) Mixed-effects models can include all data from participants, even those who terminate the study prematurely.7,8 Analyses of the sensitivity of results to the assumptions

of the analytic model are useful components of a data analysis plan. These can include use of pattern-mixture models26,27 and the assessment and application of predictors of attrition such as the two-item Intent to Attend questionnaire.28 A second observational component of an RCT is the flexible-dose study, in which those who l’ail to respond to a low dose are then offered a greater dose of the intervention. Such a design is inappropriate for dose finding because “self-selection” Inhibitors,research,lifescience,medical determines dose. Fortunately, the use of clinical trial flexible dose RCTs is more limited today than two or three decades ago. The problem of flexible dosing can be obviated by conducting a fixeddose study that allows Inhibitors,research,lifescience,medical lor a brief period of titration.29 In summary if conditions allow, a RCT is preferable for intervention evaluation. However, there are clinical contexts and patient types that do not lend themselves

to randomized treatment assignment (eg, suicidal patients). In such a case, an observational study can inform treatment choice if an appropriate adjustment, such as the propensity score adjustment, is implemented. Regardless of the design, the generalizability of the results is restricted to the type of participants Inhibitors,research,lifescience,medical included in the study. Acknowledgments Dr Leon has received Inhibitors,research,lifescience,medical research support from the National Institute of Mental Health (MH060447, MH068638 and MH092606). In the past 12 months he has served on independent Data and Safety Monitoring Boards for AstraZeneca, Pfizer and Sunovion and has been a consultant to FDA, NIMH, MedAvante and Roche. He has equity in MedAvante.
Depression occurs commonly, but not inevitably, in patients with cancer at the end of life. Although there are over 7 million cancer deaths Inhibitors,research,lifescience,medical around the world each year,1 estimates of the prevalence of depression in terminally ill cancer patients are imprecise. Most studies of comorbid cancer and depression either make no

distinction between cancer phases (eg, newly diagnosed, active treatment, survivorship, stable metastatic disease, end-stage) or fail to operationally define “end-of-life” care. Consequently, reported prevalence rates SB-3CT for depression in patients with cancer span a broad range. Best estimates are that between 15% and 50% of cancer patients experience depressive symptoms, and 5% to 20% will meet various diagnostic criteria for major depressive disorder.2-7 Similarly, few data are available with respect to the frequency with which cancer patients are appropriately treated for depression at the end of life.8,9 Only a small number of controlled clinical trials have been conducted with depressed cancer patients, whether or not they are in a terminal phase of their illness.