OBJECTIVES: A post-hoc sub-group analysis provides evidence that lacosamide when used in conjunction with a non-sodium-channel blocking AED is more effective than when used in combination with another sodium-channel blocking AED.  In order to allow patients earlier subsidised access to lacosamide (via the Pharmaceutical Benefits Scheme), a cost-effectiveness analysis was conducted.   METHODS: Three large randomised, placebo controlled trials (SP667, SP754 and SP755) were meta-analysed.  More specifically, the analysis examined lacosamide used in conjunction with a non-sodium channel AED (the sub-group) vs. lacosamide used in conjunction with at least one sodium channel AED (the complement group).  A decision tree (TreeAge) economic model reported the “cost per incremental 50% responder”.  Lacosamide was utilised in the compliment group as a proxy for other (similarly priced) adjunctive AED treatment. RESULTS: The meta-analysis, compared those trial patients meeting the proposed PBS indication (the sub-group) to its complement.   More patients in the subgroup achieved a ≥50% reduction in seizure frequency compared to the complement (51.1% vs. 34.7% respectively).  Based on the test of effect modification, there is a statistically meaningful effect modification within the proposed subgroup (p=0.03).  The modelled incremental cost effectiveness ICER, lacosamide (sub-group) costs $3064 per additional patient who achieves at least a 50% reduction in seizures compared to the compliment. CONCLUSIONS: A reimbursed listing on the PBS was sought which would limit the use of lacosamide to a refractory group and then only in combination with non-sodium AEDs.  Probabilistic sensitivity analysis was undertaken which showed that the PBAC could be confident in that 68% of the outcomes are below $4000/responder.  This supported the robustness of the ICER.  The analysis could have been strengthened had it been based on a pre-specified analysis (and therefore randomised accordingly), rather than on a post-hoc analysis.