Enhancing Care through Collaborative Practice: Status of the Multi-Site Randomized Controlled Trials

Video  |  Audio (Length:  21 min.)

Mark S. Bauer, M.D.
Bibliography

M.S. Bauer
Brown University School of Medicine, Providence VA Medical Center, Providence, RI, USA

Abstract
We have treatments of substantial efficacy for manic-depressive disorder, but their effectiveness in general clinical practice falls far short of expectations. This “efficacy-effectiveness gap,” which the US Institute of Medicine recognizes is characteristic of all medical interventions, is especially acute for chronic illnesses such as manic-depressive disorder.

Several ongoing multi-site trials address this gap by implementing multi-faceted disease management programs that focus on enhancing collaboration between provider and patient. Such programs address patient, provider, and system factors that impede the process of care.

Status of these trials are reviewed, including similarities and differences in intervention and assessment methodology. Current status and results to date are summarized and compared.

Finally, experience in these trials not only points out advances in care, but also reveals gaps and suggests next steps. Key unanswered questions include:

• What are the core components, mechanisms of effect, and theoretical bases of these programs in terms of:

o Patient-provider interactions?
o System factors?

• Based on this, what components comprise an effective, yet sustainable, second-generation program?

• Accordingly, how can such programs be disseminated to “distributed” or “open” systems such as the private healthcare sector or state- or community-based systems?

Long Term Studies of Relapse Prevention in Bipolar Disorder – BALANCE

Video  |  Audio (Length:  24 min.)

Guy Goodwin, M.D.
Bibliography

G. Goodwin
University Department of Psychiatry, Warneford Hospital, Oxford, UK

Abstract
It is widely accepted that the optimization of long-term treatment in Bipolar Disorder is a contemporary challenge for all of us. The early onset, apparently worsening course and high probability of relapse in Bipolar illness is the basis for a widely held consensus that early long-term treatment is desirable because it may actually change long-term outcomes. How can turn this aspiration into an evidence-based reality. Our strategy has been to develop large-scale simple trials to answer pragmatic questions about what single drugs or combinations of drugs we should be using in long-term treatment.  The central problems are patient recruitment and clinician capacity. It is only through randomized controlled trials that we will actually make treatment advances. Furthermore, we already know that the monotherapies that we have available are less than adequate in the majority of cases. The pharmaceutical industry will not pursue combination treatments except under unusual circumstances. Instead, it must be an activity of independent researchers, working in partnership with practitioners on the one hand and industry on the other, but the independence of trial organization, analysis and monitoring is essential.  The first fruit of this focus has been the BALANCE trial: patients who are suitable for long-term treatment are initially recruited and treated with the combination of lithium and valproate (as ®Depakote). For a four to eight week run-in period these drugs are given together to assess the tolerability of this combination. At the end of that time patients are randomized to either continue on the combination itself, or lithium alone, or depakote alone. An update on trial procedures and progress will be presented.  Planning trials takes a lot of forethought. The most important challenges for future trials that arise in our clinical practice are:

• Should we be using combination treatment from as early in the illness trajectory as possible, even after a first break?

• The long term treatment of bipolar depression is made uncertain by different interpretations of the evidence around the efficacy of “mood stabilizers” like lithium and valproate on the one hand, and conventional antidepressants, on the other. A study is required to address the short-term benefits of antidepressant efficacy against the long-term potential problems of switching from depression to mania.

STEP-BD: Update

Video  |  Audio (Length:  22 min.)

Gary S. Sachs, M.D.
Bibliography

Jane Kogan, Ph.D.

Michael Thase, M.D.
Bibliography

Mark Bauer, M.D.
Bibliography

Stephen Wisniewski, Ph.D.

G. Sachs, J. Kogan, M. Thase, M.S. Baer, S. Wisniewski
Harvard Medical School, Boston, MA, USA

Abstract
Prior to 1998, public policy and clinical practice for bipolar disorder relied on a shockingly scant fund of knowledge. As recently as this year, the NIMH Strategic Plan for Mood Disorders has highlighted huge gaps in the national research database, and the NIH/VA grant portfolios, for bipolar disorder.  STEP-BD, the collaborative effort of 22 treatment centers across the United States, has undertaken a range of bipolar research projects which will better illuminate the characteristics of the illness and provide essential data on the effectiveness of commonly used treatments. Since beginning enrollment in November of 1999, STEP investigators have collected data that has been assembled into three related datasets: Baseline assessments, Index episode/ 2- year follow-up, and Long Term Follow-up.  Through February of 2003, STEP collaborators have completed more than 3000 extensive assessments to establish a baseline data set that is projected to grow to as many as 5000 participants. Ongoing systematic clinical evaluation and serial independent assessments provide a composite longitudinal view of treatment and outcome for an index episode. The index episode dataset is currently available for 1000 participants with one and two year outcomes and is projected to include 2-year outcomes for as many as 3,000 individuals. Within this data set are three studies, which now include more than 350 participants for whom treatment was given in a randomized care pathway. These randomized studies will address specific questions about the benefit of standard antidepressant medications, psychosocial interventions for acute bipolar depression, and options of refractory depression. A double blind randomized pathway for relapse prevention proved unfeasible and was closed. The Index episode data set will also be used for a health care economics study comparing cost of treatment for patients in STEP-BD, with samples matched for demographic and clinical characteristics treated in the public sector as well as a privately insured sample.  Analyses conducted to date, have generated 5 publications and more than 24 manuscripts are under active development. The baseline data has already provided some interesting findings related to the impact of comorbid anxiety disorders and ADHD on suicidality. The first phase of study assessing the impact of Valproate on Ovarian function has been completed and sample collection has begun for genetic studies. Early prospective data analyses indicate that among individuals who achieve recovery, about 5% relapse each month and depressive episodes account for about 80% of relapses. The rate of psychiatric hospitalization is 14.2 per 100 patient years. Mortality observed over the life of the project is 0.11 per 100 patient years.  The Long-term Follow-up data set aims to evaluate treatment outcomes for 2000 subjects over a period of at least 5 years. The analyses planned for long term outcome studies utilize not only the raw data collected from prospective assessments, but also utilize methods developed by STEP which transform the serial cross sectional assessments into meaningful longitudinal outcomes. Objectives rated by the STEP-BD investigators have proposed analyses for high priority objectives that use the long-term data set:

1. Assess factors influencing suicide and non-suicide mortality.
2. Improve understanding of factors associated with poor long- term outcomes.
3. Determine if the observed course of Bipolar Disorder is consistent with the kindling hypothesis.
4. Evaluate important issues related to nosology and course of illness with specific reference to informing the process leading to DSM V.

“Next STEP” proposals build on the foundation of “First STEP” by continuing follow-up necessary to obtain 5-year data on core assessments, dissemination of the STEP model to the public sector and maintaining the investigator network for the conduct of new studies.
Conclusion
Bipolar disorder remains a devastating illness with costly public health consequences. NIMH has established a national resource able to examine the correlation between care delivery and outcome, establish collaborations with basic scientists as well as provide independent evidence addressing high priority Public Health needs. The Baseline, Index Episode, and Long term Outcome datasets offer several perspectives on the complex multidimensional manifestations of Bipolar Disorder and provide an opportunity to unify our understanding.

Through STEP-BD, NIMH also advances the field of bipolar research by offering a national organizational structure that encourages investigators to enter this important but challenging field.

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