Abstract
Background Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the real-world advantages and disadvantages of these medications. Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments (APTs). The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score, and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT). Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus APT, across 10 sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. In all, 482 participants were randomized to the study, and 364 completed the study. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants ability to pay for study medications. Conclusion We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a secondgeneration antipsychotic with broad-spectrum activity in bipolar disorder, and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 114-127 |
| Number of pages | 14 |
| Journal | Clinical Trials |
| Volume | 11 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 2014 |
ASJC Scopus subject areas
- Pharmacology
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Clinical and health outcomes initiative in comparative effectiveness for bipolar disorder (Bipolar CHOICE) : A pragmatic trial of complex treatment for a complex disorder. / Nierenberg, Andrew A.; Sylvia, Louisa G.; Leon, Andrew C.; Reilly-Harrington, Noreen A.; Shesler, Leah W.; McElroy, Susan L.; Friedman, Edward S.; Thase, Michael E.; Shelton, Richard C.; Bowden, Charles L.; Tohen, Mauricio; Singh, Vivek; Deckersbach, Thilo; Ketter, Terence A.; Kocsis, James H.; McInnis, Melvin G.; Schoenfeld, David; Bobo, William V.; Calabrese, Joseph R.
In: Clinical Trials, Vol. 11, No. 1, 02.2014, p. 114-127.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Clinical and health outcomes initiative in comparative effectiveness for bipolar disorder (Bipolar CHOICE)
T2 - A pragmatic trial of complex treatment for a complex disorder
AU - Nierenberg, Andrew A.
AU - Sylvia, Louisa G.
AU - Leon, Andrew C.
AU - Reilly-Harrington, Noreen A.
AU - Shesler, Leah W.
AU - McElroy, Susan L.
AU - Friedman, Edward S.
AU - Thase, Michael E.
AU - Shelton, Richard C.
AU - Bowden, Charles L.
AU - Tohen, Mauricio
AU - Singh, Vivek
AU - Deckersbach, Thilo
AU - Ketter, Terence A.
AU - Kocsis, James H.
AU - McInnis, Melvin G.
AU - Schoenfeld, David
AU - Bobo, William V.
AU - Calabrese, Joseph R.
N1 - Funding Information: Dr Thase reports no conflicts of interest specifically pertaining to this project. During the past 3 years, he has been an advisor/consultant to Alkermes, AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck, MedAvante, Merck & Co, Mylan, Neuronetics, Otsuka Pharmaceuticals, PamLabs, PharmaNeuroBoost, Pfizer Inc., Rexahn, Roche, Shire, Sunovion, Supernus, Takeda Pharmaceutical Company Ltd, and Teva Pharmaceuticals, as well as the US Food and Drug Administration and the National Institute of Mental Health. During the same time frame, Dr Thase has received honoraria for talks from AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck & Co., and Pfizer Inc., and he has received research grants from Alkermes, AstraZeneca, Eli Lilly and Company, Forest, GlaxoSmithKline, Otsuka Pharmaceuticals, PharmaNeuroBoost, and Roche, as well as the National Institute of Mental Health and the Agency for Healthcare Research and Quality. Funding Information: Dr McInnis has received grants for research support from NIMH, the Heinz C Prechter Research Fund, and the Michigan Institute for Clinical Health Research (MICHR). MM has received consulting income from the Qatar National Research Foundation and Merck & Co. Funding Information: Dr Bobo has received research support from the NIMH, NARSAD, and Cephalon Inc. In the past, he has received honoraria from Janssen Pharmaceuticals and Pfizer Inc. Funding Information: This research was funded by the Agency for Healthcare Research and Quality (AHRQ): 1R01HS019371-01. Funding Information: Dr Shelton has been a consultant for Bristol-Myers Squibb Company, Cyberonics Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Medtronic Inc., PamLabs, Pfizer Inc., Ridge Diagnostics, and Takeda Pharmaceutical Company Ltd. He has grant support from Bristol-Myers Squibb Company, Eli Lilly and Company, Elan Corp., Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceuticals, Naurex