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Institute of Medicine (US). Accelerating the Development of New Drugs and Diagnostics: Maximizing the Impact of the Cures Acceleration Network: Workshop Summary. Washington (DC): National Academies Press (US); 2012.

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Accelerating the Development of New Drugs and Diagnostics: Maximizing the Impact of the Cures Acceleration Network: Workshop Summary.

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1Introduction1

Extraordinary opportunities surround the development of new drugs and diagnostics. New technologies and knowledge are creating novel avenues for research and new opportunities for the discovery and clinical development of innovative diagnostics and therapies. Yet, the pathway from basic science to new therapeutics is treacherous. Only a small fraction of investigational new drugs eventually reach the patients who need them. This ever-widening gap between scientific discoveries and the translation of those discoveries into life-changing medications is a major source of frustration for patients, biomedical researchers, businesses, and policy makers.

One response to this gap has been a renewed emphasis on collaborative approaches within federal agencies, academia, and industry directed at the advancement of the drug development enterprise. Among these initiatives is the Cures Acceleration Network (CAN). Originally authorized in the Patient Protection and Affordable Care Act of 2010 (P.L. 111-148), CAN was moved to the newly authorized National Center for Advancing Translational Sciences (NCATS) within the National Institutes of Health (NIH) by the Consolidated Appropriations Act of 2012 (P.L. 112-74). The authorizing legislation for CAN requires that it be overseen by a board of 24 diverse members from several fields, including research, the U.S. Food and Drug Administration (FDA), venture capital, and patient advocacy. Though appropriated funding for its initial year was just $10 million, CAN has the potential to catalyze widespread changes in NCATS, NIH, and the drug development ecosystem in general.

On June 4–5, 2012, the Forum on Drug Discovery, Development, and Translation (the Forum) of the Institute of Medicine (IOM) held a workshop in Washington, DC, to explore options and opportunities in the implementation of CAN by NCATS. Entitled “Maximizing the Goals of the Cures Acceleration Network to Accelerate the Development of New Drugs and Diagnostics,” the workshop was held in part to respond to congressional interest in CAN expressed in the 2012 appropriations act conference report. The workshop brought together members of federal government agencies, the private sector, academia, and advocacy groups for a day and a half of informative presentations and vigorous discussion. Box 1-1 lists the objectives of the workshop.

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BOX 1-1

Statement of Task for the Workshop. This public workshop considered options and opportunities to maximize the usefulness and impact of the CAN program in order to advance translational sciences. The workshop objectives were to Identify and catalog potential (more...)

This summary of the workshop is meant to inform NCATS, the policy community, patient groups, the public, and other stakeholders as all of these parties work together to enhance the development and testing of therapies and diagnostics. This summary also is being provided to NCATS and to the newly established Cures Acceleration Network Review Board (the CAN Board) to help it identify ways to maximize the impact of CAN and accelerate and expand the availability of cures for patients.

The first chapter of this summary provides an overview of CAN and compiles an overview of the themes of the workshop. Chapter 2 examines different approaches to accelerating translational science, in part through case studies of successful drug development projects. Chapters 3 and 4 examine two unusual features of CAN: the authority to require that some of its grants be matched by funds from other sources, and the authority to use a more flexible form of contracting known as “other transaction authority” (OTA), which has contributed to the success of the Defense Advanced Research Projects Agency (DARPA). Chapter 5 presents perspectives on the role of CAN within the broader drug development ecosystem. Chapter 6 concludes this summary of the workshop with several views expressed by participants of steps CAN could take to have a major impact on the development of cures to improve human health.

THE HISTORY AND GOALS OF CAN

In the first session of the workshop, five speakers discussed the history, organization, and goals of CAN—Tom Insel, Acting Director, NCATS; Sudip Parikh, Vice President of Health Policy, and Managing Director, Centers for Public Health Research and Evaluation, Battelle Memorial Institute; Lili Portilla, Director, Office of Strategic Alliances, NCATS; Barbara McGarey, Deputy Associate General Counsel for Public Health, Office of the General Counsel, NIH; and Kathy Hudson, Acting Deputy Director, NCATS, and Deputy Director for Science, Outreach, and Policy, NIH Office of the Director. The first part of this chapter provides an integrated summary of their remarks. The latter part of the chapter provides an overview of the themes of the workshop identified individually by five speakers during the workshop’s final session. It should not be construed as reflecting consensus or endorsement by the planning committee, the Forum, the workshop participants, or the IOM.

