Showing papers on "Subgroup analysis published in 1989"
TL;DR: The various ways in which prognostic information can be included in the analysis of treatment effect in clinical trials are discussed, which are an informative and needed complement to an analysis of overall treatment effect.
62 citations
TL;DR: The "classification tree" technique is proposed, which combines the possible subgroup constellations to subgroup clusters with homogeneous response within the cluster and inferences about the interaction structure can be obtained.
29 citations
TL;DR: External validity was evident from data in the literature indicating that a rare tendency of the many drugs that prolong the QT interval to cause torsade de pointes and fatal arrhythmias is exacerbated by hypokalemia of the degree caused by potassium losing diuretics.
Abstract: Publication of the results of a large-scale randomized control trial (RCT) of the anti-serotonin drug ketanserin in patients with intermittent claudication offers an opportunity to examine the validity of retrospective subgroup analyses to generate hypotheses for further validation. This was prompted by an unanticipated adverse interaction which occurred in a subgroup of patients receiving both ketanserin and potassium-losing diuretics. The quality of the study ranked it in the 99th percentile of over 400 RCTs evaluated by a quality scoring system. The subgroup analysis resulted from the emergence during the study of a highly significant excess mortality in the patients on diuretics (relative risks 0.88 for those on ketanserin alone, 0.95 on potassium-sparing and 2.44 for those on potassium-losing diuretics (P = 0.007). External validity was evident from data in the literature indicating that a rare tendency of the many drugs that prolong the QT interval to cause torsade de pointes and fatal arrhythmias is exacerbated by hypokalemia of the degree caused by potassium losing diuretics. When the ketanserin and placebo treated patients also on potassium-losing diuretics are removed from the analyses there is a 23% reduction in endpoints which the power is no longer sufficient to detect as significant. There is also an apparent lag phase. Further study of the drug is clearly indicated.
8 citations
TL;DR: In this paper, a large sample theory of two-sample post-stratified permutational tests is developed with a broad class of restricted randomization treatment allocation rules, and the test procedures proposed here are illustrated with a real-life example.
Abstract: In a clinical trial to compare two treatments, subjects may be allocated sequentially to treatment groups by a restricted randomization rule. Suppose that at the end of the trial, the investigator is interested in a post-stratified or subgroup analysis with respect to a particular demographic or clinical factor which was not selected prior to the trial for stratified randomization. Under a randomization model, large sample theory of two-sample post-stratified permutational tests is developed with a broad class of restricted randomization treatment allocation rules. The test procedures proposed here are illustrated with a real-life example. The results of this example indicate that it is not always possible to ignore the treatment rule used in the trial in the design-based analysis.
4 citations