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Nonclinical in vivo animal studies have to be completed before starting clinical studies of the pharmacokinetic behavior of a drug in human subjects. The classic complete data design, where each animal is sampled for analysis once per time point, is usually only applicable for large animals using the traditional two-stage approach. The first stage involves(More)
Nonclinical in vivo animal studies have to be completed before starting clinical studies of the pharmacokinetic behavior of a drug in humans. The drug exposure in animal studies is often measured by the area under the concentration time curve (AUC). The classical complete data design where each animal is sampled for analysis once per time point is usually(More)
BACKGROUND Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non-inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently(More)
Statistical comparison of organ weights between treated and untreated animals have traditionally been used to predict potential toxicity for patients. The manner of presentation of organ weight data, and the value of statistical analyses have been topics of discussion. Historically, a decision tree approach has been applied for statistical comparison of(More)
Pharmacokinetic studies are commonly performed using the two-stage approach. The first stage involves estimation of pharmacokinetic parameters such as the area under the concentration versus time curve (AUC) for each analysis subject separately, and the second stage uses the individual parameter estimates for statistical inference. This two-stage approach(More)
Pharmacokinetic studies are commonly analyzed using a two-stage approach where the first stage involves estimation of pharmacokinetic parameters for each subject separately and the second stage uses the individual parameter estimates for statistical inference. This two-stage approach is not applicable in sparse sampling situations where only one sample is(More)
A bootstrap based method to construct 1 − α simultaneous confidence intervals for relative effects in the one-way layout is presented. This procedure takes the stochastic correlation between the test statistics into account and results in narrower simultaneous confidence intervals than the application of the Bon-ferroni correction. Instead of using the(More)
Biotechnology derived therapeutics may induce an unwanted immune response leading to the formation of anti-drug antibodies (ADA). As a result the efficacy and safety of the therapeutic protein could be impaired. Neutralizing antibodies may, for example, affect pharmacokinetics of the therapeutic protein or induce autoimmunity. Therefore a drug induced(More)
Neutralizing antibodies against factor VIII (FVIII) remain the major complication in the replacement therapy of hemophilia A patients. To better understand the evolution of these antibodies it is important to generate comprehensive datasets which include both neutralizing and nonneutralizing antibodies, their isotypes, and IgG subclasses. We developed(More)
Nonclinical in vivo animal studies have to be completed before starting clinical studies of the pharmacokinetic behavior of a drug in humans. The drug exposure in animal studies is often measured by the area under the concentration versus time curve (AUC). The classical complete data design where each animal is sampled for analysis at every time point is(More)