The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
E S Friedman - One of the best experts on this subject based on the ideXlab platform.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting Litmus baseline data with pre-existing placebo controlled trials.
Journal of affective disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. Copyright © 2013. Published by Elsevier B.V.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: Contrasting Litmus baseline data with pre-existing placebo controlled trials
Journal of Affective Disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Abstract Background Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. Method To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. Results As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Conclusions Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.
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Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
The pharmacogenomics journal, 2013Co-Authors: Robert D. Beech, J R Calabrese, C L Bowden, L G Sylvia, Janine J. Leffert, Aiping Lin, Sheila Umlauf, Shrikant Mane, Hongyu Zhao, E S FriedmanAbstract:Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
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Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (Litmus) for bipolar disorder.
Clinical trials (London England), 2011Co-Authors: L G Sylvia, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, Noreen A. Reilly-harrington, Christine Kansky, Michael J. OstacherAbstract:Background High attrition rates, which occur frequently in longitudinal clinical trials of interventions for bipolar disorder, limit the interpretation of results.Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Treatment – Moderate dose Use Study (Litmus) for bipolar disorder.Methods Litmus was a 6-month randomized, longitudinal multisite comparative effectiveness trial that enrolled bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium; other treatments needed for mood stabilization were administered in a guideline-informed, empirically supported, and personalized fashion to participants in both treatment arms.Results Components of the study design that may have contributed to low attrition (16%) among 283 participants randomized included the use of (1) an intent-to-treat design, (2) a randomized adjunctive single-blind design, (3) participant reimbursement, (4) assessm...
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Lithium treatment -- moderate dose use study (Litmus) for bipolar disorder: rationale and design.
Clinical trials (London England), 2009Co-Authors: Andrew A. Nierenberg, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, Noreen A. Reilly-harrington, Michael J. OstacherAbstract:Background Recent data indicate that lithium use for bipolar disorder has declined over the last decade and that lithium largely has been replaced with alternate, commercially promoted medications that may or may not result in better outcomes.Purpose This article describes the rationale and study design of Litmus, a multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. Litmus seeks to address whether initiating therapy at lower doses of lithium as part of optimized treatment (OPT, guideline-informed, evidence-based, and personalized pharmacotherapy) improves outcomes and decreases the need for other medication changes across 6 months of therapy.Methods Litmus will randomize 284 adults with bipolar disorder (Type I or II) across 6 study sites. The co-primary outcomes are overall illness severity on clinical global improvement scale for bipolar disorder and a novel measure, necessary clinical adjustments. This metric provides a composite that reflects both clinical respons...
D V Iosifescu - One of the best experts on this subject based on the ideXlab platform.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting Litmus baseline data with pre-existing placebo controlled trials.
Journal of affective disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. Copyright © 2013. Published by Elsevier B.V.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: Contrasting Litmus baseline data with pre-existing placebo controlled trials
Journal of Affective Disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Abstract Background Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. Method To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. Results As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Conclusions Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.
L G Sylvia - One of the best experts on this subject based on the ideXlab platform.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting Litmus baseline data with pre-existing placebo controlled trials.
Journal of affective disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. Copyright © 2013. Published by Elsevier B.V.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: Contrasting Litmus baseline data with pre-existing placebo controlled trials
Journal of Affective Disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Abstract Background Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. Method To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. Results As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Conclusions Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.
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Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
The pharmacogenomics journal, 2013Co-Authors: Robert D. Beech, J R Calabrese, C L Bowden, L G Sylvia, Janine J. Leffert, Aiping Lin, Sheila Umlauf, Shrikant Mane, Hongyu Zhao, E S FriedmanAbstract:Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
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Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (Litmus) for bipolar disorder.
Clinical trials (London England), 2011Co-Authors: L G Sylvia, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, Noreen A. Reilly-harrington, Christine Kansky, Michael J. OstacherAbstract:Background High attrition rates, which occur frequently in longitudinal clinical trials of interventions for bipolar disorder, limit the interpretation of results.Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Treatment – Moderate dose Use Study (Litmus) for bipolar disorder.Methods Litmus was a 6-month randomized, longitudinal multisite comparative effectiveness trial that enrolled bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium; other treatments needed for mood stabilization were administered in a guideline-informed, empirically supported, and personalized fashion to participants in both treatment arms.Results Components of the study design that may have contributed to low attrition (16%) among 283 participants randomized included the use of (1) an intent-to-treat design, (2) a randomized adjunctive single-blind design, (3) participant reimbursement, (4) assessm...
