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7
Collaborative Models and New
Paradigms for Supporting Regulatory
Science Research and Practice
Key Messages
• ollaboration involving all stakeholders is a key element to creating a new eco-
C
system that is more efficient at turning discovery into therapeutics that benefit
human health.
• eal-world pilot demonstration projects that apply regulatory science to the
R
development of therapeutics can generate important insights while keeping
collaborators engaged and committed to their partnerships.
• n initiative to create a self-sustaining Virtual Development Institute comprising
A
a network of university-based organizations could be initiated using funds from
existing translational research programs.
• “champion” for regulatory science could help define and promote the
A
discipline.
Given budgetary constraints that are unlikely to ease in the near
future, efforts to develop the discipline of regulatory science and a regula-
tory science workforce may increasingly seek to rely on indirect support
more than direct funding. To explore this issue, the workshop discussed
funding opportunities and collaborative models that would need to be
available to strengthen and support regulatory science research and prac -
tice in therapeutics development. Workshop presentations and discus -
sions also examined whether there are institutions, public or private, that
57
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58 STRENGTHENING A WORKFORCE FOR INNOVATIVE REGULATORY SCIENCE
could offer funding to create an infrastructure and ecosystem to support
innovative regulatory science.
Gigi Hirsch, Executive Director, Center for Biomedical Innovation,
Massachusetts Institute of Technology (MIT), described a new initia-
tive designed to transform the drug development ecosystem. William
Greenlee, President and Chief Executive Officer, the Hamner Institutes
for Health Sciences at Research Triangle Park, summarized the Hamner
Institutes’ approach to collaborative efforts among government, industry,
and academia. Theodore Reiss, Research Professor of Medicine, Vanderbilt
University School of Medicine, proposed a new model for research and
education that would reflect the needs of today’s world. A discussion fol -
lowed that explored the resources and stakeholder engagement needed to
build the discipline of regulatory science and establish regulatory science
career paths.
CREATING A COLLABORATIVE ENVIRONMENT
IN AN ACADEMIC SETTING1
In an attempt to repair dysfunction in the drug development eco-
system, MIT created the New Drug Development Paradigms (NEWDIGS)
initiative. NEWDIGS is a collaborative environment for innovation and
learning that takes a systems approach to transforming processes, tech -
nologies, and policy elements of innovation. The stakeholder community,
Hirsch said, includes major pharmaceutical companies, the global regula -
tory community, academia, payers, and patient advocacy groups. A group
of MIT faculty serves as strategic advisors to the initiative. NEWDIGS
emphasizes tight coordination between real-world pilot projects and aca -
demic research in engineering, science, management, and clinical medi-
cine. Lessons learned by NEWDIGS might offer useful ideas and insights
for approaches to strengthening a workforce for innovative regulatory
science in drug development, said Hirsch.
After identifying a high-impact area of need or opportunity within
the innovation space, NEWDIGS convenes a subteam that is interested
in this topic and proceeds in a modular fashion (Figure 7-1). The first
module takes a regulatory science approach to focus on “adaptive licens -
ing” (including staggered approval, progressive licensing). The second
module focuses on oncology, specifically codevelopment of two or more
investigational compounds in combination therapies and helping FDA
develop a guidance document on the subject. A proposed payer-centric
third module would examine value-driven innovation. Within each mod-
1 This section is based on the presentation by Gigi Hirsch, Executive Director, Center for
Biomedical Innovation, MIT.
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59
COLLABORATIVE MODELS AND NEW PARADIGMS
NEWDIGS
Ecosystem
Design Teams
Module 3
Module 1
Process Module 2 Value--Driven
Regulatory
Oncology Innovation
Science
Policy (TBC)
Healthcare
Information Innovation
Flows Codevelopment Ecosystem
Adaptive
of Combination
Licensing 2.0
Knowledge Treatments
Products and Modules and activities are scalable
Services
Organization
and Culture
FIGURE 7-1 The New Drug Development Paradigms (NEWDIGS) initiative in-
volves design teams that progress through established modules to engage in in -
novative regulatory science activities.
Figure 7-1
SOURCE: Hirsch, 2011. Presentation at IOM workshop on Strengthening a Work-
force for Innovative Regulatory Science in Therapeutics Development.
ule, NEWDIGS researchers build test beds that are designed to combine
stakeholders, real-world demonstration projects, and academic research
in a way that enables rapid-cycle learning.
NEWDIGS also looks across the modules it has established to find
improvements in the architecture of the overall innovation system. The
cross-module approach relies on methodologies that focus on preserv-
ing value. In this way, everything in the drug development environment
enables and contributes to innovation through understanding of how to
improve processes, policies, and information flows.
Adaptive Licensing
NEWDIGS has adopted the approach of taking advantage of an
opportunity for proactive, strategic design of policy with broad stake -
holder input, followed by the empiric evaluation of these designs to
inform discussions about change. Regulatory agencies, major pharma -
ceutical companies, two payers, and researchers from MIT and Harvard
are participating in this effort and are designing initial demonstration
projects involving compounds in development that will be implemented
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60 STRENGTHENING A WORKFORCE FOR INNOVATIVE REGULATORY SCIENCE
in Singapore in collaboration with the Singapore Health Sciences
Authority. The group has been using simulations to try to understand
what adaptive licensing might look like across different drugs and dif -
ferent drug classes.
