The National Institute of Mental Health (NIMH) funded the $42.6 million CATIE study in 1999 to compare the effectiveness of first- and second-generation antipsychotics. The first-generation antipsychotic perphenazine was chosen to be compared with three second-generation medications: olanzapine, quetiapine, and risperidone. A small number of patients were randomized to receive ziprasidone, which was approved during the course of the trial. CATIE was considered a landmark trial because of its size, duration, and public sponsorship. Furthermore, it was designed to be generalizable to real-world clinical settings through limited exclusion criteria, the enrollment of patients from diverse settings, and the flexible dosing protocols it permitted. The primary outcome measure, time to discontinuation of the study medication for any cause, was also chosen because of its relevance to clinical practice—it represents a summary measure of effectiveness that captures both the effectiveness and tolerability of treatment.