OBJECTIVES: Inclusion of patient outcome assessments in international clinical trials necessitates that cross-culturally valid instrument data be pooled across countries. Our primary objective is to discuss the development of patient outcome assessments for use in international trials of patients with upper gastrointestinal disorders. METHODS: We reviewed the literature and conducted interviews with subjects and clinical experts prior to developing symptom and quality of life (QOL) instruments for patients with upper GI disorders. The instruments were reviewed by clinical experts and cognitive debriefing of subjects was performed. Following these procedures, forward and backward translation of the instruments into twenty languages was performed. RESULTS: A total of approximately 120 subjects with gastroesophageal reflux disease, dyspepsia, or gastroparesis and 12 clinical experts from six countries were interviewed to determine symptoms and QOL issues they deemed important. The resulting instruments are the Patient Assessment of Upper GastroIntestinal Disorders-Symptom Severity Index (PAGI-SYM) and Quality of Life Index (PAGI-QOL). The PAGI-SYM contains 37 items and six modules representing heartburn, reflux/regurgitation, nausea/vomiting, abdominal pain/discomfort, bloating/early satiety/fullness and other symptoms. The PAGI-QOL has 49 items divided into two sections, QOL and a general section. The QOL section is comprised of seven modules: daily activities, concentration/sleep, social activities, clothing, diet, relationships, and psychological state/emotions. The general section contains six items measuring severity of GI problems, satisfaction, and relief. CONCULSION: Outcome measures for international trials should undergo comprehensive development and rigorous linguistic validation processes. Initial psychometric testing is currently underway to ensure the instruments will behave appropriately across countries.