Stacie Hudgens1, Lysbeth Floden2, Michael Blackowicz2, Carol Jamieson3, Vanina Popova4, Maggie Fedgchin5, Wayne C Drevets6, Kimberly Cooper7, Rosanne Lane5, Jaskaran Singh6. 1. Clinical Outcomes Solutions, Tucson, AZ, US. Electronic address: stacie.hudgens@clinoutsolutions.com. 2. Clinical Outcomes Solutions, Tucson, AZ, US. 3. Janssen Research and Development LLC, Milpitas, CA, US. 4. Janssen Research and Development LLC, Beerse, BE. 5. Janssen Research and Development LLC, Titusville, NJ, US. 6. Janssen Research and Development LLC, San Diego, CA, US. 7. Janssen Research and Development LLC, Spring House, PA, US.
Abstract
BACKGROUND:Patients with major depressive disorder who do not respond to ≥2 different pharmacological treatments within the current depressive episode are considered to have treatment resistant depression (TRD). This analysis determined meaningful change thresholds (MCT) of the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) using anchor-based methods and compared proportions of meaningful changes in patients with TRD across treatment groups from two Phase 3 trials for esketamine nasal spray (SPRAVATOTM). METHODS: Data from two Phase 3 trials in patients with TRD, TRANSFORM-1 and -2, were used in this analysis. The MCTs for the PHQ-9 and MADRS were derived using a clinician global impression of severity anchor. Blinded probability density functions displayed score distributions between anchor categories. Proportions of meaningful response were compared between treatment groups using chi-square tests supported by unblinded cumulative distribution functions of change scores. RESULTS: Baseline scores were similar for the PHQ-9 and MADRS between the esketamine/antidepressant (AD) and AD/placebo groups. The most appropriate MCT on the PHQ-9 was -6 points. By Day 28, 86.5% of patients reached or exceeded the PHQ-9 MCT in the esketamine/AD group compared to 70% in the placebo/AD group. The most appropriate MCT for the MADRS was -10 points. By Day 28, 78.2% of patients reached or exceeded the MADRS MCT in the esketamine/AD group compared to 65.0% in the placebo/AD group. CONCLUSIONS: Individual-level meaningful change for the PHQ-9 and MADRS was effectively quantified using a clinical anchor to interpret efficacy from patients with TRD and their treating clinicians.
RCT Entities:
BACKGROUND:Patients with major depressive disorder who do not respond to ≥2 different pharmacological treatments within the current depressive episode are considered to have treatment resistant depression (TRD). This analysis determined meaningful change thresholds (MCT) of the Patient Health Questionnaire (PHQ-9) and Montgomery-Åsberg Depression Rating Scale (MADRS) using anchor-based methods and compared proportions of meaningful changes in patients with TRD across treatment groups from two Phase 3 trials for esketamine nasal spray (SPRAVATOTM). METHODS: Data from two Phase 3 trials in patients with TRD, TRANSFORM-1 and -2, were used in this analysis. The MCTs for the PHQ-9 and MADRS were derived using a clinician global impression of severity anchor. Blinded probability density functions displayed score distributions between anchor categories. Proportions of meaningful response were compared between treatment groups using chi-square tests supported by unblinded cumulative distribution functions of change scores. RESULTS: Baseline scores were similar for the PHQ-9 and MADRS between the esketamine/antidepressant (AD) and AD/placebo groups. The most appropriate MCT on the PHQ-9 was -6 points. By Day 28, 86.5% of patients reached or exceeded the PHQ-9 MCT in the esketamine/AD group compared to 70% in the placebo/AD group. The most appropriate MCT for the MADRS was -10 points. By Day 28, 78.2% of patients reached or exceeded the MADRS MCT in the esketamine/AD group compared to 65.0% in the placebo/AD group. CONCLUSIONS: Individual-level meaningful change for the PHQ-9 and MADRS was effectively quantified using a clinical anchor to interpret efficacy from patients with TRD and their treating clinicians.
Authors: Hewa Artin; Sean Bentley; Eamonn Mehaffey; Fred X Liu; Kevin Sojourner; Andrew W Bismark; David Printz; Ellen E Lee; Brian Martis; Sharon De Peralta; Dewleen G Baker; Jyoti Mishra; Dhakshin Ramanathan Journal: EClinicalMedicine Date: 2022-05-06
Authors: Vinita Singh; Theresa W Gillespie; Olabisi Lane; Boris Spektor; Ali John Zarrabi; Katherine Egan; Kimberly Curseen; Maya Tsvetkova; Jan H Beumer; Roman Sniecinski; Jack W Shteamer; Jeffery Switchenko; R Donald Harvey Journal: Pharmacotherapy Date: 2022-02-21 Impact factor: 6.251