MD, PhD, MAE, FMedSci, FRSB, FRCP, FRCPEd.

Yesterday, we discussed a paper concluding (amongst other things) that there are insufficient high‐quality RCTs to judge the efficacy of acupuncture for cancer‐related pain. Today, we are looking at one that overtly contradicts this verdict.

This systematic review (published in JAMA Oncology) evaluated the existing randomized clinical trials (RCTs) for evidence of the association of acupuncture and acupressure with reduction in cancer pain. Randomized clinical trials that compared acupuncture and acupressure with a sham control, analgesic therapy, or usual care for managing cancer pain were included. The primary outcome was pain intensity measured by the Brief Pain Inventory, Numerical Rating Scale, Visual Analog Scale, or Verbal Rating Scale.

A total of 17 RCTs (with 1111 patients) were included, and data from 14 RCTs (with 920 patients) were used in the meta-analysis. Seven sham-controlled RCTs (35%) were notable for their high quality, being judged to have a low risk of bias for all of their domains, and showed that real (compared with sham) acupuncture was associated with reduced pain intensity. A favourable association was also seen when acupuncture and acupressure were combined with analgesic therapy in 6 RCTs for reducing pain intensity and in 2 RCTs for reducing opioid dose. The evidence grade was moderate because of the substantial heterogeneity among studies.

The authors concluded that this systematic review and meta-analysis found that acupuncture and/or acupressure was significantly associated with reduced cancer pain and decreased use of analgesics, although the evidence level was moderate. This finding suggests that more rigorous trials are needed to identify the association of acupuncture and acupressure with specific types of cancer pain and to integrate such evidence into clinical care to reduce opioid use.

So, which of the two conclusions should we trust?

Personally, I find the JAMA paper unimpressive to the point of being suspect. Here are some of my reasons:

  • About half of the primary studies are Chinese; and we have seen repeatedly that they are unreliable and report only positive results.
  • Many of the trials are published in Chinese and can thus not be checked by non-Chinese readers (nor, presumably, by the experts who acted as peer-reviewers for JAMA Oncology).
  • I have my doubts about the rigor of the peer-review of some of the journals that published the primary studies included in the review.
  • One paper included in the review is even a mere doctoral thesis which usually is not peer-reviewed in the usual sense.
  • The authors state that they included only clinical trials that compared acupuncture and acupressure with a sham control, analgesic therapy, or usual care. However, this is evidently not true; many of the studies had the infamous A+B versus B design comparing acupuncture plus a conventional therapy against the conventional therapy. As we have discussed ad nauseam on this blog, such trials cannot produce a negative finding even if ‘A’ is a placebo.
  • Contrary to what the authors claim, the quality of most of the included studies was extremely poor, as far as I can see.
  • One included paper which I cannot access is entitled ‘Clinical observation on 30 cases of moderate and severe cancer pain of bone metastasis treated by auricular acupressure‘. Are the review authors seriously claiming that this is an RCT?

The more I study the details of the JAMA Oncology paper, the more I feel it might be worth a complaint to the editor with a view of initiating a thorough investigation and a possible retraction.

 

10 Responses to Acupuncture/acupressure for cancer pain?

  • Thank’s for this post!

  • Thanks for this analysis. A journal of this reputation should be called out and I hope you will complain. This paper will be cited again and again by proponents of acupuncture if allowed to stand without question.

  • Can someone explain this to me, please?

    If you have an RCT comparing, say, pain control using acupuncture and acupressure with a sham control, analgesic therapy or the usual care for managing cancer (as outlined in this post), what are the ethical considerations? It would seem to me that if you have patients with pain, giving them a placebo would be at least unethical, if not cruel.

    I’m sure there is an explanation, it just doesn’t come to me intuitively.

    Thanks,

    Ron Jette, ND, NW, NWB (Not Doctor, Never Was, Never Will Be)

    • the ethics can be problematic, I agree.
      but usually the sham treatment is for a short time only, and [depending on the exact circumstances] this is deemed acceptable in the name of creating progress.

      • Thanks for that, Professor.

        I’m guessing there are no hard and fast rules with respect to when a placebo is used as each study is looking at something different. If that’s the case, because the decision is somewhat arbitrary, I’m also guessing there would be the real possibility of making bad choices.

        Interesting. Thanks, again.

    • Pain in cancer patients differs from other sorts of pain. Pain is usually a warning to avoid doing something that can cause further damage, but in the case of cancer the pain is meaningless. It is also worse at night and interferes with sleep, whereas non-malignant pain is usually eased by resting in bed. It is also fairly constant (though it can get worse with activity, usually in a predictable way). Therefore standard treatment involves trying to achieve a constant steady level of analgesia in the system. We usually start with something simple such as paracetamol, and escalate treatment until the pain is under control; the next step is to add a weak opiate such as dihydrocodeine or tramadol, and then to go onto increasing doses of a strong opiate such as morphine. NSAID’s such as ibuprofen are also useful, as are tricycle antidepressants and certain anticonvulsants, which can reduce the opiate requirement.

      This approach works for most patients, provided that it is supervised by somebody trained in the management of cancer pain – so often I have seen long-acting opiates prescribed by doctors who don’t know what they are doing, resulting in avoidable toxicity and poor pain control. However, it doesn’t suit everybody. Usually the expected side-effects of opiates (drowsiness, constipation, nausea) are either temporary or can be readily managed, but some individuals are unable to tolerate opiates, due to problems such as excessive sedation, fall in blood pressure or uncontrollable vomiting. And not everybody can take NSAID’s. There are also types of pain that are not very opiate-responsive (such as when a cancer is invading a major nerve).

      For these reasons we are always looking for anything else that might be helpful. Physiotherapy, TENS and (in chronic cases) nerve blocks can be helpful. Radiotherapy is used a lot as a single dose has very little in the way of side-effects and is usually very effective for pain at a specific site.

      Often the pain is accompanied by anxiety, which makes it much worse, both by increasing sensitivity to pain in general and by increasing muscle tension (and therefore pressure on nerves and any other sensitive site). Any measures which reduce anxiety tend to be quite effective. Simply taking the patient out of the clinical setting and making a bit of a fuss of them can make a big difference here, particularly if it involves a relaxing massage, as in reflexology or aromatherapy.

      Acupuncture is attractive to patients because of the perceived lack of side-effects, and there is no doubt that it has a strong placebo effect. Since the perception of pain is in the mind, placebos can make more difference to pain than they do to the course of a disease.

      I don’t know about China, but in the UK the subjects in a trial have to give informed consent and the information they are given is quite detailed and explained to them carefully, so I don’t think there would be any ethical problems here. In any case, as per the Declaration of Helsinki they are free to come out of the trial at any time without having to explain or justify their decision and without jeopardising their treatment in any way.

      Personally I think you could quite easily find cancer patients willing to enter a placebo-controlled trial of this kind.

      With regard to the question of peer-review, it would surprise me if the JAMA doesn’t have access to Chinese-speaking pain specialists and oncologists who could act as reviewers, though I would expect them to apply the same standards as any other reviewers.

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