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Lithium treatment -- moderate dose use study (Litmus) for bipolar disorder: rationale and design.
Clinical trials (London England), 2009Co-Authors: Andrew A. Nierenberg, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, Noreen A. Reilly-harrington, Michael J. OstacherAbstract:Background Recent data indicate that lithium use for bipolar disorder has declined over the last decade and that lithium largely has been replaced with alternate, commercially promoted medications that may or may not result in better outcomes.Purpose This article describes the rationale and study design of Litmus, a multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. Litmus seeks to address whether initiating therapy at lower doses of lithium as part of optimized treatment (OPT, guideline-informed, evidence-based, and personalized pharmacotherapy) improves outcomes and decreases the need for other medication changes across 6 months of therapy.Methods Litmus will randomize 284 adults with bipolar disorder (Type I or II) across 6 study sites. The co-primary outcomes are overall illness severity on clinical global improvement scale for bipolar disorder and a novel measure, necessary clinical adjustments. This metric provides a composite that reflects both clinical respons...
J R Calabrese - One of the best experts on this subject based on the ideXlab platform.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting Litmus baseline data with pre-existing placebo controlled trials.
Journal of affective disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. Copyright © 2013. Published by Elsevier B.V.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: Contrasting Litmus baseline data with pre-existing placebo controlled trials
Journal of Affective Disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Abstract Background Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. Method To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. Results As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Conclusions Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.
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Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
The pharmacogenomics journal, 2013Co-Authors: Robert D. Beech, J R Calabrese, C L Bowden, L G Sylvia, Janine J. Leffert, Aiping Lin, Sheila Umlauf, Shrikant Mane, Hongyu Zhao, E S FriedmanAbstract:Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
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Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (Litmus) for bipolar disorder.
Clinical trials (London England), 2011Co-Authors: L G Sylvia, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, Noreen A. Reilly-harrington, Christine Kansky, Michael J. OstacherAbstract:Background High attrition rates, which occur frequently in longitudinal clinical trials of interventions for bipolar disorder, limit the interpretation of results.Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Treatment – Moderate dose Use Study (Litmus) for bipolar disorder.Methods Litmus was a 6-month randomized, longitudinal multisite comparative effectiveness trial that enrolled bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium; other treatments needed for mood stabilization were administered in a guideline-informed, empirically supported, and personalized fashion to participants in both treatment arms.Results Components of the study design that may have contributed to low attrition (16%) among 283 participants randomized included the use of (1) an intent-to-treat design, (2) a randomized adjunctive single-blind design, (3) participant reimbursement, (4) assessm...
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Lithium treatment -- moderate dose use study (Litmus) for bipolar disorder: rationale and design.
Clinical trials (London England), 2009Co-Authors: Andrew A. Nierenberg, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, Noreen A. Reilly-harrington, Michael J. OstacherAbstract:Background Recent data indicate that lithium use for bipolar disorder has declined over the last decade and that lithium largely has been replaced with alternate, commercially promoted medications that may or may not result in better outcomes.Purpose This article describes the rationale and study design of Litmus, a multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. Litmus seeks to address whether initiating therapy at lower doses of lithium as part of optimized treatment (OPT, guideline-informed, evidence-based, and personalized pharmacotherapy) improves outcomes and decreases the need for other medication changes across 6 months of therapy.Methods Litmus will randomize 284 adults with bipolar disorder (Type I or II) across 6 study sites. The co-primary outcomes are overall illness severity on clinical global improvement scale for bipolar disorder and a novel measure, necessary clinical adjustments. This metric provides a composite that reflects both clinical respons...
C L Bowden - One of the best experts on this subject based on the ideXlab platform.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: contrasting Litmus baseline data with pre-existing placebo controlled trials.
Journal of affective disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥ 3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo. Copyright © 2013. Published by Elsevier B.V.
