Transcripts For CSPAN2 Medical Product Development And Innovation 20180109

Good morning. The cynic in me to help education letter pensions will please come to order. This is another bipartisan hearing which is what most of our hearings are which means senator murray and ive agreed on the subject and on the witnesses. In fact, i would say every member of this committee would probably agree on the subject and a witnesses today. Because this is hearing entitled implementation of the 21st century cures act, progress and the path forward for medical innovation to from dr. Francis collins, the director of the National Institutes of health, and dr. Scott gottlieb, the commission of food and drugs. Well have some mention as senator murphy will have a hearing next wednesday on another important part of the cures act which was the first reorganization of our Mental Health laws in a decade which senator cassidy and senator murphy played a major role in. We look forward to that. Senator murray and i will each have an Opening Statement and then well introduce our panel of witnesses. After our witnesses each senator left five minutes of questions. I expect we will have a large number of senators coming and going to this hearing. In 2007, doug oliver, who is in the front row i believe, a computer programmer, begin to have trouble seeing, and after a near accident had his drivers license taken away and was declared legally blind. The culprit was a rare form of macular degeneration. Doug moved to nashville, where his doctor at the Vanderbilt Eye Institute told him that while there were no cures, doug could Search Online for a Clinical Trial. Doug found a Regenerative Medicine Clinical Trial in florida, where doctors took cells out of the bone marrow in his hip, spun them in a centrifuge, and then injected those into his eye. Three days later he began to see. His eyesight eventually improved enough to get his drivers license back, and enough that he became an effective advocate for more support for Regenerative Medicine, which we included in the 21st century cures act. Earlier this year, doug gave me the cane hed used while he was blind. He said i dont need anymore. So i treasure it and the keep it in my office and i think it for his advocacy and we hope others have the same advantage. When Congress Passed the 21st century cures act, we hoped to unleash medical innovation and give americans more access to lifechanging treatments and cures, so more americans could experience medical miracles. It is especially appropriate to be having this hearing today because it marks the oneyear anniversary of the Senate Passing cures. When it became law last december, i said that president obama had signed a second christmas miracle. The first one in 2015 was the every Student Succeeds act, the law fixing no child left behind which came from this committee. Last year, it was the 21st century cures act, which majority leader mcconnell called the most important legislation Congress Passed last year. I have often said of the every Student Succeeds act that a law is not worth the paper its printed on if it is not implemented properly. I intend to ensure cures is also implemented properly, and this committee began our oversight hearings on cures with a hearing in october on the Electronic Health records provisions and, in addition to todays hearing, we will continue our oversight with another hearing on the Mental Health provisions next wednesday. Today we are hearing from dr. Collins and dr. Gottlieb on the provisions related to Biomedical Research. We are fortunate to have two talented leaders who know their agencies, are widely respected in congress, and capable of getting results. It doesnt always happen. Sometime ship capable leaders and they dont have any money or they dont have new authority. Sometimes your new authority, new money, and the leaders of have a clue what theyre doing. In this case weve got new authority. Weve got new money and we got to the most capable leaders we could have. So were delighted with that. While the legislation included provisions to improve Electronic Health records, resources to fight the Opioid Epidemic, and the first update to Mental Health programs in a decade, the major purpose of the legislation was to provide Additional Resources and authorities to speed drugs and devices through the research and Development Process into Doctors Offices and patients medicine cabinets, while ensuring the fda Gold Standard of safety and efficacy. It is not an overstatement to say that the 21st century cures act has the potential to affect virtually every American Family by taking advantage of breathtaking advances in Biomedical Research. Dr. Collins, at a Senate Appropriations subcommittee hearing in 2016, you have offered bold predictions for future Major Medical advances if we continue funding nih and ensure fda has the tools it needs. One prediction is that scientists will find ways to identify alzheimers before symptoms appear as well as how to slow or even prevent the disease. Alzheimers causes untold family grief and costs 259 billion a year. Another prediction is using a patients own stem cells, doctors could rebuild his