something in their lives. yet the numbers here are so big. i do not understand why the five that are highlighted here, there's six programs, two with the department of defense, why you can't hit those five goals. and according to the gao, like the medicare program, they've only met one of the five goals. four partially. on the two dod programs, met one of the five criteria. four are partially met. at the department of energy, one partially met, one fully met, three not met at all. so 25 years in a row. i don't want to come back and have this same hearing at the beginning of the next congress. i want you all to solve it. the committee would like to know, how are you going to do that? how are you going to do that?

and again, difficult for you to answer, but i'm telling you, y'all have painted a pretty picture, it ain't so pretty. but we want to see what it is you're actually doing. what is the action plan to create an action plan. that's the hope and goal. and that's my concern. and with that, i want to yield back. i think, if there are any members who wish to ask a second round of questions. the gentleman from ohio. >> i appreciate the chair's indulgence. if we could put up these two slides again. mr. koskinen. >> i think it was noted -- agreed by congress and mr. gaudy and the chairman and we'll come back and have a full hearing about this that we would not -- >> i fully expect that, yeah. >> but i'm happy to answer more questions, that's fine. >> that's the way it works. we call you here we're allowed to ask questions because the american people want to know why the internal revenue service violated fundamental rights. so we appreciate your willingness to answer our questions on behalf of the american people. that's awfully big of you

mr. koskinen. >> i'm just stating that we're going to have another hearing on this and i've had five hearings already. but i'm happy to answer the question. >> and we still haven't gotten the truth as evidenced by the head line yesterday mr. mr. koskinen. the press, the main street press can't even get the documents they're requesting. >> those aren't documents they're requesting from us. >> but they derive from your unlawful activity. that's the point. that's something you've got to understand. as the guy who heads the agency with as much power as you do to have that kind of attitude. that's what frustrates not just members of this committee, but all kinds of americans. mr. chairman, that is the problem. let's go back to this. because i want to know something. this is what you told me when i asked you, when did you learn you could not get all of her e-mails? you learned in april. all right? then you learned in april, and then let's put up the next slide. this is the letter you sent to senate finance telling them in june, you sent this letter. telling them you -- and you used the word confirmed, that no

backup tapes -- that backup tapes no longer exist. so i want to know between april when you learned, and june when you told the congress and the american people what you did to confirm that those tapes didn't exist, which we now know do exist. so what did you do to confirm that the tapes didn't exist, mr. koskinen? >> what i did was talked to our i.t. people who told me that when the tapes were finished with their six months, they were refused and then destroyed. and that as far as they were concerned, there was no way -- we had no capacity even if we knew where they were to extract e-mails from them. and it's taken the i.g. six months and they still haven't completed the process. >> that's all you did? you asked your i.t. people? >> right. >> was it a long conversation? did you ask them one question? what -- how -- >> i asked them questions about

how the backup disaster recovery process worked. what happened -- >> so the word confirmed is based on one conversation you had with i.t. people? is that what you're saying? >> yes, those are the experts that told me there was no way that those tapes could be found. or would be used. because if they were reused- >> that's all you did? >> that's all i did. >> really? >> we're going to leave the last couple of minutes of this hearing. you can see it in its entirety on our website c-span.org. check the c-span video library. going live now to capitol hill to the senate health committee. the committee members are examining medical innovation and the potential benefit to patients. nih director francis collins and commissioner margaret hamburg on the right there. senator lamar alexander serves as the chair of the committee. senator patty murray is ranking member. this is live coverage on c-span3, just getting under way. >> -- us to discuss that. let me see if i can put this in some sort of context. one of the -- we have -- this is

a busy committee. in the last congress, senator harkin used to point out that we completed 25 pieces of legislation which became law, and senator murray and i are working well together. and three major items that we intend to focus on in the next two years, among all the others number one fixing no child left behind. and we're working well together toward that. hope to have a markup on that after the recess. second, we're working on simplifying and reauthorizing the federal government's supervision of higher education in america. we had a hearing on that recently, and it had an impressive report. senator mikulski senator byrd, senator bennett and i have asked for about simplifying regulations. and so that will be second. but, the third topic is to deal

with this exciting new era of medicine that we have. and take a look at what we can do as a congress working with the president to reduce the cost and the amount of time it takes to go from discovery of a medicine or a treatment or a medical device and take it all the way through to the medicine cabinet or the doctor's office. now we know important work has been done in the congress on that, not so long ago. but we have an opportunity this year to make whatever contribution there is to make. and it's an area that we ought to succeed in because there's not really a political partisanship about this issue. in fact, the house of representatives is moving on a parallel track on something they call 21st century cures. president obama is extremely interested in precision medicine. i tended his announcement of

that interest at the white house recently along with dr. collins and dr. hamburg. i've talked with him about it. and with secretary burwell. and suffice it to say that i believe every single member of this committee's interested in identifying what we can do to make it easier to move those drugs, treatments and devices from discovery all the way through to the medicine cabinet. we're not just talking about moving it through the fda. sometimes it takes two, four, six, ten, twelve years to get to the fda's front door. so we're not just talking about the fda. we're talking about the whole range of issues there. dr. collins has described it this way. he wrote in 2013, drugs exist for only about 250 of the more than 4400 conditions with defined molecular causes. it takes far too long and far too much money to get a new drug in to our medicine cabinets. this is an old problem that

cries out for new and creative solutions. since dr. collins wrote that the number of conditions with defined molecular causes has increased to more than 5400. the number of new drugs approved has not kept pace with these discoveries. dr. hamburg, who is here today, has said that we are left relying on the 20th century approaches for the review of frugal and oversight of the treatment and cures of the 21st century. president obama, in his announcement of the new precision medicine initiative said 21st century business will rely on american science technology, research and development. i want the countries that eliminated polio and mapped the human genome to lead a new era of medicine, one that delivers the right treatment at the right time and some patients with cystic fibrosis this approach has reversed the disease once thought unstopal. he introduced at that white house announcement a 27-year-old

young man whose cystic fibrosis has been cured because he's one of the 4% of the sufferers with that disease caused by mutated gene for which there's now a drug. and i think the legislation senator bennet senator byrd worked on may have helped to contribute to that opportunity. so this is the discussion that can affect nearly every american. and in which we're going to take very seriously. senator byrd identified a report that issued a white paper that we've been working on for some time. it focused on the issues that we thought the committee ought to identify, and we've submitted that to senator murray and to the rest of the members of the committee for their consideration. costing too much to bring medical products through the discovery process and development process taking too long. whether fda's responsibilities include unrelated activities to what the focus should be.

the disparity and scientific knowledge of the fda and the fast pace of biomedical innovation. those are some of the issues that we focused on. but what we hope to learn today from two distinguished leaders of our government is exactly what should we be focusing on? we don't want to waste our time. we can't do everything. this train is moving through the station in the next twelve months and if our goal is to get from discovery to the medicine cabinet of the doctor's office what are the two or three things that we ought to spend our time on? i believe we can do that working to the. we're excited about it. it's a change for your agencies and the rest of the government to let us help you get the obstacles out of the way that might be in the way of your getting your job done. some of them have relate to money. some don't. some relate just to the pileup of of administrative regulations at our hearing on higher

education, there was talk about hiring a boston consulting group to assess the cost of rules and regulations to operate vanderbilt university for one year, and the answer was $150 million, $11,000 on on the -- to every student's tuition at the university. so, there are a whole range of things. i'm looking forward to this. i thank you dr. collins. i thank you dr. hamburg. i'll now turn to senator murray and we'll then turn to the witnesses. >> thank you very much, chairman alexander. dr. collins dr. hamburg, great to have you both here. i have a lot of appreciation for the work that you do to encourage innovation and improved health and well-being. dr. hamburg, as you step down from your owe at fda i especially want to thank you for your many many years of service and we're all very grateful for your leadership. so thank you very much from all of us. i'm very pleased to be working with chairman alexander and other members of the committee on ways that we can continue to

advance biomedical innovation for patients. i believe that we are at a truly fascinating moment in medical innovation right now. we increasingly have the ability to move away from a one size fits all model of treatment. and instead treat patients according to their unique characteristics. we've seen enormous growth in life sciences as the course of economic strength and job creation. my home state of washington is a great example. life sciences are the fifth largest employment sector in my state and it's growing. these are good jobs, in a industry with global reach and our country needs more of them. so it's critical we secure and build on the united states' leadership in medical innovation. to do this i believe congress has to look at how we ramp up investment in the kind of research and development that helps drive this private sector growth. that's something i will be very interested in exploring as part of our bipartisan efforts in the coming weeks and months. dr. collins i know that you are very concerned about the impact of sequestration and what it has

done to nih and i am, as well, and i hope that we can talk about that today, as well. i'm also eager to hear more about the many efforts at nih to ensure the united states remains the global leader in biomedical research and discovery. the fda drug and device approval process is another topic that i know we will receive a lot of focus. dr. hamburg, you recently announced that in 2014 the fda approved 51 new drugs which is the most in almost 20 years. you should be very proud of what that means for patients, and families across the country. i look forward to hearing from you today about ways that we can build on that progress. another priority i will be focused on is the needs of women and young children in the research, development and proveal process. when we looked at the fda approval process back in 2005, senator kennedy reminded us that when patients open up their medicine cabinets, they deserve every assurance that the medicines they take are safe and effective. and that is just as true today.

