By now, many of you have read the recent New York Times article or related news coverage, about NIH’s plan to establish the National Center for Advancing Translational Sciences (NCATS).
While we are pleased that the news media have recognized NIH’s efforts as a significant development for translational research, the Times article contains some misleading statements that we would like to clarify. Those statements suggest that a much larger shakeup of NIH is underway than is actually contemplated.
So, to set the record straight, we want to share with you what we know at this point in time:
- The proposal for NCATS is that it will be assembled primarily from existing programs within the National Center for Research Resources (NCRR), the NIH Common Fund, and the National Human Genome Research Institute (NHGRI).
- NCATS is not intended to be a drug company. It is a facilitator of translational research across the NIH and complementary to translational research already being conducted and supported on a large scale in the individual NIH Institutes and Centers. NCATS will seek ways to leverage science to bring new ideas and materials to the attention of industry by demonstrating their value.
- The final budget for the proposed center is unknown at the present time. For the most part, the budget and staff for each relocated program will remain with that program. Thus, the overall budget for NCATS will be the sum of the imported programs—an amount much smaller than the several billion dollars currently being spent on translational research by existing Institutes and Centers.
- There are no plans to “cannibalize” the budgets or programs of other NIH Institutes and Centers to form NCATS.
- NIH remains committed to continued support for basic, translational, and clinical research. The new Center will bring several existing efforts together in new ways to enhance the ability of all NIH Institutes and Centers to perform research that leads to the development of drugs, diagnostics, devices, vaccines, and strategies for prevention.
We are working together to develop important details of these plans and are gathering information from a wide range of internal and external stakeholders. This information will be used to shape NIH’s final vision for NCATS. Until that information is systematically and objectively evaluated, the plan for NCATS remains a work in progress.
However, one thing is certain: NIH will continue to seek out new ways to advance our common cause—improving human health through science—even in difficult budgetary times. Every NIH Institute and Center is pursuing novel, imaginative plans of its own, and the creation of NCATS is just one of many exciting initiatives that we, working collectively, hope to achieve this year.
Francis S. Collins, M.D., Ph.D., Director, National Institutes of Health
MEMBERS OF THE INSTITUTE AND CENTER DIRECTORS NCATS WORKING GROUP:
Eric Green, M.D., Ph.D., Director, National Human Genome Research Institute (co-chair)
Thomas Insel, M.D., Director, National Institute of Mental Health (co-chair)
Josephine Briggs, M.D., Director, National Center for Complementary and Alternative Medicine
Anthony Fauci, M.D., Director, National Institute of Allergy and Infectious Diseases
Alan Guttmacher, M.D., Director, National Institute of Child Health and Human Development
Story Landis, Ph.D., Director, National Institute of Neurological Diseases and Stroke
Griffin Rodgers, M.D., MACP, Director, National Institute of Diabetes and Digestive and Kidney Diseases
Harold Varmus, M.D., Director, National Cancer Institute
Kathy Hudson, Ph.D., Deputy Director for Science, Outreach, and Policy, NIH
Lawrence A. Tabak, D.D.S., Ph.D., Deputy Director, NIH
I applaud the effort to stimulate new drug development. As a clinician, it is frustrating that the pace of drug development has not been as rapid as other technological advances. Furthermore, I think this is an area where the United States still has a competitive advantage and we as a country need to invest in more research. It would be nice if the NIH would get some share of the revenues from any new drugs so that this project eventually would be self-funded.
What a great mission for a great institution to be involved in a direct way on developing drugs when the usual developer of drugs the pharmaceutical industry is faltering very badly in recent years. The NIH as the premier institution on research on human health for the nation has to step in because of the failure of the pharmaceutical industry to build upon the new science of molecular understanding of the malfunction of mechanisms that lead to human illness. Part of the faltering of the pharmaceutical industrie’s production of new drug capabilities is the addiction to the “block buster” concept in its various permutations which is directly tied to the bottom line. A case in point is the recent failure of very promising drugs in the treatment of cancer such as the PARP inhibitors. These drugs and others would not have failed if the concerned companies had done detailed work in the identification of patients for whom such drugs would have been appropriate by identifying biomarkers or other mechanistic studies that would have allowed the precise population of patients for whom such drugs would have been efficacious. But the concerned companie’s desire for approval of drugs for a larger population of patients which will traslate to a more robust revenue has resulted in these companies shooting thier own feet. There are no more simple diseases that can be tackled by one bullet. It is now clear that many diseases by the old definitions such as breast cancer for example is made up of several molecular types that may require individualized approaches to fit the mechanisms that are most relevant for a particular sub-type. This leads to a segmented market that is challenging the pharmaceutical businesd whose model is based on wholesale characterization based on past market success. The old adage that “there are no bad drugs but bad drug development” is really true. The new science of diseases demands a new type of development. The NIH not being constrained by the “bottom line” and having the technical capability can provide the lead and leadership that is needed to unplug the current constipation of the pharmaceutical industry’s creative capabilities through the NCATS.
Abebe Haregewoin, MD, Ph. D.
Will this require an appropriation by Congress for funding, or does this come out of the funds already appropriated to NIH?