or her heart. This personalized heart would make transplant waiting lists and antirejection drugs obsolete. And put doctors like former senator bill frisk out of business. Dr. Collins, you have made other predictions that are equally breathtaking. The development of an artificial pancreas for diabetes patients a zika vaccine, a universal flu vaccine and an hiv aids vaccine available within the decade. New nonaddictive pain medicines to help patients as we continue to battle the Opioid Crisis that kills 91 americans every day. You said this week and another hearing that might happen in as soon as five years. The 21st century cures law put in place policies that will fund Biomedical Research at a time of limitless opportunity to help make dr. Collins predictions a reality. Today, i want to find out find out from dr. Collins and dr. Gottlieb, those leading this charge, how implementation of the law is going. For example, cures included a surge of onetime funding of 4. 8 billion for the National Institutes of health, including money for the Precision Medicine initiative, cancer moonshot, and Brain Initiative. I know from talking with Vanderbilt University that the Precision Medicine initiative, the plan to map the genomes of 1 million volunteers to help researchers develop treatments and cures tailored to a patients genetics, environment, and lifestyle, has already begun enrolling patients less than one year after the program began. In addition to pmi, i am curious how the funding has been spent, and when and how you plan to Keep Congress informed of your results. Cures required a process to look at burdensome regulations on researchers. I would like to hear if this is helping researchers spend more of their time and money on research and less on administrative tasks. Cures also put in place policies at the fda to move safe and effective treatments and cures through the regulatory process more rapidly and at a lower cost. For example, senators burr, bennet, and hatch worked on a breakthrough provision for devices, modeled after a breakthrough provision for drugs. The first breakthrough approval was just last week for an exciting cancer diagnostic. Senators isakson and casey worked on removing red tape from the review of combination products. And i worked with senator murray to make sure fda had the authority to hire and pay scientists to keep up with the rapid rate of innovation. 21st century cures also added 30 million to support Regenerative Medicine and an accelerated pathway for these treatments at fda, so we can hear more stories like doug olivers. Fda has begun implementing these provisions and i look forward to hearing how fda and nih are working together to make sure the funding and authorities for Regenerative Medicine are helping to advance this important work, while ensuring bad actors do not take advantage of the hope of this exciting field to harm or defraud patients. It is going to be difficult to cover everything today, but i look forward to hearing about the progress being made to unleash medical innovation and bring new drugs and devices to patients. Senator murray. Thank you so much, chairman alexander and welcome to our guests today. Thank you for joining us, dr. Collins. Good to have another opportunity this week to talk to you again about the work in debt at an age. Dr. Gottlieb, welcome as well. Im looking for updates from fda. Next week marks the one year since the signing of the bipartisan 21st century cures act. And as i said at the time of the passage and i will repeat it now, as much as this law helped to build on americas tradition of leadership and lifesaving Public Health initiatives in medical innovation, cures was really first and foremost about providing hope. Hope to millions of people and families who are impacted by illness and disease, hope for our communities suffering at the hands of the Opioid Epidemic, for example, and like all of my colleagues including our guests today this crisis is something i hear about everyday. And i visited with countless communities back home in my home state of washington that have been devastated by addiction. So while we know we can and must do more, im glad that youre cs took an important first step and dedicated over 1 billion in new funding above and beyond the budget caps to states and communities by back against that crisis. We secured important changes to ensure this money went directly to states that need it the most. For far too long our Health System has their patients and families seeking treatment and support. That is why in cures we prioritized expanding access to quality care for Mental Illness and Substance Use disorders. We strengthened coronation between local agencies, gates in crisis intervention. So i looking forward to discussing that work further at a hearing we are next week. On todays topic im proud of her work in cures to address headon some of the hardest to treat diseases by providing nearly 4. 8 4. 