, I think it is time for a re-think and for up-dating guidelines which are out of date and misleading.

Similarly, it might be time to question for what conditions chiropractors and osteopaths, the two professions who use spinal manipulation/mobilisation most, do actually offer anything of real value at all. Back pain and SMT are clearly their domains; if it turns out that SMT is not evidence-based for back pain, what is left? There is no good evidence for anything else, as far as I can see. To make matters worse, there are quite undeniable risks associated with SMT. The conclusion of such considerations is, I fear, obvious: the value of and need for these two professions should be re-assessed.

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