The History of CAN2

In 2003, when Joe Lieberman was running in the Democratic presidential primary, he called for a $150 billion, 10-year federal initiative to bring cures for diseases quickly to the marketplace. This call contributed to the introduction of both the American Center for Cures Act of 2005, which called for a center within NIH with an authorization of $5 billion, and the similar Accelerating Cures Act of 2008. Neither bill made much progress in Congress, but the ideas contained in the bills caught the attention of Senator Arlen Specter. In 2009, as the recession severely affected the biotechnology industry, Specter began working on legislation designed to magnify the effect that patient advocates were having on the search for cures to disease. Meetings with patient advocates and venture capitalists led to the idea for a Cures Acceleration Network—a name originally suggested by the autism community, according to Parikh.3 The network was intended to have the following characteristics: authority to give large awards, a program allowing for matching grants to take advantage of the passion and expertise of patient groups, and administration outside NIH. Additional goals were to broaden the range of eligible grantees and reviewers, with the latter including venture capitalists and patients. It would have a competitive prize component and funding authorities like those granted to DARPA.

The Cures Acceleration Network Act introduced by Specter called for an entity outside NIH with a program managed by a high-level board. Independence from NIH was intended to tap into a different culture than the one prevalent at NIH. It would have authorized the use of interagency agreements, with the Center for Scientific Review performing peer review, and it would have prescribed the expertise necessary for members of the initial review group. The act would have increased the authorization for NIH to $40 billion, with $1 billion for CAN.

Many, though not all, components of this legislation were passed in the Patient Protection and Affordable Care Act of 2010. CAN was established in NIH, in the Office of the Director, not as an independent entity. (As discussed below, the program was subsequently moved to NCATS.) It had an authorized budget for fiscal year (FY) 2010 of $500 million. New award mechanisms include Cures Acceleration Partnership Awards of “not more than $15 million per project for the first fiscal year for which the project is funded”; Cures Acceleration Grant Awards of the same size; and Cures Acceleration Flexible Research Awards with a flexible, or “DARPA-like,” funding authority that could represent up to 20 percent of CAN’s budget.4 The 24-member CAN Board was to include patient advocates and venture capitalists and was to advise the NIH director about barriers to successful translation of basic science into clinical applications.

However, CAN would not exist until money was not just authorized, but appropriated for it. According to Parikh, the patient advocacy community provided enormous support for the appropriation, and several influential articles in the media argued for the kind of capacity that would be created by CAN. At the same time, industry was forming innovative partnerships with universities in an effort to create new research and development (R&D) models for the development of drugs and diagnostics.

As part of the Consolidated Appropriations Act of 2012, enacted at the end of 2011, CAN was finally launched (see Appendix B). It was placed within the newly established NCATS, which was established in the same Act for FY 2012 to catalyze the generation of innovative methods and technologies that will enhance the development, testing, and implementation of diagnostics and therapeutics (see Box 1-2). Parikh commented that NCATS, as conceived and structured, offers the culture originally envisioned for CAN—different from, while complementary to, the traditional activities and focus of NIH. The appropriated budget for CAN in FY 2012 was only $10 million.

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BOX 1-2

The Need for Translational Science. Biomedical research has now revealed the molecular basis of more than 4,000 individual diseases, Insel noted in his introductory remarks. However, only about 250 of these diseases have molecular therapies, and over (more...)

The Structure of NCATS and CAN

At this level of funding, CAN is the smallest of the four major programs and initiatives within NCATS—Clinical and Translational Science Activities, Rare Diseases Research and Therapeutics, Re-engineering Translational Sciences, and CAN.

