Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.

Objective To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients. Design Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks. Setting 23 academic asthma centres in United States, Canada, and Europe. Participants 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo). Interventions Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score. Main outcome measures Last tolerated dose of inhaled corticosteroids.Results Compared with placebo, montelukast allowed significant (P = 0.046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P = 0.01) required discontinuation because of failed rescue. Conclusions Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.

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In clinical trials with multiple primary endpoints, the effectiveness of a treatment may be established using either a composite endpoint or by employing a decision rule based on the individual endpoints. In this papec the latter method is examined. Emphasis is placed on the careful selection of primary endpoints and the need to specib the clinical objectives and statistical decision rules in advance. It is argued that Bonferroni-type adjustments are appropriate only in the case of a nonspecific hypothesis. Since requiring an intervention to demonstrate positive effects in several primary endpoints is more stringent than requiring an effect in any, some upward adjustment of individual a-levels should be allowed. In addition, physiologidsymptomatic classification of endpoints with separate decision rules for each may also be warranted in certain circumstances. An example is presented.

summaryExperiments consisting of several doses of a test agent and a zero dose control are often conducted to evaluate the effect of a compound on the response of interest.et al. (1985) proposed a trend test procedure which uses the minimum pvalue from three candidate dose scalings as a sensitive means for detecting a trend in response with increasing dose. Trend is defined here as a progressiveness, either increasing or decreasing, in response with increasing dose of the test agent. In this paper, we take a closer look at the procedure's inflated type I error rate and propose an adjustment based on the multivariate tdistribution which preserves the nominal significance level.Application of the adjusted trend test to a number of real data sets indicates that its performance is similar to that observed with Bartholomew's and Williams' tests. An evaluation of these three tests also was conducted on simulated data using an apparently novel approach which takes into account the underlying dosage regimen to generate the alternative hypotheses for a broad range of dose response relations. The simulation results indicates that the adjusted trend test is overall more powerful than its two competitors, although there are circumstances where each procedure appears superior. This broad-based power exhibited in both real and simulated settings makes the adjusted trend test an attractive approach.