8 billion in fug for the nih, including support for the beau biden cant a man shot and a Precision Medicine and Brain Initiative. All of which i would note are very important to my home state that we are spiriting much of that new research taking place as a result. Along with these investment we included provisions in the law to equip nih with the tools and authorities needed to meet the demands of Biomedical Research in the 21st century. We made it a priority to improve the inclusion of women and children and other underrepresented populations in Clinical Research so that the promise of these initiatives like Precision Medicine are extended to all patients. As part of this work i championed a provision that creates task force to better support the evaluation of drugs for pregnant and lactating women, and we addressed many of the concerns that have been Holding Back Progress in the Research Community by supporting young researchers and reducing the red tape. Cures also made sweeping reforms to fda, and one of my Top Priorities was granting the agents greater hiring authority to recruit and retain qualified individuals who understand the latest science and technology. Im interested to get an update from you dr. Gottlieb on how you are filling the positions, especially in of the hiring freeze issue is mandated by the president. We also made sure cures give fda the authority to ensure medical devices like are safe for patients. We gave more clarity to developers of drug device combination products and codified key provisions in the Prescription Drug user fee agreement, including to ensure patients are included in the drug Development Process. Im glad we have the opportunity today to talk about the ongoing implementation of cures and i will be very focused on making sure we are committed to strong congressional oversight, rejecting this administrations efforts to roll back and undermine patient protections, and doing more to provide strong investment needed at nih and fda not just to support cures, but also to advance 21st century science and innovation. In general im glad nah and have been active and timely in the permitting the law including many provisions i just talked about. Im encouraged by these efforts. I want us to keep moving in the right direction. Dr. Collins, in light of the extremely concerning direction the Top Administration has taken when it comes to health care, especially in regards to womens health, i want to hear more about what in ages and to bolster your researchers work to further science over extreme ideology. Dr. Gottlieb come during her confirmation hearing you said the 21st century cures act is a good roadmap for what you hope to accomplish as commissioner. I would like to hear about how you fda are pushing back against this administrations the regulatory approach and making sure cures is implemented. Specifically, i will be asking more about what fda is doing to ensure the medical devices patients rely on are safe and effective. Again, both nih and fda have made important steps in implementing and beating cures deadlines this year but we have a lot more deadlines coming up in 2018 and since we know funding remains an issue under 40 hearing from each of you on how we can make sure that were truly putting patients and families first. So again welcome to both of you. Thank you for being here. Thank you, senator murray. Each witness will have five minutes to give his testimony. First witness will hear from is dr. Francis collins. Hes been director of the National Institutes of health overseeing the work of the larger support of Biomedical Research in the world since 2009. The second witness will hear from is dr. Scott gottlieb. Is commissioner of food and drugs, ensuring our drugs and medical devices are safe and effective. He was formerly Deputy Commissioner of the same agency. He was confirmed on may ninth of this year. Welcome again to our witnesses. Dr. Collins, lets begin with you. Good morning and thank you, chairman alexander, Ranking Member murray and other distinguished committee members. It is an honor to be today with my college dr. Scott gottlieb the commission of the fda. As you one of the 20 futures act aimed to catalyze a very important goal shared by all americans, to speed the pace at which scientific discoveries are translated into lifesaving treatments and cures. We at nih actually really appreciate your leadership in passing this bipartisan act by a vote of 95 4 innocent exactly one year ago today, december 7. This enhances authorities and resources in ways that will help us to achieve this goal. Many thoughtful provisions are clear in the act such as reducing administrative burdens so our site is can do but more of the time to research, expanding our ability to award a prize for exceptionally creative ideas. And strengthening measures to protect patient privacy. In my written statement i submitted a comprehensive report on at nih has worked quickly to limit the provisions of the act. We are motivated by sense of urgency to the patients in need of breakthroughs. In my oral statement i would like to focus on the cures innovation fund. Among the vital areas of ni h supported research being accelerated by the Brain Initiative, the cancer moonshot, the Regenerative Medicine Innovation Project, and the Precision Medicine initiative. Lets begin with the Brain Initiative. This pioneering effort is aimed