Development and psychometric evaluation of the Diabetic Gastroparesis Symptom Severity Diary

Sheri Fehnel, Fred T Fiedorek, Lauren Nelson, Dana DiBenedetti, Sharon Spence, Robyn T Carson, Sheri Fehnel, Fred T Fiedorek, Lauren Nelson, Dana DiBenedetti, Sharon Spence, Robyn T Carson

Abstract

Background: Diabetic gastroparesis (DG) is defined as delayed gastric emptying with associated gastrointestinal symptoms, without mechanical obstruction. Patient-reported symptoms are critical for diagnosis and evaluation of treatment benefit in DG. The Diabetic Gastroparesis Symptom Severity Diary (DGSSD), a new patient-reported outcome measure, was developed for use in clinical trials to support product approval and labeling claims for DG treatments.

Materials and methods: Initial DGSSD development was based on a review of the existing instruments and qualitative research (focus groups and cognitive debriefing interviews) in 41 patients with DG. Psychometric evaluations (individual items and composite scores) were conducted using data from Phase IIa and IIb relamorelin clinical trials.

Results: Qualitative research in patients with DG resulted in a six-item DGSSD, included in the Phase IIa trial, addressing symptom severity for nausea, vomiting, abdominal pain, early satiety, and bloating, as well as vomiting frequency. An item addressing severity of postprandial fullness (PPF) was subsequently added based on regulatory advice and included in the Phase IIb trial. 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 and correlations with other measures matched hypothesized patterns; the discriminating ability and responsiveness of the DGSSD were also supported. Multiple methods supported the computation of a composite score based on items addressing nausea, abdominal pain, bloating, and PPF severity.

Conclusion: Qualitative and quantitative evidence support use of the DGSSD as a reliable and valid measure from which to derive endpoints to evaluate treatment benefit in future DG interventional trials.

Keywords: diabetes; instrument; patient-reported outcome; relamorelin.

Conflict of interest statement

Disclosure Financial arrangements of the authors with companies whose products may be related to the present report are listed here, as declared by the authors. SF, LN, and DD are employees of RTI Health Solutions, a consulting firm that received funding for the research described in this paper. RTC is an employee of and owns stock/stock options in Allergan plc. SS is a consultant with Motus Therapeutics, Inc. FTF is a former employee of Motus Therapeutics, Inc., a prior subsidiary of Rhythm Pharmaceuticals. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Descriptive statistics (mean scores and SDs) for DGSSD items at baseline and Week 4 (Phase IIa) (A) and at baseline and Week 12 (Phase IIb) (B). Note: Data include all participants with baseline vomiting severity score >0 and who received at least one dose of study drug (combined relamorelin and placebo treatment groups). Abbreviations: DGSSD, Diabetic Gastroparesis Symptom Severity Diary.
Figure 2
Figure 2
Exploratory factor analysis path diagram. Note: Diagram shows items with factor loadings >0.3. Straight arrows indicate direct relationships. Curved double-headed arrows on the same item represent variance. Latent variables (factors) are shown in ovals; manifest variables are shown in rectangles. Abbreviations: DGSSD, Diabetic Gastroparesis Symptom Severity Diary; PPF, postprandial fullness.

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