This blog was first published on 30th Novenber 2016 on https://blogs.bmj.com/aim/

When the draft clinical guideline for low back pain & sciatica was published in February 2016, it was with some resignation that I noted the 2009 recommendation in CG88 for acupuncture in low back pain (from 6 weeks to 1 year)[1] had been dropped. It was expected for a variety of off-radar reasons, from pre-guideline social media comments of anti-CAM Guideline Development Group (GDG) members to the professional activities and commercial interests of the GDG chair.

The 2009 guideline (CG88)[1] had a different scope from NG59,[2] the chair was an academic GP, and the vice chair was the president of the British Pain Society (BPS) and a professor of physiotherapy – the first president of the BPS who was not an anaesthetist. CG88 caused significant concern amongst the interventionist anaesthetists in the BPS because there was a recommendation to avoid spinal injections and positive recommendations for more conservative approaches: specifically exercise, spinal manipulation and acupuncture. The chair of the current guideline (NG59) is an interventionist. He did not call for an extraordinary general meeting of the BPS and a vote of no confidence in the president, but other interventionists did. Senior members of the BPS told me at the time of their embarrassment over this situation. Move on 3 years and we have an interventionist chair of NG59, and a recommendation for the interventionalists’ bread and butter procedure – radiofrequency denervation (RFD). Something that Cochrane suggests has no high quality evidence in chronic low back pain.[3] A coincidence perhaps… I will let the reader judge as the history unfolds.

Closer inspection of the draft guideline revealed that the situation for acupuncture was not as cut & dried as I had first thought. The evidence for acupuncture, examined in isolation, held no surprises. A clear statistical effect over sham in pain and functional outcomes, but the size of the benefit over sham (active sub-optimal needling) that did not meet the predefined required clinical relevance (in this case, for pain, 10mm on a 100mm VAS score). [I have always been puzzled by the nonsense of assessing clinical relevance over an active sham comparator (favoured by NICE) rather than usual care or the best current treatment available.]

The reason it did not appear so cut & dried this time was that very little else that was recommended (mostly conventional approaches) seemed to meet the requirements that were articulated for acupuncture (hence “Too NICE” in the title). Most notable was exercise and manual therapies. Not only did these interventions fail to show any clinically relevant benefit over shams, but exercise failed to show any benefit at all over sham. In the final guideline this has been managed by excluding the only sham controlled trial of exercise.[4] The explanation given was that the GDG decided that the sham exercises in question were not valid forms of sham exercise. Terribly convenient you might think, or you might agree with the GDG, it is difficult to conceive of what sham exercise might look like. Oh but wait a minute! What about sham acupuncture? It is equally difficult to conceive of a sham for acupuncture from a mechanistic neurophysiological (ie scientific) perspective.[5] Surely you just have to blind the patient? Since they are measuring the primary outcome in most trials of pain conditions. Or you just have to miss the point [;-) irony].[6] Modern explanations for the mechanisms of acupuncture clearly indicate that it is impossible to miss the point, as all target tissues are innervated, and can be stimulated with a needle. What about the non-penetrating needles? [You might cry]. Well in my first attempt using these for real I caused more pain and bleeding than with the real needles!

We are given a clue that sham acupuncture is an active intervention by the results of large three-armed clinical trials including a sham arm and a conventional care arm.[7] In back pain sham was 50% better than guideline based conventional care,[8] and in a large network meta-analysis sham acupuncture was significantly better than conventional care for chronic headache prophylaxis.[9] It seems strange then to be reminded that in CG150 we were told that topiramate was twice as good as acupuncture,[10] yet the data suggested that sham acupuncture exceeded the effect of the drug.[11] Now the biggest data set has confirmed this superiority of sham acupuncture.[9]

Now that we have this very large data set that has been subject to network meta-analysis,[9] we see that sham acupuncture consistently outperforms usual care (a mixture of trials including routine care and guideline-based conventional care comparators) in terms of health-related quality of life (HRQoL) – the outcome held up as most important to NG59’s GDG.