at revolutionizing our understanding of the most complex structure in the known universe, the human brain. In fiscal year 17 fiscal yeard our cures innovation funding with her annual appropriation to launch no less than 110 exciting new Brain Research projects pick some of these will develop detailed maps of neural circuits, others will create a synthesis of the cell types in the brain and still others will create powerful new tools to monitor and modulate brain activity. This will advance efforts to develop new ways of detecting and treating and preventing miniseries Brain Disorders including alzheimers disease, parkinsons and schizophrenia, autism, drug addiction, epilepsy, traumatic brain injury. A Second Research area, the cancer moonshot, is aggressively pursuing every ambitious goal, to accelerate advances in cancer prevention, diagnosis, treatment and care. To achieve that we must take a right of innovative steps and that includes enhancing the Research Infrastructure by creating a Clinical Trial network with an unwavering commitment to data sharing and intimate Cancer Treatment programs forward more rapidly. In another of these innovative moves come nih recently joined with the fda and with 12 Biopharmaceutical Companies to launch the partnership for accelerating cancer therapies, or packed. This Public Private partnership will initially develop biomarkers to speed the department of cancer immunotherapy is an exciting approach to treatment that unless the patients own immune system. Recently weve seen some amazing responses to catch a immunotherapy that we need to bring that kind of success too far more people with more types of cancer and do it quickly. They cures innovation fun with the support of this congress is helping to make that happen. The cures act also provide support for Regenerative Medicine research. This emerging area of science involves the use of cells and other technologies such as engineered biomaterials and gene editing to repair or replace damaged cells, tissues or organs. As a result of the cures act in hs launched the Regenerative Medicine Innovation Project. This recently made eight Clinical Research awards covering a Broad Spectrum and going will be on the funding specifically provided by the cures act. Some are focused on, disease including diabetes and vision disorders such as the one that afflicted doug oliver you referred to earlier. While others are rained at more rare condition such as Sickle Cell Disease and idiopathic fibrocystic partnership with the fda we are hosting a major workshop actually right now beginning yesterday and going all the way to today to explore the state of Regenerative Medicine research involving adult stem cells. We spoke at this workshop at the beginning of yesterday morning. This conference will inform our future Research Direction by helping us to identify the areas of greatest scientific and therapeutic promise. And finally i want to tell you how thrilled again that you support the Precision Medicine initiative, pmi, stop by including an authorization and funding in the cures act. The centerpiece of pmi is the all of Us Research Program which will enroll 1 million or more americans from every walk of life. These volunteers will contribute their health data in many ways over many years to create a Research Resource that will catalyze a new era of Precision Medicine. This is an ambitious goal and we know nih cannot succeed on its own so all across the nation nih is teaming up with the veterans administration, help provide organizations Health Data Center at vanderbilt and other groups to pick up the best way to recruit participants especially those that are traditionally underrepresented in Biomedical Research. Nih has partnered with five companies to create a participant technology center, and our partners are testing how wearable devices like the ones im wearing today may provide easy ways for all of us volunteers to contribute data on physical activity, sleep, heart rate and so on. Getting all these borders on board one of the nearly impossible had not the cures act included of the Transaction Authority, ota, or pmi could make it possible for an h to move forward with unprecedented speed and flexibility to carry out beta testing of all the many component and we are now scheduled to launch fully in the spring of 2018. A similar growth in a theater family under the value of a dress rehearsal before the curtain goes up. Thats what a a beta test is rt now. We have enrolled over 10,000 people but when the full launch does happen you ended when else who supported the 20 to cures act will deserve applause and by the way for to find out more about that that is the website that will keep you posted. That applause we not just for all of us but for each of the many, many ways in which cures supports the work of the National Institutes of health or as some of called us the National Institutes of hope, and senator murray resort for two. Speaking about let me just they conclude with a favorite exultation from the british poet peter levi. Hope in every sphere of life is a privilege that attaches to action. No action, no hope. So thank you for your action in enacting