There is uncertainty about the interpretation of changes in the 6-min walk distance (6MWD) in chronic obstructive pulmonary disease (COPD) patients and whether the minimal important difference (MID) for this useful outcome measure exists.Data were used from nine trials enrolling a wide spectrum of COPD patients with 6MWD at baseline and follow-up and used to determine threshold values for important changes in 6MWD using three distribution-based methods. Anchor-based methods to determine a MID were also evaluated.Data were included of 460 COPD patients with a mean¡SD forced expiratory volume in one second (FEV1) of 39.2¡14.1% predicted and 6MWD of 361¡112 m at baseline. Threshold values for important effects in 6MWD were between 29 and 42 m, respectively, using the empirical rule effect size and the standardised response mean. The threshold value was 35 m (95% confidence interval 30-42 m) based on the standard error of measurement. Correlations of 6MWD with patient-reported anchors were too low to provide meaningful MID estimates.6-min walk distance should change by ,35 m for patients with moderate to severe chronic obstructive pulmonary disease in order to represent an important effect. This corresponds to a 10% change of baseline 6-min walk distance. The low correlations of 6-min walk distance with patient-reported anchors question whether a minimal important difference exists for the 6-min walk distance.

New anticancer agents that lead to improvements in time-to-event end points also increase morbidity and treatment-related mortality. The balance between efficacy and toxicity may be less favorable in clinical practice because of selection of fewer patients with good performance status and limited comorbidities. Patients' baseline health characteristics should be considered when choosing therapy.

The aim of this study was to determine the characteristics of placebo effects in acute migraine treatment trials of triptans performed over 12 years and assess whether the use of placebo controls in trials of acute migraine treatment remains ethically and scientifically appropriate. We conducted a search for all controlled trials published in English between January 1991 and April 2002 in which adult subjects with migraine were randomly assigned to receive an oral triptan or placebo for the acute treatment of a migraine attack. Thirty-one trials met our criteria for inclusion. Placebo results for each study and pooled placebo results were calculated for the endpoints of headache response, pain-free response and adverse events. Heterogeneity was assessed using the Q statistic, and meta-regression using prespecified covariates was performed to investigate heterogeneity. The study results show a significant degree of heterogeneity. Efforts to explain heterogeneity with available data were not successful, with the exception of adverse event rates to placebo, for which study location (Europe vs. North America) partially explained differences in study results. AE rates were lower in European studies than in North American studies. Across all studies, the mean proportion of subjects who experienced a treatment response at two hours to placebo was 28.48 +/- 8.73% (range 17-50%). The mean proportion of subjects who experienced an adverse event to placebo was 23.40 +/- 14.05% (range 4.86-74%). The mean proportion of subjects who experienced a pain-free response to placebo at two hours was 6.08 +/- 4.43% (range 5-17%). Results of studies allowing use of prophylaxis did not differ significantly from those that did not allow prophylaxis. Placebo effects appear to be enhanced in studies involving children and adolescents. In contrast to an earlier, smaller review, our results do not suggest that randomization ratios influence placebo rates. We conclude that placebo effects in published trials of acute migraine medications are highly variable and often substantial. This variability in placebo response means that active control equivalence trials or the use of historical controls will not provide adequate proof of the safety or efficacy of new drugs, and will not differentiate between drugs that are active vs. placebo but of unknown efficacy relative to each other. The potential for approval of ineffective drugs, inability to compare results of studies performed in different locations, and poor characterization of the tolerability and safety profiles of new drugs represent a greater danger to migraineurs than does the limited-duration use of placebo in carefully monitored clinical trials of consenting subjects. These observations support the view that the inclusion of a placebo group remains of major scientific and ethical importance in trials of migraine medications.