Patent ID: 6041788
Filing Date: 2000-03-28
Classification: G16H

Abstract:
A method for evaluating drug effect in the a multiple dose clinical trial comprising:(a) Selecting N, the number of patients at the selected dose group by the end of trial, and .alpha. between 0 aid 1, a proportion of N patients per group enrolled by the time of dose selection,(b) Estimating drug effect of each dose group using the proportion of success among .alpha.N patients in each dose group when they finish their treatment evaluation,(c) Selecting a dose of the test drug which has the highest observed success rate,(d) Estimating the bias between the estimated drug effect and the true drug effect of the selected dose group as ##EQU25## if two doses of the test drug are tested; as ##EQU26## if three doses of the test drug are tested; or as ##EQU27## where ##EQU28## if four doses of the test drug are tested, (e) Estimating the variance of p.sub.s -p.sub.s, the difference between the estimated drug effect and the true drug effect of the selected dose group as ##EQU29## if two doses of the test drug are tested; as ##EQU30## where ##EQU31## if three doses of the test drug are tested; or as ##EQU32## where ##EQU33## if four doses of the test drug are tested, (f) If .alpha..notident.1, enrolling (1-.alpha.)N patients per group to the selected dose group and the control group; otherwise, go to step (h),(g) Estimating the drug effect of the selected dose group after dose selection using the proportion of success among the patients in the selected group enrolled after the dose selection and estimating the variance of this estimate as.sigma..sub.aft.sup.2 p.sub.aft (1p.sub.aft)/1-.alpha.)N (3).(h) Estimating the drug effect of the control group using the proportion of success in the total patients of the control group and estimating the variance of this estimate as.sigma..sub.c.sup.2 =p.sub.c (1-p.sub.c)/N (4),(i) Constructing the overall estimate for the drug effect of the selected dose asp=.alpha.p.sub.s +(1-.alpha.)p.sub.aft -.alpha.b.sub.12 (.gamma.)(5),(j) Constructing a two-sided 95% confidence interval for the difference of drug effects between the selected dose of the test drug and the control treatment as ##EQU34## (k) Calculating p value, the statistical significance of the difference for the drug effects between the selected dose of the test drug and the control treatment as ##EQU35## (l) Using the significance level in step (k), the confidence interval in step (j), the overall estimate for the drug effect of the selected dose in step (i), estimate of bias in step (d) or the estimate of the variance of p.sub.s -p.sub.s in step (e) to justify the efficacy of the selected dose of the test drug in the New Drug Application of the test drug,(m) Using the significance level in step (k), the confidence interval in step (j), the overall estimate for the drug effect of the selected dose in step (i), estimate of bias in step (d) or the estimate of the variance p.sub.s -p.sub.s in step (e) to justify the efficacy of the selected dose of the test drug in the labeling of the test drug,(n) Using the significance level in step (k), the confidence interval in step (j), the overall estimate for the drug effect of the selected dose in step (i), estimate of bias in step (d) or the estimate of the variance p.sub.s -p.sub.s in step (e) to justify the efficacy of the selected dose of the test drug in the advertisement of the test drug.