Investigating Novel Predictions of Hypoglycemia Occurrence in Real-world Models (iNPHORM)

Hypoglycemia is the most common diabetes-related adverse event. However, it is often under-reported to healthcare providers by patients and simultaneously, not often asked about by healthcare providers. As a result, little is known about how often hypoglycemia occurs and consequently, which individuals with diabetes will experience such events. The aims of this study are to determine the real- world occurrence of hypoglycemia and develop/validate real-world risk prediction models for hypoglycemia. These risk prediction models will generate a risk score that indicates an individual's risk for hypoglycemia given their socio-demographic, clinical, and/or behaviour-related characteristics. They can be used to promote clinician awareness around patients' hypoglycemia risks, guide point- of-care and patient decision-making with regard to treatment changes, inform the development and conduct of population-based interventions, and lead to tailored, cost-effective management strategies.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Hypoglycemia; Diabetes Mellitus, Type 1

Detailed Description

The overarching purpose of the proposed investigation is to develop and validate three real-world risk prediction models for: 1) severe hypoglycemia, 2) non-severe daytime hypoglycemia, and 3) non-severe nighttime hypoglycemia, that are applicable to the general population with diabetes (Type 1 and Type 2). These prediction models, which will produce risk scores, will be generated using long-term, prospective data on the frequency and multidimensional risk factors of real-world hypoglycemia. Self-reported hypoglycemia data - a pragmatic and significant patient-important outcome in the clinical management of diabetes - will collected in a non-clinical setting as they are crucial to determining the true distributional burden of events and impactful avenues for prevention, especially given the known epidemiological challenges of existent data collection strategies (e.g., via RCT- or registry-based designs). The use of real-world data will also enhance the generalizability and thus, clinical value of hypoglycemia risk prediction models.

The study will employ an ambidirectional (one-year retrospective and one-year prospective) observational cohort design such that multiple exposures (i.e., risk factors) will be collected and evaluated in relation to the occurrence of an outcome (hypoglycemia events). Participants will be enrolled into a prospective, observational cohort referred to as the 'Diabetes iNPHORM Community'. Data will be collected through online questionnaires administered at baseline (to collect retrospective data) and each month of the one-year prospective period. A pilot test will be conducted prior to the enrollment of participants into the Diabetes iNPHORM Community. The purpose of this pilot test is to test the usability of the online question platform, flow and format of the questionnaires, and the readability of the questions.

Participants will be recruited into the pilot test and the observational cohort of the study from a pre-existing online panel representative of the general public that has been developed and managed by Ipsos Interactive Services (IIS), a global leader in survey conduct. All individuals in the pre-existing online panel provided profile information and consented to be approached by IIS and its subsidiary partners to complete surveys. For this study, individuals approached to participate in the pilot tests will not subsequently be invited to participate in the observational cohort.

• Study Type: Observational
• Enrollment (Actual): 1206

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10010
      • IPSOS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited into the pilot test and the observational cohort of the study from a pre-existing online panel representative of the general public developed and managed by Ipsos Interactive Services (IIS), a global leader in survey conduct. Within the USA, IIS and its subsidiary partners manage a nationwide panel of 65,000+ people with diabetes (~10,000 with T1DM and ~58,000 with T2DM); this panel will serve as the sampling frame for the current investigation. All individuals in the pre-existing online panel provided profile information and consented to be approached by IIS and its subsidiary partners to complete surveys. For this study, individuals approached to participate in the pilot tests will not subsequently be invited to participate in the observational cohort.

Description

Inclusion Criteria:

• Self-reported diagnosis of T1DM or T2DM
• Use of insulin and/or secretagogues for at least one year at the time of enrolment
• Living in the United States of America for at least one year at the time of enrolment

Exclusion Criteria:

• Unable to read and understand English
• Currently pregnant or pregnant within the previous year
• Currently participating in an interventional clinical trial or research study

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence proportions and densities of severe hypoglycemia, non-severe daytime hypoglycemia, and non-severe nighttime hypoglycemia	Self-reported through questionnaires	Up to 12 months prospectively
Risk scores for severe hypoglycemia, non-severe daytime hypoglycemia, non-severe nighttime hypoglycemia	Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-World Models (iNPHORM) Hypoglycemia Risk Score: Risk scores using the probabilities (0-100%) from our validated multivariable prediction models will be calculated to reflect the degree of risk due to the candidate variables (low to high risk scores will denote low to high risks of hypoglycemia occurrence, respectively). Any selected ranges of predicted probabilities used as boundaries for risk stratification will be justified. Details relevant to the calculation of subject-specific risks will be reported, including the intercepts and betas from the logistic regression models and nomograms.	Up to 12 months prospectively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory causal estimates of different treatment regimens and hypoglycemia rates	Derived from data captured through questionnaires	Up to 12 months prospectively

Collaborators and Investigators

• Sponsor: Stewart Harris
• Collaborators: Sanofi
• Investigators: Principal Investigator: Stewart Harris, MD MPH, Western University; Principal Investigator: Alexandria Ratzki-Leewing, PhD(c) MSc, Western University

Publications and helpful links

General Publications

• Ratzki-Leewing A, Black JE, Ryan BL, Harris SB. Real-world risk factors of confirmed or probable COVID-19 in Americans with diabetes: A prospective, community-based study (iNPHORM). Endocrinol Diabetes Metab. 2022 Jul;5(4):e342. doi: 10.1002/edm2.342. Epub 2022 May 29.
• Ratzki-Leewing A, Ryan BL, Zou G, Webster-Bogaert S, Black JE, Stirling K, Timcevska K, Khan N, Buchenberger JD, Harris SB. Predicting Real-world Hypoglycemia Risk in American Adults With Type 1 or 2 Diabetes Mellitus Prescribed Insulin and/or Secretagogues: Protocol for a Prospective, 12-Wave Internet-Based Panel Survey With Email Support (the iNPHORM [Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-world Models] Study). JMIR Res Protoc. 2022 Feb 11;11(2):e33726. doi: 10.2196/33726.
• Ratzki-Leewing AA, Ryan BL, Buchenberger JD, Dickens JW, Black JE, Harris SB. COVID-19 hinterland: surveilling the self-reported impacts of the pandemic on diabetes management in the USA (cross-sectional results of the iNPHORM study). BMJ Open. 2021 Sep 2;11(9):e049782. doi: 10.1136/bmjopen-2021-049782.

Study record dates

Study Major Dates

• Study Start (Actual): February 10, 2020
• Primary Completion (Actual): March 30, 2021
• Study Completion (Actual): March 30, 2021

Study Registration Dates

• First Submitted: December 19, 2019
• First Submitted That Met QC Criteria: January 2, 2020
• First Posted (Actual): January 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 13, 2021
• Last Update Submitted That Met QC Criteria: April 12, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: hypoglycemia; diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Hypoglycemia
• Other Study ID Numbers: 112986

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated device product: No