So in low back pain acupuncture outperforms an active sham comparator with a greater margin than any of the interventions recommended in NG59, but it is not recommended on the basis that the benefits may all be explained by context effects. This is because the effect beyond sham is not large, but I have already argued that sham acupuncture is better than conventional care comparators. Acupuncture is clearly disadvantaged by the standard NICE approach of looking only at its effect compared to an active sham, rather than comparisons with existing conventional interventions, and its insistence that all shams and placebos are equal – this is clearly wrong,[11,12] and I call on NICE to reconsider this assumption as a matter of urgency.

Medicine in the UK is facing a massive challenge through changing demographics (an aging population), chronic disease burden (musculoskeletal, metabolic & neurological) and relative underfunding. In this environment should we not be seeking low cost effective treatments, rather than expensive patented devices and products? It doesn’t seem as if our system has the right balance. The rigour applied to acupuncture is laudable, but only if the same rigour is equally applied to conventional interventions and particularly those that have strong commercial backing… but this does not seem to be the case.

In 2010 NICE approved a treatment for overactive bladder called posterior tibial nerve stimulation (PTNS).[13] PTNS has been set within the field of neuromodulation, and the majority of papers make no mention of acupuncture, yet the technique is performed with an acupuncture needle in a location frequently used by acupuncturists. The technique is effectively electroacupuncture to the S2 myotome in the leg, and it does work in overactive bladder. There is one large sham controlled trial of the technique,[14] and rather like some acupuncture trials it used the Streitberger placebo needle in the sham stimulation group. There was a clear statistical benefit for real PTNS over sham, and the paper displays impressive results in terms of responder rates; however, the effect size of changes in symptom severity scores and symptom diaries are well below a standardised mean difference (SMD) of 0.5 for every measure. The minimum important difference applied to acupuncture in CG177 was 0.5 SMD.[15] If PTNS was actually described as electroacupuncture to SP6 or KI7, would it have got the same treatment from NICE?

Subsequently, PTNS has been approved for faecal incontinence.[16] The evidence was based on a small non-randomised sham controlled trial, in which there was no effect in the sham group. The latter is unheard of in acupuncture research. A large prospective randomised clinical trial of PTNS in faecal incontinence recorded a responder rate of 31% in the sham group,[17] and this trial failed to demonstrate a significant benefit for real PTNS over the sham. I wonder if this patented intervention will survive in the eyes of NICE? If it is dealt with in the same way as acupuncture, it will surely not survive, but then it would never have been recommended in the first place of course.

Another patented device in the field of neuromodulation has been tentatively given a nod by NICE recently. It claims to stimulate the cervical branch of the vagus via surface stimulation.[18] But rather than stimulate skin innervated by the vagus nerve within the concha of the pinna, this device is held over the front of the neck, from where it is impossible to stimulate vagal afferents without picking up motor fibres in laryngeal nerves from the vagus. This would result in closure of the glottis (ie inability to breathe during stimulation – not ideal!). Anyway, the illogical premise of the device is not the point, it is the fact that it has been approved for further use and evaluation on the basis of a couple of small open trials in which the control group received no treatment. NICE have never approved acupuncture on the basis of such comparisons. The playing field is not level here, and medicine is becoming ever more expensive as a result…

A more worrying part of this picture is that the devices designed for these forms of neuromodulation (both PTNS and transcutaneous ‘vagal nerve’ stimulation) are created with an unnecessarily limited lifespan. The lead used for PTNS from one provider that supplies the NHS in England is a single use lead that costs over £30. The lead will only function for one treatment. Virtually identical electroacupuncture leads cost a few pounds and can last for years. A transcutaneous ‘vagal nerve’ stimulator called gammaCore is designed for home use by patients, but will only last for a limited number of uses and costs from around £150 for 50 episodes of use.

This is a call to us all in medicine to wake up and stop spending excessive funds on expensive patented drugs and devices that have not been shown to outperform simple cheap alternatives such as acupuncture that are easily taught to health professionals and have a very low inherent cost.