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Using comparative effectiveness design to improve the generalizability of bipolar treatment trials data: Contrasting Litmus baseline data with pre-existing placebo controlled trials
Journal of Affective Disorders, 2013Co-Authors: E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, M J Ostracher, J Severe, D V IosifescuAbstract:Abstract Background Efficacy-based double-blind placebo controlled trials were conducted to establish efficacy and safety for FDA approval. Such designs allowed and encouraged the use of exclusion criteria to improve assay sensitivity and internal validity. The Litmus trial increased the representation of real-world individuals with bipolar disorder despite the acknowledgment that this compromises assay sensitivity. Method To maximize generalizability, Litmus used broad inclusion and narrow exclusion criteria: participants experiencing mood symptoms of sufficient intensity (at least with a CGI-BP ≥3) that would warrant a change in treatment, and that lithium treatment would be a reasonable therapeutic option if they were randomized to it. At baseline demographic, illness, clinical, and treatment characteristics were collected. The Litmus study design and baseline sociodemographic data were compared to previous efficacy studies. Results As compared to the previous bipolar disorder efficacy studies, Litmus participants were of similar age, gender, weight and illness severity; however Litmus participants were more racially and ethnically representative of the general population, had a greater number of mood episodes in the past 12 months, more Axis I/II comorbidity, a greater number of prior suicide attempts, and higher functional capacity. Conclusions Litmus was a comparative effectiveness trial that had broad inclusion and minimal exclusion criteria that produced a more representative sample comprised of real-world participants. This design enables the results of the Litmus study to be a more representative of real world pharmacotherapuetic outcomes. Limitations Limitations include possible selection bias, paucity of sociodemographic data in efficacy trials, and lack of a placebo.
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Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
The pharmacogenomics journal, 2013Co-Authors: Robert D. Beech, J R Calabrese, C L Bowden, L G Sylvia, Janine J. Leffert, Aiping Lin, Sheila Umlauf, Shrikant Mane, Hongyu Zhao, E S FriedmanAbstract:Gene-expression differences in peripheral blood between lithium responders and non-responders in the Lithium Treatment-Moderate dose Use Study (Litmus)
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Methods to limit attrition in longitudinal comparative effectiveness trials: lessons from the Lithium Treatment - Moderate dose Use Study (Litmus) for bipolar disorder.
Clinical trials (London England), 2011Co-Authors: L G Sylvia, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, Noreen A. Reilly-harrington, Christine Kansky, Michael J. OstacherAbstract:Background High attrition rates, which occur frequently in longitudinal clinical trials of interventions for bipolar disorder, limit the interpretation of results.Purpose The aim of this article is to present design approaches that limited attrition in the Lithium Treatment – Moderate dose Use Study (Litmus) for bipolar disorder.Methods Litmus was a 6-month randomized, longitudinal multisite comparative effectiveness trial that enrolled bipolar participants who were at least mildly ill. Participants were randomized to either low to moderate doses of lithium or no lithium; other treatments needed for mood stabilization were administered in a guideline-informed, empirically supported, and personalized fashion to participants in both treatment arms.Results Components of the study design that may have contributed to low attrition (16%) among 283 participants randomized included the use of (1) an intent-to-treat design, (2) a randomized adjunctive single-blind design, (3) participant reimbursement, (4) assessm...
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Lithium treatment -- moderate dose use study (Litmus) for bipolar disorder: rationale and design.
Clinical trials (London England), 2009Co-Authors: Andrew A. Nierenberg, E S Friedman, J R Calabrese, T A Ketter, A C Leon, M E Thase, C L Bowden, L G Sylvia, Noreen A. Reilly-harrington, Michael J. OstacherAbstract:Background Recent data indicate that lithium use for bipolar disorder has declined over the last decade and that lithium largely has been replaced with alternate, commercially promoted medications that may or may not result in better outcomes.Purpose This article describes the rationale and study design of Litmus, a multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. Litmus seeks to address whether initiating therapy at lower doses of lithium as part of optimized treatment (OPT, guideline-informed, evidence-based, and personalized pharmacotherapy) improves outcomes and decreases the need for other medication changes across 6 months of therapy.Methods Litmus will randomize 284 adults with bipolar disorder (Type I or II) across 6 study sites. The co-primary outcomes are overall illness severity on clinical global improvement scale for bipolar disorder and a novel measure, necessary clinical adjustments. This metric provides a composite that reflects both clinical respons...
