Creating a Culture of Biomedical Innovation

Panel Composition and Context

• The session features a cross-sector panel: Chris (NCATS/NIH Director), Amitabh (Harvard Kennedy School), Peggy Hamburg (Former FDA Commissioner/NAM), Jennifer Miller (Bioethics International/Yale), and Jason Spangler (Amgen).
• The discussion centers on defining "innovation" and "culture" within the biomedical ecosystem, specifically focusing on translating research into patient value.

Definitions of Innovation

• Chris (NCATS): Defines innovation broadly as the entire translational process, from target validation to public health impact, including post-approval stages; emphasizes that innovation requires breaking from established paths when the current process is inefficient.
• Amitabh (Harvard): Defines innovation economically as any product, process, or treatment that increases value for patients, where value is an improvement in outcomes without a price increase, or a price increase that is proportionally smaller than the outcome improvement.
• Peggy Hamburg (FDA): Defines innovation as new approaches that "matter for patients," requiring a balance where benefits outweigh risks, outcomes are superior, and the product is accessible and affordable.
• Jennifer Miller (Bioethics): Distinguishes etymological "introducing something new" from ethical innovation, which must be patient-centered, trustworthy, and focused on advancing health and well-being for all.
• Jason Spangler (Amgen): Expands innovation beyond drug discovery to include manufacturing efficiency, biosimilars, policy paradigms, pricing mechanisms, and financial models.

Strategies for Cultivating Innovation

• NCATS Approach:
  • Encourages a culture where the default is to "not do it the way it's always been done" unless a different outcome is proven.
  • Implements a "everything is an experiment" mantra to reduce the fear of permanent failure.
  • Utilizes "modeling ignorance" by leaders asking "dumb questions" to empower staff to challenge assumptions.
  • Promotes a "culture of laughter" to biologically prime the brain for receiving unexpected results.
  • Focuses heavily on aligning incentives, noting that small financial levers (e.g., grocery bag fees) significantly alter behavior.
• Amgen Culture:
  • Encourages staff to "think big, think bold" without limiting ideas due to current constraints or bureaucratic excuses.
  • Explicitly creates an environment where failure is acceptable as a necessary component of high-risk, high-reward innovation.
• Regulatory and Systemic Culture:
  • Breaking down silos between research, development, regulation, reimbursement, and policy to create a dynamic partnership.
  • FDA innovation via the "Breakthrough Therapy" designation relies on early and continuous partnership with sponsors to define efficient research agendas rather than just faster review times.

Measurement and Metrics

• NCATS:
  • Maps the translational process as a "traffic map" with 20–25 steps to identify bottlenecks (red, yellow, green zones).
  • Shifts focus from measuring "velocity" (speed) to "acceleration" (improving the rate of progress).
  • Uses "Advancing" as a core metric, acknowledging the challenge of quantifying fundamental science versus translational science.
• FDA:
  • Avoids using raw approval numbers or review times as sole metrics, as these can incentivize rushing products through with inadequate data.
  • Emphasizes post-market surveillance to catch safety issues that emerge in diverse, real-world populations.
• Amgen:
  • Measures value by analyzing the "outcomes over costs" equation, focusing on whether new therapies provide greater benefit than existing options, even if costs rise.
• Bioethics (Good Pharma Scorecard):
  • Created an accreditation/ranking system to signal and improve ethics, using six key measures:
    • Integrity of clinical trial design (generalizability of data to typical patient populations).
    • Conduct of trials (ethical treatment of populations, especially in developing nations).
    • Communication of results (avoiding selective reporting).
    • Marketing practices (consistency between ads, labels, and papers).
    • R&D spending transparency.
    • Accessibility of medicines (pricing, anti-competitive tactics, "evergreening").
  • The Scorecard has successfully prompted three companies to change policies after being benchmarked against peer standards.

Geographic and Economic Trends

• Innovation Concentration: Biopharma innovation is hyper-concentrated; the top three cities (Boston, San Francisco, San Diego) account for one-third of all worldwide biotech patents.
• Boston vs. San Francisco:
  • Boston's patent output is specific to life sciences, whereas San Francisco's output correlates strongly with general patenting capacity.
  • Since 2010, San Francisco's specific ability to patent in life sciences has declined relative to its general patenting, while Boston remains stable.
• Pipeline Misalignment:
  • Orphan Drugs: Account for 30–50% of all FDA approvals, successfully incentivizing treatment for rare diseases.
  • Disease Burden Mismatch:
    • Cancer represents 15% of the disease burden but 30% of R&D.
    • Mental health represents 15% of the burden but <2% of R&D.
    • Parkinson's has ~212 products in pipeline vs. a need for >1,000.
    • Infectious diseases kill the most globally but receive disproportionately low R&D investment.

Societal Challenges and Future Directions

• The "Alzheimer's Paradox": Despite a quadrupling of NIH funding (from $600M to $2.4B), private sector investment remains low due to high failure rates and lack of commercial viability.
• Neglected Areas: TB and neglected tropical diseases require specific "push" (public funding) and "pull" (priority vouchers) incentives, as commercial models alone fail to support them.
• One-Measure Challenge: When asked to select a single metric for improvement, panelists suggested:
  • Amitabh: Measuring the gap between the social burden of disease and the current focus of biopharma R&D.
  • Jennifer: Patient involvement as the most disruptive technology for setting priorities and designing trials.
  • Peggy: "Integrity" of science, commitment, and transparency, including learning from failure.
  • Chris: A move toward measuring the value of innovation to society as a whole, not just individual patients.
• Cultural Shift: The ecosystem is transitioning from a sequential "relay race" to a collaborative "team sport," requiring public sector leadership and foundation support to fill gaps left by commercial imperatives.