References

1. NICE guideline on low back pain: early management of persistent non-specific low back pain. http://guidance.nice.org.uk/CG88. 2009.
2. Low back pain and sciatica in over 16s: assessment and management. https://www.nice.org.uk/guidance/ng59. 2016.
3. Maas ET, Ostelo RWJG, Niemisto L, et al. Radiofrequency denervation for chronic low back pain. Cochrane database Syst Rev 2015;:CD008572. doi:10.1002/14651858.CD008572.pub2
4. Albert HB, Manniche C. The Efficacy of Systematic Active Conservative Treatment for Patients With Severe Sciatica. Spine (Phila Pa 1976) 2012;37:531–42. doi:10.1097/BRS.0b013e31821ace7f
5. White AR, Filshie J, Cummings TM, et al. Clinical trials of acupuncture: consensus recommendations for optimal treatment, sham controls and blinding. Complement Ther Med 2001;9:237–45.
6. Cummings M. Commentary: Controls for acupuncture – can we finally see the light? BMJ 2001;322:1578.PM:11431299
7. Cummings M. Modellvorhaben Akupunktur–a summary of the ART, ARC and GERAC trials. Acupunct Med 2009;27:26–30. doi:10.1136/aim.2008.000281
8. Haake M, Müller H-H, Schade-Brittinger C, et al. German Acupuncture Trials (GERAC) for chronic low back pain: randomized, multicenter, blinded, parallel-group trial with 3 groups. Arch Intern Med 2007;167:1892–8. doi:10.1001/archinte.167.17.1892
9. Saramago P, Woods B, Weatherly H, et al. Methods for network meta-analysis of continuous outcomes using individual patient data: a case study in acupuncture for chronic pain. BMC Med Res Methodol 2016;16:131. doi:10.1186/s12874-016-0224-1
10. NICE guideline on headaches: diagnosis and management of headaches in young people and adults. http://guidance.nice.org.uk/CG150. 2012.
11. White A, Cummings M. Inconsistent placebo effects in NICE’s network analysis. Acupunct Med 2012;30:364–5. doi:10.1136/acupmed-2012-010262
12. Meissner K, Fässler M, Rücker G, et al. Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis. JAMA Intern Med 2013;173:1941–51. doi:10.1001/jamainternmed.2013.10391
13. Percutaneous posterior tibial nerve stimulation for overactive bladder syndrome Interventional procedures guidance [IPG362]. https://www.nice.org.uk/guidance/IPG362. 2010.
14. Peters KM, Carrico DJ, Perez-Marrero R a, et al. Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Sham Efficacy in the Treatment of Overactive Bladder Syndrome: Results From the SUmiT Trial. J Urol 2010;183:1438–43. doi:10.1016/j.juro.2009.12.036
15. NICE guideline update on osteoarthritis: the care and management of osteoarthritis in adults. http://guidance.nice.org.uk/CG177. 2014.
16. Percutaneous tibial nerve stimulation for faecal incontinence Interventional procedures guidance [IPG395]. https://www.nice.org.uk/guidance/ipg395. 2011.
17. Knowles CH, Horrocks EJ, Bremner SA, et al. Percutaneous tibial nerve stimulation versus sham electrical stimulation for the treatment of faecal incontinence in adults (CONFIDeNT): a double-blind, multicentre, pragmatic, parallel-group, randomised controlled trial. Lancet (London, England) 2015;386:1640–8. doi:10.1016/S0140-6736(15)60314-2
18. Transcutaneous stimulation of the cervical branch of the vagus nerve for cluster headache and migraine. https://www.nice.org.uk/guidance/ipg552. 2016.

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Declaration of interests MC

This blog was first published on 4th April 2016 on https://blogs.bmj.com/aim/

Further commentary:
Low back pain and sciatica: management of non-specific low back pain and sciatica
Draft clinical guideline February 2016

This commentary follows a previous blog post.

Late last Friday night I got around to dropping the pain VAS outcome figures from the trials of acupuncture versus sham into RevMan 5 – the software used for Cochrane Reviews. I was surprised to find that the high I² value for the short-term outcome in the draft guideline did not drop substantially with the corrected data (incidentally there were errors in the data from both Brinkhaus and Leibing). Here is the corrected forest plot to replace Figure 667 [Appendix K, p 153].