so, conversations about advancing medical innovation move forward i'll be guided by his vision of upholding that assurance. in the weeks and months ahead i hope we can reach an agreement on policies that help get us safe, effective treatments to patients more quickly. that would be good for our economy, and could really make all the difference for so many families we represent. so thank you, again, to our witnesses for being here today. and thank you, chairman alexander, for holding this hearing. >> thank you, senator murray. we have good attendance already of senators. i would say that we've formed a working group of staff, a single working group, on this subject for the purpose of identifying how we'll proceed. and after this hearing, the next few weeks, the working group and senator murray and i will sit down and talk about how we can have a bipartisan process and take into account, and focus our -- and focus our efforts in a way that gets a result. in that we'll be aware of what the house is doing, and we'll

work with secretary burwell and with the president to especially on their precision medicine initiative. each witness we've asked -- i'd ask each of you to summarize, if you can, in about ten minutes, your testimony so the senator also have a chance to have a conversation with you. i thank you both for coming. dr. collins first. thank you. director of the national institutes of health, the largest supporter of biomedical research in the world. he's been director of nih since 2009. he's known for his leadership of the international human jen i'm project which led to the first completely sequenced human genome in 2003. next we'll hear from dr. hamburg commissioners of the food and drug administration. according to our staff, 25 cents of every consumer dollar that's spent in the united states you regulate, when you regulate prescription drugs medical devices, food and tobacco products. dr. hamburg has been in this role for six years.

we're glad she's retiring. i especially thank her for coming to this hearing -- i don't mean i'm glad she's retiring. i'll start that one over again. i'm glad she's here. and i'm glad she's here because she is retiring, and she has this wealth of knowledge accumulated over the last six years, and i especially asked her to come for that purpose because i knew the committee would want to hear from her. dr. hamburg, thank you very much for your service to our country. and even though you may be retired, we hope you'll continue to advise us especially during this next year as we work through -- as we work through these issues and i thank senator murray and senator mikulski for keeping me straight on my comments. all right. dr. collins? >> well, good morning.

chairman alexander, ranking member murray members of this important committee it is an honor to appear before you alongside my friend and colleague, fda commissioner peggy hamburg. our agencies have much to gain by working to the, and we have been doing so and we're committed to that effort. in fact, peggy and i spent a productive three hours just yesterday afternoon along with senior leaders from both of our agencies who make up the nih/fda leadership council discussing a wide range of projects we are working on together. i'd like to, on behalf of the nih, our employees grantees and patient community, to thank members of this committee for your continued support, and for holding this bipartisan hearing today. i appreciate the opportunity to discuss how we as a nation can drive innovation through federal investments and scientific research. breakthroughs generated by nih research, and i'm going to show you a few visuals here if you can see the screen, are behind many of the gains our country

has enjoyed in health and longevity. for example, over the past 60 years, deaths from cardiovascular disease have fallen by more than 70%. meanwhile, cancer death rates have been dropping about 1% annually for the last 20 years. likewise, hiv/aids treatments have greatly extended lives and prevention strategies are enabling us to envision the first aids-free generation. today i want to share with you a few of the many promising opportunities for biomedical research innovation. i can assure you the potential of scientific research has never been brighter than it is today. nih remains strongly committed to basic science. fundamental research that serves as the foundation for discoveries that have long made america the world leader in biomedicine and accounts for no less than 145 nobel prizes that have been awarded to our scientists and that we support through nih grants and through our intramural program. one exciting example in basic science is the brain initiative.

this bold multiagency, multiyear effort is enabling development of innovative technologies to provide a clearer, more dynamic picture of how individual brain cells and neural circuits interact in time and space. this initiative will ultimately give us the tools for major advances in brain diseases. from alzheimer's and autism to schizophrenia and traumatic brain injury. nih is also innovating in translational science for basic science findings are developed in clinical benefits. let me give you a few examples. recent advances in technology have led to the discovery of more than 1,000 risk factors for disease. but drug development is a terribly difficult and failure-prone business. a major reason for failures is that scientists often just don't know how to choose the right pathways to target for the next generation of drugs that they want to develop. so with this in mind we were

excited just a year ago to launch the accelerating medicines partnership, or a.m.p. this is an unprecedented precompetitive public/private partnership using cutting-edge scientific approaches to choose the most promising targets for therapeutic intervention. decides nih, a.m.p. partners include importantly the fda, ten biopharmaceutical firms and a number of nonprofits, including patient advocacy groups. initially, a.m.p. is focusing on three disease areas that are ripe for discovery at the next generation of drug therapyiestherapies, alzheimer's disease, type ii diabetes and the autoimmune disorders rheumatoid arthritis and lupus. through this approach we believe we can learn how to treat and cure disease faster, and we can do it together across this whole ecosystem. nih is also working to streamline the therapeutic development pipeline through effort at our newest center, impasse. more than 30% of promising

medications fail in human clinical trials because they're bound to have unacceptable toxicity. despite promising preclinical studies. could we do better? well the tissue chip for drug screening initiative is developing 3-d human tissue biochips that model the structure and function of organs, such as the lungs liver, and heart. now these organoid chips and you can see the heart chip is beating in realtime because the cells that are on that chip are cardial muscle cells that are synchronized to beat just as they would if they were in a heart. these give us the opportunity to mimic complex functions of the humgen body without putting humans at risk. enabling scientists to predict more accurately how effective a therapeutic candidate would be in clinical studies. eliminating toxic or ineffective drugs earlier in the development process. scientific advances are also accelerating progress toward a new era of precision medicine. historically, doctors have been

forced to base their recommendations for treatment on the expected response of the average patient. but recent advances, including the plummeting costs of dna sequencing, are now made possible more precise approach to disease management and prevention. that takes into account individual differences in genes, environment, and lifestyle. with this in mind, nih is thrilled to take a lead role in the multiagency precision medicine initiative that you all have already mentioned in the opening statements, and which we at nih are very excited about. in the near-term, this initiative will focus on cancer, to accelerate efforts, this project will support research aimed at understanding why cancers develop drug resistance, using noninvasive methods to track therapeutic resonses, the so-called liquid biopsies. and exploring new treatments including combination therapies targeted to the jen etic profiles of a wide range of adult and pediatric cancers. as a longer-term and very bold

goal of this initiative, nih will launch a national research cohort of 1 million or more volunteers who will play an active role in how their genetic and environmental information is used to prevent and manage a broad array of diseases. a project of this magnitude will lay the groundwork for new prevention strategies and novel therapeutics. there's no better time than now to embark on this enterprise, to revolutionize med send and move this precise personal approach into everyday clinical practice. in closing to make this clear in terms of its impact on human health, allow me to share a story that highlights the early promise of precision medicine. when maki inad nachlt was dying nosed with stage 3-b carcinoma of the lung in 2008 it was completely unexpected. she was 36 years old, never smoked a day in her life. yet her tumor was very large.

almost seven centimeters with a very low likelihood of survival beyond a year or two. as maki began the recommended standard chemotherapy her doctors, who were ahead of their time in precision medicine suspected she might have a particular mutation in a gene called the epidermal growth factor reserpt or egfr. genetic testing confirmed their hunch. she was prescribed a drug that precisely gloggs egfr's signal. and after three months of treatment, maki's large humor shrunk dramatically, as you can see. this was followed by surgery to remove cancerous tissue plus retreatment with tarcibap today seven years after her diagnosis her doctors can detect no signs of cancer. what's more, she has now completed a triathlon landed her dream job as a biology professor at ithaca college, and welcomed a healthy baby girl.

maki is the face of scientific innovation, made possible by sustained investments in biomedical research. with your support we can realize the vision of accelerating discovery across the vast landscape of biomedicine from basic science inquiries to more precise personalized approaches to treatments and cures. so thank you mr. chairman my colleagues and i welcome your questions. >> thank you, dr. collins. dr. hamburg? >> thank you mr. chairman, and members of the committee. i'm very --. thank you mr. chairman and members of the committee. i'm very pleased to be here today to discuss our shared goal of speeding innovative treatment to patients. and fda looks 2350rd to working with you on this important effort. as you have noted, this will be my last appearance before the committee, as i'm stepping down. but i want to thank you for your support over the years, and our constructive engagement with this committee to advance fda's

public health mission. i came to the agency at a time of considerable uncertainty and change in the biomedical product industry. a time when dramatic advances in science and technology, some that my colleague dr. collins just outlined demanded new models, and approaches. in turn we took a very serious look at our role in advancing biomedical product innovation to ensure that we would be a gateway, not a barrier, to the delivery of better safer and more effective treatments and cures. and, in fact, this has been a high priority for me throughout my tenure, and i'm very pleased that as senator murray noted last year we approved the most new drugs in almost 20 years and more orphan drugs than ever before and 41% of these new approvals were first in class products. resulting in a breathtaking array of truly innovative new therapies for patients. today, fda approves drugs faster on average than all other advanced nations.

