Background: Hypoglycemia prognostic models contingent on prospective, self-reported survey data offer a powerful avenue for determining real-world event susceptibility and interventional targets.
Objective: This protocol describes the design and implementation of the 1-year iNPHORM (Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-world Models) study, which aims to measure real-world self-reported severe and nonsevere hypoglycemia incidence (daytime and nocturnal) in American adults with type 1 or 2 diabetes mellitus prescribed insulin and/or secretagogues, and develop and internally validate prognostic models for severe, nonsevere daytime, and nonsevere nocturnal hypoglycemia. As a secondary objective, iNPHORM aims to quantify the effects of different antihyperglycemics on hypoglycemia rates.
Methods: iNPHORM is a prospective, 12-wave internet-based panel survey that was conducted across the United States. Americans (aged 18-90 years) with self-reported type 1 or 2 diabetes mellitus prescribed insulin and/or secretagogues were conveniently sampled via the web from a pre-existing, closed, probability-based internet panel (sample frame). A sample size of 521 baseline responders was calculated for this study. Prospective data on hypoglycemia and potential prognostic factors were self-assessed across 14 closed, fully automated questionnaires (screening, baseline, and 12 monthly follow-ups) that were piloted using semistructured interviews (n=3) before fielding; no face-to-face contact was required as part of the data collection. Participant responses will be analyzed using multivariable count regression and machine learning techniques to develop and internally validate prognostic models for 1-year severe and 30-day nonsevere daytime and nocturnal hypoglycemia. The causal effects of different antihyperglycemics on hypoglycemia rates will also be investigated.
Results: Recruitment and data collection occurred between February 2020 and March 2021 (ethics approval was obtained on December 17, 2019). A total of 1694 participants completed the baseline questionnaire, of whom 1206 (71.19%) were followed up for 12 months. Most follow-up waves (10,470/14,472, 72.35%) were completed, translating to a participation rate of 179% relative to our target sample size. Over 70.98% (856/1206) completed wave 12. Analyses of sample characteristics, quality metrics, and hypoglycemia incidence and prognostication are currently underway with published results anticipated by fall 2022.
Conclusions: iNPHORM is the first hypoglycemia prognostic study in the United States to leverage prospective, longitudinal self-reports. The results will contribute to improved real-world hypoglycemia risk estimation and potentially safer, more effective clinical diabetes management.
Trial registration: ClinicalTrials.gov NCT04219514; https://clinicaltrials.gov/ct2/show/NCT04219514.
International registered report identifier (irrid): DERR1-10.2196/33726.
Keywords: adverse event; diabetes; hypoglycemia; insulin; internet survey; model; nonsevere hypoglycemia; protocol; real-world; risk; risk model; risk prediction; secretagogue; severe hypoglycemia; survey; symptom; type 1 diabetes mellitus; type 2 diabetes mellitus.
©Alexandria Ratzki-Leewing, Bridget L Ryan, Guangyong Zou, Susan Webster-Bogaert, Jason E Black, Kathryn Stirling, Kristina Timcevska, Nadia Khan, John D Buchenberger, Stewart B Harris. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 11.02.2022.