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Evaluation

Oral Presentation

Session: Lightning Session 2

Emulating 6 Cardiovascular Outcome Trials of Antihyperglycemics in Patients with Type 2 Diabetes: A Multinational Analysis Based on 3 Asian Real-World Databases

Tuesday, August 27, 2024
1:40 PM – 1:45 PM CEST
Location: Room III

    Presenting Author(s)

  • HK

    Hwa Yeon Ko, PharmD

    PhD student
    School of Pharmacy, Sungkyunkwan University, Suwon, South Korea, Republic of Korea

    Slides

    • Co-Author(s)

  • SP

    Sohee Park, PharmD, PhD (she/her/hers)

    Lecturer
    Aston Pharmacy School, United Kingdom

  • Ahhyung Choi, PharmD, PhD

    PhD Student
    School of Pharmacy, Sungkyunkwan University, Suwon, Korea
    Suwon-si, Republic of Korea

  • HJ

    Han Eol Jeong, MPH, PhD

    School of Pharmacy, Sungkyunkwan University, Suwon, South Korea, Republic of Korea

  • Brian Meng-Hsun Li, MClinPharm

    PhD student
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Taiwan, Taiwan (Republic of China)

  • Michael Chun-Yuan Cheng, MA (he/him/his)

    Research Associate
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Taiwan (Republic of China)

  • Miyuki Hsing-Chun Hsieh, PhD

    Immediate Past Chair of the ISPE Student Council
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    Chiayi City, Taiwan (Republic of China)

  • PA

    Philip C.M. Au, MPhil

    Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, University of Hong Kong, Hong Kong, Hong Kong

  • CC

    Ching Lung Cheung, PhD

    Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong

  • Edward Chia-Cheng Lai, PhD (he/him/his)

    Professor
    Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Taiwan
    National Cheng Kung University
    Tainan City, Taiwan (Republic of China)

  • Kenneth KC Man, PhD, CStat, FRSPH (he/him/his)

    Lecturer/Assistant Professor
    UCL School of Pharmacy
    London, United Kingdom

  • IW

    Ian Chi Kei Wong, PhD (he/him/his)

    Professor
    Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong

  • Ju-Young Shin, PhD

    Associate Professor
    School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
    Suwon, Republic of Korea

Background: Numerous efforts are ongoing to evaluate the validity of real-world evidence (RWE) studies by emulating randomized controlled trials (RCTs) using real-world data (RWD).

Objectives: To assess whether RWE studies from 2 Asian RWD can yield comparable results with RCTs by emulating 6 cardiovascular outcome trials of antihyperglycemics in patients with type 2 diabetes (T2D).

Methods: We emulated 6 RCTs (CAROLINA, CARMELINA, TECOS, SAVOR-TIMI, DECALRE-TIMI, EMPA-REG) using nationwide claims data of Korea (NHID) and Taiwan (NHIRD). An active comparator and new-user design was applied to include patients with T2D who initiated antihyperglycemics (dipeptidyl peptidase 4 inhibitors [DPP4i], sodium-glucose cotransporter 2 inhibitors [SGLT2i]) of each RCT. Propensity score matching was utilized to balance the distribution of 138 covariates. The primary outcome was a composite of myocardial infarction, stroke, or cardiovascular death. Patients were followed using an on-treatment approach given the lack of adherence in clinical practice. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox models, and subsequently compared with corresponding RCT estimates. The standardized difference (SD) for effect estimates of each RCT-RWD study pair < 1.96 denoted SD agreement. Each site converted local database to common data model and executed same analytics to get the results. We pooled effect estimates using random-effects meta-analysis and assessed heterogeneity between databases using the I2 statistic.

Results: All the 6 emulations (CAROLINA: HR 0.87, 95% CI 0.82-0.93, I2 0.0%; CARMELINA: 0.92, 0.67-1.27, 56.5%; TECOS: 0.91, 0.85-0.98, 0.0%; SAVOR-TIMI: 0.63, 0.56-0.71, 0.0%; DECALRE-TIMI: 0.52, 0.29-0.91, 76.4%; EMPA-REG: 0.58, 0.51-0.65, 0.0%) presented agreement in direction and statistical significance with their corresponding 6 RCTs. Emulations for CAROLINA, TECOS, and CARMELINA also achieved estimates that was within the 95% CI from the corresponding RCTs. All emulations for RCTs of DPP4i (CAROLINA: SD 1.36; TECOS: 1.13; CARMELINA: 0.67) met SD agreement, except for saxagliptin (SAVOR-TIMI: 4.93). The emulations for RCTs of SGLT2i (DECLARE-TIMI: SD 3.01; EMPA-REG: 4.10) failed to meet SD agreement, which might stem from challenges in selecting a placebo proxy in the local clinical practice of RWE studies.

Conclusions: In this binational analysis using 2 Asian healthcare databases, emulations yielded comparable clinical conclusions with corresponding RCTs, implicating the credibility of RWE studies using Asian RWD in patients with T2D. Continued consideration is warranted for emulation challenges raising discordance depending on agreement metrics.