Pharmacokinetics-Guided Dose Allocation in Comparison with Binary Dose Spacing

Junxian Geng (), Shihai Lu, Sree Kurup, Benjamin Weber and Naitee Ting
Additional contact information
Junxian Geng: Boehringer Ingelheim Pharmaceuticals, Inc.
Shihai Lu: Boehringer Ingelheim Pharmaceuticals, Inc.
Sree Kurup: Boehringer Ingelheim Pharmaceuticals, Inc.
Benjamin Weber: Boehringer Ingelheim Pharmaceuticals, Inc.
Naitee Ting: Boehringer Ingelheim Pharmaceuticals, Inc.

Statistics in Biosciences, 2019, vol. 11, issue 3, No 10, 677-693

Abstract: Abstract In designing dose-ranging studies at early Phase II, one of the major challenges is dose allocation or dose spacing. Binary dose spacing (BDS) has been established over the years as a practical and useful way of allocating doses. In this manuscript, the pharmacokinetics (PK)-guided dose allocation, pharmacokinetics/pharmacodynamics (PK/PD)-guided dose allocations are compared with BDS. Additionally, a mixed dose allocation strategy is proposed and also compared. Simulations are performed to study various properties of these four dose allocation methods. The comparisons include 1. power of the PoC test; 2. bias on target dose estimation; 3. root mean square error (RMSE); 4. probability that the estimated dose delivers > 75% of true effect; and 5. slopes and confidence intervals of slopes. Results indicating that BDS performs reasonably well under most scenarios. The PK-guided approach performs similar to BDS, the PK/PD-guided approach performs better, if the PD information is reliable. However, if the PD information is not highly reliable, the mixed procedure could be considered.

Keywords: Dose range; Binary dose spacing; Pharmacokinetics/pharmacodynamics; Phase II; Clinical trial design (search for similar items in EconPapers)
Date: 2019
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
http://link.springer.com/10.1007/s12561-019-09261-3 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:11:y:2019:i:3:d:10.1007_s12561-019-09261-3

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

DOI: 10.1007/s12561-019-09261-3

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 ().