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  string(1604) "Background: Intravenous ketamine has shown rapid-acting antidepressant effects in numerous RCTs, but very little is currently known about which patients are most likely to benefit.
Objective: Determine what patient characteristics (alone or in combination) moderate antidepressant clinical response to IV ketamine.
Study Design: Pooled patient-level meta-analysis.
Participants: Patients with unipolar or bipolar depression who participated in qualifying randomized controlled trials comparing intravenous ketamine/esketamine to a control condition.
Main Outcome Measures: Depression reduction from pre-infusion to approximately 24-hours post-infusion, as measured by rating scales including the Montgomery-Asberg Rating Scale, Hamilton Depression Rating Scale, and/or Quick Inventory of Depressive Symptoms
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Wallace, Frank & Kraemer, A Novel Approach for Developing and Interpreting Treatment Moderator Profiles in Randomized Clinical Trials. JAMA Psychiatry, 2013, doi:10.1001/jamapsychiatry.2013.1960

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2021-4703

General Information

How did you learn about the YODA Project?: Data Holder (Company)

Conflict of Interest

Request Clinical Trials

Associated Trial(s):
  1. NCT01640080 - A Double-Blind, Double-Randomization, Placebo-Controlled Study of the Efficacy of Intravenous Esketamine in Adult Subjects With Treatment-Resistant Depression
What type of data are you looking for?:

Request Clinical Trials

Data Request Status

Status: Withdrawn/Closed

Research Proposal

Project Title: Secondary data analysis for ketamine/esketamine

Scientific Abstract: Background: Intravenous ketamine has shown rapid-acting antidepressant effects in numerous RCTs, but very little is currently known about which patients are most likely to benefit.
Objective: Determine what patient characteristics (alone or in combination) moderate antidepressant clinical response to IV ketamine.
Study Design: Pooled patient-level meta-analysis.
Participants: Patients with unipolar or bipolar depression who participated in qualifying randomized controlled trials comparing intravenous ketamine/esketamine to a control condition.
Main Outcome Measures: Depression reduction from pre-infusion to approximately 24-hours post-infusion, as measured by rating scales including the Montgomery-Asberg Rating Scale, Hamilton Depression Rating Scale, and/or Quick Inventory of Depressive Symptoms
Statistical Analysis: Individual participant level data will be used to characterize the magnitude of reductions in clinical symptoms using both continuous and dichotomous (e.g., responder vs. non-responder) outcomes. We will examine both patient-level (e.g., age, BMI) and study-level (e.g., dose, infusion schedule) moderators of clinical effects using appropriate meta-analytic methods, and also use data-driven methods to identify any potential combined moderators that improve the prediction of response when taken together. The effect of study will be examined statistically. We will assess bias in the studies included in this review using the Cochrane Statistical Methods and Cochrane Bias Methods Group's Risk of Bias Assessment Tool (Higgins et al., 2011).

Brief Project Background and Statement of Project Significance: Ketamine has recently emerged as a promising rapid-acting antidepressant treatment. Janssen has been at the forefront of ketamine clinical trials, demonstrating that ketamine is associated with rapid changes in depressive symptoms, anxiety and suicidal thoughts within minutes. Since initial publications, the ketamine antidepressant literature has expanded to include many randomized clinical trials (RCTs). Additionally, ketamine is now administered outside of research environments, including in hospital setting and specialized ?ketamine clinics.? Therefore, there is a tremendous interest in which patients may be most likely to respond to ketamine administration.
Established ketamine researchers from multiple institutions are collaborating to conduct this meta-analysis across ketamine RCTs in order to identify potential moderators of response to ketamine. A meta-analytic approach is needed, as individual RCTs are often under-powered for these types of moderator analyses.

