A new classification approach for comparing two active treatments when there is no prior projection on which one is better.

We developed a new classification approach in this paper to compare two active treatments. This approach is especially useful when there is no prior judgment on which treatment is better and the traditional hypothesis testing approach is thus not applicable. Our method classifies all the possible outcomes into categories and draws conclusions on the difference in the outcome measurement between two treatment arms according to the location of the confidence interval for the treatment difference in the response variable.

Heart rate-corrected QT interval in men increases during winter months.

Background: Sudden cardiac death increases during winter months in both men and women. The heart rate-corrected QT (QTc) interval exhibits circadian variation. However, little is known about QTc interval variation with month of year.

The fallback procedure for evaluating a single family of hypotheses.

In testing multiple hypotheses, control of the familywise error rate is often considered. We develop a procedure called the "fallback procedure" to control the familywise error rate when multiple primary hypotheses are tested. With the fallback procedure, the Type I error rate (alpha) is partitioned among the various hypotheses of interest.

Bayesian predictive approach to interim monitoring in clinical trials.

This paper reviews Bayesian strategies for monitoring clinical trial data. It focuses on a Bayesian stochastic curtailment method based on the predictive probability of observing a clinically significant outcome at the scheduled end of the study given the observed data. The proposed method is applied to derive efficacy and futility stopping rules in clinical trials with continuous, normally distributed and binary endpoints.

Impact of a soluble phospholipase A2 inhibitor on inhaled allergen challenge in subjects with asthma.

The possible roles of secretory phospholipases A2 (sPLA2) in asthma include the release of arachidonic acid from cellular membranes, generation of lysophospholipids, sPLA2-mediated activation of cPLA2 with increased leukotriene production, and surfactant degradation. LY333013 is a potent inhibitor of sPLA2. This study examined the impact of two doses of LY333013 vs.

A randomized, double-blinded, placebo-controlled clinical trial of LY333013, a selective inhibitor of group II secretory phospholipase A2, in the treatment of rheumatoid arthritis.

Objective: To evaluate the efficacy and safety of a selective inhibitor of secretory phospholipase (sPLA2), LY333013, in the treatment of rheumatoid arthritis (RA).

Methods: Two hundred and fifty-one patients with active RA despite treatment with one or more disease modifying antirheumatic drugs (DMARD) received oral doses of LY333013 (50, 250, and 1000 mg) or placebo once daily for 12 weeks. Concomitant low-dose glucocorticoids (< or = 10 mg/day prednisone equivalent) were allowed.

Neutrophil elastase inhibition in acute lung injury: results of the STRIVE study.

Objective: Neutrophil elastase is believed to be an important mediator of acute lung injury. Sivelestat (ONO-5046, Elaspol) is a small molecular weight inhibitor of neutrophil elastase. The primary objectives of this study were to determine whether sivelestat would reduce 28-day all-cause mortality or increase the number of ventilator-free days (days alive and free from mechanical ventilation from day 1 to day 28) compared with placebo in mechanically ventilated patients with acute lung injury.

Gatekeeping strategies for clinical trials that do not require all primary effects to be significant.

In this paper we describe methods for addressing multiplicity issues arising in the analysis of clinical trials with multiple endpoints and/or multiple dose levels. Efficient 'gatekeeping strategies' for multiplicity problems of this kind are developed. One family of hypotheses (comprising the primary objectives) is treated as a 'gatekeeper', and the other family or families (comprising secondary and tertiary objectives) are tested only if one or more gatekeeper hypotheses have been rejected.