Meeting ReportsDiagnostics Development

Collaborations Among Academia, Government, and Industry in the Diagnostics Space: Barriers and Some Ideas for Solutions

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Science Translational Medicine  22 Dec 2010:
Vol. 2, Issue 63, pp. 63mr3
DOI: 10.1126/scitranslmed.3001633

Abstract

The development and commercialization of diagnostic assays is distinct from that of therapeutic drugs in many important respects; for example, there are more variable regulatory requirements and reduced outside investments for diagnostics. The diagnostics industry has a pro-collaborative stance, because there is considerable mutual benefit in working in partnership with university or government researchers. However, there are substantial barriers to industry-academic collaborations. A Clinical and Translational Science Awards Industry Forum titled “Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry” was held in February 2010, and a session at this forum was organized to list some of the most important barriers to diagnostics development and to discuss some possible solutions.

Introduction

A breakout session on the topic of “Academic/Industry Issues and Barriers for Diagnostics Development” was held at a Clinical and Translational Science Awards (CTSA) Industry Forum titled “Promoting Efficient and Effective Collaborations Among Academia, Government, and Industry,” which took place in Bethesda, Maryland, in February 2010. Conference participants were charged with identifying barriers to collaboration that existed for each of the stakeholders (for example, academic, industry, government, and foundation) during the discovery, development, and commercialization of new drugs, devices, and diagnostics.

An Overview of Diagnostics Development

One of us (F.A.) gave an overview of diagnostics development from the manufacturer’s perspective. The most important consideration for diagnostics is not the analyte itself (the substance that is measured, which could be a protein, metabolite, or nucleic acid), but the information content revealed—such as the presence of a particular disease—by the measurement and use of that information in clinical care. To understand the collaborative needs of those involved with developing diagnostic tests, one must keep in mind the different players that make and deliver tests and test results. Manufacturers make platforms on which measurements are conducted, as well as test kits for specific analytes that can be measured using their platforms. Clinical service laboratories purchase both platforms and kits from manufacturers, as well as develop tests in-house to measure specific analytes. Platforms and kits sold to laboratories are reviewed by the U.S. Food and Drug Administration (FDA). Moreover, platforms typically represent a large capital investment; thus, longevity of use is highly desirable for all parties. Laboratory operations are regulated under the Clinical Laboratory Improvement Act.

Historically, manufacturers primarily sought to secure intellectual property (IP) rights for their platform while seeking to freely add specific analyte tests. The IP environment for diagnostics, however, is now changing, with a move toward securing IP rights for the analyte as well as for the platform. This change is creating better incentives for discovery and validation of novel analytes and improved diagnostics. These better incentives make partnerships between industry and academia more appealing because academia is a good source of new analytes. The changing IP environment is also altering the research and partnership environment. Manufacturers and service laboratories accustomed to unfettered access to analytes now find the need to reach use agreements for analytes in some instances. Analyte IP has also attracted venture capital and other sources of new funding for research to validate and determine the clinical utility of new biomarkers because the ability to recoup such investments is enhanced. Additionally, research and development costs are typically much less for diagnostics than for drugs; however, clinical acceptance of diagnostic tests is less certain. Lastly, prices of new or better diagnostics tend to be set by administered pricing (a formula based on the cost of similar existing approved tests) and do not reflect the added value to consumers and health systems. In this environment where diagnostics are thought to be undervalued in the marketplace, industry is more willing to invest in an unproven analyte if the development costs have been shared with an academic partner. In addition to the overall benefit of the partnership for public health brought by new commercial diagnostics, there are mutual benefits for industry researchers and university or government researchers, including industry access to patient cohorts and researcher access to industry platforms.

The Biomarkers Consortium—A Trans-Sector Model for Collaboration

D. Lee from the Foundation for the National Institutes of Health (FNIH) gave an overview of the Biomarkers Consortium. This consortium is a program of the FNIH that has launched eight biomarker projects to date in the precompetitive space—that is, the early stages of development of commercial products, during which competitors collaborate and downstream competitive commercial applications are not prevented—through a public-private biomedical partnership. Members of the Biomarkers Consortium include NIH, FDA, pharmaceutical companies, and nonprofit organizations. They have a strong track record of success in moving biomarkers—indicators of a given biological state—forward in the qualification pathway because of early and frequent FDA input. A biomarker is “qualified for use” after it has been accepted for a particular function by the appropriate regulatory agency. Before the launch of the consortium, all of the key players came to an agreement about IP-related principles, data sharing, and other traditional points of contention, which are then specifically defined on a project-by-project basis depending on each project’s risk profile and IP situation. For collaborations between academia and industry, IP rights are often the biggest challenge for the consortium to facilitate. There were brief discussions about access to the consortium’s data, the types of projects it is funding, how small companies can get involved, and the role of the government as a resource in the consortium’s work.

