So this was sent to me by a lovely GP friend of mine *waves hello*! and was a systematic literature review and meta-analysis of published and unpublished double-blind randomized controlled trials with regard to nalmefene, a new drug that was rubber stamped by NICE within the last few years for treatment of moderate adult alcohol dependence (defined as drinking no more than 1/2 a bottle of wine a day so approx 6 units). I’ve written about it lots and you can read all my posts about it here.
I’m all for any treatment option that supports and helps alcohol dependence and people’s desire to cut down or stop but the evidence supporting it needs to be robust seeing as there is a cost to the NHS involved. A quick search of the internet uncovers that this drug is £3.48 a tablet (that’s £1,270 per annum in drug costs) so not cheap!!
Here’s the full abstract:
BACKGROUND: Nalmefene is a recent option in alcohol dependence treatment. Its approval was controversial. We conducted a systematic review and meta-analysis of the aggregated data (registered as PROSPERO 2014:CRD42014014853) to compare the harm/benefit of nalmefene versus placebo or active comparator in this indication.
METHODS AND FINDINGS: Three reviewers searched for published and unpublished studies in Medline, the Cochrane Library, Embase, ClinicalTrials.gov, Current Controlled Trials, and bibliographies and by mailing pharmaceutical companies, the European Medicines Agency (EMA), and the US Food and Drug Administration. Double-blind randomized clinical trials evaluating nalmefene to treat adult alcohol dependence, irrespective of the comparator, were included if they reported (1) health outcomes (mortality, accidents/injuries, quality of life, somatic complications), (2) alcohol consumption outcomes, (3) biological outcomes, or (4) treatment safety outcomes, at 6 mo and/or 1 y. Three authors independently screened the titles and abstracts of the trials identified. Relevant trials were evaluated in full text. The reviewers independently assessed the included trials for methodological quality using the Cochrane Collaboration tool for assessing risk of bias. On the basis of the I2 index or the Cochrane’s Q test, fixed or random effect models were used to estimate risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% CIs. In sensitivity analyses, outcomes for participants who were lost to follow-up were included using baseline observation carried forward (BOCF); for binary measures, patients lost to follow-up were considered equal to failures (i.e., non-assessed patients were recorded as not having responded in both groups). Five randomized controlled trials (RCTs) versus placebo, with a total of 2,567 randomized participants, were included in the main analysis. None of these studies was performed in the specific population defined by the EMA approval of nalmefene, i.e., adults with alcohol dependence who consume more than 60 g of alcohol per day (for men) or more than 40 g per day (for women). No RCT compared nalmefene with another medication. Mortality at 6 mo (RR = 0.39, 95% CI [0.08; 2.01]) and 1 y (RR = 0.98, 95% CI [0.04; 23.95]) and quality of life at 6 mo (SF-36 physical component summary score: MD = 0.85, 95% CI [-0.32; 2.01]; SF-36 mental component summary score: MD = 1.01, 95% CI [-1.33; 3.34]) were not different across groups. Other health outcomes were not reported. Differences were encountered for alcohol consumption outcomes such as monthly number of heavy drinking days at 6 mo (MD = -1.65, 95% CI [-2.41; -0.89]) and at 1 y (MD = -1.60, 95% CI [-2.85; -0.35]) and total alcohol consumption at 6 mo (SMD = -0.20, 95% CI [-0.30; -0.10]). An attrition bias could not be excluded, with more withdrawals for nalmefene than for placebo, including more withdrawals for safety reasons at both 6 mo (RR = 3.65, 95% CI [2.02; 6.63]) and 1 y (RR = 7.01, 95% CI [1.72; 28.63]). Sensitivity analyses showed no differences for alcohol consumption outcomes between nalmefene and placebo, but the weight of these results should not be overestimated, as the BOCF approach to managing withdrawals was used.
CONCLUSIONS: The value of nalmefene for treatment of alcohol addiction is not established. At best, nalmefene has limited efficacy in reducing alcohol consumption.
So not what I would call robust then ……. limited efficacy in reducing alcohol consumption. Based on this research review maybe NICE should be doing a review of their guidance and recommendations then seeing as it was controversial in the first place?
Edited to add 7th June 2016:
A drug to treat alcohol problems was licensed for use in the UK despite insufficient evidence it was effective, researchers in Scotland have found | BBC, UK
Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers
[Open access]. Problems with the registration, design, analysis and reporting of clinical trials of nalmefene did not prevent it being licensed and recommended for treating alcohol dependence. This creates dilemmas for primary care clinicians and commissioning organisations where nalmefene has been heavily promoted, and poses wider questions about the effectiveness of the medicines regulation system and how to develop the alcohol treatment evidence base | Addiction, UK
Nalmefene (Selincro) is an opioid antagonist medication that was approved for the treatment of alcohol dependence by the European Medicines Agency (EMA) in 2013 and recommended by the National Institute for Health and Care Excellence in the UK in 2014 (NICE, 2014). Its approval was controversial, because some doctors were skeptical about the quality of the evidence | Mental Elf Blog, UK
Edited to add 28th July 2016:
A recently published study published in the journal Addiction has raised questions over the validity of evidence that led to the approval of nalmefene as a drug for the treatment of alcohol dependence | Alcohol Policy UK, UK
Edited to add: 2nd September 2016
‘A pill for every ill’ is the gist of attacks levelled at the approval of nalmefene under the trade name Selincro. Market positioning as a breakthrough which extends the benefits of pharmacotherapy to non-physically dependent drinkers has been criticised as medicalising psychological dependence. Controversy is heated: is Selincro just a clever marketing ploy, or are there real benefits? We conducted an in-depth assessment.
Seems I’m not the only one questioning NICE and their recommendation of this drug …..