40 days faster than japan 70 days faster than canada and 174 days faster than europe. and fda has made substantial improvements in the efficiency of medical device reviews as well. moreover, we've accomplished this while remaining the gold standard around the world for safety and effectiveness. yet despite these successes, too many diseases still await treatments and cures. serious public health needs such as treatments for alzheimer's disease are not being met. and rising r&d expenditures are not matched by a proportionate discovery of new treatments. in this context i want to address concerns raised by some that fda regulation is the principle obstacle to the development of innovative treatments and suggestions that fda's authority for procedures must be fundamentally restructured. as a physician, i know that if you incorrectly diagnose a patient's condition, the treatment that you'll prescribe is unlikely to work.

unless we correctly diagnose why cures are still lacking for many diseases, we're unlikely to find the solution that will actually deliver those cures. so let me give you three examples of misconceptions. first, the incorrect but commonly repeated assertion that fda's approval of new drugs lags behind other countries. reality is starkly different. over 75% of the new drugs approved by japan eu, canada australia, switzerland, and fda between 2014 to 2013 were approved first by the fda according to a recent report by the british based center for innovation and regulatory science. and the result is that americans are, in fact, far more likely to get first access to new medicines. second, fda has set the rigid and inflexible in its approach to requesting and using data for approval of a new drug. in fact, fda's clinical trial

requirements have been steadily increasing in flexibility. 45% of new drugs are approved based on a surrogate input. one-third are approved based on a single clinical trial. last year we used expedited approval processing for more drugs than ever before. about 66%. and thanks in part to the new authority that you gave us 74 drugs have received the new breakthrough designation. my final example is a concern that investment in biotechnology has dropped precipitously in the united states, and that the fda is to blame. but in the words of the national venture capital association biotechnology investment dollars rose 29% in 2014 to $6 billion placing it as the second largest investment sector for the year in terms of dollars invested. and jonathan leff the leading biotechnology investor affiliated with nvca said that

one of the two reasons for the increased investment in biotechnology is the improved regulatory climate in recent years at fda. i cite these examples to suggest not that the world of biomedical research and product development is all fine, but to urge that we start with the right diagnosis. we do not want solutions based on inaccurate diagnoses. i caution against solutions that seek to lower the safety and effectiveness standards for approval of the medical products on which americans rely. remember, that the great leaps forward in evidence-based medicine of the last 50 years have come in part because of the high standards for product approval that congress put in place after a series of disaster disasters involving unsafe and ineffective medical product. those standards have also boosted the confidence that americans placed in medical product, and that the world places in the american buy yee medical product industry.

together, we can build on the progress that has been made in recent years to further advance biomedical science and improve the lives of patients. and there are some areas from the fda perspective that i believe we can all agree need to be improved. first, patients are uniquely positioned to inform medical product development. treatments can better meet their needs if we can capture science-based disease specific patient input to incorporate in the development and review process. second, more attention needs to be given to the development of biomarkers and surrogate end points. these can help scientists identify and target successful medical treatments and shorten drug development times as dr. collins was noting in his remarks. fda has accepted hundreds of biomarkers and surrogates such as blood pressure changes, blood sugar reduction and tumor shrinkage yet biomarkers are still lacking for many diseases such as alzheimer's. the biggest obstacle is that scientists do not sufficiently

understand the causes of alzheimer's and other diseases. to identify drug targets, or identify which patients will benefit from certain drugs. to solve this problem, we must support the establishment of strong public/private partnerships, bringing the best minds to the to develop the science that we need. third, real world data provides a vital tool to monitor medical product in use in the marketplace. fda sentinel initiative with more than 170 million lives is one of the largest uses of big data in health care and proving vital for monitoring safety in emerging safety concerns. the science of using big data to establish product effectiveness is still in its infancy. real progress demands we develop the methodology needed to harness the promise of real world data. and fourth, fda and industry agree that the agency must be able to attract and retain talented scientists to review cutting-edge product. and we look forward to working with you to improve our ability to hire and retain these

experts. so let me close by underscoring that speeding innovation, while maintaining standards for safety and efficacy serves patients well. supports the needs of our health care system. and has enabled the medical product industry in this country to thrive. and so i thank you for your support, for our efforts at fda, the work that you're going to be doing, going forward to advance that work, and the work of all of our colleagues in the biomedical research community so that we can deliver on the promise of science for patients. thank you. >> thank you dr. hamburg. we'll now have -- begin the round of five minute questions. i'll start. i only have two questions. i've got a short one which i hope to get a short response from dr. collins so each of you will have a chance to answer the second question. the first one is this. the national academies have done a couple of studies that show that 42% of an investigator's time is spent on administrative

tasks. the taxpayer spends about $30 billion through nih, 80% of that goes in to research. in a conversation they had at national academy said about 10% would be a reasonable amount of time for an investigator, although it would vary depending upon the investigation. what are the opportunities for reducing that 42% down more toward 10% or 12% or 15% for saving money so that we could have more multiyear investigations? and are there things that we can do to change the law to make that easier for you to do? >> well, thank you for the question, senator. we, too, are very concerned about the idea that investigators are spending 42% of their time dealing with administrative matters, instead of directly engaged in research and we're part of the support of that survey. which showed that number has not really changed from 2005 to 2012. we are undertaking a number of things that we have the ability

to do to try to limit the amount of administrative oversight but not all of that falls within our purview. some of it comes from other directions. some of it is from the universities themselves. things that we have done are to standardize the biographical sketch, the cv that individuals have to provide when they apply for a grant. that actually turns out to be a substantial asiance. something we're in the middle of, where perhaps some help could be offered, is a revision of how to interpret the common rule that oversees the research involving human subjects which has not gone through a revision in 20 years and which does not currently take account of the risk involved in study and applies a great deal of oversight to some studies that are truly low risk, as if they were, in fact, invasive drs >> dr. cons may i interrupt in this way. could you be willing to work with us to identify what those things are specifically so that during this next several months we can -- we need to make changes in the law that we can help with that? because i want to ask you and dr. hamburg this question. >> yes. >> and give you. we don't want to waste our time

in the next year. and we can't do everything. so could you say now, and then if you want to submit it later in addition to your statement, what would you -- what are the one or two or three things that we should focus on and in order to make the greatest contribution to the goal of moving medicines, devices, and treatments from discovery to the medicine cabinet as you put it, or to the doctor's office? and each of you. >> senator i appreciate that question. and i have a long list and i very much look forward to talking with you at greater opportunity -- >> we'll do that. >> but if you want me to name two, one which sounds pedestrian but is an incredibly vexing situation, and terribly wasteful for sciences' time is the rigorous oversight of attendance of scientists at scientific meetings. this applies to both nih and fda. we're currently spending about $16 million and using run dreads

of employees to go through a process which as far as i can say has relatively little, if any, added value. all of this triggered by some misas ventures by other agencies who convene conferences in places like las vegas, for which we are all now paying the price. but scientists going to conferences is a critical part of how we move things forward. how new ideas emerge. and it is very much being inhibited by this very heavy handed oversight and we could much benefit from your help there. the second one i could say, nsf and the department of energy and their scientific budgeting that happens every year, they're allowed to carry funds over into a second year. we are not. so we have come up to the end of september, oftentimes with money that we need to spend, or it goes away. if we had the opportunity to carry that over wouldn't cost another dime, we could be more flexible in how we spend the taxpayers' money. >> thank you dr. collins. dr. hamburg? >> i certainly agree with what dr. collins said. are you looking specifically for administrative issues or broader? >> anything. i just want to make sure we

don't waste our time. that we focus on getting a result. one or two things, whatever you think. >> let me step to a slightly higher level in terms of what i think are two critical and related needs in terms of being able to advance fda's activities, and, in fact, support biomedical research and product development. one is that i do believe we need to invest more money in regulatory science that develops the knowledge and the tools and approaches and strategies that really enable to assess in an effective and efficient way the safety efficacy, quality and performance of a product. it's been an underappreciated underdeveloped, and underinvested in area of our overall biomedical product enterprise and it's proving to be really essential as we are trying to take that last set of steps from research and development, into a product that will really make a difference in people's lives. and that we've laid out, i

think, an important exciting research agenda. and we've done work with nih in this domain. i think the other areas to recognize is that fda and our scientists have a huge amount to contribute to the overall process of product development, as well as our important responsibility for review. and you know certainly for us to be able to engage in a consistent way earlier, as research plans are being shaped so that the right studies are done, so that the return on investment of moneys in research all along the way are really driving towards a product that works. >> thank you very much. senator murray? >> thank you very much. dr. hamburg, before i go to broader topics, i wanted to ask you about the recent outbreaks of drug resistant bacterial infections that are associated with the use of the special medical scopes known as duodenoscopes. one in my home state of

