A sequential procedure for a phase II efficacy trial in hypercholesterolemia.

The design of a phase II placebo-controlled efficacy trial to evaluate a new treatment for hypercholesterolemia using a sequential procedure is presented. The sequential procedure used is the triangular test which offers flexibility of monitoring and allows early stopping even when the null hypothesis is "accepted." The primary response is reduction in total serum cholesterol level, which is assumed to be normally distributed with unknown variance. The treatment difference is parameterized in terms of the standardized difference between the means. The accuracy of the error rates of the triangular test using this parameterization is compared with the test based on the difference between the means.

[1]  M A Fischl,et al.  The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[2]  F. J. Anscombe.  Normal likelihood functions , 1964 .

[3]  M A Fischl,et al.  The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. , 1987, The New England journal of medicine.

[4]  S. Pocock.  Group sequential methods in the design and analysis of clinical trials , 1977 .

[5]  D. A. Sprott.  Normal likelihoods and their relation to large sample theory of estimation , 1973 .

[6]  C. Meinert,et al.  A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results. , 1970, Diabetes.

[7]  A A Tsiatis,et al.  Exact confidence intervals following a group sequential test. , 1984, Biometrics.

[8]  P. O'Brien,et al.  A multiple testing procedure for clinical trials. , 1979, Biometrics.

[9]  K. K. Lan,et al.  Discrete sequential boundaries for clinical trials , 1983 .

[10]  Anastasios A. Tsiatis,et al.  Exact confidence intervals following a group sequential trial: A comparison of methods , 1988 .

[11]  John Whitehead,et al.  On the bias of maximum likelihood estimation following a sequential test , 1986 .

[12]  P. Armitage,et al.  Repeated Significance Tests on Accumulating Data , 1969 .

[13]  P. Armitage.  Sequential Medical Trials , 1961, Biomedicine / [publiee pour l'A.A.I.C.I.G.].

[14]  J Benichou,et al.  Application of the triangular test to phase II cancer clinical trials. , 1990, Statistics in medicine.

[15]  N L Geller,et al.  Interim analyses in randomized clinical trials: ramifications and guidelines for practitioners. , 1987, Biometrics.

[16]  S. Pocock,et al.  Size of cancer clinical trials and stopping rules. , 1978, British Journal of Cancer.

[17]  T. W. Anderson.  A MODIFICATION OF THE SEQUENTIAL PROBABILITY RATIO TEST TO REDUCE THE SAMPLE SIZE , 1960 .

[18]  J. Whitehead,et al.  An improved approximation for calculation of confidence intervals after a sequential clinical trial. , 1990, Statistics in medicine.

[19]  J. Whitehead.  Overrunning and underrunning in sequential clinical trials. , 1992, Controlled Clinical Trials.

[20]  K K Lan,et al.  The B-value: a tool for monitoring data. , 1988, Biometrics.

[21]  D. Siegmund.  Sequential Analysis: Tests and Confidence Intervals , 1985 .

[22]  J. Whitehead,et al.  A FORTRAN program for the design and analysis of sequential clinical trials. , 1983, Computers and biomedical research, an international journal.