1. Retreat Topics iPSC Opportunities in NIAMS Diseases
Science Management Forum: Leveraging and Strategic Funding Collaborations
Atopic Dermatitis
Advancing Research on Tendon and Ligament Biology
Clinical Trials Portfolio Analysis and NIAMS Goals for Clinical Research

2. iPSC Opportunities in NIAMS Diseases: Topics
What NIAMS diseases/conditions and research areas are poised to take advantage of recent advances in iPSC technologies, and would adoption of iPSC approaches accelerate progress? What are the current limitations in the use of iPSCs for these applications?
Are there appropriate in vitro cellular models for common and rare diseases of interest to NIAMS that could be generated from patient-specific iPSCs?

3. iPSC Opportunities in NIAMS Diseases: Topics, cont.
Are any of these models ready for 1) studies of disease pathogenesis, 2) functional studies of gene variants, 3) high-throughput drug screening, 4) drug toxicity studies, and 5) studies of gene repair?
What are the technological hurdles, and are special resources required to overcome them?
What are the opportunities for leveraging and partnerships?

4. iPSC Opportunities: Discussion
Best Practices/Goals:
Challenges
Streamline communication and enhance collaboration throughout the community
Efficient and reliable cell reprogramming and differentiation techniques and protocols
Standardize terminology and protocols
Cell sorting and purification
Establish common regulatory and tech transfer protocols
Safe and efficient genetic “correction” methods
Opportunities
Complex diseases
Immune response
Monogenic diseases
Therapeutic delivery methods
Disease-specific and /or personalized tissue models
Centralized resources (repository, cell manufacturing facilities, iPSC control lines)

5. Leveraging and Strategic Funding Collaborations: Topics
What partnerships—within NIH and externally—can leverage the NIAMS research investment?
Collaborative funding: benefits and challenges
Pilot project/seed funding
Sustaining registries
Infrastructure for planning groups
Industry expertise and resources in therapeutic and biomarker research

6. Leveraging and Strategic Funding Collaborations: Discussion
Collaborative funding strategies with NIH
Public-private partnerships
Involvement of funding partners and patient advocacy groups
Cooperation of multiple Institutes and Centers to understand complex diseases/comorbidities
The Osteoarthritis Initiative example
Co-development of initiatives
Buy-in from industry leaders
Common Fund
Unique resources provided by industry partners
Leveraging funding from non-federal not-for-profit organizations
Important leadership role for NIH
“Proving ground” for innovative concepts
Bridge funding for new investigators seeking NIH support

7. Atopic Dermatitis: Topics
What are the opportunities for accelerating research in atopic dermatitis (AD) that can lead to new therapeutic targets?
What are the main factors that contribute to severe AD?
What translational research opportunities have emerged from recent studies on the biology of AD?
What are the opportunities, needs, and barriers to proof-of-concept trials in AD?
What challenges arise with conducting trials in specific patient populations (e.g., children, variation in disease severity), and how can they be overcome?
How should comorbidities be addressed, and what insights do they provide?

8. Atopic Dermatitis: Discussion
Mechanisms of disease/disease susceptibility
Future research directions
Identification of primary disease etiology: barrier defect or immune dysfunction?
Barrier disruption
Better characterization of barrier defects and immune system effects on barrier function
Immune dysfunction
Clinical presentation and clinical research
Comorbidities
Emerging opportunities for intervention
Phenotyping complications
Challenges with pediatric trials
Molecular messengers (cytokines) in immune function
Treatment modalities: systemic vs. topical
Regulators of epidermal barrier and cell-cell junctions
Quality of life outcomes

9. Advancing Research on Tendon and Ligament Biology: Topics
What are the opportunities for exploring the basic biology of tendons and ligaments?
How can knowledge of tendon and ligament developmental biology inform tissue engineering and regenerative medicine approaches?
Are failures and limitations of the current “bedside” approaches to tendon and ligament injuries pointing to gaps in our understanding of the basic biology of these structures?
What are the most immediate clinical needs, and how can these gaps be addressed by investment in basic science?

10. Advancing Research on Tendon and Ligament Biology: Topics, cont.
What are the obstacles in exploring the basic biology of tendons and ligaments?
Does this area have a sufficient workforce/pipeline in basic research relevant to tendons and ligaments?

11. Tendon and Ligament Biology: Discussion
Basic research opportunities
Clinical needs
Repair and rehabilitation strategies
Tendon and ligament structure and mechanical properties
Engineered grafts don’t behave like normal tendons and ligaments
Pre-injury degeneration
Tendon development and healing
Strategies to repair large tears of the rotator cuff
Obstacles
Role and appropriate use of growth factors
Better animal models
Small research community
Role of inflammation (+/-)
Platelet-rich plasma
Stem cells

12. Clinical Trials Portfolio Analysis and NIAMS Goals for Clinical Research: Topics
How do we define the impact of completed studies? What are the most meaningful measures of success or predictive performance indicators?
Are there over- or under-represented areas in the NIAMS portfolio?
What approaches could be used to determine whether NIAMS is supporting the most important studies and how to achieve that goal?
What is NIAMS’ role in promulgating results of significant clinical trials and studies?

13. Clinical Trials: Discussion
Impact
Questions to consider before accepting a clinical trial application
Beyond influencing clinical practice and public health policy – the most important goals – trials may inform future research particularly if they contain some mechanistic studies.
If this trial is successfully completed, will findings guide the field? Will they tell us about more than just the disease being studied?
Dissemination
How timely is this trial – will events make it meaningless?
Requirement to provide results to clinicaltrials.gov may not be sufficient
Do investigators have evidence (e.g., from electronic medical records) that they can recruit enough patients for a meaningful study?