Lyrica/pregabalin continued…… Integrity of research is maintained under an accord struck with journal publishers, whereby trial results will only ever be reported if the goal is declared upfront when the study is registered with a govt agency. This ensures inconclusive or negative results aren’t hidden in secrecy, and thus trial NCT00333866 in 2009 is open to scrutiny – a sponsor’s restrictive agreement on investigators publishing or discussing trial results notwithstanding. Under the leadership of Lynne Pauer (a Pfizer Director) 73 facilities worldwide randomly allocated fibro patients to either placebo control or else one of three dosages of pregabalin. 30% dropped out over the 14 weeks, and only the 450mg dosage yielded a statistically significant result in efficacy for pain. Paracetamol was allowed as a rescue therapy, surprisingly the amount needed for pain relief increased with higher dosages of pregabalin. Data from this and other trials was analysed by Oxford University who determined the Number Needed to Treat at 450mg to obtain one person benefiting by a moderate 30% reduction in pain intensity was eleven. On the other hand, worsening side-effects with increased dosage led a rheumy with a sense of humour to plot the Schwindel.
Pfizer has a patent thru’ to Dec 2018 on Lyrica however, and if all you have is a hammer then everything looks like a nail. American audiences are aware of their ad campaign which follows the “Here’s your answer, regardless of your problem” school of thought. Diabetic neuropathy? The ads announce “No worries”, although others are concerned about suicidality. And NonSignificant result study at 300mg dosing shows it’s every bit as good as placebo in reducing pain.
Writing in the Medical Journal of Aust this year, rheumatologist Prof Rachelle Buchbinder complains that NationalHealth&MedicalResearchCouncil “funding is disproportionally low compared with the burden of these (musculoskeletal) conditions”. Her co-author Prof Chris Maher should impress then, in obtaining a $618,590 NHMRC grant for the PRECISE study trialing pregabalin as a treatment for sciatica. Coincidentally, The Age newspaper published on 24th July their promotional article against standard care claiming that: “This month the prestigious NEJM published a paper reporting that steroid injections are no more effective than a sham …”, but if you read Friedly and Jarvik et al’s report the placebo was lidocaine. Yeah right, an anaesthetic is a sham control! Experts condemned the trial, writing: “This critical assessment shows that this study suffers from a challenging design, was premised on the exclusion of available high-quality literature, and had inadequate duration of follow-up for an interventional technique with poor assessment criteria and reporting.” Discouraging guided lumbar injections is pleasing to a Govt cutting health funding in 2015, since imaging is expensive. Pills can keep the pain at bay.
PRECISE trial protocol cites Pfizer’s Dr Zahava Gabriel on the cost-effectiveness for pregabalin, who previously participated in a team providing supposedly independent evidence with ‘A Systematic Review and Mixed Treatment Comparison of the Efficacy of Pharmacological Treatments for Fibromyalgia’ – whose conclusion “confirms the therapeutic efficacy of pregabalin”. The NHMRC’s funding submission includes the justification: “Currently there is limited, direct, high quality research to inform the use of pregabalin in the treatment of people with sciatica. A small prospective randomised trial of patients with chronic low back pain (n = 36), which included some patients with sciatica, suggested that pregabalin may produce a statistically significant reduction in back pain in the short term”. The cited pilot study by Romano & Mineo et al wasn’t placebo controlled – patients being allocated to consecutive periods on either pregabalin, an NSAID celecoxib, or both. The least improvement was shown by the pregabalin only group, so surely Maher’s colleague Prof Ric O’Day would endorse additional celecoxib therapy (especially after having served on Pfizer’s advisory committee)? Unless coming off-patent next year resulted in a commercial decision to dump Celebrex? A supposed risk of cox-2 inhibitors cardiovascular disease hasn’t been investigated, which makes Pfizer’s March 2014 contest against generic manufacturers in Court appear financially risky (tho’ rash judgements are rather clouded by memories of Vioxx corruption! 2015 update here suggests that 200mg is a safe dosage).
Money appears to be not a factor in NHMRC deliberations, otherwise $4.6bn in sales of Lyrica last year would have deemed that Pfizer themselves can reinvest to break a new market with backpain. Hopefully they’ll read other New England Jnl of Medicine articles before gifting in future.
Regulatory compliance appears to have been taken to an all-time low within health research ….. obedience to industry! It also shows how hit and miss medicine is based on commerce rather than science – pregabalin having been developed as an anticonvulsant for epilepsy echoes Pfizer’s subsidiary Searle re-purposing of misoprostol (declared protective against ulcers by Dr Fred Silverstein & co) for inducing labour. A $70m birth injury litigation set a record, and spawned an industry for lawyers suing hospitals for off-label use of mistoprostol.
PRECISE trial has concluded and published: http://www.nejm.org/doi/full/10.1056/NEJMoa1614292
No difference between Lyrica and placebo for leg pain due to a bad back. Supplementary Appx table S6 is informative however. A total of 61.5% of Lyrica users were satisfied with the treatment (despite 40% suffering dizziness) vs 63.4% of those on placebo. People were happy, just to get some caring – the Hawthorne effect.
A manuscript at https://www.researchgate.net/publication/318199773_Pregabalin_for_pain_exploiting_regulatory_weaknesses details the scandal of approval.