As Insel emphasized, most of the translational science being supported by NIH is going on through the 26 institutes and centers other than NCATS. However, those other institutes and centers need NCATS to catalyze the tools that enable the rest of NIH to do things better, faster, and cheaper. There was discussion during the workshop of what Hudson called “cool tools,” such as an ongoing partnership with pharmaceutical companies to find new uses for old drugs. NCATS was established in part to support the development of these tools and thereby catalyze projects elsewhere in NIH. Insel also noted that the center’s Clinical and Translational Science Award (CTSA) consortium—a national consortium of about 60 medical research institutions that accounts for more than 80 percent of NCATS’ $576.5 million budget in FY 2012—“has created the potential for a national network that can be the flagship for what we do in translational science at academic sites around the country.”

The legislation for CAN authorizes three award programs: the Cures Acceleration Partnership Program, the Cures Acceleration Grant Program, and the Cures Acceleration Flexible Research Program. The legislation also authorizes large grants, not to exceed $15 million per fiscal year. Congress must explicitly appropriate funds for CAN or its programs in order for NIH to fund them, observed McGarey. NIH is specifically prohibited from using any funds from its general appropriation to fund CAN activities. According to McGarey, this is unusual for NIH authorities, though she noted that she did not anticipate it being a problem, “unless, of course, Congress appropriates no money for CAN.” Insel also noted that CAN has the potential to work in partnerships with other NIH institutes and centers, including the CTSAs in NCATS, even though funds cannot be transferred into CAN.

The purpose of CAN is to accelerate the development of high need cures through the development of medical products and behavioral therapies (see Box 1-3). The statute defines both medical products and high need cures very broadly, with a significant amount of discretion to work strategically in the translational science arena. CAN has the typical NIH program authority to conduct or fund both intramural and extramural activities. Also, one of the specifically articulated functions of CAN is to facilitate review by FDA of the research funded by CAN for high need cures. McGarey commented that this is an interesting purpose conferred under statute for an NIH program, which will allow NIH to undertake or fund activities targeted to coordination of research in FDA review.

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BOX 1-3

Functions of CAN in Authorizing Legislation. Conduct and support revolutionary advances in basic research, translating scientific discoveries from bench to bedside. Award grants and contracts to eligible entities to accelerate the development of high (more...)

The CAN Board is to have 24 members appointed by the Secretary of the Department of Health and Human Services. 5 It is to have

  • at least one member eminent in each of the following areas: basic research, medicine, biopharmaceuticals, discovery and delivery of medical products, bioinformatics and gene therapy, medical instrumentation, and regulatory review and approval of medical products;
  • at least four members recognized as leaders in venture capital or private equity investing; and
  • at least eight members representing disease advocacy organizations.

The congressional conference language from the 2012 appropriations bill encourages the CAN Board to create measurable outcomes to track CAN’s successes.

Insel noted that advisory boards at NIH have different characteristics at the different institutions and centers. At NCATS, the responsibilities of the CAN Board are to advise and provide recommendations to the Director of NCATS regarding the policies, programs, and procedures for carrying out the duties of the Director and to identify significant barriers to the successful translation of basic science into clinical application, including issues under the purview of other agencies and departments. The CAN Board will provide a second level of review for projects, but, said Insel, it also will provide “a lot of wisdom beyond just those individual projects.” The membership of the CAN Board and the NCATS Council will overlap so that there is synergy rather than conflict between their respective scope and responsibilities.

There are mechanisms other than congressional appropriations that could potentially fund CAN activities. For example, NCATS, like all other NIH institutes or centers, can accept gifts, either unconditionally or with strings attached, though offers can be rejected if the conditions are unacceptable. NIH also can work through the Foundation for the NIH (FNIH) to generate ideas for collaborative projects. These projects still need to go through the NIH review process, which can impose delays that are unacceptable to outside collaborators. But NCATS can interact with FNIH not only by raising an idea for funding but also by providing matching funds for an idea, which has not been possible in the past.

