Flexible designs for phase II comparative clinical trials involving two response variables.

The aim of phase II clinical trials is to determine whether an experimental treatment is sufficiently promising and safe to justify further testing. The need for reduced sample size arises naturally in phase II clinical trials owing to both technical and ethical reasons, motivating a significant part of research in the field during recent years, while another significant part of the research effort is aimed at more complex therapeutic schemes that demand the consideration of multiple endpoints to make decisions. In this paper, our attention is restricted to phase II clinical trials in which two treatments are compared with respect to two dependent dichotomous responses proposing some flexible designs. These designs permit the researcher to terminate the clinical trial when high rates of favorable or unfavorable outcomes are observed early enough requiring in this way a small number of patients. From the mathematical point of view, the proposed designs are defined on bivariate sequences of multi-state trials, and the corresponding stopping rules are based on various distributions related to the waiting time until a certain number of events appear in these sequences. The exact distributions of interest, under a unified framework, are studied using the Markov chain embedding technique, which appears to be very useful in clinical trials for the sample size determination. Tables of expected sample size and power are presented. The numerical illustration showed a very good performance for these new designs.

Smoking cessation effectiveness in smokers with COPD and asthma under real life conditions.

INTRODUCTION: Although smoking cessation is strongly indicated by international guidelines as an effective therapeutic tool for patients with COPD and Asthma, a large proportion of them do not quit smoking and they are regarded as a "difficult" target group. AIM: To study the effectiveness of an intensive smoking cessation program in smokers with COPD and asthma under real-life conditions. METHODS: 166 smokers with COPD, 120 smokers with asthma and 1854 control smokers attended the smoking cessation program in the out-patient patient Smoking Cessation Clinic of the Pulmonary Department in Athens University. Continuous Abstinence Rate (CAR) was evaluated in 3, 6, 9 and 12 months after the target quit date. RESULTS: Short-term CAR (in 3 months) was 49.4% for COPD smokers, 51.7% for asthmatic smokers and 48.0% for the control group of smokers. 12 months after the initial visit the CAR was 13.9%, 18.3% and 15.9%, respectively. No statistically significant differences between groups at any study period were found. Smokers with good compliance with the program had higher long-term CAR after 12 months: 37.7% in COPD smokers, 40.0% in asthmatic smokers and 39.3% in control smokers. High CAR was observed at all stages of COPD severity. CONCLUSION: The results support the view that smokers with respiratory obstructive airway diseases of any severity should be offered an intensive smoking cessation program with regular and long-term follow-up. This will help them to achieve high abstinence rates and prevent relapses.