the cures act. Id be happy to take your questions. Thank thank you, dr. Collins. Ive sometime during the q a you have chance to comment on your belief that the other Transactions Authority, which already have, would be helpful in other areas to help us get what you want to go. Dr. Gottlieb. Thanks a lot, chairman alexander, Ranking Member murray, members of the committee. Thank you for the invitation to testify at this hearing to discuss the implications of the 21st century cures act. Cures sit at the unattached on the path and set out to optimize investments in science on modernizing fda oversees breakthrough technologies. U. S. Is todays innovations more efficiently while maintaining our Gold Standard for protecting patients. This focus on innovation could not come at a better time. Across multiple fields of science we stand at Inflection Point in medicine where new technology is creating foundational opportunities to treat and cure disease and ways that when a possible just a short time ago. Take for example, our recent experience with gene therapy. We have seen to recent approvals of car teeth therapies to cancer were where patients own immune cells are reengineered using the tools of gene therapy to target a patients individual cancer. This form of gene therapy represents a whole new paradigm of treating cancer and the eary results are changing the way we treat serious tumors. This experience shows how a single fundamental breakthrough insight and open up a whole new way of combating disease. In gene therapy that break to spend the development of vehicles that can deliver genes were officially to the target inside the body. These are often referred to as vectors and if they can form of viruses that are specifically engineered for this purpose. In particular the advent of specific kind of largely inert virus was Inflection Point in this field. I like in the advent of the vectors to the feldman of processes for making antibody drugs and making his medicines nearly identical to fully human cells that they were mimicking. And the fighters represent a promising field breakthrough medicines in the 1990s but for a long time these therapeutic drugs fell short of their promise. That was because these drugs were made with antibodies from mice and antibody drugs as a person rejected by patients in insistence. Then came the science dehumanize these antibodies so they would more fully mimic the normal human counterparts. But he soon we saw many breakthrough drugs result. I believe were at a Cemetery Point when it comes to gene therapy. Over the next over years well see this approach become a mainstay of treating and probably chewing a letter most devastating and intractable illnesses. At fda where focused on establishing the right policy framework to capitalize on the scientific opening. Researchers at mit estimated about 40 gene therapies might win fda approval by the end of 2022 mr. Kirk pipeline of 932 development candidates. The estimate 45 of total gene therapy drugs are expected to target cancer. I cant do from the estimate but i can confirm there at the early stages of a transformation in medical treatment as the consequences of new technology and the benefits are likely to accelerate quickly. The advance of this field is not riskfree. Yet theres good examples of the fda embrace in the cures act and her efforts to build what congress is about to do in bouncing say to its scientific promise is expanding our ability to capitalize on this breakthrough innovation. In this case cures provide a pathway to receive expedited review by fda through the designation to. We extended that opportunity. Fda has considered car key products reform of gene therapy since the key therapeutic manipulation thats made themselves a surging product delivery by a vector. Fdas new draft guidance on Expert Program for general medicine therapies versus conditions can fda clarified the region of medicine therapy would include gene therapies at least durable modifications of cells and tissues including genetically modified cells. This would include car t products when this gene therapy products lead to a durable cells and tissues and, therefore, deliver sustainable, effect in the body. For example, if a gene therapy alters tissue to allow the body to express certain therapeutic proteins or fa car tcells has his agency and maintains its present and delivers the sustainable therapeutic effects we would consider them to be Regenerative Medicine therapies paper fda taking the sciencebased decisions it means gene therapies including rt may be eligible for the designation. Next year will be building on these opportunities and begin issuing a suite at the c specific guidance documents on development of specific gene therapy products. We intend to let out modern and more efficient parameters including new clinical measures for the evaluation and approval and review of gene therapy for different high priority diseases with a platform as being targeted. We plan to focus the first guidance document on use of gene therapy in hemophilia. Other documents will address clinical areas where theres a lot of interest in using these techniques such as certain more