BACKGROUND: Diabetic gastroparesis (DG) is characterized by delayed gastric emptying with debilitating and recurring symptoms of vomiting, nausea, abdominal pain, bloating, early satiety, and postprandial fullness (PPF). We developed a patient-reported diary addressing the symptoms of DG appropriate for use in clinical trials to support product approval and labeling claims.
METHODS: Initial development of the Diabetic Gastroparesis Symptom Severity Diary (DGSSD) was based on review of the literature and existing instruments and qualitative research (focus groups and cognitive debriefing interviews) in 41 patients with DG. Psychometric evaluations of the DGSSD (individual items and composite scores) were conducted using data from both Phase 2a and Phase 2b clinical trials of relamorelin.
RESULTS: Qualitative research in DG patients resulted in a six-item version of the DGSSD addressing severity of nausea, vomiting, abdominal pain, early satiety, and bloating, as well as vomiting frequency. While participants described feeling excessively full compared to the amount eaten, early satiety and PPF were generally not described as separate symptoms. Only early satiety was included in the Phase 2a DGSSD; however, a PPF item was later added based on regulatory advice. As results of the psychometric evaluations were consistent, and the PPF item was included in Phase 2b only, reported results focus on the second evaluation. Measurement properties were generally strong for weekly averages of daily item and composite scores. Item-level intraclass correlation coefficients ranged from 0.79 to 0.97, Cronbach’s alpha for various 3- and 4-item composites ranged from 0.85 to 0.93, and correlations with other measures matched hypothesized patterns. Each DGSSD score was significantly lower among patients reporting less severe symptoms and higher among those reporting more severe symptoms on both global and symptom-specific status items (p<0.0001), and three effect-size methods demonstrated the responsiveness of the item-level and composite measures. Notably, the measurement properties of the PPF item were generally superior to those of the early satiety item, and vomiting frequency was highly skewed.
CONCLUSIONS: The qualitative and quantitative evidence corroborate use of the seven DGSSD items and a symptom severity composite as support for product approval and labeling claims in future DG trials. The composite formed from the four items addressing the severity of bloating, abdominal pain, nausea, and PPF may be most appropriate, given the performance of the PPF item compared to the early satiety item and the lack of distinction between PPF and early satiety from the patients’ perspective. Additionally, an endpoint based on vomiting-free weeks may be preferable to one based on a reduction in the number of episodes given the skewness of the frequency data.