washington there were 32 patients infected and although it's not clear what caused their deaths, 11 have died. how -- fda was supposed to have been regulating these scopes. can you explain how this could have happened and what actions fda has taken? >> the doodenoscopes are important medical devices that serve a critical role in patient care and diagnosing and treating a series of important problems and they are, in fact, used in more than 500,000 procedures a year in this country. usually with great benefit to patients, and it allows an approach that is less invasive than open surgery, and overall has less attendant risks to the patient's health and safety. over time, we saw isolated cases of problems in terms of infection, and duodenoscopes and

we would investigate those and they were always associated with some lapse in the disinfection protocols. in 2013, late 2013 we learned for the first time of some outbreaks, unfortunately involving an antibiotic resistant strain of bacteria where on investigation it seemed as though all of the procedures for disinfection had been followed. and after that we began to work closely with our colleagues at the cdc, with the health care provider community and with the companies making these to try to understand what are some intrinsic design challenges in order to enable the scope to do its job, or have to kind of twist around and has what's called an elevator mechanism. so we are actively engaged in trying to come up with better strategies for disinfection and recommendations to increase the

margin of safety. we're going to be hosting an advisory committee meeting. we're working with -- >> can you submit the full fda review to me so we can understand how this happened and protect against it happening? because i'm deeply concerned about it. >> as are we. we are very actively engaged a lot of activities are going to be happening moving forward as we continue to try to strengthen the safety of patients and improve what are very important medical devices for care. >> i appreciate that. on a broader issue dr. collins, the united states has always been a global leader in biomedical research and innovation. but today as you and i both know sequestration really threatens that leadership and i think it's critical that we build on the bipartisan budget deal that i reached with congressman ryan last year. the house rolled back those cuts from sequestration. we're just about to enter another budget process. can you explain to all of us today now sequester impacted research at nih?

>> well, thank you for the question. it certainly was a serious blow to momentum. the 1.55 billion dollars that were taken away from our budget in the middle of the fiscal year. resulted in our inability to fund about 750 grants that otherwise would have been funded that year and those very good ideas basically got left on the table. as you know we were able to make up some of that ground in the subsequent years but in 2015 we did not recover the entire $1.5 billion that was lost in 2013. the results of that in terms of what they've done to investigators who are already struggling with difficulty in getting their grants funded really has been quite significant. the overall likelihood, if you send your best ideas to nih of having that supported, has dropped over the course of the last ten years, since the budgets became flat and inflation has been eroding away.

and our ability to support research. and it is important to point out, and you've made this point, that this is something which puts america at a limited competitiveness status, as well. if you look to see what other countries are growing to show your graph here from 2011 to 2013 in the change in percentage of gdp invested in research you can see that countries like china and brazil, south korea and so on, are substantially increasing their investment. they're reading from our playbook from the 1980s and '90s, whereas we stand alone in this graph as actually losing ground. the consequences of that is we are also losing opportunities for science. we're losing jobs. and we're potentially at risk of losing young investigators who are beginning to wonder whether there's a future for them, and some of them are starting to think about it. >> and the threat of that sequestration going in again in a few short months, what's that doing to you? >> that hangs over us like a dark cloud. because if sequestration is not dealt with we stand to lose

another $19 billion. we've gone to medical research over the coming years and the consequences of that are really painful to consider. >> thank you. >> thank you senator murray. senator burr and then senator mikulski. >> dr. collins dr. hamburg welcome. dr. collins in your testimony you highlighted the potential to better target medicines to specific patient needs. what role does biomarker qualification employ in advancing these patient focused therapies? >> again i appreciate the question. i mentioned that we had a three-hour meeting yesterday between nih and fda and one of our topics was biomarkers because of our shared interest in trying to move this agenda forward. as dr. hamburg said in her opening statement there are lots of biomarkers that have been used for a long time. measuring your blood pressure is basically a biomarker that we use to assess risk of cardiovascular disease and stroke. we would love to see biomarkers develop for something like alzheimer's disease which she

also mentioned. i pointed out this accelerated medicines partnership that we're doing jointly with industry as that is one of its goals for alzheimer's so we're making sure that all clinical trials that are trying out new ideas about prevention of alzheimer's disease use the same set of biomarkers. so that if something starts to work, maybe it's a blood test. maybe it's a major protein in the spinal fluid. maybe it's a scan of something like an amyloid in the brain we would know that and we'd be able then to begin to utilize for therapeutics. >> you're both nih and fda participant in the biomarker consortium. >> yes. >> so let me ask since the consortium was established in 2006, how many biomarkers has it qualified? >> the biomarkers consortium has partnership from nih, from industry and from patient organizations it is not itself charged with doing biomarker qualification. it's charged with identify possible biomarkers that need more research and making sure the research happens.

the fda has the role of qualifying the biomarkers if they have reached that standard. >> so, they've got full determination based upon what the consortium comes up with as to whether they recognize the biomarker? >> they need to evaluate, and i'll certainly depend on dr. hamburg to specifically state the process. whether the science is strong enough for a particular biomarker to be considered validated, qualified so that it can be used for rigorous studies have shown that it actually is a predictor of what you want it to predict. >> dr. hamburg, let me turn to you, if i could. fda's drug development tool qualifications programs notes the importance of developing animal models for use under the animal rule. a few weeks ago your colleague was before the committee as part of an oversight hearing. as you know human efficacy studies are not feasible and some medical countermeasures. therefore fda's animal rule is particularly important for such products, which is why i

emphasize the importance of finalizing animal rule guidance with dr. boryo before this committee. as far as i can tell there's been no further movement on this issue since that hearing so i'd like to ask you, when is the animal rule guidance going to be finalized as required by law? >> well let me first begin by thanking you for all the extraordinary work you've done to advance public health preparedness, and the development, and availability of important medical countermeasures and the animal rule, as you note, is an aspect of this that is key because we do need to develop medical countermeasures against certain threats where the disease may not exist in nature, and would certainly never want to expose people to the disease to actually see if the new drug or vaccine, actually works. we have taken the animal rule very seriously. it's one of those areas of regulatory science that is challengeing because we want to

be able to know that using animal data, which is often imperfect, we can make a good enough assessment of safety and effectiveness and appropriate use of a product against what is generally going to be a terrible life threatening disease, so we have been working on the animal rule for quite awhile in the best scientific strategies engaging with the research community and obviously companies, as well. we did put forward a draft guidance and comment i think ended on that back in august 2014. we got a lot of response, and we've had a lot of meetings -- >> is this a priority? >> it is a priority absolutely. >> when are we going to have a final rule? >> well i think it will be soon. i can't say that you'll have it before i step down at the end of the month. but it has been a priority of mine from very early in my tenure, as you may know. i've been working on many of these kinds of issues before i joined the fda.

but it is a scientific challenge, and in fact the guidances, and the work and the draft guidance has shaped work that's being done and moving that's being done in moving forward. it hasn't stopped prorks edped progress, but we will get it done and i will go back and remind the team there's a very important senator waiting for that as are the american people. >> if i didn't mention the same time, about a similar pathways. and the fact that we have yet to have that final guidance and -- response senator murray's statement on what happens in sequestration. there's no consistency, you can't fund the things you think might generate. i would only say this. there are a lot of companies and

efforts out there waiting for a pathway. we just approved the first bio similars in fda and we don't have a pathway. we don't have a final guidance for the other manufacturers out there, so you've got a company that had one approved, but nobody else knows how to get theirs approved because there's no guidance on how to approach it. my only suggestion is this is as important as how we fund research. that having enough markers qualified, having financial guidance for bio similar ises, having a funl rule on the animal rule is all part of how we have a robust response to disease and we change the outcomes of patients in the future. i thank both of you. >> thank you, senator burr. >> thank you, mr. chairman and thank you for both convening this hearing in the spirit in

which you did. a bipartisan effort that you would promote science innovation in this country. which leads to you new ideas, new research, new products that not only save lives, but create jobs in our own community. i would also welcome dr. collins and hamburg here. i have great joy of having -- in my state. we have really every day and every way, think about how they can advance the mission of these agencies. i'd like to thank them for hanging in there because many of the impediments that are created are impediments we create ourself ourselves. not only do we try to find new ideas, but maybe we need to get back to some old fashioned ideas of working together like the chairman has said. dr. hamburg i know you're

leading the fda, but you're going to continue to serve in many capacities and they say you're the longest serving i'm the longest serving and here we are, each turning a new page. i'd also like to take this opportunity to thank the men and women who work at these agencies, nih n fda. you have to know for my 20 years of service is to wake up every day and think about how i can make the world a better place and i have these two fabulous agencies where my job is to help you be you. and i cannot tell you the pride and enthusiasm and joy that that has brought me. so, let me get to what i think are the three criteria for reform and get to my questions. number one, let's respect the mission or the agency and let's respect the men and women who work at the agency. i think respect goes a long way to improving moral. moral goes a long way in

increasing productivity and i would hope the congress of the united states would embrace the idea of respecting the men and women who work in our federal agencies and not treat them as cheap thrill reminds on talk shows. the second is adequate resources so you can do the job and have the tools you need and then third, let's approach reform in a targeted way the chairman has indicated. let's focus on specific problems and specific solutions. so so, i -- to my members here to think about the three rs. respect, resources and reform that's targeted. which then goes to my question dr. collins, and you, dr. hamburg. senator murray raised the question of sequester. that then goes to predictability. which you share with the committee the impact because each one by dr. hamburg, many of

