Former FDA Chief on Modernizing Drug and Device Approvals

Introduction

John C. Reed, MD, PhD: Hello, and welcome to Medscape One-on-One. I'm Dr. John Reed, Professor and CEO of Sanford-Burnham Medical Research Institute. Joining me today at the Celebration of Science Conference at the National Institutes of Health (NIH) is Andrew C. von Eschenbach, President of Samaritan Health Initiatives, former Commissioner of the US Food and Drug Administration (FDA), and former Director of the National Cancer Institute (NCI). Welcome.

Andrew C. von Eschenbach, MD: Great to be with you.

The Collaboration of Government, Industry, and Academia

Dr. Reed: At this conference, you spoke about the interaction of government, industry, and academic centers. The relationship among these 3 entities is often challenging, but also crucial to the advancement of science. Can you give us a couple of examples how these partnerships are working well, and also some ideas of how we can improve collaboration among these groups?

Dr. von Eschenbach: I think we both appreciate that caring for patients, solving their problems, and curing their diseases is a team sport. We all have a part and a role to play in this. Government, academia, industry -- we need to come together to figure out how to create these comprehensive systematic solutions to problems.

It starts with discovery. Academic centers and researchers like you are really revealing the mysteries of the underlying mechanisms of these diseases, and are making it possible for industry to start creating and developing solutions and interventions that can target those mechanisms and alter the outcome of those diseases -- whether it's eliminating suffering and death due to cancer or solving the problem of Alzheimer disease.

Government has to play a critical role in catalyzing and fostering that collaboration. A great example of where I saw this occurred was when I was at the NCI. When I looked at the government's investment following the National Cancer Act in 1971, which enabled the NCI to create cancer centers, I could see 65 cancer centers all over this country. But what I also saw was that around these centers, there were these clusters of state-of-the-art care. There were these clusters of emerging biotechnology and the pharmaceutical industry coming together and creating an ecosystem that would be able to go from discovery and development to delivery.

Another great example is the state of Georgia, which did not have a cancer center at that time. But the state took money from the tobacco settlement, put it into a private endowment, and went about the business of creating the Winship Cancer Institute at Emory University in Atlanta. That attracted a united effort, including government funding from our cancer nanotechnology initiative. It brought in other academic institutions, such as Georgia Tech, and even private philanthropy from such institutions as Home Depot, for example.

We can make this work. We can bring the parts and pieces together as a team to use the brilliance of the science that you, Dr. Reed, have been doing, and others here at NIH and in academic institutions all around the world have been doing, and recognize that science is the means. The end is that we solve people's problems, and we do it together.

Translating Life-Science Advancements Into Disease Cures and Prevention

Dr. Reed: That's a great example of the catalytic role that government funding can play in economic development as well as advancing healthcare. You gave the example of Georgia. We've seen the same thing happen in the state of Florida, where tobacco settlement monies were used to create a seed investment. That spawned additional development of hospitals, and a government investment that turned a couple hundred jobs into tens of thousands of jobs for the state.

Let me change subjects. You were previously involved in laboratory and clinical research. Can you talk about how advancements in the field of life sciences are paving the way for possible cures and preventions for such diseases as prostate cancer? You used to be an urologist, and prostate cancer is a disease you worked on a lot. There are also neurodegenerative diseases, such as Alzheimer's disease, which we're all worried about. What are you excited about in these areas?

Dr. von Eschenbach: If I get a chance to talk to students and they ask what they should do in life, I tell them this is the most exciting time to go into medicine. And we are in the midst of the most profound transformation to ever occur in history in medicine going all the way back to Hippocrates. Throughout the history of medicine, physicians such as myself have been practicing a model based on our observations of the manifestations of disease.

I feel a lump in a woman's breast. I see a shadow on a chest x-ray. I'm seeing the manifestations of an underlying disease, but it tells me nothing about what to do about it. All of our therapies and all of the things that we do about those observations have been empiric. Today we're going from observing manifestations to actually understanding the mechanisms of the disease. We're beginning to recognize the genes, the molecules, and the cellular processes that are responsible for and driving those disease processes. Once we have that knowledge of an underlying mechanism, it intuitively leads us to what the right solution is, to intervene in that mechanism and alter the outcome of that process.

Cancer, for example, is a disease process. It begins with our susceptibility, and that process ends with unfortunate suffering and death. But there are all these steps in between, and you have contributed personally to understanding some of those fundamental mechanisms.

Now physicians can be strategic. We can intervene in that process in a strategic way. Call it "personalized medicine" if you will. Get the right intervention for the right reason to the right patient at the right time, and you can prevent that process from happening. You can detect disease very early. You can eliminate it, or you can modulate and change its behavior and its outcome. You can alter the slope of the curve and allow patients to live the rest of their life never threatened by it.

This is the new frontier for medicine and for physicians. We will enter into this frontier with tools that we never had before. We can visualize biology with new imaging. We now have new therapies that are becoming available to us that will alter and change disease in radical ways. No longer is it just for cancer, surgery, chemotherapy, and radiation. The future for physicians is the most exciting, and yet it is a future that we have to grasp.

Dr. Reed: As a former director of the NCI, do you see a day where cancer patients will be treated not on the basis of whether their cancer arose in the lung or the colon, or the prostate, but on the basis of the underlying genetics of the cancer? By matching the mutations to the medicine -- is that how you think it will look in the future?

Dr. von Eschenbach: Absolutely. We've been immersed in categorizing diseases on the basis of what we could observe, what we could see. We call something "breast cancer" because we feel a lump in a woman's breast, or we call something "lung cancer" because it's in the lung.

