Source:http://linkedlifedata.com/resource/pubmed/id/18084008
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2008-6-19
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| pubmed:abstractText |
Late-onset (LO) toxicities are a serious concern in many phase I trials. Since most dose-limiting toxicities occur soon after therapy begins, most dose-finding methods use a binary indicator of toxicity occurring within a short initial time period. If an agent causes LO toxicities, however, an undesirably large number of patients may be treated at toxic doses before any toxicities are observed. A method addressing this problem is the time-to-event continual reassessment method (TITE-CRM, Cheung and Chappell, 2000). We propose a Bayesian dose-finding method similar to the TITE-CRM in which doses are chosen using time-to-toxicity data. The new aspect of our method is a set of rules, based on predictive probabilities, that temporarily suspend accrual if the risk of toxicity at prospective doses for future patients is unacceptably high. If additional follow-up data reduce the predicted risk of toxicity to an acceptable level, then accrual is restarted, and this process may be repeated several times during the trial. A simulation study shows that the proposed method provides a greater degree of safety than the TITE-CRM, while still reliably choosing the preferred dose. This advantage increases with accrual rate, but the price of this additional safety is that the trial takes longer to complete on average.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1468-4357
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
9
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
442-57
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| pubmed:meshHeading |
pubmed-meshheading:18084008-Bayes Theorem,
pubmed-meshheading:18084008-Brain Neoplasms,
pubmed-meshheading:18084008-Clinical Trials, Phase I as Topic,
pubmed-meshheading:18084008-Dose-Response Relationship, Drug,
pubmed-meshheading:18084008-Drug Design,
pubmed-meshheading:18084008-Drug Evaluation,
pubmed-meshheading:18084008-Drug Monitoring,
pubmed-meshheading:18084008-Drug Therapy,
pubmed-meshheading:18084008-Drug Toxicity,
pubmed-meshheading:18084008-Humans,
pubmed-meshheading:18084008-Markov Chains,
pubmed-meshheading:18084008-Maximum Tolerated Dose,
pubmed-meshheading:18084008-Monte Carlo Method,
pubmed-meshheading:18084008-Radiation-Sensitizing Agents,
pubmed-meshheading:18084008-Research Design,
pubmed-meshheading:18084008-Risk,
pubmed-meshheading:18084008-Time,
pubmed-meshheading:18084008-Treatment Outcome
|
| pubmed:year |
2008
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| pubmed:articleTitle |
Monitoring late-onset toxicities in phase I trials using predicted risks.
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| pubmed:affiliation |
Department of Biostatistics, MD Anderson Cancer Center, Houston, TX 77030, USA. bbekele@mdanderson.org
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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