The Early Detection Research Network—A Model for Collaboration in the Cancer Biomarker Space

S. Srivastava from the Cancer Biomarkers Research Program of the National Cancer Institute (NCI) gave an overview of the NCI’s Early Detection Research Network (EDRN). The purpose of this network, which has 45 participating institutes and organizations, is to develop and validate biomarkers by serving as a concierge for a “handoff” partnership system between discovery and reference laboratories (clinical service laboratories that perform tests of validated biomarkers as part of patient care). The EDRN is seeking more partnerships and more biomarker validation projects to ensure that an economy of scale is developed to create maximum productivity. The EDRN works to resolve issues between collaborating parties such as publication and IP rights, the resolution of which can delay partnerships for more than a year. The EDRN has developed several standard rules for IP and is working to create standard material transfer agreements (MTAs)—contracts between organizations that describe the conditions of transfer and uses of research materials—and confidential disclosure agreements.

Discovery and Validation of Early Biomarkers for Type 1 Diabetes

J. Hutton from the University of Colorado at Denver described his work to discover and validate biomarkers to predict the development of type 1 diabetes (T1D). There are some features about the pathogenesis of T1D and its treatment that suggest that the current small market for diagnostics in this area may rapidly expand in the next 5 to 10 years as new preventive therapies are discovered and developed. This possibility in turn poses important questions about how best to gear research and commercial development of biomarker assays to match the timeline for therapeutic developments. T1D is caused by an autoimmune response that destroys insulin-producing cells in the pancreas. Of the four assays available to detect relevant autoantibodies, no single analyte has the sensitivity required to predict the disease, and yet a combination of such assays can pick up 95% of cases. The current assays do not yet have the sensitivity and specificity needed for population screening. As a consequence, there is little incentive at present for industry to further develop, standardize, and market these assays. Timing the development of biomarker assays with the advances in therapeutics will be critical and requires a continuing dialog between academia and industry.

Use Case: A Collaboration Between Industry and Academia for the Development of a Diagnostic Test for Acute Myelogenous Leukemia

J. M. Jessup from the NCI’s Diagnostics Evaluation Branch discussed how academic laboratories and small businesses that are developing cancer assays are most interested in having access to improved tissue resources, especially tissues with clinical annotation, and advice for study design and staffing. IP rights are a major problem in this area. Jessup described the specific case of a diagnostic test for acute myelogenous leukemia that was used for research purposes in ways not described in the original patent, but that still encountered substantial IP-related problems from a U.S. company that had obtained an exclusive license for the patent on the analyte. Issues surrounding the diagnostic were eventually settled, but the clinical trial in children with acute myelogenous leukemia was delayed for nearly a half year to the detriment of a number of patients. This use case demonstrates that a solution to such IP-related issues is needed that allows clinical research to occur in an IP-protected space while the value of the diagnostic is assessed in a clinical trial. Also, early identification of patents and their licensure in the multiple tiers of IP (referred to in the Overview, above) would foster negotiation that may help avoid IP-related conflicts in clinical trials.

General Discussion

Several topics were discussed by the panel and audience members, including (i) the tension between the need for commercially viable diagnostics by the pharmaceutical industry and the clinical need for a useful tool; (ii) the need to work issues out collaboratively, rather than through lawyers and legal action; (iii) the need for industry to give feedback on proposals received from academia; (iv) the need for a streamlined, standardized institutional review board (IRB) process; and (v) the need for academics to have commercial advice early on in the research process. The group also discussed the need for standardization of processes, agreements, and definitions of terms—an area in which CTSAs from the NIH may be able to play a substantial role. Another discussion centered on a misalignment of interests between industry and academia. Many academic researchers do not organize their work in a way for it to be viable for venture capital funding, licensing, or FDA approval, and thus, it is not as useful from an industry perspective.

Summary

The major themes from this breakout session were as follows:

(i) Diagnostic development is distinct from drug development, especially in terms of reimbursement.

(ii) Academics must have a more realistic idea of what they bring to the table in collaborations with industry and a better understanding of diagnostic development and approval.

(iii) Early agreement on IP rights, publication rights, and data sharing is key for a collaborative project’s success.

(iv) Larger-scale partnerships can build structures for research and create standardized document templates and IRBs to reduce costs and streamline processes. These large-scale research structures should enable IP-protected clinical research and biomarker validation.

(v) The Biomarkers Consortium and the NCI’s EDRN can serve as models for future collaborative efforts.

(vi) The NIH can serve as an honest broker with the FDA to resolve regulatory gaps and increase transparency in regulatory processes to encourage investment in product development.

Finally, the following needs and opportunities were identified:

(i) Define IP policies that protect all stakeholder interests.

(ii) Establish better communication between industry and university technology transfer officers.

(iii) Standardize the biomarker validation process, data sharing between industry and universities, MTA language, and the overall material transfer process.

(iv) Encourage early participation in the process of biomarker validation to better align university investigators and industry and to reduce risks associated with projects.

Footnotes

  • Citation: G. Evans, F. Austin, Collaborations Among Academia, Government, and Industry in the Diagnostics Space: Barriers and Some Ideas for Solutions. Sci. Transl. Med. 2, 63mr3 (2010).

Note

  1. Funding: This project was funded in whole or in part with Federal funds from the National Center for Research Resources, NIH, through the CTSA program, which is part of the Roadmap Initiative, Re-engineering the Clinical Research Enterprise. The manuscript was approved by the CTSA Consortium Publications Committee. Competing interests: F.A. holds equity interest in Hoffmann-Roche. G.E. declares that he has no competing interests.

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