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Institute of Medicine (US). Genome-Based Therapeutics: Targeted Drug Discovery and Development: Workshop Summary. Washington (DC): National Academies Press (US); 2012.

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Genome-Based Therapeutics: Targeted Drug Discovery and Development: Workshop Summary.

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6Forging Collaborative Strategies for the Development of Personalized Medicine

Important Points Highlighted by Individual Speakers

  • New paradigms in drug discovery and development will be achieved only through the collaborative efforts of multiple groups.
  • Successful collaborations require a shared and compelling vision along with a well-defined timeline and deliverables, and each party in a collaboration needs to benefit.
  • A particular focus of collaboration needs to be the establishment of biorepositories, databases, patient repositories, and other information resources for drug development.
  • Universal participation in biomedical research is a goal that would require overcoming major obstacles, but it would generate an enormous amount of safety and efficacy data that would benefit everyone.

Throughout the workshop, individual presenters and workshop attendees commented on the changes that would be necessary for new paradigms in drug discovery and development to take root and flourish. As with the examples described in the previous chapter, most of these changes involve the establishment of collaborations within a broad “ecosystem” of public and private stakeholders.

In the final session of the workshop, four presenters described pathways toward effective collaborations: Deborah Dunsire of Millennium Pharmaceuticals, Inc.; Victor Dzau of Duke University and Duke University Health System; Margaret Hamburg of the FDA; and Kathy Hudson of the NIH. This chapter summarizes their remarks along with those of other workshop participants who addressed the broad issues associated with collaborative strategies for the development of personalized medicine.


Translating genomic discoveries into patient benefits is a “team sport,” Dunsire said. No one organization has all the capabilities and resources needed to realize the promise of personalized medicine. Only through partnerships can success be achieved.

This collaboration needs to extend from the research laboratory to the clinic, Dunsire added. As such, collaborations can involve a very wide range of stakeholders, including industry, academia, regulators, health care providers, and patient organizations. A particularly important set of stakeholders that should be part of these collaboration efforts, Dzau said, consists of the various payers, such as the Centers for Medicare & Medicaid Services (CMS). Payers should be eager for evidence that a particular approach would save money. “That conversation has to occur,” Dzau said.

Austin emphasized that a successful collaboration requires a shared vision. In the collaboration among NCATS, the University of Kansas, and the Leukemia & Lymphoma Society, all of the partners had experience with drug development and shared knowledge of the process. In addition, the project used management practices standard in industry, with project managers in each of the three institutions who worked closely together to ensure that the project met its timelines.

Each party to a collaboration needs to benefit, even though each has different capabilities, Frueh said. “You need to look at what everybody brings to the table and really define the benefit to each entity, to each party, that participates.” On this issue, Pacanowski pointed to the importance of clear deliverables. “Knowing what to expect as a product that would benefit all of the [partners] is probably the most critical piece.” Finally, Capone observed that the vision must be not only shared but compelling in order to motivate and align the partners.

Frueh made the point that a balance needs to be drawn between less formal and more formal arrangements to reduce the demands on the members of a collaboration. In addition, the larger any group gets, the more complex it gets. Davies observed that companies need to focus on what they do well. “Are we spreading ourselves too thin?” he asked. “Is there an area where we can have more impact than other areas?”

Many collaborations occur in the precompetitive space where all partners can benefit from new knowledge without losing competitive advantage. Foundations can play a central role in such collaborations, Capone said, because the absence of a profit motive can keep the focus on the science and on the benefits to patients. In that regard the parties to a collaboration need to recognize the potential threats to a collaborative enterprise. For example, efforts to protect intellectual property, either by industry or academic partners, can stymie partnerships and thereby limit scientific advances. If all the information generated by a partnership is available, no party feels that it is being disadvantaged versus other parties in the group. Transparency requires effective governance structures and accountability. If these cannot be achieved, Capone said, it may be necessary to find different partners.


A particularly important partner in many collaborations is the FDA, which was represented at the workshop by its commissioner, Margaret Hamburg. The FDA has been working with sponsors, patient groups, and academia to get into the marketplace new products that represent the opportunities of personalized medicine, she said. These collaborative efforts have generated real benefits for patients with treatments being developed that affect the underlying mechanism of disease rather than treating symptoms, such as with ivacaftor, and that affect the appropriate use of medications, as represented by the more than 110 drugs that now have genetic information on their labels.

Research collaborations will be increasingly important to the FDA in the future, because it does not have the resources to do all of the research needed to develop the regulatory tools and knowledge needed for the agency to do its job as efficiently and effectively as possible, Hamburg said. Biomarkers need to be identified, characterized, and validated. Standards for whole-genome sequencing and SNP panels need to be established. Innovative clinical trial designs need to be developed that are faster, cheaper, more adaptive, and use smaller populations of patients, particularly in projects to identify subpopulations of patients that can benefit from a drug or that would react poorly to a drug.

One complication for the FDA is that many potential therapies cut across its traditional domains of product activity. The combination of a diagnostic with a therapeutic intervention falls into two centers within the FDA with different regulatory frameworks. The FDA’s challenge is to deal with such products in ways that “are efficient and reflective of where the science is and where these products are,” Hamburg said. The FDA will continue to work with its sponsors to break down barriers to co-development and to help create an effective scientific and business framework.

