Medical College of Wisconsin
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Optimizing the concentration and bolus of a drug delivered by continuous infusion. Biometrics 2011 Dec;67(4):1638-46



Pubmed ID


Pubmed Central ID




Scopus ID

2-s2.0-83655164291   8 Citations


We consider treatment regimes in which an agent is administered continuously at a specified concentration until either a response is achieved or a predetermined maximum infusion time is reached. Response is an event defined to characterize therapeutic efficacy. A portion of the maximum planned total amount administered is given as an initial bolus. For such regimes, the amount of the agent received by the patient depends on the time to response. An additional complication when response is evaluated periodically rather than continuously is that the response time is interval censored. We address the problem of designing a clinical trial in which such response time data and a binary indicator of toxicity are used together to jointly optimize the concentration and the size of the bolus. We propose a sequentially adaptive Bayesian design that chooses the optimal treatment for successive patients by maximizing the posterior mean utility of the joint efficacy-toxicity outcome. The methodology is illustrated by a trial in which tissue plasminogen activator is infused intraarterially as rapid treatment for acute ischemic stroke.

Author List

Thall PF, Szabo A, Nguyen HQ, Amlie-Lefond CM, Zaidat OO


Aniko Szabo PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Brain Ischemia
Clinical Trials as Topic
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Drug Therapy, Computer-Assisted
Fibrinolytic Agents
Infusions, Intra-Arterial
Survival Analysis
Survival Rate
Tissue Plasminogen Activator
Treatment Outcome
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a