Collaboration among the participants is well integrated. Data sharing
about drugs currently in the pipeline is undertaken pursuant to formal
confidentiality agreements. The work includes an active academic and
educational component, including monthly research seminars. Hirsch
noted that some 30 students are participating and learning about regula-
tory science through the project.
Developing a Collaborative Workforce
Hirsch described a regulatory science workforce as a virtually col-
laborative workforce of individuals from different disciplines and market
sectors. She offered the following observations for supporting such a
workforce:
• Establish a “safe haven” environment through specific ground
rules for workshops as a critical element for enabling learning and
innovative thinking. These ground rules include items such as “no
decisions are made in workshops” and “individuals do not speak
on behalf of their organizations.”
• Systems approaches to design and problem solving are critical
but challenging given the enormously complex interdependencies
across disciplines and the silos that inhibit communication and
sharing. NEWDIGS has been experimenting with a variety of
systems engineering methodologies, finding that they are falling
somewhat short when they are applied across an entire industry. In
addition, a diversity of expertise and perspectives is critical. Thus,
it is particularly important to involve individuals from outside of
the health care industry.
• Having a safehaven “test bed” for ideas is important not only for
making progress but to fight “consortium fatigue” and to keep
participants involved in working on solutions to problems involv-
ing regulatory science. Ability to demonstrate that the learning and
innovation activities that fuel continuous improvement in execu-
tion have been central to the sustainability of NEWDIGS.
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61
COLLABORATIVE MODELS AND NEW PARADIGMS
A COLLABORATIVE MODEL FOR RESEARCH,
TRAINING, AND BUSINESS DEVELOPMENT2
The fundamental philosophical paradigm of the Hamner Institutes
is that publication of findings is not the end game of research. Rather,
the goal is to capture research knowledge in a way that will improve
global public health by driving the development of safer medicines,
informing public health policy, and realizing economic development.
The Hamner Institutes’ Institute for Drug Safety Sciences was
launched 3 years ago in partnership with the University of North Carolina
at Chapel Hill (UNC), and involving faculty from Duke University and
North Carolina State University. This new entity operates on the principle
that modernizing toxicology is not about hazard identification. Rather, it
is about understanding environmental perturbation on biological systems
and being able to understand the health outcomes of that perturbation.
The institute is developing approaches that link postmarketing surveil-
lance, clinical studies, and advanced animal model systems. The institute
is also collaborating with investigators in China to develop virtual models
of the Caucasian and Asian liver to understand subtle differences in drug
response between these two populations.
The Hamner Institutes is now developing additional partnering rela-
tionships that aim to bring academia, industry, and government to the
same table as a means of accelerating drug development. These new
partnerships will also involve the Hamner Biosciences Accelerator, which
has dedicated staff, education and training support through postdoctoral
fellowships, and a business development mindset to move discoveries
into technology development programs and out into the market. One
partnership that has developed out of this effort involves an effort to
accelerate drug development in China under U.S. regulatory standards
with the goal of bringing products to market worldwide.
REGULATORY SCIENCE: SOLVING FOR A LARGER CONTEXT3
Regulatory science must be addressed within a broader context to
address important public health needs and accelerate drug development.
This broader context starts with the drug development environment; the
pharmaceutical industry is experiencing transformational trends, including
very difficult scientific challenges and rapidly increasing expenses and price
pressures, while the public sector and academia are developing new skills
2 This section is based on the presentation by William Greenlee, President and Chief Execu -
tive Officer, the Hamner Institutes for Health Sciences at Research Triangle Park.
3 This section is based on the presentation by Theodore Reiss, Research Professor of Medi -
cine, Vanderbilt University School of Medicine.
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62 STRENGTHENING A WORKFORCE FOR INNOVATIVE REGULATORY SCIENCE
and capabilities for drug discovery and development. Taken together, these
trends suggest collaborative solutions for a new and broader educational,
scientific, and funding environment. Reiss laid out a set of foundational
principles for collaboration around development and regulatory science:
• Addressing issues piecemeal will have limited impact.
• Industry, government, and academia must collaborate to create a
vision for a more integrated biomedical science environment.
• Academia must value and promote translational, development,
and regulatory thinking, and it must bring industry scientists to
the table to help with this transformation.
• The new environment must be efficient and robust and leverage
structures already in place, such as the CTSA institutions.
A model organization would be university centered, according to
Reiss, and would involve NIH, with a department of “bench-to-bedside
science.” The faculty would have expertise in development, regulatory
issues, and translation and would serve as a center for collaborative
translational projects. These projects would include scientists from other
academic departments as well as from industry, regulatory agencies, and
foundations. The department would serve as a center to teach transla-
tional, development, and regulatory science, instilling a team-oriented,
collaborative mindset in students and postdoctoral fellows. It also would
be linked across institutions through the CTSAs into what Reiss termed a
“Virtual Institute of Drug Development.”