common single gene disorders will provide individual advice and velvet pathways including potential accelerate approval in points. Gene therapy is one opportunity of transforming medicine. This year fda may be on track to approve the highest or secondhighest number of novel medicines across our combined biologics and Truck Centers in fdas entire history. We will approve the highest number of generic medicine ever and on pace to prove the highest number of novel medical devices in our modern history. All this year, all at one time. The result of these benefits measure product approvals and some highly novel medicines like a gene therapies but ultimately its measures in its human impact. I look for to add to your questions and dont have my call is at it yet i you for your support of our mission. Thank you, dr. Gottlieb it will navigate around a fiveminute questions. In my five minutes i have several questions, so let me go through them pretty quickly. Both of you talk about Regenerative Medicine. Your testimony has more about it. The odd number of senators, including majority leader, who are interested in it and are trying to get more money and more legislation to have his continued interest. Would each of you in the next few weeks synteny and two senator murray a brief written report summarizing what you done in the area of Regenerative Medicine, that kind of thing that imagine that help doug oliver . Both about how you create more hope for people like doug but also what youre doing about the bad actors in the field. Id like for it to be the kind of memo i could give two other senators who are interested in this to show that youve taken some action in the first year. Absolutely. So thank you for that. Dr. Collins, could you say in about 30 or 45 seconds what you mean when you say other Transactions Authority has been helpful to you and you like to have more of it . Of the Transaction Authority allows us to move very flexibly in an area of high need and where technology is advancing rapidly. It means we can bring partners together without taking the whole year that it often takes to issue an opportunity for grants to be submitted a thrust to do the reviews and make the awards, plus it gives us the flexibility to decide when a a particular part is that meeting milestones and we can cut them off without any further to do. This is something darpa has used it were delighted to have that for our common fund and for all of us the Precision Medicine, it makes this possible much faster. Where do you want that you dont have it . We could use this in the Opioid Crisis. We have a big plan we want to move forward quickly. This would be a great advantage that as one of the tools. Senator murray and scent of blood and the Appropriations Committee i believe have for the third Consecutive Year reported out 2 billion increase in nih funding. Can you summarize and less than a minute why you believe that as we appropriate money for opioids that some of that money ought to go for research into nonaddictive pain medicines . The critical solution for the future is to have alternatives for opioids, for people suffer from chronic pain. There are 25 million of them in the United States right now that happening every day. We need to have better alternatives. There are ways to get there with some exciting new drug targets that have emerged working with industry, with a lot of contributions of nih. We believe we can accelerate that process, take a with ota to office. And he be able to have available for those people have had that kind of pain, answers and your document using additional appropriations and additional private money in a Publicprivate Partnership to accelerate that, correct . Exactly that we would expect companies to be willing to put some other funds in this just as we do with other partnerships with diabetes, alzheimers and parkinsons. Finally, start with dr. Gottlieb, it takes sometimes ten, 12 years to take a breathtaking new medical innovation from idea to the Doctors Office. The whole goal of cures if you shorten that time and shorten that cost, and still do in a way that a safe and effective. What are you doing, can you give me some specific examples of how fda at nih and cms, which has to do with funding, are working together so that we dont make a lot of progress in research, for example, have sit on the shelf what fda works on Something Else or make a lot of progress at the fda and have sit on the shelf of cms deciding whether to fund it. Dr. Gottlieb . A lot of our ability to make the Development Process itself more efficient and lower cost is trying to develop better tools, better scientific tools to evaluate products better that are being brought to develop a process to ascertain their safety and effectiveness and more efficient ways, in ways that are faster, they can be done at lower cost. That is a process of developing better sides, better regulatory science for evaluating technology. Theres a lot of work were doing in concert with the nh ann collaboration with dr. Francis, a couple of initiatives i would point to you by the tissue on the chip initiative which is for developing better tools for toxicology and looking