Information about underlying genetic traits and markers can be applied to help determine whether drugs will be effective as well as to predict their toxicological effects. It is important to feed this type of information as well as knowledge about why drugs have failed in the past back into earlier parts of the drug development process so that if a drug will fail it is identified as early as possible, not after hundreds of millions of dollars have been spent. While the FDA is not allowed to share the confidential commercial information it receives, the agency is working with companies to make this information more available to inform drug development and applications of existing drugs, Hamburg said.

The FDA has many opportunities to apply better computational approaches, improved data mining techniques, better pattern recognition strategies, and other cutting-edge techniques to identify promising applications of existing drugs and better-defined pathways for drug development. Such applications of cutting-edge science will often require bringing together people with different perspectives and different expertise.

Hamburg concluded her formal remarks by pointing to the complex ecosystem involved in biomedical product development and innovation. Many policies besides regulatory policies affect this ecosystem, including intellectual property protections, access to capital, reimbursement policies, and direct government investments. All of these policies matter, said Hamburg. “If we’re going to have success in realizing the opportunities in science, we need to be thinking about investing in and supporting the ecosystem that will be the engine of success.”


Another increasingly important partner in collaborative efforts will be NCATS, which was represented at the workshop by its acting deputy director, Kathy Hudson. The mission of NCATS is to catalyze the generation of innovative methods and technologies in order to enhance the development, testing, and implementation of diagnostics and therapeutics. The goal is to develop the tools that will make drug discovery and development better, faster, and cheaper, Hudson said. “We are not in the drug development business.”

This is a nontraditional approach for NIH. It requires working collaboratively with all of the 27 NIH institutes and centers that are each conducting translational research; with its sister agencies, including the FDA; with industry; with patients; and with academic medical centers. “[Collaboration] is really essential and vital to our success,” Hudson said.

Hudson mentioned several examples of innovative work that NCATS is undertaking in a precompetitive space. Like the FDA, NCATS has an interest in new kinds of clinical trials that are faster, cheaper, and involve smaller groups. A resource it can use to develop such trials is the set of institutions that have received Clinical and Translational Science Awards, which represents 60 of the best academic medical centers in the country networked together to do human subjects research across a range of diseases. The second example she mentioned is NCATS’s project in drug repurposing—described in the previous chapter—which is seeking to find beneficial compounds with known safety profiles that companies have abandoned, with all of the work done under a set of pre-negotiated three-way agreements with the pharmaceutical companies, academic universities, and the NIH. This will alleviate some of the barriers to entering into a formal agreement and speed the process of setting up the initiative. Finally, NCATS is working with FDA and the Defense Advanced Research Projects Agency (DARPA) to develop a chip that will closely mimic the physiological behavior of normal tissues. The goal is to develop a validated tool that companies and academic medical centers can use to test the responses of tissues to specific compounds, allowing compounds to be tested in vitro before testing them in humans.

NCATS is taking a DARPA-like approach to the drug repurposing and “tissue on a chip” projects. Both will be milestone-driven with funding removed if goals are not met.


The evolving landscape of genomics creates a tantalizing opportunity to bring forward medicines that are more effective because of the ability to identify patients for whom a particular drug will work best or have the least downside risk, Dunsire said. However, data are not always available to truly select therapies as a routine. Establishing biorepositories, databases, patient registries, and other information resources will allow drugs to be reevaluated as new information is derived. Examples like the collaboration between Millennium Pharmaceuticals and the Multiple Myeloma Research Foundation on the latter’s Personalized Medicine Initiative discussed in Chapter 5 show what is possible, Dunsire said. Patients with the same genetic condition can be targeted, and patients with other mutations can be encouraged to participate in different trials. Patients can donate specimens and data at diagnosis and throughout the progression of their disease. In this case, a patient advocacy organization is driving inclusion, but other mechanisms could be equally or more effective.

Hamburg noted that a wide variety of information, including that derived from registries, could be used in both prospective and retrospective analyses. Reports of adverse effects, information about existing clinical trial networks, and identified potential patient populations all could be valuable resources. “All of these things make us better positioned to ask and answer critical questions in a timely and cost-effective way and strengthen the infrastructure that is so critical for our ability to maintain a cutting-edge position in these important areas of science,” she said. Dzau added that a strong electronic health record and a robust information technology rapid learning health care system also need to be developed to make a difference in drug discovery and development.

Hamburg also pointed to the many ways in which new technologies can forge connections with patients and collect information, potentially at lower cost than through clinical trials. For example, data collection could be pushed closer to the patient for some diseases. This “is an area where we feel we need to open our thinking,” she said. Similarly, Dunsire said, different registries and databases can be linked in the precompetitive space.

Both phenotypic and genomic data, Dzau said, need to be gathered from multiple patient populations, including those suffering from rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, cardiovascular disease, and other diseases, not just cancer. The intention must be to apply information so that everyone is placed into a subpopulation. This will be how linkages between diseases are identified and will facilitate novel applications for existing drugs or the development of new therapeutics.

