Pharmacometrics application in the time-to-event modelling of recurrent stroke among patients with type 2 diabetes mellitus
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1
School of Pharmaceutical Sciences, University of Science Malaysia, Malaysia
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2
Clinical Research Center, Hospital Seberang Jaya, Malaysia
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3
Clinical Research Center, Hospital Sultanah Nur Zahirah, Malaysia
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4
Department of Biological Science, Faculty of Science, Universiti Tunku Abdul Rahman (UTAR) Kampar Campus, Malaysia
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5
National Clinical Research Center, Malaysia
Background
Pharmacometrics approach is a better alternative than traditional methods to perform the time-to-event analysis, as it allows parametric quantification as well as taking into account censoring and time components into the analysis. The objective of this study was to develop a time-to-event (TTE) model in patients with type 2 diabetes mellitus (T2DM) using pharmacometrics modelling.
Methods
The data from 4622 patients with T2DM were obtained from the Malaysian National Stroke Registry and were analyzed using NONMEM. The maximum time of follow-up years was 10.8 years. TTE models of exponential, Gompertz and Weilbull were fitted to the data for the base model. The event was described as having a recurrent stroke after the first attack. The best base model was chosen for univariate analysis of covariates, for examples demographics, etc. The likelihood ratio test with a significance level (α) of 5% was used for the analysis. The final model was chosen based on the lowest objective function value, graphical and numerical evaluation as well as the scientific plausibility.
Results
Out of 4622 subjects, 227 (4.91%) developed a recurrent stroke within the maximum 10.8 years follow-up. The best base model was Gompertz with the baseline hazard for the Gompertz distribution was 0.0213 year-1. The hazard of developing recurrent stroke from the previous attack decreased with time with a half-life of 2.06 years, CI [0.83, 1.17]). Ischemic heart disease and hyperlipidemia increased the risk of recurrent stroke (HR, 2.06; 95% CI [1.55-2.75] and HR, 1.82; 95% CI [1.41-2.35], respectively).
Conclusion
Pharmacometrics analysis is a useful approach in performing the survival analysis. IHD and hyperlipidemia were significantly increased the risk of recurrent stroke after the first attack. The results in this study may add into the knowledge related to this issue, thus may help to guide the management for the prevention of recurrent stroke in T2DM patients.
Keywords:
pharmacometrics,
Recurrent stroke,
type 2 diabetes mellitus,
covariates,
Time-to-event
Conference:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019.
Presentation Type:
Oral Presentation
Topic:
Metabolic diseases
Citation:
Sheikh Ghadzi
S,
Harun
S,
Abidin
N,
Tangiisuran
B,
Zainal
H,
Looi
I,
Ibrahim
K,
Sidek
N,
Loo
K,
Lee
K and
Abdul Aziz
Z
(2019). Pharmacometrics application in the time-to-event modelling of recurrent stroke among patients with type 2 diabetes mellitus.
Front. Pharmacol.
Conference Abstract:
International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18)
“Seizing Opportunities and Addressing Challenges of Precision Medicine”.
doi: 10.3389/conf.fphar.2018.63.00076
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Received:
11 Oct 2018;
Published Online:
17 Jan 2019.
*
Correspondence:
Dr. Siti Maisharah Sheikh Ghadzi, School of Pharmaceutical Sciences, University of Science Malaysia, Penang, 11700, Malaysia, maisharah@usm.my