The recent news in the press of the ‘weak evidence of nalmefene’ or, as the BBC and other such long-lost quality organisations put it, ‘Alcohol treatment drug nalmefene ‘not effective” has certainly caused some ripples of discontent and concern for those organisations, such the European Medicines Agency (EMA), who licensed it for use in Europe, and NICE, who licensed it for use on the NHS in the UK, AND those either taking nalmefene or considering taking nalmefene. Be aware of poor journalism and make your own decision based on the information contained in the actual authored report, many of the facts of which I have included as part of this article. Sensationalist journalism gets views, but does not necessarily provide you with all the facts. For your information, the report is entitled ‘Weak Evidence on nalmefene creates dilemas for clinicians and poses questions for regulators and researchers’.
It is fair to say, that in my belief and understanding of reading the actual report itself, there may have been short-cuts, bordering on dishonesty, taken by the manufacturer of Selincro, Lundbeck, in order to get the medication licensed. These short-cuts include the use of post-hoc analysis of the three clinical tests that they, themselves, ran (which leaves them open to accusations of bias at the very least), and the exclusion of certain information that could have influenced the licensing decision negatively.
There have been over 120 studies and clinical trials of opioid-blocking medication, such as naltrexone, nalmefene and naloxone, which show overwhelmingly that The Sinclair Method using either naltrexone or nalmefene is a safe and effective treatment.
For the EMA and NICE approval, Lundbeck chose to rely almost exclusively on the results of their own 3 clinical trials – named Essence 1, Essence 2 and Essence 3. Other clinical trials were only used by Lundbeck as a supportive tool to show the most effective dosage – they were not presented to the approving committee of either the EMA or NICE to support the efficacy of the medication, when used as per The Sinclair Method way of prescribing. I am not privy as to why the previous clinical testing was not used, but I can only assume (maybe incorrectly, of course!) that Lundbeck did not want any comparisons to naltrexone showing success in the same prescribing method.
This is absolutely CRITICAL, in my opinion, because the licensing decision of whether this treatment was effective vs. cost effectiveness is at the heart of the issue that these authors are informing the industry about, and is based almost solely on 3 clinical trials. The decision makers received a ‘picture’ of Selincro from Lundbeck, and that picture did not include the past many, many years of research, but only what Lundbeck wanted them to see.
Based on this limited ‘picture’, then I have studied their evidence and come to my own conclusion that agrees with the authors – if the committee had seen the full picture, then the licensing approval for Selincro to be used in a free-to-access primary care setting across Europe may well have been in doubt, simply because it does not appear to provide either excellent efficacy or value for money for the respective healthcare providers across Europe. I believe there was the potential for the licensing to have been declined pending further investigations and trial evidence – all of which would have cost Lundbeck money, of course.
It may surprise some of you to hear me say that but please understand what I am saying here…. based on the limited evidence provided by Lundbeck, it appears the licensees made the incorrect decision to license. They were provided with a ‘snap-shot’ of information on which to base their licensing decision.
The authors are NOT saying that nalmefene is not effective – they are saying that on this particular licensing decision for Selincro, the wrong decision was possibly made to license a new and expensive product because the trials were subject to bias and there was an alternative and cheaper medication available.
It does appear to be true, from the evidence that was investigated by the authors of the report, that:
- Lundbeck chose to stray away from the normal way of analysing clinical testing in favour of their own style of post-hoc analysis. Post-hoc analysis uses the assumption that an event that occurred was a direct result of some input into it prior. In this case, it appears that if someone reduced their consumption during the trial period, then it was 100% due to the nalmefene – this way of reporting, therefore, excludes the possibility that the person could have been influenced by something else completely, or perhaps influenced by something else IN ADDITION to taking the nalmefene.
- Definitions of what constitutes some of the wording were amended by Lundbeck AFTER the publication of the clinical trial papers – e.g. what constitutes a ‘heavy drinking day’.
- Although NICE noted that there appeared to be higher than expected drop-out rates during the clinical trials, this does not appear to have received further investigation. Sensitivity analyses were performed by Lundbeck, but not made public. This information, had it been presented, COULD have influenced the decision to license Selincro. Many people are showing to be VERY sensitive to the medication, and physicians deserved to have this taken into account before licensing was agreed. This sensitivity is proving such a barrier that many people do stop taking the medication before pharmacological extinction occurs – they are not being made aware that, though perhaps severe, any sensitivity does eventually reduce considerably, in not completely.
- Under the Declaration of Helsinki, in order to make an informed decision about licensing, comparisons of the treatment MUST be made if another suitable medication is available. In the case of the licensing of Selincro, Lundbeck successfully argued that naltrexone and nalmefene have ‘a different biochemical profile’ therefore not a suitable comparison. The authors of this report, have found this to be a suspect decision. Again, had the treatment been tested using both naltrexone and nalmefene, then licensing probably wouldn’t have been granted as naltrexone is so much less expensive than Selincro and therefore, offers higher cost effectiveness than Selincro to the healthcare providers.
- Lundbeck presented the Finnish clinical trials as evidence of the 70%+ success rates BUT they presented this in a fashion that indicated treatment, and therefore the results, were based on treatment undertaken in a Primary Care setting. Most of the Finnish trials actually took place in a private clinic setting. Therefore, Lundbeck adversely influenced a decision about where Selincro-based treatment is placed.
- There was no comparison between different types of psychosocial support to establish whether a different type of support system would provide increased results.
As part of the investigation, the authors of the report only researched the most recent clinical trials involving nalmefene. They did not research naltrexone clinical trials.
Based on the alleged ‘massaged’ evidence that Lundbeck presented to the European Medical Agency, and to NICE, it certainly gives the indication that Selincro works better than the actual 3 clinical trials show that it did. These were their own funded trials, in which they also had an influence on how the results were analysed.
So, we have a situation where it appears that a multi-national company has been economical with the truth in order to get a product onto the market, and make profit. Those of us that are old enough to understand, know that this is the way of the world now. I am not surprised at that in the slightest.
However, this reliance on their own clinical testing makes it apparent that the decision to license Selincro does indeed, appear to be the incorrect decision based on this information alone, but it does NOT the fact that upon further viewing of ALL the clinical trials using opioid-blocking medications such as naltrexone and nalmefene, pharmacological extinction treatment (The Sinclair Method) IS a safe and very effective treatment for Alcohol Use Disorder.