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P31 analyzing chemosensitivity assays for Acute Myelogenic Leukemia
129s
Abstracts
the setting up of the European Medicines Evaluation Agency (BMEA) and adoption of the EU CPMP Note for Guidance on Biostatistical Methodology in Clinical Trials. Of the 14 full respondents, three (Sweden, Germany, and UK) reported employing professional statisticians to review licence applications and/or clinical trial protocols. In most countries only selected licence applications are reviewed statistically, selected on statistical complexity by non-statistical assessors. There are some restrictions on discussion of applications/protocols with statisticians working for the sponsors. As a result of adoption of the (CPMP) Biostatistical guidelines, Germany is intending to employ more statisticians and the possibility is under consideration in the Netherlands, Greece and Switzerland. Almost all of the remaining respondents report that they do not intend to employ (more) statisticians. However, Austria, Belgium, Denmark, Ireland and Finland are proposing to make more use of statistical advisors. The evident range of resource provision and procedures may indicate possible obstacles to rapid and effective international harmonization. F31 ANALYZING CHEMOSENSITIVITY ASSAYS FOR ACUTE MYELOGENIC LEUKEMIA P.M. Simpson, M. Hamre, S. Buck and Y. Ravindranath Wayne State University Detroit, Michigan Treatment for Acute Myelogenic Leukemia patients has improved over the last 20 years. Increasingly, in vitro drug sensitivity results seem important and appear to offer strong prognostic evidence to modify treatment and hence outcome. However, the methodology associated with analyzing patients’ assays is often crude, with linear interpolation used to calculate the concentration of a chemotherapeutic agent which provided a lethal dose to 50% of the cells. No error estimates are possible with this analysis. With the possible use of these in vitro samples in the design of clinical trials it will become imperative to evaluate assays in the best way, so that indices may be developed which will give high sensitivity and speciticity for response to chemotherapy. We have observed cellular proliferation as high as 700% occurring during the assay. In addition there is some evidence that there- is otten a mixture of dierent types of cells or a dual response in these assays. This suggests the need for improved analytic methods. To fit assay data, we generalize T-CChou’s median effects model and use the National Cancer Institute’s recommendations for drug screening with proliferating cell lines, to fit non-linear mixture models giving 95% profile limits. With anthracyclines, we find a mixture of two distributions seems optimal whereas with other drugs one distribution may be adequate. We argue that our analysis results in an improved stmrmary of the available data and we investigate how our results can improve sensitivity and specificity of derived predictive factors in the plaming and analysis of a clinical trial.
Abstracts
the setting up of the European Medicines Evaluation Agency (BMEA) and adoption of the EU CPMP Note for Guidance on Biostatistical Methodology in Clinical Trials. Of the 14 full respondents, three (Sweden, Germany, and UK) reported employing professional statisticians to review licence applications and/or clinical trial protocols. In most countries only selected licence applications are reviewed statistically, selected on statistical complexity by non-statistical assessors. There are some restrictions on discussion of applications/protocols with statisticians working for the sponsors. As a result of adoption of the (CPMP) Biostatistical guidelines, Germany is intending to employ more statisticians and the possibility is under consideration in the Netherlands, Greece and Switzerland. Almost all of the remaining respondents report that they do not intend to employ (more) statisticians. However, Austria, Belgium, Denmark, Ireland and Finland are proposing to make more use of statistical advisors. The evident range of resource provision and procedures may indicate possible obstacles to rapid and effective international harmonization. F31 ANALYZING CHEMOSENSITIVITY ASSAYS FOR ACUTE MYELOGENIC LEUKEMIA P.M. Simpson, M. Hamre, S. Buck and Y. Ravindranath Wayne State University Detroit, Michigan Treatment for Acute Myelogenic Leukemia patients has improved over the last 20 years. Increasingly, in vitro drug sensitivity results seem important and appear to offer strong prognostic evidence to modify treatment and hence outcome. However, the methodology associated with analyzing patients’ assays is often crude, with linear interpolation used to calculate the concentration of a chemotherapeutic agent which provided a lethal dose to 50% of the cells. No error estimates are possible with this analysis. With the possible use of these in vitro samples in the design of clinical trials it will become imperative to evaluate assays in the best way, so that indices may be developed which will give high sensitivity and speciticity for response to chemotherapy. We have observed cellular proliferation as high as 700% occurring during the assay. In addition there is some evidence that there- is otten a mixture of dierent types of cells or a dual response in these assays. This suggests the need for improved analytic methods. To fit assay data, we generalize T-CChou’s median effects model and use the National Cancer Institute’s recommendations for drug screening with proliferating cell lines, to fit non-linear mixture models giving 95% profile limits. With anthracyclines, we find a mixture of two distributions seems optimal whereas with other drugs one distribution may be adequate. We argue that our analysis results in an improved stmrmary of the available data and we investigate how our results can improve sensitivity and specificity of derived predictive factors in the plaming and analysis of a clinical trial.