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SUMMARY:Optimizing the Concentration and Bolus of a Drug Delivered by Cont
 inuous Infusion - Thall\, P (M.D. Anderson Cancer Center)
DTSTART:20110818T150000Z
DTEND:20110818T154500Z
UID:TALK32400@talks.cam.ac.uk
CONTACT:Mustapha Amrani
DESCRIPTION:We consider treatment regimes in which an agent is administere
 d continuously at a specified concentration until either a therapeutic res
 ponse is achieved or a predetermined maximum infusion time is reached. Add
 itionally\, a portion of the planned maximum total amount of the agent is 
 administered as an initial bolus. Efficacy is the time to response\, and t
 oxicity is a binary indicator of an adverse event that may occur after inf
 usion. The amount of the agent received by the patient thus depends on the
  time to response\, which in turn affect the probability of toxicity. An a
 dditional complication arises if response is evaluated periodically\, sinc
 e the response time is interval censored. We address the problem of design
 ing a clinical trial in which such response time data and toxicity are use
 d to jointly optimize the concentration and size of the initial bolus. We 
 propose a sequentially adaptive Bayesian design that chooses the optimal t
 reatment for each patient by maximizing the posterior mean utility of the 
 joint efficacy-toxicity outcome. The methodology is illustrated by a clini
 cal trial of tissue plasminogen activator (tPA) infused intra-arterially a
 s rapid treatment for acute ischemic stroke. The fundamental problem is th
 at too little tPA may not dissolve the clot that caused the stroke\, but t
 oo much may cause a symptomatic intra-cranial hemorrhage\, which often is 
 fatal. A computer simulation study of the design in the context of the tPA
  trial is presented.\n\n\n
LOCATION:Seminar Room 1\, Newton Institute
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