Sections 4.1 to 4.26 reflect the committee's consideration of the evidence submitted in December 2013 for the original appraisal and the subsequent responses to consultation received during the development of NICE technology appraisal guidance 371. The company included 2 randomised controlled trials in its original submission: EMILIA and TH3RESA. Both trials were international, open-label trials evaluating the safety and efficacy of trastuzumab emtansine (3.6 mg/kg every 3 weeks) for human epidermal growth factor receptor 2 (HER2)-positive, unresectable, locally advanced or metastatic breast cancer. EMILIA compared trastuzumab emtansine with lapatinib plus capecitabine, and TH3RESA compared it with the clinician's choice of treatment. The company used 4 additional randomised controlled trials, together with EMILIA, in a mixed treatment comparison of trastuzumab emtansine and the other comparators listed in the scope. Sections 4.27 to 4.35 reflect the committee's consideration of the evidence submitted for the Cancer Drugs Fund reconsideration. The new evidence included additional follow-up data from EMILIA, which was used to model overall survival. New cost-effectiveness analyses were done using a complex patient access scheme. The patient access scheme considered by the committee was subsequently replaced by a commercial access agreement between Roche and NHS England. The commercial access agreement provides similar reductions in the total costs of treatment to the latest patient access scheme offer, and a simpler operational approach. The details of the agreement are commercial in confidence.