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Workshop Agenda

Multimodal Therapies for Brain Disorders: A Workshop

June 14-15, 2016

Keck Center
500 Fifth Street, NW | Room 100
Washington, DC 20001

Background: Multimodal therapy approaches (i.e., combinations of interventions aimed at different aspects of a disease) are emerging as potential ways to enhance clinical outcomes for patients with psychiatric and neurological disorders. This could include, for example, concomitant prescription of a drug along with a device, biologic, or behavioral/psychosocial intervention (including, e.g., cognitive remediation, lifestyle adjustment, dietary intervention, or animate therapy). Another example would be the simultaneous use of a neuromodulation device during performance of a specific neurocognitive task. While such a multimodal approach is consistent with the common clinical practice of combining interventions, there are important questions regarding how these interventions interact (in terms of additive, subtractive, or synergistic therapeutic as well as adverse effects), how they should be used, in what subsets of patients, and in what amounts or for what period of time. Further discussion is needed about methodologies for determining efficacy and safety in multimodal therapies compared with monotherapies and for comparing across multiple types of multimodal therapy. Multimodal therapy approaches also raise a number of important regulatory issues, both regarding combinations of regulated products (e.g., drug plus de-

vice) and approaches in which only one product is regulated (e.g., drug/device plus psychosocial intervention). Related questions arise for reimbursement, for example, would payers only pay for care if it includes both drugs and psychotherapy if that is what the data show is effective?

This workshop, hosted by the Forum on Neuroscience and Nervous System Disorders, will bring together key stakeholders to examine scientific, clinical, regulatory, and reimbursement issues related to multimodal approaches and identify potential opportunities to enhance clinical outcomes for individuals with psychiatric and neurological disorders. Rather than delving deeply into specific interventions, the workshop will aim to examine general principles, barriers, and potential solutions and opportunities that may apply across multimodal therapy development for brain disorders.

Meeting Objectives:

• Explore recent advances in the development of multimodal therapeutic approaches for psychiatric and neurological disorders and approaches to using these therapies (e.g., earlier versus later in disease progression), and discuss future research needs to further advance understanding of these approaches.
• Highlight disease areas in which a multimodal approach could be particularly useful (e.g., areas in which the pathophysiology is well understood, or areas in which mono-modal approaches have been insufficiently effective).
• Discuss methodologies for establishing efficacy and safety for multimodal therapies compared to monotherapies, including clinical trials and statistical considerations.
• Consider regulatory issues for multimodal therapies, including for approaches in which only one component is regulated (e.g., drug plus psychosocial intervention), and discuss potential opportunities for addressing challenges.
• Consider reimbursement issues for multimodal therapies for nervous system disorders, and discuss potential opportunities for addressing challenges.
• Incorporate lessons learned from other therapeutic areas in which multimodal approaches are more frequently used (e.g., cardiology, diabetes, cancer).

DAY ONE: June 14, 2016

SESSION I: STATE-OF-THE-SCIENCE IN MULTIMODAL THERAPIES FOR BRAIN DISORDERS

Session Objectives:

• Explore examples of recent advances in the development of multimodal therapeutic approaches for brain disorders and approaches to using these therapies.
• Discuss future research needs to further advance understanding of these approaches.
• Highlight disease areas in which a multimodal approach could be particularly useful.

SESSION II: REGULATORY AND REIMBURSEMENT CONSIDERATIONS

Session Objectives:

• Consider regulatory and reimbursement issues for multimodal therapies, including for approaches in which two components are regulated (e.g., drug plus device) and approaches in which only one component is regulated (e.g., drug plus psychosocial intervention).
• Explore evidentiary standards needed for regulation and reimbursement, and consider how different approval pathways and evidentiary standards across FDA centers impact multimodal approaches.
• Discuss potential opportunities for addressing challenges.

DAY TWO: June 15, 2016

KEYNOTE TALK: FUTURE DIRECTIONS IN CLINICAL TRIALS AND REGULATORY APPROACHES FOR MULTIMODAL THERAPIES

SESSION III: ESTABLISHING EFFICACY AND SAFETY IN MULTIMODAL THERAPIES FOR BRAIN DISORDERS

Session Objectives: Discuss methodologies for establishing efficacy and safety for multimodal therapies compared to monotherapies, including clinical and statistical considerations. Potential topics may include

SESSION IV: INDUSTRY PERSPECTIVES

Session Objectives:

• Discuss industry perspectives on particular technical, scientific, and commercial challenges to bringing these systems to market, and examine lessons learned from successful examples of collaborations on multimodal approaches.
• Explore potential mechanisms for addressing challenges and enabling multimodal therapy development programs.

SESSION V: MOVING FORWARD

Session Objectives:

• Discuss the roles of NIH, other research agencies, and disease-specific organizations in supporting the development of multimodal therapies.
• Synthesize and discuss key highlights from the workshop presentations and discussions and, most importantly, identify next steps and promising areas for future action and research.