DDMODEL00000104: Time to conversion of acute A-fib after intravenous digoxin

  public model
Short description:
A model characterizing time to conversion to sinus rhythm under digoxin and placebo in acute atrial fibrillation
Original code
  • Characterizing time to conversion to sinus rhythm under digoxin and placebo in acute atrial fibrillation
  • Stefanie Hennig, Lena E. Friberg, Mats O. Karlsson
  • PAGE-meeing(18), 6/2009
  • Department of Pharmaceutical Bioscience, Uppsala University, Sweden
  • The underlying trial was a randomized, double-blind comparison of intravenously administered digoxin and placebo in patients with acute atrial fibrillation (DAAF). The primary end point was conversion to sinus rhythm within 16 h after randomization, while effect on heart rate (HR) was a secondary end point. The primary publication concluded: “There was no clear correlation between serum concentration of digoxin and changes in ECG or HR”. A later analysis reported on the population pharmacokinetics (PK) of digoxin and a HR model. Here, the aim was to evaluate if any predictor of conversion to sinus rhythm can be found using a Time-to-event (TTE) analysis.
Shijun Wang
Context of model development: Clinical end-point;
Long technical model description: Data from the studies were analyzed using the Laplace method in NONMEM VI. The F_Flag functionality was used to simultaneously predict the continuous data (PK and HR observations) and estimate probabilities for the categorical data. Since the PK and HR analyses were performed previously, PPP&D[3] was used for the combined PKPD and TTE analysis. The final model was also rerun fitting the HR and the conversion data simultaneously. The assessment of statistical significance of additional parameters was based on the difference between the OFV at 5% significance. The predicted performance of the TTE analysis was assessed using Kaplan-Meier VPC graphics.;
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: Randomized, double-blind comparison of intravenously administered digoxin and placebo in patients with acute atrial fibrillation.;
Modelling task in scope: estimation;
Nature of research: Clinical research & Therapeutic use;
Therapeutic/disease area: Cardiovascular;
Annotations are correct.
This model is not certified.
  • Model owner: Shijun Wang
  • Submitted: Dec 11, 2015 2:07:19 PM
  • Last Modified: Jun 3, 2016 11:14:58 AM
Revisions
  • Version: 12 public model Download this version
    • Submitted on: Jun 3, 2016 11:14:58 AM
    • Submitted by: Shijun Wang
    • With comment: Edited model metadata online.
  • Version: 4 public model Download this version
    • Submitted on: Dec 11, 2015 2:07:19 PM
    • Submitted by: Shijun Wang
    • With comment: Edited model metadata online.
 
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