the reports they say there's been a big turnover at fda. whether that's numerically justified, i'm not sure. so many accusations aren't just justified, but could you share with us what that means in terms of the predictableility, sustainability as well as the addequacy adequacy. what will predictability and certainty mean at fda? >> certainly the it is key. we hear it from the industries that we regulate in terms of how we oversee them and it's essential to us to be able to do our job. we need to be able to lay out programs that are not occurring in one year time frames, but over time, we need to be able to recruit the best and the brightest scientists and other professionals that we can that are highly competitive, outside of fda so they need to know that they're going to be working in an environment where they're going to get the resources that

they need and the support they need in a continuing way. we certainly need every dollar that we get as was noted we have a very broad span of roles and rommeties overseeing products that matter greatly to every american, every single day and we are stretched very thin so, uncertainty and instability in our funding programs make it harder for us. >> recruit and retain. and therefore, get the experience. >> and to make wise choices. the other then with the predictability, what about you, dr. collins? >> i appreciate the question and senator, your strong support has been incredibly valuable and we are all grievinging the fact you're planning to move away in two years and we hope this can be an opportunity for lots more conversation mountain

conversation in the meanwhile. i think the idea of stability is is just crucial. especially for those who are early in their careers. they have visionary ideas. they're fearless about taking on the problems that couldn't be approached before but the technology now makes it possible. but when they're uncertain about long-term support for that, that's discouraging. another grab i'll show you, mostly troubles i think today invest gitigateors is what's happened to your likelihood of getting supported by nih, which has run around 30%. it's below 20% now. running about 16 or 17%. that means five chances out of six, your idea is going to get a no. and that a means your science is left on the table unattended. that is enormously discouraging. if we could turn that corner and the president's budget as you can see that little uptick there, aimed to try to do that we could turn this whole circumstance around in the united states. we could refwan gain the kind of momentum and leadership we've had unquestioned over the past

many decades, but it is at risk. >> so, one is adequacy. i know my time is up, but i just bring to my committee, two things. during the sequester, fda couldn't use the user fees the private sector was paying in. but here's the private sector giving the money after an arduous work to create a contemporary bah due pha. there was one. and the very day before sequester, they announced they lower ed lowered cancer rates in this country 12%, so instead of pinning medals on people we were getting ready to print pink slips. i don't think that's the right way to govern. >> senator isaacson and -- >> thank you mr. chairman. this is my first time publicly to be able to acknowledge the great contribution of senator mccull ski to public health in american and i just want to publicly thank her for all these done.

it's been a pleasure to serve her on this committee. dr. hamburg, senator burr is right on target and this is a long lead up to a question and i apologize for that, but it's a very important question that needs to be answered. you made a reference in your statement some blame the lack of investment and bio technology on the fda and you refuted that, but investment follows certainty and certainty follows regulatory processes that work, so i find it troubles the fda has so much difficulty working through the regulatory process and last year's user fee bill congress directed you to fix the problems that have affected manufacturers and suppliers of medical gas. that was a year ago, yet we're still waiting on a report and some say we're heard there's resistance in the agency to doing so in issuing new regulations. instead, the fda seems to rely

heavily on approaches such as guidances and untitle working letters. these don't over certainty and in the case of untitled edd letters they fail to inensure any letters and stakeholders who are similarly situated. last may, the chairman and many members of this community sent you a letter posing questions about the agency's use of draft guidance. we received the response last night. 12 hours before this hearing. in the letter, you attached 172 outstanding draft guidance issues. one of which goes back to 991988. show this effective regulation and effective process? >> well, we are taking a very active look at the various guidances and what stage they're in. it's important to understand that a guidance is just that. it's a guidance to inform industry about our current thinking and the process of developing a draft guidance to a

final guidance is all extremely useful in that process, when the draft guidance goes forward, it enables us to put forward how we are thinking about the problem and to ask some questions and get information back to further engage with all of the critical stakeholders. and it's an ongoing process. guidances are not regulations with the force of law, but it helps provide especially when there is a more dynamic issue at hand, it provides a mechanism to begin an important conversation with a broader set of stakeholders and continue it to the final guidance. i agree with you that we should not have that many guidances in draft. i think that while the process of moving from a draft to a final guidance has value as well having the final guidance

is important and provides more certainty as we were discussing, so i hope it won't be me coming back before you, but i hope that soon, you know, we will be able to demonstrate what has been done with respect to some of those guidances that are in draft that may no longer really need to be and those where we can translate it into final and this is an area where frankly you know we are not the only ones involved in shapeing the guidance process and it does have to go through a series of other reviews before it can be published as final, but i take your point. >> one other question that relate to that point in a different way. i'm a victim of melanoma twice and the surgeon general issued a report saying it costs america 8 $.1 billion a year in health. it's a major portion of his recent statements. i hear little from the fda regarding that and we worked

hard on the sunscreen expedition act to try to expedite the ingredients to be approved for overthe counter sunscreen products. can you tell me why they are so reluck cant reluctant to follow through. >> we are committed to following through and preventing melanoma is a -- prevention comes first. we're committed to what was laid out in the sunscreen innovation act in terms of responding to the identified timelines and process. we do need to work with industry to get the data that we need to assess safety and effectiveness and that is of course because these products are used widely applied often and hopefully with the right amount, they're used chronically and they we need to understand about their absorption of these chemicals and what that means for safety and efficacy in the individuals

using them, including many young children who may be at greater risk in terms of chronic use, so, we want to move forward. we want to have the american people to have more options in terms of sunscreen products and the protection it can afford, but we want to work with industry to make sure the ingred yents in those work and that they're safe, especially for chronic use. >> my time is up, but i'd like to urge you to do everything you can to expea diet those approvals. thank you very much. >> thank you, senator. i'm calling on senators in order of seniority if they were here at the time of the gavel. senator bennett. >> thank you, mr. chairman. thank you very much for holding this hearing and thank you both for your leadership and dr. hamburg, i'm sorry to see you go, which i know is chairman feels as well and i'd like to ask a number of years ago the

colorado bioscience community came to me and said we can't raise venture capital anymore in the united states. it's all going to europe asia. a lot of that had to do with the -- as you know to team up with senator burr, senator hatch to write the breakthrough therapy legislation, a new leadership that is responsible for the, a lot of people thought there were only one or two drugs in that pipeline, but there have been 22 drugs approved as a result of that legislation and there are 55 more drugs in the pipeline as i understand it. it has succeeded beyond our wildest dreams. it's fair to say and i want to thank you for that. as you begin to leave and ask you to talk a little bit about the shift in the culture at the fda as a result of that designation and how we're quoinggoing to keep that going after you leave. >> well first, let me thank you

for the work that you did on breakthrough and so many other things and for inviting me to talk to your bio tech community in colorado and i've done it in many other places as well. including recently, massachusetts. and those kinds of listening sessions with the medical device and pharmaceutical and bio tech industries is incredibly important because we hear, we heard loud and clear early in my tenure yur and we looked at programses and how we could strengthen them. the breakthrough designation has been enormously successful as you know. more successful than we thought and it did not come with -- so, it's an example of something you want to be able to be able to extend, but it comes at a cost, but an incredibly important lesson that comes with breakthrough being confirmed is the value of early engagement by

the fda with the product sponsor to really help shape the product development and research agenda and then continuing contact and that has really made a difference. we see it in breakthrough, in other areas as well as we look at some of our recent approvals. we can see an informal analysis that when we engage early, especially pre ind, we can really help the product development process take critical time and cost off of their product development because we can really say you don't need to do that study, but do this study. use this approach because it will get to the answers that will really make a difference in our approval process, so i think that's been enormously exciting, but it does signal changes for the future in how fda organizes itself and how we work with the broader research and industry community. >> i hope that's right. i've heard the same thing from

developers of these drugs, they're saying they feel the fda is engageing with them in a more productive way. my hope is that medical quiss and other things going forward i would ask you one other question. over the last few weeks, we've heard about infections and even deaths in california and north carolina hospitals from cre, i apologize for my voice today, i'm glad there are two doctors. >> we don't always have the treatments you need. >> cdc has called a nightmare bacteria. another has been directly affecting our wounded troops returning home from iraq and senator hatch you and i know we've been working on relation to establish -- to treat serious and life threatening infections. legislation is is support of

antibiotic developers, public health groups and provider groups. your team has been enormously helpful in working with us on legislation. could you describe how this new pathway will protect patients' safety while ensuring the parpts who have unmet needs for antibiotics gain use to these important drugs? >> it's important as we face a world where resistance is is growing that we ensure we have new antibiotics in the pipeline especially for infections that are resistant to the available antibiotics. and we see increasingly outbreaks in many different settings including the -- where antimike robe yal resistance is cause causing a preventable burden of disease and death because we can't treat those infections. the pathway you're describing is is an important one because if you look at an infectious organism in the disease caused,

