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. The study says that 'weak evidence' raises dilemmas for clinicians and poses questions for the alcohol field and the process for approving drugs.
Indeed when nalmefene (under the brand name Selincro®) first gained attention in 2013 following approval by the European Medicines Agency (EMA), we published a guest post by Clinical Nurse Manager Dylan Kerr highlighting a number of the issues addressed in the new study. For example, what is the exact role the drug plays in relation to 'psychosocial intervention' which are a necessary component alongside prescribing of the drug. What are the implications for this in practice given difficulties in implementing even simple 'brief interventions' in Primary Care settings? Arguably distracting from such questions, dubious media coverage and headlines followed, such as the Mirror's 'New £3 pill to 'cure' alcoholism can stop binge boozing'.
Asides from the questions over the validity of the evidence, nalmefene's target group itself was already regarded as controversial by some. Unlike most pharmacological treatments for alcohol problems it was authorised to support those seeking to reduce their drinking rather than abstain, but not to be prescribed to drinkers with signs of physical dependency. As such, the drug is aimed at 'low to moderate severity' dependent drinkers who would typically be offered only psychosocial or other non-drug based interventions if engaging in support.
With regard to the questions over the evidence for the drug's effectiveness itself, the abstract of this open access study concluded that nalmefene was licensed and recommended despite 'problems with the registration, design, analysis and reporting of clinical trials' for the drug. Whilst not directly questioning the fact that three of the main trials were funded by the producer of nalmefene – Lundbeck - the study highlights that 'concerns exist regarding industry influence in health technology assessment more widely'.
Furthermore another study, a meta-analysis of research trials also casts doubt over the effectiveness of the drug, finding no impact on mortality and raising other issues such as the level of side effects and withdrawal of participants from trials.
The issues and concerns raised by these two publications over the evidence for nalmefene were also explored in a Mental Elf blog feature. The blog explores various issues identified with the trials including why they did not compare nalmefene with naltrexone, a drug with a similar mechanism of action. Indeed naltrexone is already used in substance misuse treatment but as a generic drug and is considerably cheaper. The Lundbeck sponsored trials also used a psychosocial intervention known as 'BRENDA', but this has been questioned since BRENDA is less intensive than the psychosocial interventions recommended by NICE for the treatment of alcohol dependence.
Clinicians and policymakers left to weigh it up?
As the Addiction paper suggests, this may leave those involved in alcohol treatment with a number of dilemmas over the possible use of nalmefene. Indeed there may not be a clear consensus on the exact role pharmacology should play in alcohol addiction treatment, particularly when seeking to reach larger populations of 'lower severity' dependent drinkers. Generally guidance says that drugs can play a useful role for some individuals, particularly alongside evidence based approaches such as psychosocial therapies. However many may feel that 'low utilisation' of pharmacotherapy is not the main barrier to improving treatment uptake and outcomes, particularity for those without physical dependence.
As for the future of nalmefene itself, only time will tell whether it becomes a more widely used option, or if further research trials will be conducted taking account of the issues raised. Lundbeck however no longer appear to be prioritising nalmefene in the UK despite having sponsored and supported a range of alcohol initiatives over recent years such as conferences and local alcohol resources.
NICE responded to the Addiction paper by stating that the decision to approve the drug had followed standard procedures and their 'appraisal process for nalmefene thoroughly interrogated the evidence base'. The authors of the study though are unlikely to feel this addresses the core issue; the paper states the 'investigation makes clear the need to study the involvement of the pharmaceutical industry in alcohol treatment trials and the resulting implications for the literature'. It adds, 'alcohol problems are complex, and require evidence unbiased by vested interests' - a position few in the addiction field would disagree with.