Our local Guru of EBM, Brian Doyle, hosts a monthly Journal Club for the locals. In the spirit of consolidating knowledge and sharing this with the world, with permission, here is a re-post of one of the articles discussed.
For more juicy journals served on a platter, head over to Brian's JC blog: EmergencyMedJc
But I was equally surprised to see a negative high quality RCT of pregabalin published in the highest impact journal on the planet!
Surely Pfizer was crazy when they funded and performed this study? Well… of course they weren’t… it was some other crazy authors.
This Australian NHMRC funded double-blind controlled trial randomized 209 participants to either pregabalin or placebo. The primary outcome was a leg-pain intensity score at the 8 week mark.
How much did the pregabalin help?
Zero, zip, zilch, nada…
There was no statistical improvement in the primary or any of the secondary outcomes. About the only thing we are sure of is the incidence of adverse events was significantly higher in the pregabalin group.
Although this was a small study (i.e. risk for Type II error), it probably had adequate power to detect a clinically meaningful difference in pain scores. And the results trended a favour towards placebo anyway.
Of course, no study is perfect. If I was working for Pfizer, I would point out that only a minority of the participants were likely to have neuropathic pain as measured on the PainDETECT score. So of course my drug wouldn’t work… while I sit on my horse made of gold.
As an aside…
I’ve been dubious of these neuopathic pain drugs. A disturbing study published in the NEJM demonstrated what looks like systematic research misconduct with gabapentin which is very closely related to pregabalin. This only was discovered during litigation and release of internal company documents. (This is probably my favourite journal club paper of all time…)
So what’s the take home message for the emergency docs?
Pregabalin probably does not help sciatica. But I would also be sceptical as to the benefits in a wide range of other indications… Especially with industry sponsored research.
Show me the money!
Mathieson S, Chiro M, Maher C, et al. Trial of Pregabalin for Acute and Chronic Sciatica. N Engl J Med 2017;376:1111-20.
About the Author
Dr Brian Doyle is an emergency physician originally from the United States but now very much calls Tasmania his home. Unfortunately, it will now be a bit more difficult to deport him from the country as he passed his Australian citizenship test a few years ago. (He was able to answer that Phar Lap won the Melbourne rather than the Davis Cup). His main interests are mostly the clinical aspects of emergency medicine but also in education, ultrasound and critical appraisal of the literature. He spends much of his time annoying people to help out with conferences.