Large-scale evidence generation and evaluation across a network of databases for type 2 diabetes mellitus (LEGEND-T2DM): a protocol for a series of multinational, real-world comparative cardiovascular effectiveness and safety studies.

Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE

Original Publication: [London] : BMJ Publishing Group Ltd, 2011-

Diabetes Mellitus, Type 2*/chemically induced ; Diabetes Mellitus, Type 2*/drug therapy ; Dipeptidyl-Peptidase IV Inhibitors*/therapeutic use ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use; Adult ; Humans ; Hypoglycemic Agents/adverse effects ; Reproducibility of Results ; Sulfonylurea Compounds/therapeutic use

Introduction: Therapeutic options for type 2 diabetes mellitus (T2DM) have expanded over the last decade with the emergence of cardioprotective novel agents, but without such data for older drugs, leaving a critical gap in our understanding of the relative effects of T2DM agents on cardiovascular risk.
Methods and Analysis: The large-scale evidence generations across a network of databases for T2DM (LEGEND-T2DM) initiative is a series of systematic, large-scale, multinational, real-world comparative cardiovascular effectiveness and safety studies of all four major second-line anti-hyperglycaemic agents, including sodium-glucose co-transporter-2 inhibitor, glucagon-like peptide-1 receptor agonist, dipeptidyl peptidase-4 inhibitor and sulfonylureas. LEGEND-T2DM will leverage the Observational Health Data Sciences and Informatics (OHDSI) community that provides access to a global network of administrative claims and electronic health record data sources, representing 190 million patients in the USA and about 50 million internationally. LEGEND-T2DM will identify all adult, patients with T2DM who newly initiate a traditionally second-line T2DM agent. Using an active comparator, new-user cohort design, LEGEND-T2DM will execute all pairwise class-versus-class and drug-versus-drug comparisons in each data source, producing extensive study diagnostics that assess reliability and generalisability through cohort balance and equipoise to examine the relative risk of cardiovascular and safety outcomes. The primary cardiovascular outcomes include a composite of major adverse cardiovascular events and a series of safety outcomes. The study will pursue data-driven, large-scale propensity adjustment for measured confounding, a large set of negative control outcome experiments to address unmeasured and systematic bias.
Ethics and Dissemination: The study ensures data safety through a federated analytic approach and follows research best practices, including prespecification and full disclosure of results. LEGEND-T2DM is dedicated to open science and transparency and will publicly share all analytic code from reproducible cohort definitions through turn-key software, enabling other research groups to leverage our methods, data and results to verify and extend our findings.
Competing Interests: Competing interests: This protocol is undertaken within Observational Health Data Sciences and Informatics (OHDSI), an open collaboration. RK is a founder of Evidence2Health, and receives grant funding from the US National Institutes of Health. MJS and PBR are employees of Janssen Research and Development and shareholders in John & Johnson. GH receives grant funding from the US National Institutes of Health and the US Food & Drug Administration and contracts from Janssen Research and Development. HMK receives grants from the US Food & Drug Administration, Medtronics and Janssen Research and Development, is co-founder of HugoHealth and chairs the Cardiac Scientific Advisory Board for UnitedHealth. MAS receives grant funding from the US National Institutes of Health, the US Department of Veterans Affairs and the US Food & Drug Administration and contracts from Janssen Research and Development and IQVIA.
(© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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K23 HL153775 United States HL NHLBI NIH HHS; R01 LM006910 United States LM NLM NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; R01 HG006139 United States HG NHGRI NIH HHS

Keywords: Cardiology; DIABETES & ENDOCRINOLOGY; Health informatics

0 (Dipeptidyl-Peptidase IV Inhibitors)
0 (Hypoglycemic Agents)
0 (Sodium-Glucose Transporter 2 Inhibitors)
0 (Sulfonylurea Compounds)

Date Created: 20220609 Date Completed: 20220613 Latest Revision: 20230325

20231215

PMC9185490

10.1136/bmjopen-2021-057977

35680274