The main clinical evidence for mexiletine comes from MYOMEX, a randomised crossover trial of 26 patients with NDM comparing mexiletine with placebo. Supporting clinical evidence came from 3 other studies which were used to inform some economic model parameters and scenario analyses. The committee concluded that all the evidence, combined with the statements that mexiletine has been standard practice for over 15 years, suggest mexiletine is effective for relieving myotonia symptoms. However, the committee noted that there were no comparisons of mexiletine with an active comparator. Also, the committee also noted that a higher dose of mexiletine was used in the MYOMEX trial than people would normally have in the NHS, so the cost of mexiletine is uncertain. The economic model does not compare mexiletine with other sodium channel blockers that are used in the NHS. Because of this, mexiletine's clinical benefit compared with these medicines is uncertain. However, the cost-effectiveness estimates for mexiletine compared with best supportive care are within the range that NICE considers a cost-effective use of NHS resources. Using the scenario with the 429 mg dose, the incremental cost-effectiveness ratio (ICER) was £19,039 per QALY gained for mexiletine compared with best supportive care. When the 600 mg dose was used, the ICER exceeded £30,000 per QALY. The committee considered that comparison with best supportive care was not appropriate and the indicative evidence review group (ERG) analysis comparison with lamotrigine suggests this would increase the ICER if lamotrigine's treatment effect was greater than placebo. It accepted that if the utility gain associated with an active comparator was very modest, the ICER would remain below £20,000 per QALY gained. The committee recognised the serious limitations in the cost-effectiveness modelling. However, it also acknowledged that the evidence base is necessarily weaker for some technologies, such as those used to treat rare diseases. On balance, and taking into consideration the likelihood of decision error and its consequences, the committee concluded that mexiletine was a cost-effective use of NHS resources and recommended it for routine commissioning.