Inspired by Kong J-T et al 2020.
EA – electroacupuncturekey to acronyms
cLBP – chronic low back pain
PROMIS – patient reported outcome measurement information system
NIH – National Institute of Health (US)
RMDQ – Roland Morris disability questionnaire
QST – quantitative sensory testing
CSQ – coping strategy questionnaire
Jiang-Ti Kong is an academic anaesthetist from Stanford – you can read her bio here. She trained at Stanford and then spent some time in Harvard and got involved with some of the fMRI research there. Back in Stanford again, now as an academic, she has been focussing on chronic pain and sensory testing, as well as the effects of EA.
In my mind I had her name associated with imaging trials,[2,3] so when this paper popped up I was at first a bit surprised, so I tracked her down and her bio explained.
This is an interesting paper, and clearly a rather ambitious and expensive trial judging by all the fancy testing that went on. It took the team 2 years to get just over one hundred patients with cLBP through 12 sessions of real or sham EA – 121 randomised, 103 completed.
The primary outcome was pain intensity measured using the PROMIS pain intensity instrument (PPII) from the NIH. But this seems to have changed quite dramatically since first being described, and necessitated at protocol revision. A secondary outcome was the RMDQ.[5,6] As well as these clinical outcome measures, 14 factors were measured or recorded pre-treatment. These included demographic items, QST measures and psychometric scores.
The trial protocol was published as a supplement to the main paper, and it explains some of the thinking behind the study design. It certainly was ambitious to not only try to measure differences between real and sham EA, but to try to correlate demographic, QST and psychometric items with changes in clinical outcomes.
Over 10 years ago, Haake et al (n=1162) failed to measure any significant difference between real and sham acupuncture in a three-arm trial with nearly 400 patients in each arm. So attempting the same with just over 50 in each arm was surely destined to fail? Perhaps they were hoping that EA versus non-penetrating sham EA was different enough from manual acupuncture versus superficial needling. Well normally you do not leave things to hope… you do a power calculation. So, I checked that, and the power calculation was not based on the a between group change in the primary outcome. Instead, it was based on being able to measure a moderate (clinically meaningful) correlation between a baseline factor (eg temporal summation) and a change in pain intensity.
The ambition to measure a difference is reflected in quite an intensive EA treatment regime, with 12 sessions of 45 minutes over 6 weeks and a variety of different protocols from which to choose involving at least 20 needles. The sham looked fairly convincing with 4 sets of points in total in the back and limbs. Now they used a small Japanese EA device (IC1107), which has 3 outputs, and they do not specifically state that they used more than one device per patient, but I have to assume that they did, since for some sessions they would have needed 12 needles stimulated electrically, ie 6 pairs.
Now to the results… well they are a little underwhelming I’m afraid. There was no difference in pain intensity reduction between groups. At least no significant difference, but the reduction in pain was 4.33 in the EA group and 2.30 in the sham EA group, so this looks like a type II statistical error, which is unsurprising as the trial was not powered for this comparison. That is probably the most remarkable thing about this research, the fact that it got funded without being powered for the primary outcome.
The pain intensity reduction in the EA group correlated with just 2 factors out of the 14 measured, and they were among the cheapest to measure. CSQ scores correlated positively with pain reduction, and white race correlated negatively. So, none of the original hypotheses were confirmed, and none of the fancy stuff (QST measures) showed anything of interest.
It was not all bad news, as there was a significant difference in RMDQ… only just, and the absolute reduction in the EA group made it into the range considered clinically significant. RMDQ reduction of 2.77 versus 0.67.
As I was searching for papers for this blog, I came across a published protocol for what I took at first to be this paper, but no, they are trying again! The same (or similar) team from Stanford are planning another sham controlled trial of EA in cLBP, but they have made some changes to the measures and their prediction of what will correlate with what. Unfortunately, they have not adjusted the power, so it is still perilously small for a sham controlled trial in chronic pain. Importantly they have changed the primary outcome from pain intensity to pain bothersomeness. They have kept the RMDQ as a secondary measure, and will focus again on QST (temporal summation and conditioned pain modulation) and three psychometric measures (expectation, catastrophising and self-efficacy) in trying to predict the size of the effect.
4th November 2020: update from Dr Dirk
My friend and colleague Dirk de Vries is an interventionist pain clinician from the Netherlands. He likes pulsed radiofrequency, but has referred to this intervention as an expensive form of EA. Anyway, he drew my attention this morning to a recent paper in the journal Spine. It is an update of a model used to assess cost effectiveness (compared with usual care) of 17 non-pharmacological interventions in cLBP. The original model was published last year including data from 10 trials. Five more trials, including Haake et al, the biggest acupuncture trial in cLBP, were added for this update. The data from Haake et al is not better in terms of the effects of acupuncture compared with usual care, but since usual care in this study (German guideline-based conventional care) was quite expensive, the societal cost saving from using acupuncture was increased from around $600 to $1300 per patient… I’ll show you the graphs tonight.
1 Kong J-T, Puetz C, Tian L, et al. Effect of Electroacupuncture vs Sham Treatment on Change in Pain Severity Among Adults With Chronic Low Back Pain. JAMA Netw Open 2020;3:e2022787. doi:10.1001/jamanetworkopen.2020.22787
2 Kong J, Gollub RL, Webb JM, et al. Test-retest study of fMRI signal change evoked by electroacupuncture stimulation. Neuroimage 2007;34:1171–81. doi:10.1016/j.neuroimage.2006.10.019
3 Kong J, Kaptchuk TJ, Webb JM, et al. Functional neuroanatomical investigation of vision-related acupuncture point specificity–a multisession fMRI study. Hum Brain Mapp 2009;30:38–46. doi:10.1002/hbm.20481
4 Cook KF, Dunn W, Griffith JW, et al. Pain assessment using the NIH Toolbox. Neurology 2013;80:S49-53. doi:10.1212/WNL.0b013e3182872e80
5 Roland M, Morris R. A Study of the Natural History of Back Pain. Spine (Phila Pa 1976) 1983;8:141–4. doi:10.1097/00007632-198303000-00004
6 Roland M, Morris R. A study of the natural history of low-back pain. Part II: development of guidelines for trials of treatment in primary care. Spine (Phila Pa 1976) 1983;8:145–50. doi:10.1097/00007632-198303000-00005
7 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
8 Kovacs FM, Abraira V, Royuela A, et al. Minimal clinically important change for pain intensity and disability in patients with nonspecific low back pain. Spine (Phila Pa 1976) 2007;32:2915–20. doi:10.1097/BRS.0b013e31815b75ae
9 Kong J-T, MacIsaac B, Cogan R, et al. Central mechanisms of real and sham electroacupuncture in the treatment of chronic low back pain: study protocol for a randomized, placebo-controlled clinical trial. Trials 2018;19:685. doi:10.1186/s13063-018-3044-2
10 Herman PM, McBain RK, Broten N, et al. Update of Markov Model on the Cost-effectiveness of Nonpharmacologic Interventions for Chronic Low Back Pain Compared to Usual Care. Spine (Phila Pa 1976) 2020;45:1383–5. doi:10.1097/BRS.0000000000003539
11 Herman PM, Lavelle TA, Sorbero ME, et al. Are Nonpharmacologic Interventions for Chronic Low Back Pain More Cost Effective Than Usual Care? Proof of Concept Results From a Markov Model. Spine (Phila Pa 1976) 2019;44:1456–64. doi:10.1097/BRS.0000000000003097