Optimizing the concentration and bolus of a drug delivered by continuous infusion. Biometrics 2011 Dec;67(4):1638-46
Date
03/16/2011Pubmed ID
21401568Pubmed Central ID
PMC3137757DOI
10.1111/j.1541-0420.2011.01580.xScopus ID
2-s2.0-83655164291 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
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 OOAuthor
Aniko Szabo PhD Professor in the Data Science Institute department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Brain IschemiaClinical Trials as Topic
Data Interpretation, Statistical
Dose-Response Relationship, Drug
Drug Therapy, Computer-Assisted
Fibrinolytic Agents
Humans
Infusions, Intra-Arterial
Stroke
Survival Analysis
Survival Rate
Tissue Plasminogen Activator
Treatment Outcome
