Background: Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical.
Epub ahead of print: Notcutt et al. A placebo-controlled, parallel-group, randomised withdrawal study of subjects with symptoms of spasticity due to multiple sclerosis who are receiving long-term Sativex(R) (nabiximols). Mult Scler. 2011 Aug 30.
“In open-label studies the MS’ers know what they are taking; results from open-label studies are always questionable, but are not meaningless. Observational or open-label studies are often the reason to justify investigating the intervention in blinded studies.”
Objective: To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term symptomatic relief of spasticity in MS, and to assess the impact of sudden medicine withdrawal.
Methods: Eligible subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5-week placebo-controlled, parallel-group, randomised withdrawal study. Each subjects’ previous effective and tolerated dose was continued.
Results: A total of 18 subjects per group were enrolled. Demographics showed a mean duration of MS of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years (median 3.4 years) and a mean daily dose of 8.25 sprays.
Primary outcome of time to treatment failure was significantly in favour of Sativex (p = 0.013). Secondary endpoints showed significant changes in the Carer and Subject’s Global Impression of Change scales in favour of Sativex.
Conclusions: Maintenance of Sativex efficacy in long-term symptomatic improvement of spasticity to a group of subjects with MS has been confirmed using this study design.
“The problem with the Sativex’s spasticity data is that the company who sponsored the studies never collected health economic data, which means it is impossible for NICE to rule on whether or not it is cost-effective to use in the NHS. This means that when we want to prescribe Sativex NHS Commissioners’ typically say no and use the fact that NICE has not ruled on Sativex’s cost-effectiveness as the reason. This puts Neurologists in a difficult position and some MS’ers perceive the problem as being due to us, i.e. that neurologists don’t want to prescribe the drug. This is not correct. Preparing an individual funding application for Sativex, or any other drug for that matter, can take anything from 30 to 45 minutes to complete. It is then submitted and can take 4 to 8 weeks to get a response. Usually an individual funding application results in a further round, or rounds, of written or verbal correspondence. between ourselves and the Commissioners. This all eats up valuable time, before you receive a formal rejection letter. Once you have one application rejected, based on the lack of cost-effectiveness data, it is pointless reapplying unless you have new data to support the application. This is why we seriously need some good quality Sativex studies performed that focus on the cost-effectiveness of the drug and its impact on quality of life. No one is arguing that Sativex does not work as an anti-spastic agent, what we need is the data to convince NICE and the NHS Commissioners that it is worthwhile prescribing, i.e. it improves MS’ers quality of life at a price that is affordable to the NHS.”
“Who thought being a neurologist was about harassing or being harassed by Commissioners? Welcome to the brave new world of medicine.”