Efforts to construct and link such information sources are under way, though much more needs to be done. One pressing question, Dzau said, is “Should we biobank every single patient who comes through the door? Should we sequence everybody? These kinds of questions come up every single day for us.” A related question is whether patients should have to opt out of engaging in research instead of choosing to opt in. If people had to opt out rather than opting in, much larger banks of specimens and data would be available to do anonymized research.

Dzau proposed the creation of a national consortium of academic centers in which particular centers would choose diseases, cohorts, or pathways they want to study in depth. The consortium could include NIH, FDA, and CMS as well. Cohorts could be of sufficient size to do phenotyping and molecular imaging in detail and centers could be supported by both government and industry with sharing of data.

Major impediments would need to be overcome to build such a resource of specimens and data. Wylie Burke from the University of Washington pointed out that patients have expectations about such issues as re-consent, learning what happened with their samples, and the return of results. There are also cultural sensitivities which factor into low minority participation, she said. Hudson noted that NIH is trying to provide human subjects protection and regulations to remove some of the impediments to participation. More broadly, Dzau observed, such a system would have to be related to the larger issues of health care delivery and reform.

Austin pointed to the value of having all of the data available on currently approved drugs in a public database, at least for generic drugs. Having such data available would make it possible to narrow candidate drugs for a condition beyond the possibilities that can be identified without such data. It also would allow for the review of safety and efficacy data in repurposing drugs. These data are now available, but they belong to private companies, which constrains their release.

The FDA also has a tremendous amount of data developed as part of drug development projects, but it does not have the infrastructure, the resources, or the authority to analyze these data and make them available. Austin pointed out that having only summary data released by the FDA would not be acceptable since the analyses could not be verified. One option, said Pacanowski, might be for the FDA to draw together the parties that own the data to work out legal agreements so the data can be used. “That would potentially be very valuable.”

The allocation and protection of intellectual property are troublesome issues, however. For example, Trusheim observed that the developers of diagnostics can create tremendous value but are often poor at capturing that value. Instead, payers, patients, and drug developers collect much of that value. Only when diagnostic companies have strong intellectual property protection have they been able to force other partners to pay what a diagnostic is worth. Additionally, Austin said, many owners of the data believe that their release would be detrimental. For their part, private companies do not have an upside in releasing data that might be used to undercut the value of a compound. “Even when they would want to do it, they can’t.”

Companies need the exclusive use of data that they generate to receive returns on their investment. Otherwise, the development costs have to be paid up front. “It’s one or the other,” Austin said.


Hamburg said that a criticism sometimes made of personalized medicine is that it will serve only elites, but personalized medicine has at least the potential to do the opposite and help reduce the health disparities that exist among population groups today. By understanding more about the mechanisms and natural history of diseases, researchers can help uncover the reasons why groups differ in their susceptibility to disease and in their responses to therapy.

Hudson agreed, adding that intergroup differences emphasize the need for much more widespread participation in research. Minorities are still underrepresented in many clinical studies and NIH has many projects to increase participation, although the results have been “depressing.” The Clinical and Translational Science Awards have a specific focus on health disparities along with community engagement and implementation research. Also, the new National Institute of Minority Health and Health Disparities has created new programs to address disparities. “I am optimistic that they are really going to be able to make some real catalytic changes,” Hudson said.

Dunsire observed that the response of population groups to drugs can differ not only within the United States but around the world. Phase I trials cannot be done just in the United States and Europe, with the drug then being taken around the world, because the drug can act differently with different populations. Health disparities do not necessarily arise from genetic factors, she said, but genetic factors need to be taken into account. Dzau agreed, adding that the social, cultural, and environmental influences on health point to the need to involve social scientists in collaborations. For instance, one way of involving social scientists would be to have anthropologists help develop culturally specific ways of encouraging participation and gathering information in research.


Particular attention needs to be directed toward patients and physicians in the drug development ecosystem, several presenters said. According to Ginsburg, only 5 percent of oncology patients are currently in clinical trials in the United States. Patients need to be educated about why their tissues are needed, how they will be used, and how that use could change treatments, Dunsire said. She noted that we are at a critical junction for patients regarding their understanding of the importance of participation and the benefits for doing so. Hudson said that a much better job needs to be done of communicating to prospective participants what the potential value and risk is to them for participating in research. “Ideally, we would all be, as patients, also participating in research.”

A national dialogue about research participation could enhance the ability “to get people to participate and sign that form that says, ‘Yes, I would like my tissue and my clinical information to be a part of future research studies,’” Hudson said.


In his concluding remarks, Ginsburg pointed out that the workshop began with an industry in crisis. It ended with a discussion of how collaborative efforts could lead the way toward a new era of drug discovery and development that could provide immense benefits to human health.

The essential resource that will enable this transformation is scientific knowledge, Ginsburg said. “We need to understand the biological underpinnings of the diseases and the pathways that we’re trying to affect.”

Copyright © 2012, National Academy of Sciences.
Bookshelf ID: NBK116443


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