it can been quite hetero genius from more minor infections to the resistant ones. as you look across the whole spectrum of patients who are infected, you have a very different risk benefit calculation than if you focus on the more extreme serious life threatening cases where there's antibiotic resistance, so if we can develop a product that's targeted to that part of the spectrum, the risk benefit calculations can come into a clearer focus. f we know we need drugs and the risks can be higher because the benefits are higher in that context. we need to make sure that fi physicians using these drugs understand they're really being approved for a limited use, a special population and should be

labeled as such. but it will enable more products to be developed rapidly and then -- as they're in use and perhaps extend the indications for use, but it enable us to move more quickly off the dime and creates new incentives for companies to get involved because they can see a pathway that perhaps is shorter and more streamlined. >> thank you senator bennett. now, i have senator casse di whitehouse and warrens. >> one, great job. you've done a remarkable progress, thank you for that. >> thank you. >> you've recently put out your fda's transparency initiative ch i have tried to understand your agency, but don't understand it

as you, but it seems like there's different divisions that do different quality of work in terms of approving new applications and there are some which have higher turnover than others. i suspect those with lower turnover are the ones with better output. now, is there, i see that as a diagnostic. frankly, i think that indicates in those divisions with high turnover and lower output, there's probably some issue there that in management leadership, you name it, that is a problem. will there be more information regarding that so that we in oversight can look at that on a granular level trying to get a sense how your successor could perhaps improve those processes? >> certainly, the transparency initiative was a multifaceted undertaking intended to expand under undering of what the fda is, what we do, how we do it and why. but also to hold us accountable

in critical areas of activity and really post for everyone to see the progress we're making on critical issues. you're right, the different parts of the fda are functioning with you know, somewhat different performance with respect to aspects of their work. you know, it relates to both management and assuring that we have consistent, high quality management and oversight. >> but the resources flow between the two, so one division would it have far more resources than the other? >> not always because -- >> so if not -- >> we were talking about the user fees before. >> i just have limited time. back to my point because i have a question for dr. collins. if you could make that information more available, i think that would help us as we look on a granular level because that is our responsible tiility the provide that oversight. >> just one point there. the user fees are often targeted

to specific programs through a negotiation programs so they have a bit more flexibility and hopefully more predictability in terms of resources. >> i'm a doc and apparently dr. bennett doesn't want a gast row enterologist taking care of his cough. now, some of your mds and some go to ph.d.s. do you track what percent of the grants go on to ph.d.s and those which go to mds result in transitional research? is there a difference? >> we do track that. as you know, our workforce is made up of a variety of individuals with different backgrounds. pafd ph.d.s are the majority. in general, the mds tend to be more focused on translation or clinical efforts but some are doing basic science. >> i get that.

and what percent of the put it this way. that taxpayer wants translational research. i come from academics and some are content with write inging a parp but not necessarily looking forward the to translation. so, when you track, how much weight is given to someone's success in translation and if someone really successful in translation, perhaps not as good some place else, but really good with translation how much would that weight with their future being awarded? and if you have precise statistics, i would like to know what percent to have grants go to md phds or mds. how many are translated result in translational research, and if there is a difference, it seems more like we should wait to the md phd if their bias is

translation. >> i can provide that data for the record. we have of course encouraged translation at nih by the mounding of this new center, the center for advancing translational sciences, which is providing resources to enavailable the kind of science they might have trouble doing by themselves. so we're very focused on this. i would say we need to be careful not to discount the value of that fundamental basic science, which has been the mainstay of nih's suck says. >> i accept that, but i know there are some that don't have the entrepreneurial kind of next step and we can help with that. and that's, lastly, i'm just going to say this because i've said it before. in your testimony, you mentioned about the great success that we have had with hiv in terms of eradicating. i'll point out it still seems to be 10% of your budget and the dementia is what $800 million and hiv is 3 billion which is 10% of the bucket.

and cbo just released, our national debt, which they say by 2025 will be 77%, which they say is dangerous to our future. knowing that we're going to go into a period of strained resources because of our last six years escalating national debt i would again push that if hiv aids as you mentioned, is substantially addressed still problems, but substantially, and dementia is a balloon medicare and medicaid are just going to go bankrupt dealing with this. we should start shifting more aggressively resources from that which has been addressed to that which we are confronting. >> thank you senator. >> thank you both for being here today. we tend to have a lot of small

entrepreneurial companies and i'm concerned that when there is fda or other regulatory disadvantage that a company must bear to bring a product online, that hits a lot harder on the small company than it does on the big one. i know i notice that in the accelerating medicines partnership, all the participant participants seem to be the big manufacturers and obviously, if you're a big manufacturer a world in which only big manufacturers can succeed is a good world because you don't face disruptive, so you're probably not going to get a lot of objection. how do you push back against the incentive of big manufacturers to squeeze out little onings and

make sure that little manufacturers get the attention they need and are included in these types of process and are helped through your process? as i mentioned, accelerating medicines partnership, start with you, dr. collins and ask dr. hamburg is same thing. >> i appreciate the question because we are very much in support of the idea that all the partners in this ecosystem need to flourish in the public and private and aims to try to do that by making all the data immediately accessible to efrk and recognize that the pharma's taking part pay for half the cost, over five years, half from nih. all sitting around the same table to design the process, so, it should empower everybody. what we learned through this process and making data

accessible. that would be the only way nih could see this as something we could support and the companies have gone along with it which is quite impressive on their part. in terms of other things, we have a vigorous small business program that supports a lot of start up birks io tech companies and i could cite you a number of stories that are highly profitable that started out on the basis of an nih grant and we are increasing our support of sbir proposals and shortening our timetables. we need that initial infusion of grant cash to do the experiments, so we're very invested in this space. i think probably one of my relationships in terms of working with the industry is the bio organization, going to their meetings every year, listening to their concerns and being synergistic with the whole effort they're trying to mount in terms of finding new cures,

devices and diagnostics. >> where there's a controlled pharmaceutical, the dea has a process that begins at the end of the fda process. that delays the ultimate approve. to my knowledge, ga has never come to a conclusion that is different than the fda's conclusion. which makes me wonder why we put that additional demand on the process if the outcome is inevitable so if you could talk about those two things, the da process and making sure that small providers have a shot up against the big guns. >> try to be quick. on the maul business question, it's a very serious area of focus and concern for us because many of the medical product companies we regulate are small on the medical device side and in the bio tech world and as dr.

collins noted, often, they are one product approval and or a few weeks away from going under. but yet that's where a lot of innovation occurs. we have tried both to streamline our regulatory processes and provide more outreach and assistance through the process for small businesses, to help with that process, to be more responsive and provide that additional clarity. we also, this is one of the reasons why this investment regulatory science is is really important because there are common tools and approaches that can be used by smaller companies that can't make the same investments whether it's in the bio markers area or the -- we are working on small business, high priority. dea, it's a complicated system. it's really not one we've put in place and would it be the way we

would structure the process if we were starting from scratch. we make our decisions based on public health and medical care. and our perspective doesn't always align with dea. we do try to work closely with them. in critical aspects of making important drugs available for people. and in appropriate oversight of the use of scheduled drugs, but i would be disengeneral yous if i said i didn't see some of the disconnects you've seen and i think it might be an appropriate time to look at how best to align these different players in an important area of work. >> thank you. >> thank you, senator whitehouse. senator collins and warren. >> dr. hamburg, first let me thank you for your service. you and i have discussed many times, the technological breakthroughs that are making a real difference for people who are living with diabetes.

and an example of that is the continuous glucose monitor, which is helping patients control their blood glucose levels, which is key to preventing costly and sometimes deadly diabetes complications. the nih and fda have been extremely supportive of these innovations in diabetes care and that is why i was so surprised and troubled when cms decided that it would not reimburse or pay for insulin dependent medicare beneficiaries to continue to have their continuous glucose monitors so we have a situation now where an

individual with type i, who is covered with private insurance gets to be the age where they age into medicare and they lose the coverage for the cgm. this has led me to question whether cms consults with the fda and nih in making its coverage decisions. do they consult with you and were your two agencies con ultimate sulted in the case of this denial of coverage? >> i have to tell you, i was not aware of this situation and i can see why it's concerning to you and i think we're going to have a lot more important breakthroughs in terms of medical devices and new treatments for diabetes that will make a difference. we work with cms. we can work more with cms. we've done some pilot projects with cms to look at how can we do some of our decision making

in parallel rather than in series so that as data is being collected in the product development space, data that will meet the needs of both agencies can be gatheredened examined. you know, there are obviously decisions with cms on various specific products. and as i said, i think you know in our modern world, we need to do more of that. i would also say your point speaks to an issue that's been a high priority for me and that i leave fda feeling like we still haven't adequately addressed. which is that we have to look at the whole ecosystem for bio medical product development and use and recognize that each of different components that often operate in silos are very interdependent and one of the things i'm hearing now more and

more from investors is that it's not the fda regulatory process that's worries them. it's reimbursement issues and getting that right, so i think we really need to take that ecosystem approach. >> thank you. dr. collins, i'm going to switch to a different issue because of the interest in time, but i hope you'll respond for the record to my question. >> happy to. >> thank you. you put up a fascinating chart in which you show the tremendous progress that we've made with cardiovascular disease, with cancer deaths and with hiv aids. and what they all have in common is congress has made a sustained investment over the years in nih research and it's paid dividends in better treatments and in falling death rates. i am as you know very concerned about the trajectory of

alzheimer's disease, which is fast becoming our most costly disease in this country. as a society, we spend $226 billion a year caring for people people. out of that, 153 billion comes from the medicare and medicaid programs as dr. cassidy says. the trajectory is frighteninging, it's going to bankrupt our health care system and it's causing such suffering for the victims and their families. i know you mentioned the amp and the brain initiatives and i'm excited about those. but shouldn't we be doing even more to do a concerted effort targeted attal simers given the trajectory?