Inc., Novartis, Otsuka Pharmaceuticals, PamLabs, Pfizer Inc., Repligen Corp., Ridge Diagnostics, St. Jude Medical Inc., and Takeda Pharmaceuticals. Funding Information: Dr Deckersbach has received research support from NIMH, NARSAD, TSA, OCF, Tufts University, NIH, NIA, Janssen Pharmaceuticals, the Forest Research Institute, Shire Development Inc., Medtronic, Cyberonics Inc., and Northstar. He has received honoraria, consultation fees, and/or royalties from the following: Medacorp, MGH Psychiatry Academy, BrainCells Inc., Systems Research and Applications Corporation, Boston University, Tufts University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, and Oxford University Press. Funding Information: Dr Calabrese receives federal funding from the Department of Defense, Health Resources Services Administration, and NIMH; he receives research funding or grants from the following private industries or nonprofit funds: Cleveland Foundation, NARSAD, and Stanley Medical Research Institute; he receives research grants from Abbott Laboratories Inc., AstraZeneca, Cephalon Inc., GlaxoSmithKline, Janssen Pharmaceuticals, Eli Lilly and Company, and Lundbeck; he serves on the advisory boards of Abbott Laboratories Inc., AstraZeneca, Bristol-Myers Squibb Company, Dainippon Sumitomo Pharma, Forest, France Foundation, GlaxoSmithKline, Janssen Pharmaceuticals, NeuroSearch, OrthoMcNeil, Repligen, Schering-Plough, Servier, Solvay/Wyeth, Takeda Pharmaceutical Company Ltd, and Supernus Pharmaceuticals; and he reports CME activities with AstraZeneca, Bristol-Myers Squibb Company, France Foundation, GlaxoSmithKline, Janssen Pharmaceuticals, Johnson & Johnson, Schering-Plough, and Solvay/Wyeth. Funding Information: Dr Ketter receives research support from the Agency for Healthcare Research and Quality, AstraZeneca Pharmaceuticals LP, Cephalon Inc., Eli Lilly and Company, National Institute of Mental Health, Pfizer Inc., and Sunovion Pharmaceuticals. He receives consultant fees from Allergan, Inc., Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Cephalon Inc., Forest Pharmaceuticals, Janssen Pharmaceuticals, LP, Merck & Co, Sunovion Pharmaceuticals, and Teva Pharmaceuticals. He has lecture honoraria from Abbott Laboratories Inc., AstraZeneca Pharmaceuticals LP, GlaxoSmithKline, and Otsuka Pharmaceuticals and receives publication royalties from American Psychiatric Publishing, Inc. In addition, Dr Ketter’s spouse is an employee of and holds stock in Janssen Pharmaceuticals. Funding Information: Dr Singh has received research funding from AstraZeneca and Novartis. He is on the Speaker Bureau for Merck & Co and Sunovion. Funding Information: Dr Nierenberg is a consultant for Abbott Laboratories Inc., AstraZeneca, Basilea, BrainCells Inc., Brandeis University, Bristol-Myers Squibb Company, Cephalon Inc., Corcept, Eli Lilly and Company, Forest, Genaissance, GlaxoSmithKline, Innapharma, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Lundbeck, Merck & Co, Novartis, PamLabs, PGx Health, Pfizer Inc., Ridge Diagnostics, Roche, Sepracor, Schering-Plough, Shire, Somerset, Sunovion, Takeda, Targacept, and Teva Pharmaceuticals. He is a stakeholder in Appliance Computing, Inc. (MindSite), BrainCells Inc., and InfoMed (potential share of income). He receives research support from AHRQ, Bristol-Myers Squibb Company, Cederroth, Cyberonics Inc., Elan Corp., Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceuticals, Lichtwer Pharma, Eli Lilly and Company, Mylin (formerly Dey Pharmaceuticals), NARSAD, NIMH, PamLabs, Pfizer Inc., Shire, Stanley Foundation, and Wyeth-Ayerst. Honoraria include MGH Psychiatry Academy in the past 3 years (prior to 3 years, honoraria from Bristol-Myers Squibb Company, Cyberonics Inc., Forest Pharmaceuticals, GlaxoSmithKline, Eli Lilly and Company, Shire, Wyeth-Ayerst). Dr Nierenberg receives other income from legal case reviews for CRICO, MBL Publishing for past services as Editor-in-Chief of CNS Spectrums, Slack Inc. for services as Associate Editor of Psychiatric Annals, and Editorial Board, Mind Mood Memory, Belvior Publications. He has copyright joint ownership with MGH for Structured Clinical Interview for MADRS and Clinical Positive Affect Scale and additional honoraria from ADURS, American Society for Clinical