As part of its single technology process, the National Institute for Health and Care Excellence (NICE) invited the manufacturers of aripiprazole (Otsuka Pharmaceutical Co. and Bristol Myers Squibb) to submit evidence of the clinical and cost effectiveness of aripiprazole for the treatment and prevention of acute manic and mixed episodes in bipolar I disorder in children and adolescents. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the manufacturers' submission to NICE. The evidence, which was derived mainly from a double-blind, phase III, placebo-controlled trial of aripiprazole in patients aged 10-17 years, showed that aripiprazole performed significantly better than placebo in reducing mania according to the primary outcome measurement (the Young Mania Rating Scale at 4 weeks). Safety outcomes indicated that aripiprazole was significantly more likely to cause extrapyramidal symptoms and somnolence than placebo. The manufacturers also presented a network meta-analysis of aripiprazole versus other atypical antipsychotics commonly used to treat manic episodes (olanzapine, quetiapine and risperidone) to show that aripiprazole performed similarly to the comparator drugs in terms of efficacy and safety. Aripiprazole was demonstrated to perform better in safety outcomes of (1) less weight gain than olanzapine and quetiapine; and (2) less prolactin increase than olanzapine, quetiapine and risperidone. Results from the manufacturers' economic evaluation showed that use of aripiprazole second-line dominated all of the other treatment strategies that were considered. However, there was considerable uncertainty in this result, and clinical advisors indicated that the actual treatment strategy employed in practice is likely to be dependent upon the patient's characteristics. The ERG demonstrated that if this personalised medicine resulted in improved cost effectiveness for any of the other treatment strategies, then they had the potential to dominate use of aripiprazole second-line. In conclusion, whilst a strategy including aripiprazole appeared to be cost effective relative to a strategy without it, there was not robust enough evidence to recommend a specific place for aripiprazole within the treatment pathway.