Is it easier to find what you are looking for if you think you know what it looks like?

Eli Lilly, Indianapolis, Indiana, United States
Journal of Clinical Psychopharmacology (Impact Factor: 3.76). 05/2007; 27(2):121-5. DOI: 10.1097/JCP.0b013e3180387820
Source: PubMed
  • 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
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    ABSTRACT: The increasing rate of failure of antidepressant clinical trials has led to the assertion that antidepressants do not have meaningful clinical benefits. Our hypothesis was that the decrease in antidepressant-placebo differences in antidepressant clinical trials over the past three decades could be explained by changes in research design features rather than a lack of potency of the antidepressants being tested. We collected data from 130 double blind placebo controlled antidepressant clinical trials conducted between 1981 and 2008 that included 35,122 depressed patients with 23,157 patients assigned to antidepressants and 11,965 assigned to placebo. We conducted a hierarchical regression analysis of change in HAM-D scores in antidepressant and placebo groups separately with year of publication, and research design features as independent variables. We found that antidepressant-placebo differences in antidepressant clinical trials have declined markedly over the past three decades. Decline in change scores in the antidepressant group was related to mean total baseline HAM-D scores in the trial, the version of HAM-D used, and duration of trial. Similarly, decline in change scores in the placebo group was related to mean total baseline HAM-D scores, duration of trial, and year of publication. Overall, we found that antidepressant-placebo differences were statistically significantly higher in trials that used HAM-D 21 rather than HAM-D 17 and in trials that lasted 6 weeks or less. These data suggest that, apart from the efficacy of the antidepressant being tested, factors such as baseline HAM-D scores, version of HAM-D used and duration of trial have a significant impact on outcome. As such a clinician's assessment of the usefulness of antidepressants should not be based solely on the results of such clinical trials. In the meantime there is a need for continuing research to improve the methodology of antidepressant clinical trials. These data suggest that many aspects of the design of antidepressant trials have a significant impact on outcome. Further, these data suggest that the results of more recent placebo controlled trials do not adequately inform clinicians about the potential utility of antidepressants.
    CNS Neuroscience & Therapeutics 08/2010; 16(4):217-26. DOI:10.1111/j.1755-5949.2010.00151.x · 3.78 Impact Factor