But now, as we're looking at these underlying mechanisms, guess what? We're finding out that some subsets of lung cancer look exactly like another kind of cancer. And therefore, from that point of view, they have the same treatment. You can use a drug for chronic myelogenous leukemia and it works exceedingly well in gastrointestinal stroma, tumors of the stomach, as well. Even more important, we understand a mechanism for cancer based on angiogenesis in the abnormal growth of blood vessels. We develop a drug for that to retard or slow down the cancer, and it turns out it's one of the most effective drugs for macular degeneration of the eye.

For physicians and for those of us who are practicing medicine, we're going to see disease through a different prism. When we see it through that different prism, we're going to be able to see new ways of conquering many diseases. Cancer is just the lead here. But we're going to be seeing the same kinds of dramatic changes and breakthroughs in neurocognitive diseases, diabetes, and cardiovascular disease along the way.

We're also seeing it disseminate very rapidly. It's no longer centers and then community practice. We're seeing the opportunity now with new technologies even outside of medicine. We now have information technologies that will help us see a full continuum for every patient. It will mean absolutely state-of-the-art care by every physician, regardless of where you're located.

Speeding Drug and Device Approvals

Dr. Reed: For these exciting new therapies to come to reality, they have to be approved by the FDA. You are a former commission of the FDA. Some clinicians are frustrated with the time it takes to get new medical devices and drugs approved by the FDA. You've been more sympathetic to the agency and the lack of resources it has to help it through a mighty tough job.

What do you think we should be doing -- either the American people or the federal government -- to better support the FDA and its efforts to get much needed treatments to patients more quickly?

Dr. von Eschenbach: The importance of the FDA can't be overemphasized. It's absolutely critical to this entire process of progress that I've been talking about. Let's go back to our model of discovery, development, and delivery enterprise in medicine. It's no longer linear -- from the bench to the bedside. It's actually circular.

What we're seeing in terms of physicians delivering care is that there are tools that are now available to help us better understand the human biology of disease. When we treat disease or intervene in a human being, through functional imaging or whatever, it is actually a discovery platform making this process circular.

The success of the process of discovery, development, and delivery is going to be based on speed. How quickly can we do that? How quickly can we keep cycling that revolution of knowledge and intervention? At the hub of that wheel is the FDA. It can be the brake, or it can be the accelerator. It clearly is critical to how rapidly we're going to be able to move from your brilliant discovery in the laboratory to the point where we've actually made a difference in a patient's life.

Regulation has to be modernized. It's a matter of making sure that the agency has the capacity and the capability. Funding resources are critically important. But what's more important is we need a new way of doing business. We can no longer use a regulatory process and framework that served us well in the 20th century, but is woefully inadequate for this new reality in the 21st century.

For physicians, especially physicians out in the community, a simple piece of that equation is that we will play a critically important role in the perspective of clinical trials. The way we approve drugs now in phase 1, phase 2, and phase 3 of clinical trials is not commensurate with the mechanistic view of disease. So we're going to change the FDA. And in doing so, we're going to fulfill the promise for people.

Dr. Reed: We're excited to hear that. At the Celebration of Science Conference, we heard a representative from the FDA, Janet Woodcock, talking about that very issue of having more adaptable clinical trial designs. That is an opportunity for us to increase the speed of learning and turnover with real-time feedback from imaging and biomarkers, which allows us to see whether the medicine is working.

Dr. von Eschenbach: The FDA has to practice regulation in the way that physicians practice medicine. Every patient, first of all, wants personalized medicine. They all want to know what's right and what's best for me. Doctor, what should I do? We now have the tools to become much more precise about that.

But every patient, also in a way, becomes their own experiment. We apply a therapy, and a rational physician makes a very sophisticated educated guess but never knows whether it's actually going to work in that one patient. We monitor, and when we observe outcomes, we change. We alter the treatment until we get to that desired outcome.

Why don't we approve drugs that way? Why don't we use adaptive trial designs so that we learn as we go, and do that routinely rather than using this stepwise fashion that we've been locked into? We have to be open to change.

Promising New Methods of Treating Disease

Dr. Reed: You were once a practicing urologist, and you went on to become director of the NCI. In recent years, you've been active in a number of organizations dedicated to researching and developing new methods of treating a variety of diseases. Tell us one of the things that you're most looking forward to.

Dr. von Eschenbach: Cancer had the opportunity to be at the forefront and the vanguard of this radical transformation. In 1970, cancer was a disease that was devastating us with regard to the human toll of suffering and death, and the economic consequences. At that time, the science of cancer was just beginning to become apparent in a way that we could begin to understand the cancer cell and the living normal cell at its very fundamental genetic and molecular level. That created this enormous cascade of progress.

What we're seeing now is that the lessons learned and the progress made in cancer can now be disseminated to all the other diseases. For example, Alzheimer disease and neurocognitive and neurologic disorders are probably today where cancer was in 1970. Those diseases have a huge, devastating impact on human life and will bankrupt us in terms of the overall cost of healthcare and the cost of caring for patients affected by these diseases. But science is now emerging to help us better understand these diseases.

It's a privilege to have lived the life of a cancer physician and researcher, and now I can transpose that experience to ask how we can do that for all diseases. That's my passion today; it's not just about cancer. It's no longer cancer-centric, but it is cancer-led. Everyone will profit from the tremendous progress that researchers are making in the science that we will translate into cures for people.

Dr. Reed: Dr. von Eschenbach, thank you for joining us today. For Medscape One-on-One, I'm John Reed.