Reiss acknowledged that there are real barriers to creating such an
organization. Universities lack exposure to and comfort with this type
of broad versus deep thinking. The cognitive framework of academia
will need to change from one focused on absolute knowledge to one that
considers confidence in benefits and risks based on significant, consistent
evidence. The polarization among academia, industry, and the regulatory
sector will need to be reduced. The lack of reward structure for transla -
tional, development, and regulatory projects is a significant barrier, as is
the lack of coordinated teaching, training, and research programs within
today’s academic structure.
Funding such an initiative will require a concerted effort from all stake-
holders. Reiss suggested that initial funding should come from the proposed
NCATS, with universities following by providing matching infrastructure
funds, adding that NIH should ensure that there is a balanced portfolio of
funding initiatives between discovery and development projects.
Reiss noted that such an initiative would provide a critical signal to
investigators regarding potential careers in development, translational,
or regulatory science.
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63
COLLABORATIVE MODELS AND NEW PARADIGMS
Other sources of funds also need to be available, said Reiss. The phar-
maceutical industry—both large and small companies—and foundations
should contribute through collaborative projects and by participating
operationally in the Virtual Development Institute. Though a tax may
currently have trouble finding support, Reiss argued that an “approval
tax” on drugs, or a revenue tax on sales exceeding $1 billion, should be
considered at some point to provide a self-sustaining source of funding.
CLOSING PANEL4
In a closing panel session, several workshop speakers engaged in a
panel discussion with the workshop co-chairs and the workshop par-
ticipants to discuss resources, stakeholder engagement, and next steps
needed to build a discipline of regulatory science and establish career
paths in innovative regulatory science. This section lists ideas presented
by the panelists and workshop participants. Statements, recommenda -
tions, and opinions expressed are those of individual presenters and
participants and are not necessarily endorsed or verified by the Forum or
the National Academies, and they should not be construed as reflecting
any group consensus.
The following are observations by the panelists:
• There is increasing participation by the nonprofit sector to advance
the discipline of regulatory science.
• There continues to be a lack of respect within academia for the field
of regulatory science.
• There are roles for every sector in the drug discovery ecosystem to
participate in the development of a regulatory science workforce.
• Existing programs in regulatory science do not include or empha-
size the social sciences.
• Without a separate discipline of regulatory science, it will be diffi-
cult to train a workforce with the necessary mindset to understand
the needs of regulatory versus discovery science.
4Participants in the summary panel were Barry Coller, Vice President for Medical Affairs,
Physician-in-Chief, and David Rockefeller Professor, The Rockefeller University; Elaine
Gallin, Principal, QE Philanthropic Advisors; Steven Galson, Vice President for Global
Regulatory Affairs, Amgen Inc.; William Greenlee, President and Chief Executive Officer,
the Hamner Institutes for Health Sciences at Research Triangle Park; Gigi Hirsch, Executive
Director, Center for Biomedical Innovation, MIT; Carl Peck, Professor of Pharmacology and
Medicine, UCSF; Theodore Reiss, Research Professor of Medicine, Vanderbilt University
School of Medicine; and Alastair Wood, Partner and Managing Director, Symphony Capital
LLC.
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64 STRENGTHENING A WORKFORCE FOR INNOVATIVE REGULATORY SCIENCE
• There are more career opportunities and paths for regulatory scien-
tists than might be commonly understood, including international,
national, and state regulatory agencies, the Federal Trade Commis-
sion, Congress, payers, investors, and journals.
• The collaborative, multidisciplinary nature of innovative regula-
tory science may undermine the ability to identify a champion or
lead stakeholder charged with advancing the science.
• Considering that one goal of the investment in basic health sciences
research is to improve health outcomes, investing in regulatory sci-
ence could support the case for such investment.
The following are suggestions for a way forward from the panelists:
• Create a standing panel sponsored by FDA and/or NIH that would
focus on ways to strengthen the regulatory science workforce.
• Ensure that social science research and evidence is built into regu-
latory science research and practice.
• Identify a champion that can take responsibility for advocacy for
support of regulatory science and the workforce to support regula-
tory science. It was suggested that proposed NCATS could serve as
a key champion for the discipline.
• Design regulatory science training programs to reflect the differ-
ent training backgrounds of the individuals who come to reg-
ulatory science. The “menu” approach applied in the European
PharmaTrain program could be a good model.
• Convene a series of conferences that would be charged with defin-
ing the big needs or “big questions” in regulatory science. Link this
effort to RFAs that would support pursuit of these big questions.
• Opportunities to increase interest in the discipline among students
and investigators include reinvigorating and expanding research
fellowships in clinical pharmacology and embedding regulatory
science research fellowships in translational medicine and thera-
peutics through such programs as the CTSA institutions and the
proposed NCATS.
• Researchers who have lost jobs as the pharmaceutical industry has
downsized could offer a pool of scientists that could be recruited
to do regulatory science in the federal agencies and in academia
through innovative and creative pilot projects.
• Make it clear that “if innovation is the goal, regulatory science is
essential.”
