Inclusion of older women in randomized clinical trials: Factors associated with taking study medication in the fracture intervention trial

OBJECTIVES: The purpose of this study is to describe the early study medication discontinuation (SMD) experience during the first year of follow-up in a randomized clinical trial in older women and to determine the associations between various baseline characteristics and risk of SMD. DESIGH, SETTING, AND PARTICIPANTS: The authors studied 6459 postmenopausal women aged 55 to 80 from 11 clinical settings during their first year of participation in the Fracture Intervention Trial (FIT). This trial was designed to test the efficacy of alendronate (Fosamax) on fracture prevention among women with low bone mass. RESULTS: Study medication discontinuation was greatest in the first month post-randomization (2.2%) and declined thereafter. Cumulative rates of study medication discontinuation were 4.8% (n = 31l) at 3 months and 11.1% (n = 717) at 12 months. SMD was not associated with age, marital status, alcohol consumption, regular exercise, past estrogen replacement therapy use, bone mineral density, or personal or maternal fracture history. After adjusting for covariates and markers of comorbidity, the strongest predictor of SMD was fair-to-poor self-rated health (relative risk (RR) 2.10; 95% confidence interval (CI) 1.47, 2.99). Having four or more depressive symptoms was also a significant predictor and had a risk associated with SMD (RR vs none 1.34; 95% CI 1.05, 1.71) similar to that seen for individuals with good self-rated health (RR 1.49; 95% CI 1.16, 1.91). CONCLUSIONS: Results from this cohort emphasize that clinical trials in older women with multiple concomitant conditions can achieve high levels of adherence. Thought should be given to measuring self-rated health and depressive symptoms before randomization to help identify individuals to be targeted for special assistance programs that focus on encouraging adherence.