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- SourceAvailable from: Alan Lenox-Smith
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- "Therefore, we hypothesize that the smaller ES in patients with a baseline HAM-D 18 was probably due to the proximity to the HAM-D inclusion cutoff of the study rather than due to a specific HAM-D severity score that eliminates mild patients. The problem of baseline score inflation in antidepressant clinical trials has been identified in several reports (Kobak et al., 2007; Rutherford and Roose 2013; Mundt et al., 2007a). "
ABSTRACT: An increasing rate of antidepressant trials fail due to large placebo responses. This analysis aimed to identify variables influencing signal detection in clinical trials of major depressive disorder. Patient-level data of randomized patients with a duloxetine dose ≥60 mg/day were obtained from Lilly. Total scores of the Hamilton Depression Rating scale (HAM-D) were used as efficacy endpoints. In total, 4661 patients from 14 studies were included in the analysis. The overall effect size (ES), based on the HAM-D total score at endpoint, between duloxetine and placebo was -0.272. Although no statistically significant interactions were found, the following results for factors influencing ES were seen: a very low ES (-0.157) in patients in the lowest baseline HAM-D category and in patients recruited in the last category of the recruitment period (-0.122). A higher ES in patients recruited in centers with a site-size at but not more than 2.5 times the average site-size for the study (-0.345). Study characteristics that resulted in low signal detection in our database were: <80% study completers, a HAM-D placebo response >5 points, a high variability of placebo response (SD > 7 points HAM-D), >6 post baseline visits per study, and use of an active control drug. Simpler trial designs, more homogeneous and mid-sized study sites, a primary analysis based on a higher cutoff blinded to investigators to avoid the influence of score inflation in mild patients and, if possible, studies without an active control group could lead to a better signal detection of antidepressive efficacy.Journal of Psychiatric Research 01/2014; 51. DOI:10.1016/j.jpsychires.2014.01.001 · 4.09 Impact Factor
- Journal of Clinical Psychopharmacology 11/2007; 27(5):535-7. DOI:10.1097/JCP.0b013e31814f2c14 · 3.76 Impact Factor
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ABSTRACT: Placebo response is thought to be a primary contributor to uninformative (failed) trials in clinical drug development. This study describes the development of a patient-reported assessment to detect likely placebo responders. A novel scale, the Placebo Response Screening Scale (PRSS), was developed to assess domains expected to be associated with placebo response. The scale was administered during the screening visit of a 4-week, placebo-controlled study of alprazolam and an investigational compound in 211 patients with generalized anxiety disorder (GAD). Items that predicted placebo response were identified. Sensitivity and specificity of the instrument were used to determine a threshold score for use in screening likely placebo response. The PRSS was then evaluated by comparing active treatment and placebo groups and subsetting the groups based on subject PRSS scores. Twenty items were selected for being predictive of patient global improvement rating, clinician global improvement rating, or improvement on Hamilton Rating Scale for Anxiety (HAM-A) scores in placebo-arm patients. Receiver operating characteristic concordance values ranged from 0.77 to 0.96 for the different definitions of placebo responder. A cut-score of 50 on a scale of 0-100 was chosen to maximize sensitivity (range 0.67-0.79) and specificity (range 0.78-1.00). Fifty-six patients with scores of 50 or higher were flagged as potential placebo responders. Excluding these 56 patients from the analysis resulted in a greater separation of active treatment from placebo. The PRSS is a promising tool for predicting placebo response in clinical trials and requires further use and validation.Journal of Psychiatric Research 06/2009; 43(15):1224-30. DOI:10.1016/j.jpsychires.2009.04.001 · 4.09 Impact Factor