Without radical changes at the FDA (the real bottleneck in bringing drugs to patients!), this initiative is doomed to failure. The leadership at the two agencies (FDA and NIH) need to work harder to form liaisons with each other, so a true “pipeline” exists.
In its current form, the actions of the FDA (and in particular the outspoken individuals on certain of their advisory panels) serve as a huge disincentive to both the large and small pharmaceutical industry. For small companies, who invest millions of dollars in drug development only to be shot down with very little warning due to seemingly intractable reasons (e.g. arbitrary changes in preferred end points for a given disease), such actions lead to failure and death of the company. For big pharma’, one only has to look at the hemorrhage of people and investment in R&D programs by the big players, to see that they too are scared of what’s at the end of the pipe. Why spend billions on what basically amounts to a gamble on what side of bed the review panel got up this morning?
The problem is not that we have too few drug candidates, it is often that perfectly good candidates (which are often approved in other countries) are being turned down due to a small number of serious side effects (in particular CV events and suicides). These are all issues that can be resolved by proper labeling and post-marketing monitoring.
Please, do not ignore the overarching role of the FDA in this entire drug development process, and please include overhaul of their review and approval process as part of any drug-development initiatives.
RE: Commentary from stakeholder in unrepresented “innovator biotech/pharma company” sector
Dear Dr. Tabak,
Commenter/Organization Background: I received my MD and PhD from Cornell Medical College, and have been President and CEO of Syntrix Biosystems, Inc. since 2001. Over the last decade, I have served on numerous NIH/CSR RO1 and SBIR study sections related to drug development.
Syntrix has several drugs in its pipeline whose discovery and translational development, including Phase 1 and 2 clinical trials, have been supported by NIH funds through the SBIR program (NHLBI, NCI, NIAMS, NIAID and NIDA). Syntrix was selected to present at the NCI SBIR Investor Forum on November 5, 2009 at Boston University that showcased the top 14 NCI companies among several hundred in their portfolio.*
The company has written a publicly available White Paper entitled “Translational Accelerated Research Consortia (Trans-ARCs): A Novel Transformative Strategy for Bringing New Drugs Across ‘The Valley of Death’” in response to the “Commercialization of University Research” Request for Information (RFI) in the Federal Register authored by James Kohlenberger, Chief of Staff, Office of Science and Technology Policy and Diana Farrell, Deputy Assistant to the President for Economic Policy, National Economic Council (March 25, 2010, Volume 75, Number 57, Page 14476-14478).**
* http://www.bu.edu/otd/newventures/nci-sbir-investor-forum
** http://www.eda.gov/PDF/107_Syntrix%20Biosystems.pdf
Commentary: I have read in detail the final SRMB report from the NIH Translational Medicine and Therapeutics (TMAT) Working Group from December, 2010. I applaud Dr. Collin’s aim to develop the NCATS and support its rationale. The dearth of new drug development and funding in the private sector is real and is a true concern, especially given the concomitant explosion in new therapeutic targets and knowledge about disease processes. The reasons for this, as the final SRMB suggests, are complex and multi-factorial.
One concern with the final SRMB report is that the rosters for the SRMB as well as for those who gave several days of public commentary (Appendix A in the TMAT report) reveal a significant bias in representation primarily from federal, academic, and other non-profit/patient advocacy organizations (N = ~50 of 54 total), with only two individuals from “big pharma” (Pfizer and Lilly) and one from the VC community (Domain Associates).
However, the vast majority of high-risk translational drug development in the United States (i.e. development that ‘crosses the valley of death’ and thus is most responsive to Dr. Collin’s objectives) is in actuality performed by a network of numerous private companies like Syntrix, each having under 200 employees (and more typically well under 50). These are the so called “innovator biotech/pharma companies” that have been the source of the majority of truly new therapies and their translation from the laboratory to the clinic (in the past, mostly through private equity investment and/or partnership deals with big pharma).
Thus, any discussion of the most appropriate and best implementation of a future NCATS would be grossly incomplete without input and/or participation from this sector. There is great concern that this group was unrepresented in the deliberations that formed the implementation plan for NCATS. I am therefore taking this opportunity to write you now to make available stakeholder commentary from this sector that may be useful in best implementing Dr. Collin’s objectives.
Although bold in its original drafting to the RFI, most of the key capabilities of this sector that could best synergize with the objectives of the NCATS are addressed in the above publicly available White Paper, and I encourage the Director and/or SRMB to review it. Understanding the strengths and weaknesses of this sector vs. the non-profit academic sector in translating basic research to the clinic is key to best match organizational capabilities and values with objectives in order to have the maximum chance that the new NCATS will actually achieve success and meet its 2 and 5 year “success” metrics as defined on page 18 of the final SRMB report.
Furthermore, the above White Paper outlines a bold model for how innovator biotech/pharma companies can be leveraged by the NIH, or in a smaller scaled-down model with NCATS, to efficiently and rapidly translate to “clinical proof-of-concept” NIH’s most promising discoveries.
Finally, I would be happy at the request of the Director and/or SRMB to volunteer to serve in an advisory capacity to the Director, SRMB and/or any component of NIH regarding the potential participation of this sector with the future NCATS in order to best implement translational drug development consistent with Dr. Collin’s vision. If this is of interest, I may be freely contacted.