Matching Grants and OTA

CAN’s authorizing legislation gave it several authorities that are uncommon for government agencies, and for NIH in particular:

  • The Cures Acceleration Partnership Awards have a one-to-three matching requirement. The match is waivable by the NCATS Director. (These matching requirements are the subject of Chapter 3.)
  • The legislation also provides CAN with the authority to use the full scope of government funding mechanisms, including cooperative agreements, contracts, and OTA. (Chapter 4 explores the features of OTA in detail.) Flexible research awards exercising OTA are limited to 20 percent of the total funds appropriated to CAN in a fiscal year. Also, the NCATS Director must have determined that the goals and objectives of the awards cannot adequately be carried out through conventional contracting agreements.

OTA “is best described as what it is not,” said Portilla. It is not a grant, contract, or cooperative R&D agreement. Instead, it provides for greater flexibility in putting together an agreement to get a project done. Congress must explicitly authorize an agency to use OTA to obligate funds. Although NIH has historically had the authority to use OTA, only a single NIH staffperson was trained to work with it, and the authority was little used.

Under OTA, certain government regulations and policies do not necessarily apply, including the Federal Acquisition Regulation (FAR), provisions of the Bayh-Dole Act, and NIH peer-review requirements. This authority thus allows an agency to attract nontraditional partners who would otherwise have concerns about conventional federal regulations and policies. In other agencies that have used OTA, the timelines to getting projects done have been shorter than elsewhere in government. OTA also has the effect of encouraging cost sharing among partners, both public and private.

OTA can eliminate some of the barriers to establishing unique partnerships, said Portilla. However, because each arrangement conducted under OTA is different, so too are the metrics designed to evaluate the success of an agreement. “Up front you are going to have to determine what the metric is that you are trying to measure with each one of these agreements,” said Portilla.

Unique Features of CAN

Hudson emphasized several of the features of CAN that collectively set it apart from not only programs of other NIH institutes and centers but from those of other government agencies. The first is that CAN is designed to be catalytic, which will be essential given its small initial budget. (The first year of CAN funding is about the same as is authorized for a single award.) Under such circumstances, what is needed, said Hudson, are ways to “catalyze interesting, novel collaborations, get work done faster, and make a real difference in patients’ lives.”6

A second prominent feature of CAN will be its collaborative nature, a feature that it will share with NCATS. Collaborations already under way at NCATS with DARPA, FDA, the pharmaceutical industry, and patient advocates all demonstrate this commitment to partnerships, Hudson said.

Third, both CAN and NCATS are committed to open communication and information gathering from the community. “Today’s workshop is an example of that,” said Hudson. “We are seeking to hear from the community, broadly defined, what are the barriers that are standing in the way of developing new cures and diagnostics and devices, and how can we focus our attention on developing tools that will help speed the development of those drugs.”

Finally, NCATS and CAN will be countercultural, with a different culture than the rest of NIH. Though as Parikh had explained, CAN was originally meant to be separate from NIH; its placement within NCATS maintains the opportunity for it to have a distinct culture. NCATS represents “a different culture growing inside of NIH,” Parikh said. “It complements NIH.”

Questions for the Workshop

Insel concluded his talk by raising several questions pertinent to the core mission of CAN for consideration at the workshop:

  • How will CAN have the greatest impact?
  • What tools, methods, and approaches can accelerate translational science?
  • What is the best use of the matching and flexible research authorities established in legislation?
  • How will CAN assist public–private partnerships?
  • How will CAN interact with the ongoing regulatory science initiative at FDA?

He also emphasized the need for some “early wins” from CAN. “We need to be able to show how this can be used to do something that hasn’t been done before.”

OVERVIEW OF THE THEMES OF THE WORKSHOP

In the final session of the workshop, speakers individually identified the themes that emerged over the course of the workshop. These themes are described here as a way of providing an overview of the major topics discussed at the workshop that encapsulate the key issues surrounding the creation of CAN and its future course.

Approaches to Accelerating Translational Science7

CAN does not yet have the funding to support major projects, but it can be a crucial catalyst for innovation within NCATS. To do so, Bill Chin, Executive Dean for Research, Harvard Medical School, noted that it needs to foster a bidirectional flow of information between basic scientific research and the process of translating scientific results into products. It also needs to create new knowledge through interactions among diverse groups. In particular, barriers to collaboration still exist between the academic and industrial talent pools.

