Defining estimands in clinical trials: A unified procedure.

The ICH E9 (R1) addendum proposes five strategies to define estimands by addressing intercurrent events. However, mathematical forms of these targeted quantities are lacking, which might lead to discordance between statisticians who estimate these quantities and clinicians, drug sponsors, and regulators who interpret them. To improve the concordance, we provide a unified four-step procedure for constructing the mathematical estimands. We apply the procedure for each strategy to derive the mathematical estimands and compare the five strategies in practical interpretations, data collection, and analytical methods. Finally, we show that the procedure can help ease tasks of defining estimands in settings with multiple types of intercurrent events using two real clinical trials.

Specific Relapse Predictors: Could Cognitive-Behavioral Treatment for Smoking Cessation Be Improved?

Relapse remains a frequent and complex phenomenon that is not yet well understood. An under-researched area of study that may provide relevant information concerns the assessment of specific post-treatment variables, rather than the composite measures commonly used to predict smoking relapse. The current study sought to examine the effects of post-treatment smoking-related variables, including withdrawal symptomatology, abstinence self-efficacy, and smoking urgency in negative-affect situations and smoking relapse at the 3 month follow-up. The sample comprised 130 participants who achieved abstinence for at least 24 h through a cognitive-behavioral smoking cessation treatment. Regression analysis was conducted for both composite measures and specific subscales and items. Data showed that composite measures of tobacco withdrawal, self-efficacy, and smoking urgency in negative-affect situations were not significant predictors of smoking relapse. However, the analysis including subscales, and specific items showed that lower self-efficacy in negative-affect-related situations (OR = 1.36) and three withdrawal symptoms-irritability/frustration/anger (OR = 2.99), restlessness/impatience (OR = 1.87), and craving (OR = 2.31)-were significant predictors of relapse. These findings offer new insights into the role of different smoking-related post-treatment variables in short-term relapse. Considering and specifically targeting these variables after achieving abstinence may potentially contribute to reducing smoking relapse.