EconPapers    
Economics at your fingertips  
 

Recurrent events modelling of haemophilia bleeding events

Andrew C. Titman, Martin J. Wolfsegger and Thomas F. Jaki

Journal of the Royal Statistical Society Series C, 2021, vol. 70, issue 2, 351-371

Abstract: A pharmacokinetic–pharmacodynamic (PK‐PD) approach is developed for modelling the recurrent bleeding events in patients with severe haemophilia to investigate the relationship between factor VIII plasma activity level and the instantaneous risk of a bleed. The model incorporates patient‐level pharmacokinetic (PK) information obtained through measurements taken prior to the study which are used to fit a non‐linear mixed‐effects two‐compartment PK model. Dosing times within the study are combined with the PK model to provide the estimated factor VIII plasma level for all patients, which is used as a time‐dependent covariate within the recurrent events model. Methods are developed to correct the attenuation in covariate effects that would otherwise arise due to the discrepancy between estimated and true factor VIII. In contrast to existing methods proposed for such data, such as count data regression or time‐to‐event analysis, the new method allows all the bleeding times to be used to investigate the relationship between current factor VIII and risk of a bleed. The performance of the proposed estimators are assessed via simulation and found to outperform the naive estimator, which treats the estimated factor VIII levels as if they were measured without error, both in terms of bias and mean squared error.

Date: 2021
References: Add references at CitEc
Citations: Track citations by RSS feed

Downloads: (external link)
https://doi.org/10.1111/rssc.12462

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:bla:jorssc:v:70:y:2021:i:2:p:351-371

Ordering information: This journal article can be ordered from
http://ordering.onli ... 1111/(ISSN)1467-9876

Access Statistics for this article

Journal of the Royal Statistical Society Series C is currently edited by R. Chandler and P. W. F. Smith

More articles in Journal of the Royal Statistical Society Series C from Royal Statistical Society Contact information at EDIRC.
Bibliographic data for series maintained by Wiley Content Delivery ().

 
Page updated 2021-05-12
Handle: RePEc:bla:jorssc:v:70:y:2021:i:2:p:351-371