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Activity Number:
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425
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Type:
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Contributed
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Date/Time:
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Wednesday, August 6, 2003 : 2:00 PM to 3:50 PM
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Sponsor:
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Biopharmaceutical Section
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| Abstract - #300733 |
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Title:
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Comparing Two Treatments by Using a Biomarker with Assay Limit
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Author(s):
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Y. H. Josh Chen*+ and A. Lawrence Gould and Michael L. Nessly
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Companies:
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Merck Research Laboratories and Merck Research Laboratories and Merck & Co., Inc.
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Address:
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PO Box 4, West Point, PA, 19486,
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Keywords:
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biomarker ; assay limit ; limit of quantification (LoQ) ; Mann-Whitney-Wilcoxon rank test ; HIV clinical trials
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Abstract:
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The plasma level of HIV RNA has been shown to be a strong prognostic biomarker for clinical progression and death in HIV infected patients and is widely used as the primary outcome in clinical trials to evaluate antiretroviral treatments. Currently approved assays to measure plasma HIV RNA level have a lower limit of reliable quantification (LoQ). In the current regulatory guidelines, the proportion of patients achieving HIV RNA levels below the assay limit at a certain time (e.g., 24 or 48 weeks) should be the primary endpoint for regulatory approval. However, for patients who have failed many other antiretroviral therapies, having a substantial decrease in the viral load without achieving LoQ is also considered beneficial. We introduce a rank test which incorporates the treatment difference in the proportion of patients achieving HIV RNA levels below LoQ and the difference in the viral decrease in patients with HIV RNA levels above LoQ. The experimental treatment with more patients achieving HIV RNA below LoQ and a greater HIV RNA decrease in patients with HIV RNA levels above LoQ is better than the control. An example is used to illustrate this approach.
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