No additional treatment (the mix of traditional antiepileptic drugs alone) was not considered as an initial option, but it was considered following withdrawal due to adverse events. It is possible that none of the interventions were cost-effective compared with traditional antiepileptic drugs. The authors stated that the comparison with lamotrigine was a secondary analysis due to a lack of evidence, but this was not good reason to make the comparison secondary. They also did not explain how the evidence was lacking for this treatment, as the effectiveness parameters reported were more precise for lamotrigine than those for the other treatments.
The literature search was not described. No head-to-head comparisons between the drugs were found and an indirect comparison was made, which seems to have been appropriate. A lifetime horizon was not considered because the authors found no evidence of long-term effectiveness. There was little discussion of the adverse events, which were modelled to occur within the first three months and it was not clear if this was based on evidence from the trials.
A micro-costing approach was used and all those costs relevant to the reported perspective seem to have been included. The authors stated that the medical resource costs and the costs of treating adverse events were expected to be lowest with rufinamide, but they did not explain this and rufinamide had the highest cost per day and the highest adverse event rate. The average daily doses for each treatment were the opinions of clinical experts. These could have been tested in a sensitivity analysis, using the doses recommended in their Summary of Product Characteristics.
Analysis and results:
According to the authors' assumptions, topiramate was dominated by lamotrigine, as lamotrigine was cheaper and more effective, and so it should not be considered as an option for these particular patients. The main comparator for rufinamide was therefore lamotrigine, and rufinamide was unlikely to be cost-effective compared with lamotrigine, at the usual NHS willingness-to-pay threshold. Rufinamide should therefore have limited use as a second-line therapy, such as when lamotrigine cannot be used and an adjunctive therapy is considered necessary. The cost-effectiveness of each treatment compared with no adjunctive treatment was not assessed, meaning that it is possible that rufinamide is never cost-effective. It wasn't clear if distributions were applied to all the parameters for the probabilistic sensitivity analysis. The authors stated that one-way sensitivity analysis was used to test the uncertainty in the model parameters, by varying them by ±20%; it was unclear how well an arbitrary ±20% represented the uncertainty in each parameter.
There were significant issues with the methods of this analysis and the conclusions were not appropriate for the evidence presented.