This paper outlines methodological challenges encountered in producing an independent economic evaluation for the National Institute for Health and Clinical Excellence (NICE) to inform its technology appraisal process. The analysis used to highlight these challenges is a recent evaluation of pharmacological treatments for attention deficit hyperactivity disorder (ADHD). The NICE reference case for economic evaluation is compared with the methods necessary to complete an evaluation given the evidence base for ADHD. The primary analysis deviated from NICE methods guidelines most noticeably in the time horizon. Identifying appropriate utility data was challenging, and the results were sensitive to the values used. Issues found in this evaluation are common to many technology appraisals. Although challenging to undertake, economic evaluation in disease areas such as ADHD has great potential to add value, making the limitations of the data explicit, combining available evidence in a systematic and transparent framework and identifying future research needs.