Having skimmed through, I just want to add my applause to NICE. The committee making the decision made good use of patient and clinician experts. They listened when patients said that trying another course of treatment that, in reality, is unlikely to work isn't, in the words we hear so often, 'better than nothing'. Actually, it's worse than nothing because of the hopelessness it causes when it eventually becomes clear that the treatment doesn't work and because of the effort and time that it takes to try it. But the committee clearly understood that there is a need for new, more effective treatments.
And the committee listened when a patient expert who had recovered explained how the illness can make people feel helpless and, I assume, not feel able to be proactive when a treatment isn't working. The committee listened when a clinical expert said that a lot of people keep taking medication for depression for a long time after it is clear that it isn't helping.
I think a lot of these things apply to any significant chronic illness and certainly to ME/CFS.
The patient experts explained that people with treatment-resistant depression often feel hopeless because treatments are ineffective. The clinical expert noted that people will try different courses of treatments to alleviate symptoms. The patient experts highlighted that, when multiple courses of treatment do not work, the feelings of hopelessness get worse. They added that this was an inherent aspect of the 'treatment-resistant' nature of the condition. A patient expert who had recovered from treatment-resistant depression emphasised the importance of independence and return of character upon remission. The clinical expert noted that a large proportion of people keep taking antidepressants that are not working, sometimes for a year or more. The committee concluded that the effectiveness of current treatments for treatment-resistant depression is limited and that there is an unmet need for new treatment options.
I thought this was notable too. Results from two studies the company provided were dismissed on the grounds that the studies were too small and were observational (i.e. not blinded with a comparison treatment). Too small was 160 people and 32 people.
In its response to consultation, the company provided data from 2 real-world studies to support the evidence for esketamine's treatment efficacy. One was a retrospective, observational study of 160 people (157 people were included in the analysis) taking esketamine who had treatment-resistant depression and who had an average of 2 suicide attempts during their life. The other study was a compassionate use study in Spain of 32 people whose depression had not responded to 2 or more antidepressants, 1 augmentation therapy and a non-pharmacological therapy. The company acknowledged there were a low number of people in both studies. The observational study showed a decrease in MADRS scores from baseline over 6 months. However, this was a single-arm observational study so there were no estimations of the effects of a comparator treatment. The ERG was unclear how the studies would overcome concerns regarding the generalisability of esketamine to the NHS. The committee acknowledged the effort of the company to identify additional supporting evidence but noted the low numbers of people in the studies and limitations of the observational evidence.
Perhaps it was relatively easy for the committee to reject the drug, as it sounds as though its administration is costly and burdensome, involving hospital visits. But still, for as far as I got in reading the report, I thought the committee (and the NICE staff supporting them) did a good job. I wish that they would review the chronic primary pain guideline.