>> i appreciate the question and share the concern when you look at the cost and care of individuals afflicted, not to mention the suffering their families duothrough, that swrid go through. we are on a trajectory that anybody has to be deeply concerned about. we are certainly ramped up research at a pretty unprecedented rate. between 2011 and the president's proposal for 2016, there will be a 46% increase for research, greater than any other area nih supports. is it enough? no. frankly, we don't have enough that i could argue to support all the ideas and lots of other areas. the good news is that research is in a very exciting place. that we do have new ideas. we have the able to do drug screens on cells growing in tissue culture that represent the disease compared to normal in a way we would not have

dreamed to have that ability as a model. these are human cells. we can really start to figure out how to address therapeutic in a rational way and there's a lot of excite nmt the field about seeing that go forward. we are doing everything we can to find those partnerships. amp is one of them to make sure we're building and the patient advocates are a wonderful group of supporters, but frankly, it is an example of the fact we've lost about 23% of our purchasing power for research since 2003. we need to be able to get back on a stable trajectory. that would deal with a lot of other things that are looming out there as our population ages. >> thank you very much. >> thank you senator collins. senator warren. >> thank you, mr. chairman and thank you, dr. collins dr. hamburg for being here. i want to say as others have thank you, doctor, for your many years of service. the nation owes you a great debt. over the past 50 years, the american system of medical

innovation has transformed the health of literally billions of people around the world. new treatments have given hope to people diagnosed with leukemia leukemia, hiv, breast cancer and other diseases that were once a death sentence. the basic mechanism for those remarkable achievements has -- that turn that into viable products. of the 21 drugs with the highest therapeutic impact approved between 1965 and 1992 two-thirds stem directly from discoveries made through government supported research. a recent study in health affairs found most of our truly transformtive modern drugs have their roots in public funding. this is no accident as we've talked about here for decades. congress grew the budget of the national institutes of health year by year. in the late 1990s, both parties

worked together to double the budget for nih. since 2003, the budget hasn't kept up with inflation. its purchasing power is down nearly 25%. can you tell us how the collapse in congressional nih funding has hurt the american pipeline of bio medical innovation? >> thank you for the question. because this is the thing that worries me most and keeps me up at night is that we are not taking advantage of the remarkable abilities of american science to innovate to come up with new ideas that prevent and treat disease. one can simply look at the way in which nih has to deal with the ideas that come to us and basically leave about half of the ideas on the table that traditionally, we would have funded and that tells you what we're doing here in terms of slowing down the process of innovation. all the way from basic science through to clinical trials.

and you might ask, well maybe the part we're leafing on the table is not as good as the stuff we're funding. we've fwal looked at that. and because when you look at the top third of applications, this is the really great science we can't retrospectively go back and say that those that scored in the 25th% tile weren't as good. they're indistinguishable. that says we are leaving great stuff. and we are of course the foundation in many ways for this wonderful success story of american science, which is public and private working together and what we discover has led to those breakthroughs that now people take for dwranted but we can't keep taking for granted. >> first priority here would be to figure out how the nih, the resources it needs to replenish the pipeline that is the foundation for better treatments

and reliable cures, but instead congress is focused on whether we lower the fda's standards for approving drugs. i hear the arguments, but this is a dangerous game. vioxx made it through the fda's process, but was later found to cause heart attacks. by one estimate, it killed 38,000 americans before being pulled from the market. dr. hamburg what impact would lowering the fda's safety and effectiveness standards have on public health? >> i think lowering the standards would be very, very dangerous. detrimental to health and safety of patients, bad for the health care system, but also bad for our wonderful preimminence in terms of our pharmaceutical bio tech and medical device industries in terms of their

ability to actually deliver products for people who need them. we know that fda standards and our requirements around safety and efficacy over thes years have helped to shape how research get done. this notion of really structuring our investments and research, we don't just publish papers, but we make sure that we're leveraging the opportunities in science and technology to get important treatments preventive strategies and cures. >> so, you're saying if ip understand it, the high standards are important not only for public safety but also for help shaping the research that's going to give us the treatments that we need. >> absolutely. >> i just want to say i am certain there are changes we could make at the fda to help speed up the approval process and get rid of unnecessary bure ok oksy when science sporlts change, i am eager to make change.

but lowering fda's approval standards will not increase innovation. we could abolish the fda tomorrow and we'd see tons of new products on the market but the goal isn't new products. we don't want another vioxx. the goal is innovative, transformtive products that are safe and effective that will cure diseases save money save lives and to achieve that goal, we need to start with the nit. nearly everyone in congress says they support funding that agency. but talk is cheap and congress has decimated the nih's budget. single handedly choking off the projects that could lead to the next breakthrough in many other diseases. we could dismantle the fda, but that won't produce new cures for the diseases that maim or kill us, if we're serious about

better health for children and seniors, then congress has to step up and make a real commitment of real dollars for scientific research. >> senator baldwin. >> thank you, mr. chairman and ranking member. i am encouraged by this bipartisan effort to examine the entire discovery and development process for medical treatments. as someone who was raised by her grandparents and my grandfather was an nih funded scientist at the university of wisconsin madison, you can understand that i have a long-term passion for a strong, strong federal investment in basic research. but i remain concerned that budget cuts mandated by the budget control act has put medical research at risk. in fact, we've been talking about that this morning. in fact, dr. collins, you have cautioned that we are putting an entire generation of scientists at risk.

the average age of a researcher receiving her or his first grant is increasing. and budget cuts are discouraging young scientists from entering the field or forcing them to in some cases, leave the country in order to continue their research. to help address this last congress, i introduced the next generation research act that would coordinate efforts within nih and streamline current programs to improve opportunities for new investigators. it would also promote new policies to help increase diversity and improve the success of investigators who are applying for their second grants. dr. collins, we've discussed this issue a number of times before and i'm encouraged that you share that interest and passion here. can you please discuss with the committee any progress that has been made through nih's existing

programs such as the early stage investigator program and the director's new innovator award to bolster this emerging research workforce? >> i really appreciate the question because this is such a fundamentally important issue if we're going to have a future where american medical research continues to flourish. we have in fact instituted a number of programs that are aimed to try to encourage that to see a path for themselves as successful and visionary researchers. one thing that has been helpful is to make sure if you're an early stage investigator who hasn't come to nih before with a proposal proposal, that you compete against others of that sort as opposed to being thrown into the main pool with others who have been at this for a while and that has done quite a bit to equalize the success rates very those who have been in this

business. that is one thing. another thing we've done is to increase the number of awards which are a bridge to independence. which we are finding to be a very successful way to make that leap from a training position to an independent faculty position in a research intensive university. we're making sure we have our graduate students exposed to multiple career paths because not all of them -- in an intensetive university, jobs and industry, jobs in policy and journal journalism and we want to be sure people find the right match for themselves. we have started new programs and early independence award, one i'm quite excited about, which basically allows a very talented

phed. it's the most exciting day of the year for me because their vision and their ideas. similarly, we have this new innovator award where you can apply if you previously -- and your idea has to be out of the box, a little whacky for you to be allowed to apply nor that proposal and when we look at the output of that, it has been truly impressive. all that is great but it doesn't solve the main problem we have, which is the loss in purchasing power in research. we can try to protect those young investigators. we need to turn the corner. >> i appreciate that and you know, resources are obviously key to this as well as the coordination of programs that we've discussed in the bill that i've introduced and will be shortly reintroducing. the flip side is what would be

impact be of nih's current programs for new researchers as well as the impressive new initiatives if congress should not reverse sequestration? >> i think we continue to see this downward curve, which is troubling indeed. surveys have indicated close to 20% of researchers supported by nih are not contemplating moving to another country or kind of career path because of the concern they have. i just spent last week, i was in san diego. i met with the md training students in so-called medical scientist training program. there was a room full of the most incredibly gifted, talented future physician scientists you could imagine. in the past when i've met with groups lib that ten years ago, it was all about the science and how excited they were, but this was a group who's brows were furrowed. that's what i meant to say who

were really deeply anxious about whether there's a path for them. their questions weren't so much about science as to whether i could give them a sense of optimism about their future. i tried, but it wasn't as easy as it should have been given the talent in this room. >> senator casey. >> thank you, mr. chairman. >> these are deadly serious issues, about the impact of funding given the impact of funding. and sometimes, it comes down to one name, one person, one case. there's a young girl in pennsylvania, 9-year-old, who thankfully is healthy right now. emily whitehead, who had a particular kind of leukemia and

the only way her life was saved was because of an experimental t cell therapy pioneered by folks researcher, i should say, nih funded researchers at children's hospital in philadelphia. i have to ask after these debates about funding levels, which frankly are rather bizarre when you consider the outcomes, positive outcomes that we have through nih, have to ask what if down the road because we didn't make the investment because congress failed, would the next emily whitehead be saved? so, i think it's worth not just contemplating, but using those examples as a spring board to action. dr. collins, i just want to go back to something you mentioned before. and i know it's by way of reiteration, but it's important to repeat ourselves around here. you'll get the message a little better. did you say that nih has lost