Specific Aims of the Project: The aim of the project is to identify which patient characteristics (alone or in combination) moderate antidepressant clinical response to IV ketamine/esketamine.
The main outcomes will be depression reduction from pre-infusion to approximately 24-hours post-infusion, as measured by rating scales including the Montgomery-Asberg Rating Scale, Hamilton Depression Rating Scale and/or Quick Inventory of Depressive Symptoms.
Additional/secondary outcomes will include: suicidality and anxiety reduction from pre-infusion to 24-hours post-infusion, as measured by rating scales including the Beck Scale for Suicide Ideation, Columbia Suicide Severity Rating Scale, Hamilton Anxiety Rating Scale and State-Trait Anxiety Inventory, and individual relevant items and subscales included in other depression measures.
Individual level data will be solicited from study sites for these depression and anxiety outcomes and for potential moderator variables that may have been collected (e.g., age, gender, race, BMI, vitals, psychiatric Axis I and Axis II diagnoses/comorbidities, medical comorbidities, concurrent medications, chronicity of depression, suicidal ideation at baseline). By pooling participant-level data from eligible RCTs, robust moderating variables will be identified.

Study Design:

What is the purpose of the analysis being proposed? Please select all that apply.: New research question to examine treatment effectiveness on secondary endpoints and/or within subgroup populations Confirm or validate previously conducted research on treatment effectiveness Participant-level data meta-analysis Meta-analysis using data from the YODA Project and other data sources

Software Used: R

Data Source and Inclusion/Exclusion Criteria to be used to define the patient sample for your study: All RCTs of patients with elevated depression scores at baseline that used one or more eligible depression outcome scales were identified via PubMed search of records through 01/19/21.

Primary and Secondary Outcome Measure(s) and how they will be categorized/defined for your study: The main outcomes will be depression reduction from pre-infusion to approximately 24-hours post-infusion, as measured by rating scales including the Montgomery-Asberg Rating Scale, Hamilton Depression Rating Scale and/or Quick Inventory of Depressive Symptoms.

Main Predictor/Independent Variable and how it will be categorized/defined for your study: Study treatment group (ketamine vs. control)

Other Variables of Interest that will be used in your analysis and how they will be categorized/defined for your study: Individual level data will be solicited from study sites for potential moderator variables that may have been collected (e.g., age, gender, race, BMI, vitals, psychiatric Axis I and Axis II diagnoses/comorbidities, medical comorbidities, concurrent medications, chronicity of depression, suicidal ideation at baseline).

Statistical Analysis Plan: Pooled patient-level meta-analytic regression methods implemented in R to quantify 1) effects of treatment group on continuous and dichotomized (responder vs. non-responder; remitter vs. non-remitter) depression score outcomes, and 2) interactions between each moderator and treatment group, with a random intercept and slope for each study. Data-driven 'combined moderator' analyses, as described in Wallace, Frank & Kraemer, JAMA Psychiatry, 2013, will also be applied.

Narrative Summary: The overall project is a meta-analysis of ketamine randomized clinical trials. Ketamine has recently emerged as a promising rapid-acting antidepressant treatment. Since initial publications, the ketamine antidepressant literature has expanded to include many randomized clinical trials (RCTs). Additionally, ketamine is now administered outside of research environments, including in hospital setting and specialized ?ketamine clinics.? A meta-analytic approach is needed in order to identify potential moderators of clinical response, as individual RCTs are often under-powered for the identification of moderator variables.

Project Timeline: Data compilation from eligible RCTs has already begun and will continue for approximately 6 months. Once data has been compiled, data analysis will be completed within the space of approximately 3 months. Manuscript drafted and submitted for publication approximately 1 year from now. Results reported back to YODA Project at that time.

Dissemination Plan: Study manuscript will be submitted to higher-impact psychiatry journals (e.g. JAMA Psychiatry).

Bibliography:

Wallace, Frank & Kraemer, A Novel Approach for Developing and Interpreting Treatment Moderator Profiles in Randomized Clinical Trials. JAMA Psychiatry, 2013, doi:10.1001/jamapsychiatry.2013.1960