Margaret Hamburg has been the Commissioner of the Food and Drug Administration (FDA) since 2009. In the below entry, part 1 of 2, Dr. Hamburg discusses critical issues in FDA drug policy, including the use of surrogate endpoints and the development of new regulatory tools. The interview was conducted by Ryan Hohman, Managing Director, Policy & Public Affairs of Friends in the Commissioner's Office in White Oak, Maryland. As always, if there's anything you'd like to add to the conversation, we invite comments, contributions, and engagement. Be part of the conversation and pitch your ideas for future contributors on Twitter @CancerResrch using #EngageInnovation or email us at email@example.com.
Can you briefly describe the state of biomedical research and innovation in the United States?
"Well, it’s a critical time for biomedical research and innovation. The opportunities have never been greater but we know that we're not translating all of the exciting new discoveries and opportunities and science into real world products that matter for people. And I think this is the time to really galvanize around that clinical principle of science in the service of people. And it’s going to involve a number of factors, but importantly, making sure that we have the best possible science, the best possible scientists and the next generation of young scientists who are ready to step up to the plate."
What is FDA's role in a globalized community?
"Operating in a globalized world is a challenge for the FDA but it's one that we are embracing with enthusiasm because it is the reality and will only be more so going forward. We think that it's important to obviously maintain our identity as the FDA and our mandate and mission is to promote and protect the health and safety of the American people. But we actually can only do our job and do it well if we do it in partnership with other nations, with counterpart regulatory authorities, with companies that are operating around the world, with the scientific community, which is a global community, and recognizing their critical shared needs and unmet medical care and public health concerns. FDA is the gold standard for the world in terms of what a regulatory agency should be in how we approach our regulatory responsibilities. We feel we have a lot to offer to others around the world as they are building regulatory capacity and we now really think about being a global regulatory community and bringing some of what we can offer to bear, helping developing economies build their regulatory capacity, trying to harmonize standards and approaches across the world. We realize that not every country or region is going look like the FDA, and they shouldn't. But how can we work together to ensure some fundamental baseline capacity that cuts across all nations and regions of the world? And we have really stepped up to the plate to try to be good global citizens and global partners in what is an increasingly complex and challenging world."
The recent Ebola outbreak has drawn attention to the use of experimental drugs in serious and life-threatening contexts. Can you comment on the FDA's perspective?
"Well the Ebola outbreak has just been a devastating medical and public health crisis, certainly in the West African region but actually it really should be a wake-up call for the world. The issue about how to get novel therapies, vaccines and diagnostics to people who need to use them to both manage for the spread of this outbreak and treat patients who are critically ill is a huge challenge. In a setting like this, we have a mechanism called "Emergency Use Authorization" when there's a declared public health emergency that is one mechanism for expanded access. In other settings, non-Ebola and Ebola, when there isn’t a declared emergency, we have mechanisms for compassionate use, expanded access, and emergency INDs. We feel very strongly that when there are not other therapies available, that the FDA, working with companies, with healthcare providers, and with patients, has an obligation to look at “Can we make still unproven therapies available?” Of course, our first choice is to have a portfolio of FDA-approved drugs and we're fighting hard to keep that pipeline going so that we have, even for rare diseases, the right armamentarium to prevent, treat, and cure disease. But this is a very important area that we're working on and we’re always trying to balance risks and benefits to advance the science and to do what's best for patients."
How has the FDA toolkit changed in your years as Commissioner? In particular, how do you see the Breakthrough Therapy pathway being used?
"This is been a really exciting time at the FDA in terms of new opportunities that have come from advances in science and technology and new opportunities that have come from getting new authorities and responsibilities in this area as well. So there's been a lot of progress in really strengthening regulatory science, in developing some of the new scientific tools we need to support the research and development process for new products and our regulatory review. The Breakthrough Designation has been, I think, a very significant advance. It has really allowed us to say: the early clinical promise of this particular candidate drug is so significant and meaningful in terms of other therapies or lack of other meaningful therapies that we need to not treat it as business as usual and we need to mobilize, we need to fast track in terms of moving forward as quickly as we can. We need to make sure that the review teams are fully engaged in working with the company early and often as the R&D process goes forward so that the right studies are done, that those studies are streamlined and as scientifically sophisticated as possible, and making sure also that high-level senior scientists and managers at the FDA are engaged as well so that all potential obstacles are eliminated so that we can move as quickly towards the goal line as we can as long as the science supports the safety and advocacy and overall clinical benefit of this this product for people."
Can you comment on the value of surrogate endpoints in shortening clinical trials?
"The concept of using surrogate endpoints in how we evaluate new drugs is a really important one and one that we need to continue to develop. But I also want to remind people that it's not a new concept. Back in the early days of HIV/AIDS, it was really an important advance when it was recognized that you didn't have to wait to see the impact of the drug on the progression of HIV and the development of full-blown AIDS in order to determine if the drug was having a benefit—you can look at the CD4 count as a measure of viral load. And it was recognized that that did have a meaningful impact on the ultimate clinical outcome. And so with that we were able to move more quickly to get important drugs approved, to get important drugs to people and it has transformed the landscape with respect to the treatment of HIV/AIDS and the kinds of lives those individuals are living today. And I think that that's a concept we need to apply more broadly. We’re seeing its benefit in other areas: importantly, in cancer, but other areas as well. It's an area where we need to work together to develop the research base to truly identify what are those clinically valid surrogate end points that can be applied to research and advancing innovation."
Can you talk a little bit about FDA's role in developing the Lung-MAP clinical trial?
"I think that FDA played a critical role in developing Lung-MAP, helping to sort of catalyze an idea and then working with others to define how the scientific studies could be structured, what would be required in terms of development, design, and expectations of the work. But it was only possible because of the partnership. The role of Friends of Cancer Research was absolutely central to making this real and bringing all of the stakeholders around the table to shape this new approach. . .It’s an example of how scientists, patient advocacy groups, and the regulators can come together to create a novel platform for studying a really important disease. . .The Lung-MAP protocol is so exciting and so important. It’s going to save lives. It’s going to save time and money as well. And it’s a model that can be extended to other diseases as well."
How does FDA encourage young scientists?
"We have a lot of wonderful scientists within the FDA and many rising stars, but we need more. We need to make sure that people early in their training in medicine and science and public health think about FDA as a career opportunity and potential pathway. We need to make sure that our scientists and leaders here in the FDA take the time to mentor young scientists as well. And I think that broader engagement with the biomedical research community, academia, and industry is essential as well because we want great scientists making those discoveries, we want great scientists in companies helping to really scale up and move those promising pharmaceutical candidates into products, and we want those people here at the FDA doing their important work to speed and advance innovation."