2 results
149 Evaluation of Individual Items on the PHQ-9 and SDS in Patients with Treatment-Resistant Depression Treated with Esketamine Nasal Spray
- Lysbeth Floden, Stacie Hudgens, Carol Jamieson, Vanina Popova, Wayne Drevets, Kimberly Cooper, Jaskaran Singh
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, p. 295
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Introduction:
Major depressive disorder (MDD) is a global long-term condition and is the leading cause for disability in most countries. The objective of this study was to evaluate individual items of the PHQ-9 and SDS to show differences by treatment arm over the course of treatment.
Methods:The TRANSFORM-2 study (NCT02418585) was a Phase 3 short-term trial that evaluated efficacy and safety of flexible esketamine nasal spray (56 mg or 84 mg) doses in combination with newly initiated oral antidepressant (ESK+AD) vs oral AD + placebo nasal spray (AD+PBO) in patients with treatment resistant depression (TRD). The study population, men and women aged 18-64 years, who met the Diagnostic and Statistical Manual of Mental Disorders, Edition 5 diagnostic criteria for single-episode or recurrent MDD, but excluded subjects with suicidal ideation/intent to act within 6 months prior to study. Patient reported outcomes (PROs) were integrated to evaluate the patient perspective of treatment using instruments capturing concepts of importance. The 9-item Patient Health Questionnaire (PHQ-9) is a PRO instrument to assess self-reported depression symptoms, and the SDS a PRO instrument to assess function and disability. Individual items on each of these instruments represent a symptom or aspect of functioning. Respective items for PHQ-9 and SDS, are summed together to generate a total score: 0-27 for the PHQ-9 and 0-30 for SDS. Each total score reflects a single construct of depression severity for the PHQ-9 and functional disability for SDS. Change from baseline in SDS and PHQ-9 total scores at Day 28 were analyzed using a mixed-effects model using repeated measures based on observed case data. Generalized estimation equations of logistic regression models were used to estimate the likelihood of improvement by ≥ 1 point on the individual items of the PHQ-9 and SDS.
Results:Full analysis set included 223 patients (ESK+AD: 114; AD+PBO: 109). Change in SDS total score from baseline to Day 28 numerically favored ESK+AD. The LS mean treatment difference (95% CI) was -4.0 (-6.28; -1.64). Change in PHQ-9 total score from baseline to Day 28 numerically favored treatment with ESK+AD. The LS mean difference (95%CI) was -2.4 (-4.18; -0.69). Most patients experienced improvement on all PHQ-9 items and more patients experienced greater improvement in the ESK+AD treatment arm compared to the AD+PBO arm (odds ratio range 1.367-2.767; favoring ESK+AD). Improvements were seen across all items of the Sheehan Disability Scale (odds ratio range from 1.994 – 3.378; favoring ESK+AD).
Conclusions:This study shows that while the magnitude of improvement varied on individual items, ESK+AD treatment leads to greater symptom improvement across the multiple symptoms included in the PHQ-9 and SDS compared to the AD+PBO. This assists interpretation of the total scores generated by these PRO measures since total scores on the two measures was not driven by a single item.
Funding Acknowledgements:Study was funded by Janssen Global Services, LLC.
175 Determining Meaningful Change in Depression Symptoms Assessed with PHQ-9 and SDS in Treatment-resistant Depression Trials of Esketamine Nasal Spray
- Stacie Hudgens, Lysbeth Floden, Michael Blacowicz, Carol Jamieson, Vanina Popova, Maggie Fedgchin, Wayne Drevets, Kimberly Cooper, Rosanne Lane, Jaskaran Singh
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- Journal:
- CNS Spectrums / Volume 25 / Issue 2 / April 2020
- Published online by Cambridge University Press:
- 24 April 2020, pp. 311-312
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Introduction:
Major depressive disorder (MDD) has been ranked among the top causes worldwide of years lived with disability. In this study we assessed meaningful change for the PHQ-9 and the SDS and determined the meaningful change threshold (MCT) using anchor-based methods, which could be used to compare meaningful differences in patients within different treatment arms.
Methods:TRANSFORM-1 (NCT02417064) and -2 (NCT0241858) were Phase 3 trials that evaluated the efficacy and safety of fixed and flexible doses of esketamine nasal spray (56 mg or 84 mg) in combination with newly initiated oral antidepressant (ESK+AD) vs oral antidepressant + placebo nasal spray (AD+PBO) in TRD patients. Patient Reported Outcomes (PROs) were integrated into these trials to evaluate the patient perspective of treatment using instruments capturing concepts of importance to patients. The 9-item Patient Health Questionnaire (PHQ-9) is a PRO instrument used to assess self-reported depression symptoms and the Sheehan Disability Scale (SDS) is a PRO for self-reported function and disability. Blinded trial data (combined treatment groups) from TRANSFORM-1 was used for the anchor-based analysis. The Clinical Global Impression - Severity (CGI-S) was used as an anchor and patients were classified into response groups depending on their level of change over the course of the study. Patients were classified among all possible change categories (15 levels, ranging from -7 to 7 where negative change scores indicate improvement). Cumulative Distribution Function (CDF) curves of change from baseline to day 28 were generated using unblinded data from TRANSFORM-2 to visualize the range of responses demonstrated in the respective treatment groups for the PHQ-9 and SDS. MCT values were used to as thresholds to evaluate percentage of responders in each treatment group.
Results:In anchor-based analyses using TRANSFORM-1 combined treatment groups, the correlation between change on the CGI-S and change on the PHQ-9 at Day 28 was high (> 0.60) with anchor-based MCTs ranging from 5 to 8 points. The magnitude of change (standardized effect size estimate within-subject change) for patients improving was exceptionally high (> 0.80). Similar results were observed on the SDS: high correlation of CGI-S and SDS at Day 28 (0.75), moderate SES (0.66), with suggested MCT ranging from 3 to 7 with an MCT value of 5 pts. CDF curves from TRANSFORM-2 showed clear separation between the ESK+AD vs AD+PBO across a number of responder definitions inclusive of those identified with the anchor-based analyses.
Conclusions:The current study is the first to derive an MCT on the PHQ-9 and SDS in TRD to measure meaningful change from the perspective of the patient using regulatory-preferred psychometric anchor-based methodology. These analyses assist with interpretation of meaningfulness of esketamine phase 3 clinical trial results from the patient perspective.
Funding Acknowledgements:Study was funded by Janssen Global Services, LLC.
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