23% of its purchasing power since 2003? is that accurate? >> that is accurate and i can show you a graph that will make that more clear. if you look at the yellow line, that is the budget adjusted for effects of inflation. you can see the doubling up to 2003 and the steady deterioration since then and that adds up to about 22, 23% loss in purchasing power over the last 12 years. >> and the other part of this, this is one i had not heard. the percent of those contemplating moving the u.s. because of the either lack of funding or i guess it would be uncertainty regarding funding, what percent of that is resernlers? >> in this particular survey, it was 18% who said they were significantly contemplating that kind of drastic step. i really appreciate your raising emily whitehead as an example of

what we need to have more of. i met her in the white house. senator alexander was there as well. emily was there for the announcement by the medicine initiative as was her doctor, carl june. this is the kind of amazing success story that we believe is out there in greater numbers, but we have to be sure that we're investing in all of the steps it takes to get there. what happened with emily you can trace back 50 years of hard work understanding immune system and understanding cancer. ultimately getting to that point. it didn't just arise out of nowhere. >> doctor, i wanted eded to ask you about the president's initiative, the precision medicine initiative. in that, in the context of emily and other children, tell me about how that can and any other undertaking or initiative that nih will be involved in, will focus more on the pediatric research the pediatric research at least of those breakthroughs.

>> well, the precision medicine initiative aims to have an early focus on cancer and a longer term effort to try to build this million strong cohort across the nation, to try to take advantage of a ko les ens of really exciting technological opportunities. one is of course the genomic revolution, to get information about dna at a low cost. another is the advent of electronic health records which is now the norm in many health care systems. the other is the able tiility to use wearable sensors to detect various aspects of human physiology. whether it detects blood glucose or something that is monitoring your environmental exposures or your diet blood pressure. across gender geography we

could really begin to figure out what are the risk factors for disease and what can we do about them and how can we monitor and treat chronic disease more effectively. having that very large scale effort this is a joint effort between nih, our partners at fda and the folks at onc involved with electronic health record. we're excited about the way this could transform our understanding of bio medicine. >> can i just add one brief comment? i just want to underscore that as you think about what can be done to really harness the extraordinary advances in science that are occurring today, and the resources that nih so rightfully needs and desperately needs to ensure that important work basic clinical and translational gets done, that you not forget that in order to see those products, those ideas become real world products, it has to be

accompanied by appropriate investments in fda that give us the opportunities to develop our area of science to afford that final bridge to a real world product and to help make sure that the investments and the research at nih are being done in the most efficient and streamlined way as they are trying to actually move that product through the development pipeline into the product and one of the disconnects that worries me a lot and i'm sorry but i have to say it that everyone thinks that if you want to deliver on the promise of science, more investment in nih, that is critical and foundational, but you do not want an fda that isn't fully equipped to oversee the products that are coming before them that isn't well staffed to do efficient, modern regulatory reviews and you want to be able

to bring the knowledge and expertise of the fda and product development into these early stages. >> i heartily agree with my colleague and would like to endorse and would endorse everything she just said. >> thank you for your indulgence. >> thank you. >> thank you mr. chairman for calling this hearing and thank you to you both for your service and dr. hamberg and thank you -- working closely with you on a couple of things and thank you for your service and we are sorry to see you go. one of the -- and i also apologize for just getting here. i had a hearing in judiciary that was also very important. i'm proud to represent minnesota, as you know, dr. hamberg. and our medical device industry. and we've spent some time working together.

and when i first got in this job and had some -- dr. sherwin came to minnesota and had some discussions with the industry, round tables with him and i noticed a kind of a different culture between the regulators and the device manufacturers and i wondered why that would be. and a life science alley along with the fda, did something i think for the first time ever, a private-public consortium on regulatory science. and i just want to know -- ask you, how you believe that is going. it -- the name of it escapes me. >> medical deviceino vasive

consortium mdic. >> yes. how is that working? >> it is an example of the kind of thing we can and should be doing. as you know, bringing together private industry academic searchers, not for profit organizations and government together under one organization that is committed to advancing the regulatory science needed to advance medical device development. it has grown enormously since it was started. there was initially some skepticism perhaps. but it has grown. and it has identified critical areas of research whereby it will benefit medical device development much more broadly because it is doing things like helping to design innovative

clinical trial approaches that will make the clinical trials less cumbersome and making it easier to develop safer and efficacy and developing models and other simulations where without the cost -- the time and the potential risk to patients you can examine whether a device will work and how the design should be tweaks et cetera how can we better integrate patient-reported outcomes and their experience of using a device into the development and review process. so focusing on some of the most important issues before us doing it in a way that advances the science and doing it in a way that creates knowledge that becomes a common good for other product development in the future. >> thank you. and glad that it -- we're proud of that private-public partnership and that it is

working. i want to talk a little bit about precision medicine and what it has done. and sometimes when i think about precision medicine i think i was born a little too early. i think of all -- what things will be like 20 30, 40, 50 years from now. let's talk about ldt's. the university of minnesota has developed a panel of more than 1200 genetic variations that can be tested for -- to identify risks for specific genetic diseases. the mayoin click in rochester minnesota, has made significant progress in identifying ldt's but something not thoughtful or

careful enough could hamper the potential of ldt's undermine the target of root causes of disease. i applaud the chairman and the ranking member for working with the fda and industry efforts to hold a series of briefings on this relatively new topic. but dr. collins, i would like to know what role nih will have in advising nih for ldt's and to what extent you are engaged with one another which i think senator collins talked about, no relation, and what is your view on how the two agencies should work together for safe and effective technologies that is ethical and safe for patients without interfering with the innovative work you are doing. >> thank you for the question. and this is a way nih and others

are working closely right now to accomplish what you said, to make sure that the kind of laboratory developed test in the field of genetics where things are growing so quickly are offered to patients in a way that benefit them and doesn't slow down innovation but has appropriate oversight particularly in high-risk situations, where a false result can lead to decisions that can be quite harmful. fda released back in the fall guidance on risk-based oversight of laboratory developed tests. we think that is a thoughtful document that has now become the fundation for multiple -- foundation for multiple workshops, including one february 20th held on the nih campus to try to get additional input about this. what we can do that is turning out to be a nice partnership in a specific way is we have already a data base called clin var that is across what has been

reported as far as this dna innovation with this particular disease or disease risk. so that data base is being curated in ways people can find the information. but you can't look at that and know which you can rely upon and be a result that one person found and another one you can't. and a group we called clin gen clinical clinical genomics, and looks at whether a particular variation has been shown with a medical risk, like a mutation with people with breast cancer and with a certainty and what they think about the whole set of variations. fda is very interested in that particular nih-funded effort for them to be able to have expert advice about what you can trust and what you can't. but we're not the regulators. fda has that role.

this is a great opportunity for our relative roles to be nicely inter-dig tated and it will be critical for medicine as we see more of this playing out with this cohort of people as we play information back that it is right and they can trust it and reviewed by experts and the regulatory agency. >> and dr. hamburg and since this is your last hearing in your current capacity would you like to have the last word on that question or any other question before we wind the hearing up. >> on that question i would just say that the world of diagnostics is complicated but it is very important because at the end of the day, it is what guides the ability of a health care provider or a patient consumer to make sure they are getting the best possible treatment for the condition that they have. it also -- having accurate

reliable diagnostic tests is crucial to doing the fundamental research that will reveal the opportunities in treatment, prevention and care. because if the test is inaccurate, all of that research isn't going to mean much. so we think that at the core of all of this, it is our responsibility to make sure that diagnostic tests work. whether they are laboratory-developed tests or much more advanced nick generation sequencing which dr. collins was talking about using diagnostics to give us vastly expanded information so one diagnostic tells you about thousands, millions of variants and not just one diagnostic disease, but at the end of the day our goal is not to create unnecessary regulation but to assure the american people their health care providers and the companies that make these products that when a product

goes into the market place it will do what it says it will do and, in fact, that kind of regulatory foundation is common sense, it also is what enables innovation to be driven forward. because when you have some tests that aren't held to the same standard as other tests then the incentive for those who are coming from the device -- the traditional device industry developing fda-related diagnostics, incentive for them to stay in the business when someone else can create it without market and review is problematic. so it is kind of an interesting example of why things get very complicated but at the end of the day the fda role is to help speed innovation to patients who need that innovation but we want innovation that works and innovation that will make a difference in promoting and protecting their health and that will benefit our