The total mean difference in pain now reaches clinical significance, and remember that is the difference over gentle needling, not an inactive placebo intervention. However, the heterogeneity remains unexpectedly high. The outlier now is Haake. This was a huge multicentre trial with some 300 different centres, where the participant clinicians did not meet for instruction on intervention procedures, as the 26 in Brinkhaus did. The primary outcome in Haake showed both real and sham acupuncture were twice as good as guideline based conventional care, so we might hypothesise that the sham was closer to real acupuncture than in Brinkhaus. Excluding Haake removes all heterogeneity.

So one large trial where we suspect substantial differences in the comparator (sham acupuncture) creates all the heterogeneity. But large trials are usually held out to be more statistically reliable, so there does remain some uncertainty in interpretation. I should point out that within RevMan the pain results for Haake are positive, so whether you think the sum of the smaller trials (n=610) or Haake (n=749) are more reliable, both demonstrate a biological effect of average acupuncture over gentle acupuncture.

Moving to the long term analysis (pain VAS >4 month), there was a data entry error here too. Hard to spot, but glaring when noticed – the pain VAS outcome for Leibing was a negative value! How can a pain score be negative? The negative figure is clearly a change value, not an absolute value of pain at the relevant time point (this is the same data entry error made for the Brinkhaus data). Here is the corrected Figure 668 [Appendix K, p 153].

Statistically positive and no heterogeneity, this represents a clear long term biological effect of average acupuncture over gentle acupuncture, although the difference is not in the range that would be regarded as clinically significant by NICE, if indeed you can judge clinical significance in an explanatory (sham controlled) model. The heterogeneity result seems to be explained by a reduction in the mean difference between acupuncture and sham in the smaller trials, and no change in that of Haake, so in effect the smaller trial results got closer to the results of Haake. In terms of absolute pain scores, it seems that, on average, the patients in Haake continued to improve, whereas those in the smaller trials deteriorated slightly.

In summary, whilst there remains some uncertainty about interpretation of the clinical relevance of this data, it is clear that average acupuncture is superior to gentle acupuncture for low back pain in both the short and long term outcomes, and this data is clearly more convincing than the equivalent data for either the exercise or the manual therapies recommended in the draft NICE guideline for low back pain.

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Declaration of interests MC

This blog was first published on 31st March 2016 on https://blogs.bmj.com/aim/

Commentary:
Low back pain and sciatica: management of non-specific low back pain and sciatica
Draft clinical guideline February 2016

NICE clinical guidelines are very large pieces of work. This draft runs to over 1000 pages with the addition of around 2500 pages of appendices, and data extracted and analysed from nearly 600 RCTs. Having sat on the guideline development group (GDG) meetings for CG88 I had a firsthand view of the size and difficulty of the task, and the GDG in this case is to be congratulated for their work in completing this draft.

In this discussion I will focus on a very small section, and highlight key data entry errors within the analysis. I hope that a careful reconsideration of the data may result in a positive recommendation for acupuncture in low back pain.

Acupuncture techniques have been used in the UK for at least 200 years, but their strongest association is with traditional East Asian medicine, and therefore they can seem conceptually alien to our contemporary scientific medicine. Whilst the GDG recognised the modern interpretation of acupuncture, and its scientific basis, under the heading of Western medical acupuncture (WMA), they went on to apply an additional requirement to acupuncture that apparently was not applied to similar interventions (exercise & manual therapies).

The GDG first discussed the necessity of a body of evidence to show specific intervention effects, that is, over and above any contextual or placebo effects. [draft 1, p 493]

So this involves a focus on sham controlled trials of acupuncture, which nearly always compare two forms of needling – a gentle superficial form at sites away from the most common points used (minimal or sham), and an average style of routine acupuncture usually at muscle level. The comparison of normal and sham acupuncture certainly excludes contextual and placebo effects, but it also excludes the effect of gentle needling, and therefore underestimates the whole effect attributable to needle acupuncture. Consequently it would be inequitable to place too strong a reliance on the clinical relevance of this difference, but appropriate to focus on this for biological plausibility of the technique, before moving on to consider more pragmatic comparisons with usual care.

