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Failed attempt to replicate “astounding” effect of methylene blue on back pain

PainSci » bibliography » Kallewaard et al 2019
Tags: treatment, back pain, injections, bad news, intervertebral disc, spine, pain problems, medicine

One article on PainSci cites Kallewaard 2019: The Complete Guide to Low Back Pain

PainSci notes on Kallewaard 2019:

This study is a little bit special: it is a failed attempt to replicate the dramatic, promising results of a previous study (see Peng et al) of methylene blue injection for spinal disc pain. It was “astounding, unprecedented and unrivalled … if the results are true” (Bogduk).

That was a big “if.”

The results seemed more true after a follow-up study in 2012 (Kim) — but, admittedly, those results were not exciting on their own.

And then in 2018 — “only” several years after the original results were declared “astounding if true” — they have been declared probably untrue in the same journal. Another good quality attempt at replication was straightforwardly negative. There was just no meaningful difference between patients who got methylene blue versus a placebo plus lidocaine. Nothing astounding, unprecedented, and unrivalled this time.

The only obvious weakness of the study is that it was a little on the small side. But it wasn’t tiny, and a genuine potent effect should still show up in a small sample size most of the time.

On the one hand, this is a story that has been told many times in medical science: initial results are “promising,” people get excited, perhaps it even spawns an empire of clinics offering the “evidence-based” treatment, but then follow-up research eventually establishes that it wasn’t so great after all. The failure of most treatment ideas is an obvious pattern in medical science over the decades. In scientific terms, betting against the null hypothesis is like betting against the house.

On the other hand, that corrective process is usually slow and tortuous. It’s rare to get a good quality failure to replicate “only” a few years after the initial hype. We don’t usually get to see one good-looking study loudly declaring “looks like something!” and then another clearly saying “sorry, just not seeing it!” For every case this clear, there are a hundred where the body of evidence is larger and messier, and a hundred more where there’s simply no serious attempt at replication whatsoever.

original abstract Abstracts here may not perfectly match originals, for a variety of technical and practical reasons. Some abstacts are truncated for my purposes here, if they are particularly long-winded and unhelpful. I occasionally add clarifying notes. And I make some minor corrections.

A study published in PAIN in 2010 showed remarkable effects of intradiscal methylene blue (MB) injections compared with placebo on pain intensity in patients with chronic discogenic low back pain (CD-LBP). Both groups received lidocaine hydrochloride injections for pain associated with the procedure. We replicated the design of the previously published study and performed a multicenter, double-blind, randomized, placebo-controlled trial to assess whether the extraordinary effects of MB on pain intensity could be confirmed. The primary outcomes were treatment success defined as at least 30% reduction in pain intensity and the Patients' Global Impression of Change 6 months after the intervention. We included 84 patients with CD-LBP of which 14 (35%) in the MB plus lidocaine group showed treatment success compared with 11 (26.8%) in the control group who received placebo plus lidocaine (P = 0.426). Twenty-seven percent of all participants treated with MB stated that their overall health improved much or very much (Patients' Global Impression of Change), vs 25.6% in the placebo group (P = 0.958). We were unable to confirm that intradiscal MB injections are better capable of significantly reducing pain in patients with CD-LBP 6 months after treatment compared with placebo. We observed that over one-quarter of patients receiving only lidocaine injections reported treatment success, which is in contrast with the previously published study. Our results do not support the recommendation of using intradiscal MB injections for patients with CD-LBP.

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