A group of researchers publishing in the journal Addiction have performed a systematic review of evidence supporting the efficacy of the drug nalmefene, approved in the UK for the treatment of alcohol dependence. They report problems in the methodology of clinical trials upon which this approval was based, and suggest that their conclusions may create dilemmas for clinicians prescribing the drug.
Prof. Matt Field, Department of Psychological Sciences at the University of Liverpool, said:
“This report describes a very important investigation into the evidence base for the effectiveness of the drug nalmefene for the treatment of alcohol dependence. The authors identified a number of problems with the way that key clinical trials were conducted and reported, including switching of primary outcome measures after trial registration, emphasizing results from sub-groups of participants who were identified after results were known (rather than before the trials were started), and failure to compare the drug with naltrexone, a similar but considerably cheaper drug. These and other problems are, unfortunately, all too common in trials of novel medications for psychiatric disorders, although it is important to note that people are working hard to improve this situation (e.g. http://www.alltrials.net/).
“One of the authors’ observations is that the large trials of nalmefene emphasized findings from sub-groups of participants who did NOT reduce their drinking after 1-2 weeks of simply monitoring how much they drank. At face value this was reasonable because findings from trials of other treatments have shown that problem drinkers tend to reduce their alcohol consumption as soon as they start to monitor it, and this drop in alcohol consumption could obscure any beneficial effects of medication over placebo. Indeed, the power of simply monitoring one’s own drinking behaviour, and of the placebo effect and ‘non-specific’ responses to treatment, are very promising important topics for study, arguably more so than identification and evaluation of novel medications that differ only slightly from drugs that are already available. But, importantly, the problem with the nalmefene trials is that the decision to focus on these sub-groups may have been taken after results were known, rather than in advance of data collection starting. As Fitzgerald and colleagues note, ‘(this) post-hoc sample refinement should not be regarded as anything other than hypothesis-generating’. In other words, these post-hoc data from subgroups of patients should have been followed up with an additional clinical trial in which the effect of nalmefene in this specific population was evaluated. To my knowledge, such a trial has not been conducted. The data from the existing trials are not robust enough to justify NICE’s decision to recommend nalmefene as a treatment for alcohol dependence’”
‘Weak evidence on nalmefene creates dilemmas for clinicians and poses questions for regulators and researchers.’ by Niamh Fitzgerald et al. published in Addiction on Monday 6 June 2016.
Prof. Field: I have received research funding from the Medical Research Council, Economic and Social Research Council, Wellcome Trust, and Alcohol Research UK. I am a member of the UK Centre for Tobacco and Alcohol Studies (UKCTAS) alongside the lead author of this paper, Niamh Fitzgerald. I have not previously been involved in any research into nalmefene or indeed any other medications for the treatment of alcohol dependence.