Psychopharmacology and Zucker Hillside Hospital and Forest and Janssen Pharmaceuticals, Biomedical Development, Boston Center for the Arts, University of Pisa, University of Wisconsin at Madison, University Texas Southwest at Dallas, Health New England and Harold Grinspoon Charitable Foundation and Eli Lilly and Company and AstraZeneca, Brandeis University, International Society for Bipolar Disorder, Second East Asian Bipolar Forum, Mid-Atlantic Permanente Research Institute, Up-to-Date. Funding Information: Dr Kocsis has received research grants and contracts from AHRQ, NIMH, NIDA, Burroughs Wellcome Trust, Pritzker Consortium, Takeda Pharmaceutical Company Ltd, Forest, AstraZeneca, and Roche. He is on the speaker’s bureau at Pfizer Inc. and Merck & Co. and on the advisory board at Corcept.
PY - 2014/2
Y1 - 2014/2
N2 - Background Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the real-world advantages and disadvantages of these medications. Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments (APTs). The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score, and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT). Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus APT, across 10 sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. In all, 482 participants were randomized to the study, and 364 completed the study. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants ability to pay for study medications. Conclusion We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a secondgeneration antipsychotic with broad-spectrum activity in bipolar disorder, and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial.
AB - Background Classic and second-generation antipsychotic mood stabilizers are recommended for treatment of bipolar disorder, yet there are no randomized comparative effectiveness studies that have examined the real-world advantages and disadvantages of these medications. Purpose We describe the strategic decisions in the design of the Clinical and Health Outcomes Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE). This article outlines the key issues and solutions the investigators faced in designing a clinical trial that would maximize generalizability and inform real-world clinical treatment of bipolar disorder. Methods Bipolar CHOICE was a 6-month, multi-site, prospective, randomized clinical trial of outpatients with bipolar disorder. This study compares the effectiveness of quetiapine versus lithium, each with adjunctive personalized treatments (APTs). The co-primary outcomes selected are the overall benefits and harms of the study medications (as measured by the Clinical Global Impression-Efficacy Index) and the Necessary Clinical Adjustments (a measure of the number of medication changes). Secondary outcomes are continuous measures of mood, the Framingham General Cardiovascular Risk Score, and the Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT). Results The final study design consisted of a single-blind, randomized comparative effectiveness trial of quetiapine versus lithium, plus APT, across 10 sites. Other important study considerations included limited exclusion criteria to maximize generalizability, flexible dosing of APT medications to mimic real-world treatment, and an intent-to-treat analysis plan. In all, 482 participants were randomized to the study, and 364 completed the study. Limitations The potential limitations of the study include the heterogeneity of APT, selection of study medications, lack of a placebo-control group, and participants ability to pay for study medications. Conclusion We expect that this study will inform our understanding of the benefits and harms of lithium, a classic mood stabilizer, compared to quetiapine, a secondgeneration antipsychotic with broad-spectrum activity in bipolar disorder, and will provide an example of a well-designed and well-conducted randomized comparative effectiveness clinical trial.
UR - http://www.scopus.com/inward/record.url?scp=84893942236&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84893942236&partnerID=8YFLogxK
U2 - 10.1177/1740774513512184
DO - 10.1177/1740774513512184
M3 - Article
C2 - 24346608
AN - SCOPUS:84893942236
VL - 11
SP - 114
EP - 127
JO - Clinical Trials
JF - Clinical Trials
SN - 1740-7745
IS - 1
ER -