Collaboration can de-risk drug development efforts through public–private partnerships. Many of these efforts will be precompetitive, but at least some could be in the product development space where private-sector competition exists. Chin argued that the traditional technology transfer model in academia needs to be transcended, and more drug discovery and development data need to be shared. The CTSAs could also be a vehicle for training investigators who would then be prepared to collaborate by virtue of their education and experience.

The organization of translational science could enable progress. Collaborative teams of passionate investigators can pursue ambitious goals. Therapeutic discovery could be decentralized, decision making streamlined, bureaucracy reduced, and flexibility enhanced. Planning and project prioritization need to be done on a programmatic, not episodic or grant-by-grant, basis for maximum effect, and effective project management is key. Open-source models of innovation are tremendously exciting. Other novel approaches include crowdsourcing, prizes, or other incentives.

A virtual model of drug discovery could produce important advances. In the area of tools development, CAN could help explore how technology can positively affect the translational process. Key areas of both scientific and technological development cited at the workshop include

  • development of better animal models;
  • use of stem cells;
  • development and promotion of scientific areas such as

    systems biology,

    chemical biology,

    regulatory science, and

    informatics;

  • development of molecular libraries;
  • innovation in clinical trial design; and
  • improvement of target validation.

Chin cited as a provocative suggestion mentioned at the workshop the development from scratch of a more effective and efficient regulatory process. For example, efforts could focus on creation of a new development and regulatory pathway for more rapid approaches to proof of concept or proof of mechanism in a Phase 1B or 2A. After feasibility assessment, implementation could be undertaken for those aspects of that system that are thought to be feasible.

Matching Authority8

As the demands on resources become greater, matching grants offer an opportunity for both collaboration and synergy. They also reduce the risk for partners who are willing to experiment, and successful experiments on a small scale then can be replicated and disseminated. Nancy Sung, Senior Program Officer, Burroughs Wellcome Fund, noted that it is important to get partners engaged with each other early in the process. Through early involvement, partners can shape the project from the start.

Agency support for partnerships can vary from a relatively hands-off approach to active solicitation, management, and support of partnerships. CAN will need to pick a place along this continuum that best takes advantage of the corresponding opportunities. Similarly, partnerships can range from one-on-one interactions to large multistakeholder forums. It will be important to bring partners up to speed, help them understand the context, and forge personal connections.

Training for those who are interested in commercializing discoveries can be extremely valuable. Tailored curricula, mentoring, and webinars are all possible ways of building skills and knowledge. What makes a project attractive to investors? What kind of reproducibility do regulators expect? What kinds of information need to be treated confidentially, and what kinds of information can be freely shared? Widespread understanding of such topics through training strategies can reduce the need for written agreements, especially during the early stages of collaboration.

The risks associated with projects funded by CAN will not be the same as the risks of other NIH projects. Projects will be done not just faster and better, but differently. The risk profile of CAN’s portfolio of projects will need to be actively monitored to find the “sweet spot” where risks are taken but also are manageable.

OTA9

While OTA has not necessarily been essential to the success of DARPA and other agencies, it is an effective tool for those who have access to it. It allows federal agencies to partner with organizations, and particularly large companies, that have concerns about the standard federal contracting process.

OTA essentially allows a government agency to start with a blank piece of paper in writing a contract with a nongovernmental organization. According to Daniel Wattendorf, Program Manager, Defense Sciences Office, DARPA, success requires that the people who are relevant to the discussion be represented and that they are able to convey to each other what they want to achieve. They also need to discuss issues, such as intellectual property, where there may be concerns and address those concerns at the beginning of a project so that all of the partners to an agreement know what is expected. Staff training and competencies are key elements. A strong relationship between the program manager and the contracting officer has contributed to many of the successes of DARPA. OTA contracts can be more time-consuming to set up at the outset, but they can be easier to execute because everyone understands the terms of the agreements.

Wattendorf noted that a major function of DARPA has been to serve, in essence, as the venture capital arm of the Department of Defense (DoD), and OTA helps make that role possible. In the same way, the use of OTA could help make CAN and NCATS the venture capital arm of NIH.

