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Critical Path Initiative


Statement of

Andrew C. Von Eschenbach, M.D.
Commissioner of Food And Drugs

before

the Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies
Senate Committee on Appropriations

June 1, 2007

INTRODUCTION

Good morning. It is a pleasure to join you at this field hearing to discuss one of the FDA's highest priority projects, the Critical Path Initiative. This project has the potential to transform the way medical products in the U.S. are designed, developed, tested, and used. I want to thank the Subcommittee on Agriculture, Rural Development, Food and Drug Administration, and Related Agencies for inviting me to Utah to discuss the benefits the Critical Path Initiative promises to generate for the health of the American public.

I also want to thank you, Senator Bennett, for being the first to provide funding for this important initiative while you served as chairman of the Subcommittee during the 109th Congress. Your support of the FDA's public health mission in general – and the Critical Path in particular – reflects your vision for and commitment to better health care for all Americans.

Let me also thank the University of Utah, our hosts today and early collaborators on important work already taking place under the auspices of the Critical Path. University researchers have joined with the Cardiovascular Research laboratory of Intermountain Healthcare in a collaboration with FDA to improve the safe use of a widely prescribed drug. I'll have more to say about that project momentarily.

Holding this event at the University of Utah, under the auspices of the Subcommittee and with the cooperation of Senator Bennett, is important symbolically. In today's world of health care and medicine, we are on the brink of unprecedented advances in our ability to predict, diagnose, and treat diseases across the board. But we also face unprecedented challenges in moving those products from the laboratory to the bedside – and in providing access to those treatments.

That's why it's so important to capitalize on the synergies that are created when public health agencies such as the FDA work closely with stakeholders in academic research community, industry, consumer groups and elsewhere to solve problems that affect us all.

THE TRANSFORMATION OF MEDICINE

Close cooperation has become particularly important because what we are witnessing in health care today is the most profound change in the history of medicine. Approximately one hundred years ago, our ability to understand disease moved from the macro level, where we were limited to what was visible to the naked eye, to the micro level – when we gained a microscopic view of disease at the cellular plane. But in the last decade or two, we have been able to approach disease at the molecular level, where we now can observe and understand disease as a process.

This is what I have called the "molecular metamorphosis in medicine," because it represents a phase change similar to the transformation of a caterpillar to a butterfly. As a result of this metamorphosis, the future of health care will be no more like its past than a butterfly is like a caterpillar.

The payoff is that, as our knowledge of genetic molecular mechanisms evolves, and our understanding improves, we will be uniquely positioned to develop interventions against disease processes at the molecular level. The potential result is that medicine of the future could be personalized, predictive, preemptive, and participatory.

But there's a problem. Despite an unprecedented increase in funding for biomedical research, both in the private sector and through Federal funding through the National Institutes of Health, this increased research has not translated into many new medical products being available in the medical marketplace. For example, close to nine in 10 pharmaceutical products in phase I testing are never approved for marketing, and half of all phase III clinical trials end in failure. There must be a way to help expedite and simplify this process.

THE CRITICAL PATH INITIATIVE

That is why in 2004 FDA advanced the notion of focusing on the critical path which medical products must travel, from the earliest stages of development to their use in patients. The Critical Path Initiative is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured. The Critical Path provides an essential a tool kit of prospects and initiatives that will enable FDA to make regulatory decisions that will define personalized medicine in this new age of molecular medicine.

To jump start this process, FDA has been working with the academic community, the public, the pharmaceutical industry, and other Federal health agencies to identify the projects most likely to modernize and transform the development and use of medicines. After intensive consultation with many stakeholders, last year we published our "Critical Path Opportunities Report," which details 76 specific scientific projects with great promise for smoothing the path from lab to bedside. Last December, we followed up by announcing more than 40 very promising scientific projects that we have helped get underway.

The Critical Path Initiative presents many major opportunities for improving the process. It includes ways of qualifying biomarkers (which are measurements that can predict or monitor responses to therapy) for in-vitro diagnostics, imaging, and preclinical toxicogenomics. It represents an opportunity to modernize clinical trials to make them more effective and efficient, and we are issuing guidances on advanced clinical trials. It will allow us to harness the potential of modern information technology tools, and it should help us modernize manufacturing by building in quality up front through such systems as quality by design and process analytical technology.

