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L V Rubinstein

Publications and source records attributed to L V Rubinstein.

22 records · Page 2Linked to original sources

Monitoring rules for stopping accrual in comparative survival studies.

It is useful to separate the decision to stop accrual from the decision to perform a final data analysis in comparative survival trials. Rules for monitoring survival studies are presented that allow for early termination of accrual if evidence mounts against one therapy and if the decision to stop accrual will not prolong the time to analysis unduly. It is shown that these rules for stopping accrual do not detectably perturb the final analysis, which includes a logrank test of no treatment effect and estimation of the log relative hazard with confidence intervals. These methods take advantage of the reservoir of information represented by patients still at risk at the time accrual ceases. Especially with moderate or rapid accrual rates the average number of patients accrued is often reduced substantially and the time to analysis prolonged only slightly.

Clinical Trials as Topic↗

Glucose metabolism and the percentage of glucose derived from alanine: response to exogenous glucose infusion in tumor-bearing and non-tumor-bearing rats.

Glucose and alanine metabolism were investigated in non-tumor-bearing (NTB) and tumor-bearing (TB) male F344 rats after a 24-hr fast and during the infusion of either 0.9% NaCl solution or glucose at 0.67 or 2.35 mg per 100 g total body weight per min. During 0.9% NaCl solution infusion, the plasma glucose level was higher (98.2 +/- 4.0 versus 85.8 +/- 8.1 mg per di; p less than 0.05), the whole-blood lactate level was lower (5.8 +/- 0.8 versus 8.3 +/- 1.6 mg per di; p less than 0.05), the glucose turnover rate was lower (0.72 +/- 0.04 versus 0.88 +/- 0.13 mg per 100 g total body weight per min; p less than 0.05), alanine turnover rate and the percentage of glucose derived from alanine was measured by [14C]alanine in the NTB and compared to the TB animals. In response to glucose infusions, the whole-blood lactate level rose in both groups but remained lower (7.1 +/- 0.9 versus 10.5 +/- 2.4 mg per dl at 0.67 mg per 100 g total body weight per min, p less than 0.05; 9.1 +/- 1.1 versus 19.3 +/- 5.5 mg per dl at 2.35 mg per 100 g total body weight per min, p less than 0.05; NTB versus TB) in the NTB than in the TB animals. The endogenous production rate of glucose as measured by [3H]glucose displayed a similar response to exogenous substrate in the NTB and TB animals but required a higher plasma glucose concentration to effect a similar degree of suppression in the TB group. The alanine turnover rate rose to a similar level, and the percentage of glucose derived from alanine was similarly depressed in the NTB and TB animals at each glucose infusion rate.

Alanine↗

Discrimination techniques applied to the NCI in vitro anti-tumour drug screen: predicting biochemical mechanism of action.

The National Cancer Institute currently tests approximately 400 compounds per week against a panel of human tumour cell lines in order to identify potential anti-cancer drugs. We describe several approaches, based on these in vitro data, to the problem of identifying the primary biochemical mechanism of action of a compound. Using linear and non-parametric discriminant procedures and cross-validation, we find that accurate identification of the mechanism of action is achieved for approximately 90 per cent of a diverse collection of 141 known compounds, representing six different mechanistic categories. We demonstrate that two-dimensional graphical displays of the compounds in terms of the initial three principal components (of the original data) result in suggestive visual clustering according to mechanism of action. Finally, we compare the classification accuracy of the statistical discrimination procedures with the accuracy obtained from a neural network approach and, for our example, we find that the results obtained from the various approaches are similar.

Antineoplastic Agents↗