This paper is an account of a Phase III placebo-controlled clinical evaluation of an experimental treatment for stroke. The motivation for choosing a sequential design is discussed, as well as the technique for determining the triangular stopping boundaries used. The primary patient response was an ordinal performance scale evaluated three months after treatment. Plans made for incorporating delayed observations and baseline evaluations into the analysis are described.
The trial has now been completed. The conduct of the interim and final analyses are described, and the study results and conclusions presented.
WhiteheadJ. The Design and Analysis of Sequential Clinical Trials. 2nd Edition. Chichester, United Kingdom: Ellis Horwood; 1992.
2.
WhiteheadJBrunierH. PEST2.0 Operating Manual. Reading, United Kingdom: Reading University; 1989.
3.
HackettGHHarrisMNEPlantevinOMAnaesthesia for out-patient termination of pregnancy, a comparison of two anaesthetic techniques. Br J Anaesthesia. 1982;54: 865–870.
4.
JonesDRNewmanCEWhiteheadJ. The design of a sequential clinical trial for the comparison of two lung cancer treatments. Stat Med.1982;1: 73–82.
5.
StorbRDeegJWhiteheadJMethotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med.1986;314: 729–735.
6.
MontanerJSGLawsonLMLevittNCorticosteroids prevent early deterioration in patients with moderately severe pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS). Ann Inter Med.1990;113: 14–20.
7.
MahoneyFIBarthelDW. Functional evaluation: the Barthel index. Maryland State Med J.1965;14: 61–65.
8.
ArmitageP. Sequential Medical Trials. 2nd Edition. Oxford, England: Blackwell; 1975.
9.
PocockSJ. Clinical Trials: A Practical Approach. New York: Wiley; 1983.
10.
WhiteheadJ. Overrunning and underrunning in sequential clinical trials. Controlled Clinical Trials. 1992;13: 106–121.
11.
ArmitagePBerryG. Statistical Methods in Medical Research. Oxford, United Kingdom: Blackwell; 1987.
12.
MannHBWhitneyDR. On a test of whether one of two variables is stochastically larger. Ann Math Stat. 1947;33: 498–512.
13.
SiegelS. Nonparametric statistics for the behavioral sciences. Tokyo: McGraw-Hill, Kogakusha; 1956.
14.
OrgogozoJMDartiguesJF. Clinical trials in acute brain infarction. The question of assessment criteria. In BattistiniN (eds): Acute Brain Ischemia. Medical and Surgical Therapy. New York: Raven Press; 1986, 282–289.
15.
McCullaghP. Regression models for ordinal data. J R Stat Soc. 1980;42: 109–142.
16.
SAS Institute Inc.SAS/STAT™ User's Guide, Release 6.03 Edition. Cary, NC: SAS Institute Inc.; 1988.
17.
SAS Institute Inc.SAS/IML™ User's Guide, Release 6.03 Edition. Cary, NC: SAS Institute Inc.; 1988.
18.
SAS Institute Inc.SAS® Technical Report P-200, SAS/STAT® Software: CALIS and LOGISTIC Procedures, Release 6.04. Cary, NC: SAS Institute Inc.; 1990.