Yours truly,
John A. Zebala, MD, PhD
President and CEO
Syntrix Biosystems, Inc.
jzebala@syntrixbio.com
Comments relating to the NCRR task force’s straw model have been moved to the straw model post
Dear Drs Francis Collins, Josephine Briggs, Anthony Fauci, Eric Green, Alan Guttmacher, Thomas Insel, Story Landis, Griffin Rodgers, Harold Varmus, Kathy Hudson and Lawrence Tabak,
Last night I had a dream. And the dream was that:
1. The attributes, activities, and functional capabilities of an effective translational medicine initiative for advancing therapeutics development HAD BEEN IDENTIFIED and TIRELESSLY IN ROUTE. It had crystallized, among many other realities, in a national, beautifully decentralized Consortium, with CTSA institutions sharing and expanding their common vision to improve human health by transforming the research and training environment to enhance the efficiency and quality of clinical and translational research. Their leader’s name was NCRR.
2. Their leader, NCRR, had been providing and supporting resources and human capital to effecting the medical advances of institutions and investigators worldwide, outreaching less-privileged scientific and medical communities and minorities institutions. And, in doing so, they have shown the potential for successfully closing the gap in health disparities and economic development in the US. They are ready, upon US health needs, to house targeted activities such as CAN and many others.
3. The NCRR demonstrated commitment to engage but not to undermine, duplicate or inappropriately compete with the successful activities undergoing within NIH ICs or extramural institutions. By working with such an inclusive conceptual, factual and translational framework, they had shown the potential for maximizing the capabilities and use of the NIH Clinical Center as their National Consort Clinical Facility with Adjacent Pre-Drug Development Unit to effect the most efficient “bedside-bench-bedside” strategy worthy of the hopes, needs and economic efforts of the country.
4. I saw that they have grown taller and taller and their name might not be fitting their achievements and potential.
Dare to dream!. Dare to dream that their tireless efforts and accomplishments will not be frivolously and selfishly swept under the carpet, as if they had never existed.
I am not Martin Luther King but a mesmerized, absent-minded follower who, last night, happened to visit for sometime the NCRR website and relevant videocasts on the matter.
Thank you for the opportunity to dream.
I have been a scientist at a National Primate Research Center for 35 years and served as director of that center for more than ten years. I am currently director for translational technologies and resources in the CTSA program at the same institution. I have also been a grantee and a reviewer of grant applications for NCRR. The flow of information from basic science to clinical practice in NCRR programs has been exciting and very gratifying for many of us who do basic research and are dedicated to improving human health.
The portfolio of programs in NCRR has provided the infrastructure for the process of translational science for many years. This infrastructure is much more than buildings and administration; it has enabled cutting-edge research and essential training for scientists, clinicians and veterinarians to provide for interdisciplinary programs in the future. It has served as the substrate on which much of the work of NIH’s categorical institutes is nourished and cross-disciplinary projects are catalyzed. The addition of the CTSA program has given additional energy to the process. The accomplishments of NCRR are due in no small degree to the relatively seamless coordination of inter-connected programs. The committed staff of NCRR have been instrumental in this success.
At my institution we have benefitted greatly from synergies supported by NCRR to advance translational research. Grants and supplements from NCRR have enabled construction of an research animal vivarium in close proximity to clinical programs to enhance access by clinical investigators, funded projects that entail parallel studies of human subjects and nonhuman primate models to investigate genetic risk for disease, allowed for purchase of high end instrumentation that serves both clinical and basic science investigators, encouraged pooling funds for collaborative pilot projects across disciplines, leveraged institutional support and promoted the development of informatics systems that manage data and improve access to information. We have been perhaps unusually fortunate at our university, but we are not unique and other institutions have had similar successes through NCRR programs.
I fear that dismantling NCRR will impede the kind successes that are being accomplished in the present organization. I recognize the political advantage that comes from establishing a new center named explicitly for accelerating translational science, but to realize such acceleration will require careful orchestration of disparate essential programs. The NCRR has been doing a pretty good job of this. What is the anticipated benefit of separating the comparative medicine program from the CTSA program? New drugs and devices certainly need to be tested in animal models before they are tried in humans. The function of various genes is usually discovered in animals before their role in human health and disease is understood. Fragmentation of NCRR is a very risky step to take. I plead for very careful consideration of strengthening the existing structure rather than taking it apart and losing the synergy that has been made possible by the current adjacency of programs within NCRR.
You reap what you sow. When you are making statements such as that this is “a truly goundbreaking moment to move academic investigators funded by NIH into the opportunity to develop therapeutics” while moving “at lightning speed”, you should not be surprised that the science press get somewhat confused that NCATS is not really about full-on drug development. When you say “You know, if I were trying to do this 5 years ago, it would have been too soon. If I had waited until 5 years from now, it would have been too late.” and then say that NCATS is largely a repackaging of existing programs (most of which Dr. Collins championed in his previous role as director of NHGRI), it is easy to get confused about how bold and new the programmmes within NCATS really are.