Situating CAN Within the Drug Development Ecosystem10

The ecosystem for the development of cures is complex and resistant to change, but momentum currently exists to change the system. In particular, patient groups have played an increasingly powerful part in motivating and helping to generate new cures. This prominent new role of patient groups will be a major consideration as CAN takes shape.

Public–private partnerships are essential but require time, effort, and communication to succeed, Margaret Anderson, Executive Director, FasterCures, observed. Partnerships are particularly needed where resources are constrained, as is the case with the current funding levels of CAN. However, patient groups have demonstrated that even small amounts of funding, if strategically applied, can have major effects.

To accelerate the development of cures, CAN will need to function differently rather than emulating other government programs. At the same time, it needs to work closely with other agencies, including other parts of NIH and FDA. In particular, CAN and FDA will need to communicate early and often. Officials from FDA have expressed their eagerness to work with CAN because of CAN’s potential to help them solve problems they face. This cooperation could be a model for interagency collaboration, and this collaboration could form the basis for much broader changes in the drug development ecosystem.

The planning committee’s role was limited to planning the workshop, and the workshop summary has been prepared by the workshop rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not necessarily endorsed or verified by the Forum or the Institute of Medicine (IOM), and they should not be construed as reflecting any group consensus.

This subsection is based on remarks given by Sudip Parikh, Vice President of Health Policy, and Managing Director, Centers for Public Health Research and Evaluation, Battelle Memorial Institute.

Parikh was at the time a congressional staff member working on the legislation with Senator Specter.

This authority is also known as “other transaction authority” (OTA). See Chapter 4 for further discussion of the “DARPA-like” authority.

The CAN Board composition was announced on August 30, 2012. The members are listed at http://www​.ncats.nih​.gov/about/org/advisory​/can-board/roster/roster.html (accessed August 30, 2012).

Parikh also emphasized the potential for CAN’s budget to grow. “What you are planting is a seed that over time will grow pretty quickly, especially depending on the submissions that are made by NIH and by the White House. It may be $10 million today. Your post-docs will hopefully have more to work on.”

This subsection is based on remarks given by Bill Chin, Executive Dean for Research, Harvard Medical School.

This subsection is based on remarks given by Nancy Sung, Senior Program Officer, Burroughs Wellcome Fund.

This subsection is based on remarks given by Daniel Wattendorf, Program Manager, Defense Sciences Office, DARPA.

This subsection is based on remarks given by Margaret Anderson, Executive Director, FasterCures.

Footnotes

1

The planning committee’s role was limited to planning the workshop, and the workshop summary has been prepared by the workshop rapporteurs as a factual summary of what occurred at the workshop. Statements, recommendations, and opinions expressed are those of individual presenters and participants, and are not necessarily endorsed or verified by the Forum or the Institute of Medicine (IOM), and they should not be construed as reflecting any group consensus.

2

This subsection is based on remarks given by Sudip Parikh, Vice President of Health Policy, and Managing Director, Centers for Public Health Research and Evaluation, Battelle Memorial Institute.

3

Parikh was at the time a congressional staff member working on the legislation with Senator Specter.

4

This authority is also known as “other transaction authority” (OTA). See Chapter 4 for further discussion of the “DARPA-like” authority.

5

The CAN Board composition was announced on August 30, 2012. The members are listed at http://www​.ncats.nih​.gov/about/org/advisory​/can-board/roster/roster.html (accessed August 30, 2012).

6

Parikh also emphasized the potential for CAN’s budget to grow. “What you are planting is a seed that over time will grow pretty quickly, especially depending on the submissions that are made by NIH and by the White House. It may be $10 million today. Your post-docs will hopefully have more to work on.”

7

This subsection is based on remarks given by Bill Chin, Executive Dean for Research, Harvard Medical School.

8

This subsection is based on remarks given by Nancy Sung, Senior Program Officer, Burroughs Wellcome Fund.

9

This subsection is based on remarks given by Daniel Wattendorf, Program Manager, Defense Sciences Office, DARPA.

10

This subsection is based on remarks given by Margaret Anderson, Executive Director, FasterCures.

Copyright © 2012, National Academy of Sciences.
Bookshelf ID: NBK114624
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