Let me provide a specific example of a Critical Path project that is already underway. It involves work related to cancer, in which FDA is working with a host of other organizations to identify relevant biomarkers and – what is crucial – qualify them for use in the development of medical products.

To achieve these goals FDA and many colleagues established a public-private biomedical partnership supported by the Foundation for the National Institutes of Health. Launched last October, the Biomarkers Consortium strives to accelerate the delivery of successful new technologies, medicines, and therapies to prevent, detect early on, diagnose, and treat a wide variety of diseases, including cancer. Specifically, it seeks to identify biomarkers and develop tests to determine whether a drug is appropriate for an individual patient. It is also working to find markers that will show whether the drug is having the right effect in the patient.

The example of Iressa and Tarceva, two drugs used to treat lung cancer, demonstrates the potential benefits of having appropriate and validated biomarkers. Each of these drugs has had strikingly positive benefits for some of the patients who have taken them, reducing tumors by up to 50 percent and extending life expectancy. Unfortunately, only 10 percent of patients treated with the drugs actually experience these benefits. Researchers have found that the patients who respond to these drugs have a common genetic mutation in their tumors. This mutation can serve as a "marker" to identify the patients who are best treated with these medications. Over time, similar discoveries related to other tumors and drugs are expected to yield a major public health impact – and that is the point of the Critical Path.

A CRITICAL PATH PROJECT IN UTAH

I would be remiss if I did not point out that one of the most promising Critical Path projects is underway right here in Utah. The University of Utah, the Critical Path Institute based in Arizona, and the FDA have established the Cardiovascular Drug Safety and Biomarker Research Program. Its goal is to establish an evidence-based framework for determining the clinical usefulness of cardiovascular biomarkers. For example, in the first of what we hope will be many such projects, researchers in the program are working on ways to establish better dosing of the widely used anti-coagulation drug warfarin. They are attempting to identify the genetic variants in people that determine how they respond to the drug.

This is a medical matter of no small importance to individual patients, because the medical consequences of improper dosing can be severe. Too much warfarin can lead to life-threatening bleeding, and too little can result in equally dangerous blood clots. The overall impact on the U.S. health care system is also profound. Warfarin is the second most common drug, after insulin, implicated in visits to emergency rooms – causing 43,000 ER visits annually.

The goal of this collaboration is to improve our ability to get the warfarin dose right for each patient when they begin treatment with warfarin. Last June FDA and the Critical Path Institute convened a warfarin summit that brought together many experts in this field, including researchers from the University of Utah. We are looking for ways to find the genetic differences that make patients more likely to metabolize warfarin differently.

As in so many of these Critical Path projects, the goal is to get the right medicine to the right patient, in the right dose, and at the right time.

CONCLUSION

Let me conclude simply by emphasizing that the sort of collaboration that is occurring every day here at the Cardiovascular Drug Safety and Biomarker Research Program, under the auspices of the Critical Path Initiative, represents the best way, the only way, to take full advantage transformation of modern medicine. It will make innovative medical products available sooner, it will increase our ability to monitor their safe use once they have reached the medical market, it will provide for personalized diagnosis and treatment, and it will introduce great efficiencies while reducing risk.

I should also emphasize that this transformation must take place in the context of a health care system. That's why it is so essential to have a thoughtful national discussion about our health care delivery system, and why it is so helpful to have the constructive engagement of leaders like Senator Bennett.

Finally, I want to commend the University of Utah for adopting this collaborative model. The opportunities – and the challenges – presented by the new age of molecular medicine are so promising and so complex that no one agent can possibly manage them alone. As the body that reviews information about and applications for medical products across the board, FDA is uniquely situated to see the bigger picture. But we are far from having all the answers about how to integrate and capitalize on all the new understandings of medicine at the molecular level.

We share the goal of finding the best way to get promising new interventions to patients. That's where institutions like the University of Utah and Senators like Senator Bennett come in. We need the help, support, and expertise of you and many other partners like you if we are to take full advantage of the opportunities the Critical Path Initiative offers.

Thank you for your time and attention today, and for kindly inviting me to be with you.