For the purposes of this discussion I will focus on the sham-controlled evidence for exercise, manual therapies and acupuncture, and compare and contrast the strength of evidence and the subsequent recommendations.

Exercise was recommended, and the GDG commented:

The GDG noted that there was some evidence of benefit for all exercise types compared to sham, usual care or other active comparators,… [draft 1, p 303]

By contrast I could not find any evidence of an effect of exercise over sham. Indeed there were only two trials that included data. Appendix K p 60 shows a forest plot (Fig 219) with data from Albert 2012 – this plot seems to demonstrate an effect of exercise over sham for pain ≤4 months, but the data in this plot is different from that extracted from the paper and included in the table of Appendix H p 146. Indeed the original paper reports no difference between exercise and sham in the primary outcomes, and the responder rate was actually slightly greater for sham. Only secondary outcomes of neurological signs relevant to sciatica were in favour of exercise over sham.

The second paper with data relevant to the comparison of exercise over sham reported no significant benefit in terms of the only outcome reported – psychological distress. [Appendix K, p 70]

So there is no sham-controlled data supporting exercise interventions, yet the GDG made a positve recommendation. This positive recommendation was therefore based either on error from faulty data entry, or on low quality data that could have been entirely attributable to contextual effects, those that the GDG insisted on excluding when considering data on acupuncture.

Manual therapies were also recommended. Two small trials tested massage against sham, and there was a borderline effect over sham for pain <4 months – the lower 95% confidence interval (CI) crossed the line of no effect by 0.02. [Appendix K, p 115] Five trials (533 patients) were combined for manipulation over sham for pain ≤4 months. The mean difference in VAS (0-10) was -0.26, and the lower 95% confidence interval (CI) reached zero. [Appendix K, p 122] There were no long-term effects >4 months. This is very weak data on which to base a positive recommendation.

The meta-analysis of acupuncture over sham (minimal needling) for pain ≤4 months included a major data entry error. [Appendix K, p 153] Brinkhaus 2006 data was entered as values representing a decrease in pain score from baseline rather than as the absolute value after treatment. This error flipped the point estimate for the mean difference to the wrong side of the zero effect line ie favouring sham instead of acupuncture. This resulted in a reduction in the total effect size, and more importantly an erroneously high heterogeneity (I² = 76%). Both of these potentially resulted in a reduction in the ‘quality of evidence’ (GRADE) for this item, which was consequently presented as Low quality, rather than High or Moderate. It was this uncertainty that resulted in the GDG statement:

Heterogeneity was observed in the meta-analysis that was unexplained by pre-specified subgroup analysis of type of acupuncture or duration of pain. [draft 1, p 493]

Despite this error, the point estimate was -0.8, and the lower 95% CI was well clear of the zero effect line, resulting in a highly statistically significant result in favour of acupuncture over sham for pain ≤4 months. This analysis included 7 RCTs and a total of 1359 patients. Furthermore, the effect of acupuncture over sham in the long-term (>4 months) was also positive, with no heterogeneity, 4 RCTs and 1159 patients.

This data clearly demonstrates the biological plausibility of normal acupuncture over gentle needling. For clinically relevant effects we should look at the data compared with usual care. This analysis demonstrates clinically relevant effects for pain ≤4 months, but high heterogeneity. The latter is clearly related to the differences in the usual care comparisons in the larger trials: Brinkhaus 2006 used a waiting list control; and Haake 2007 used rather intensive guideline-based conventional care (physician visits, physiotherapy, NSAIDs). Despite this obvious clinical heterogeneity in the control groups, the GRADE category for quality was automatically reduced. The GDG stated that the benefits on pain were not sustained beyond 4 months; [draft 1, p 494] however, the forest plot for acupuncture compared with usual care for pain >4 months clearly demonstrates a statistically significant benefit. [Appendix K, p 159]

I note that the health economic data demonstrates a more favourable cost per quality adjusted life year (QALY) for acupuncture compared with the cost of either exercise or manual therapies. [Appendix I, p 29, p 18, p 27]

Taking all this together, I call for the GDG to look again at their data with the errors corrected, and invite them to consider a more equitable recommendation for acupuncture in low back pain.

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Declarations of interest MC