Estimating Treatment Effects for Recurrent Events in the Presence of Rescue Medications: An Application to the Immune Thrombocytopenia Study

Fei Gao, Donglin Zeng, Helen Wei, Xuena Wang and Joseph G. Ibrahim ()
Additional contact information
Fei Gao: University of North Carolina
Donglin Zeng: University of North Carolina
Helen Wei: Global Biostatistical Science, Amgen Inc.
Xuena Wang: Global Biostatistical Science, Amgen Inc.
Joseph G. Ibrahim: University of North Carolina

Statistics in Biosciences, 2018, vol. 10, issue 2, No 12, 473-489

Abstract: Abstract In many clinical studies, patients may experience the same type of event of interest repeatedly over time. However, the assessment of treatment effects is often complicated by the rescue medication uses due to ethical reasons. For example, in the motivating trial in studying the Immune Thrombocytopenia (ITP), when the interest lies in evaluating the treatment benefit of investigational product (IP) on reducing patient’s repeated bleeding, rescue medication such as platelet transfusions may be allowed to raise platelet counts. Both the intention-to-treat analysis and treating the intermediate rescue medication as covariate tend to attenuate the treatment benefit, and the estimates can be biased if interpreted as causal. In this paper, we propose a general causal framework when intermediate rescue medications are informative. We adopt the inverse weighted estimation approach to estimate the treatment effect, where weights are constructed to reflect time-dependent medication use probabilities. The proposed estimators are shown to be asymptotically normal and are demonstrated to perform well in small-sample simulation studies. The application to the ITP studies reveals a stronger benefit of using IP in reducing bleeding.

Keywords: Causal effect; Immune thrombocytopenia; Inverse weighted estimating equations; Recurrent events; Rescue medication (search for similar items in EconPapers)
Date: 2018
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
http://link.springer.com/10.1007/s12561-016-9164-x Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:spr:stabio:v:10:y:2018:i:2:d:10.1007_s12561-016-9164-x

Ordering information: This journal article can be ordered from
http://www.springer.com/journal/12561

DOI: 10.1007/s12561-016-9164-x

Access Statistics for this article

Statistics in Biosciences is currently edited by Hongyu Zhao and Xihong Lin

More articles in Statistics in Biosciences from Springer, International Chinese Statistical Association
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().