at issues of safety and effectiveness in the partnership for somebody cures which is another collaboration where developing these tools. If we can develop this better size this is the case will we can have the best of both worlds, the process of our cost and more efficient but also would give us a better measure of safety and effectiveness, the ability to form those parameters. At a time but as we continue our oversight, and im sure youre going to do this, we need to think of this as a seamless process, and we need to go from idea to the Doctors Office to the patient and we need to get to the Research Come into the fda, through cms to make these things work. I hope youll pay a great deal of attention to that. Senator murray. Thank you very much dr. Gottlieb. Thank thank you very much. As you know we had some deadly outbreaks of antibiotic resistant infections that were linked to contaminated scopes to a host and across the country and a chip in a provision in the 21st century cures that provide fda some additional tools to make sure the safety, at the safety reprocess medical devices. I really appreciated the fda meeting its guideline to publish the list of devices for which the agency now requires valid evidencebased cleaning procedures. Can you update us on how many products now have these validated cleaning protocols because of this law . Thank you, senator. Ill preface my answer by saying we think this is a very important authority and dynamic robust use of it because you mention we put in place the provision in august 2013. Have not been 14 products i believe to date that it got through the process outlined in this legislation. We have many more we havent discussions with and i can get you a fully uptodate number because it is evolving that it is the 14th. I want to stay updated on this because i think we do need to respond quickly and appropriately when problems occur with these medical devices. Patients need to trust what is being used so i really appreciate that. Dr. Collins, i was very proud to champion provisions in the cures act to improve the inclusion of historically underrepresented populations as i mentioned, women, racial ethnic minors, chilled and seemed into Clinical Research. One of the provisions with a task force to improve the evaluation of drugs are pregnant and lactating women. They are in a very difficult position offered today whether its treating morning sickness or chronic condition because their social Research Today on her medication might impact them. We all know if they dont get an edge answer from the doctor they go online. That just to me is unacceptable in todays world. I want to ask you, how do you plan to integrate the task force worked into the broader efforts to advance innovation and, in fact, Clinical Research . Thank you for the question. We welcomed that recommendation in the legislation and weve moved quickly to set up this group for the prg lac chaired by doctor kathy who is a very respected neonatologist and ob gyn expert at nih. The group has met twice and is going to meet again twice more in the next coming months, and by may of 20 team will have a series of recommendations which we intend to take with great seriousness to as you understand very clearly this is an issue where we want to be sure that were carrying out the appropriate Clinical Trials to understand about efficacy and safety during pregnancy and lactation but also know those are very sensitive types in terms of not greater risk comes to getting the balance just right is what this committee is wrestling with. Its a strong grip. Theyve gotten frequently engage. I think youll see something very substantial come out of this. On hearing from a lot of women who are very concerned about the direction our country is going today, with its Family Planning or allowing employers to deny access to birth control, so they are looking for good information and i know that one of the things we did in cures was strike a a balance between members of the federal government and external stakeholders on the task force. And today the nonfederal members have not been hired by the task force and have been able to fully participate, and i wanted to ask you how you are ensuring that the noncommittal voices that congress regard to be included in this are heard from and the incorporated fully into the. We very much want those voices to be critical. They are probably the most critical parts of this. Even attending all of the meetings after speaking to the promise getting them officially point which means going through college of ethics clear clinch. Im a short that by the february meeting the wall of god to the process and will be fully installed and able to ask her not just be present but also to vote. Thats really important. Can you keep me updated on that . Dr. Gottlieb, just wanted to ask, just a few seconds left but were living in a new digital age. Its been mentioned several times and some of the products our low risk, some of them have a big impact on patients and their safety. People are wearing wearables theyre voicing a lot of different things, apps that use camera phones to diagnose diseases. These are really promising but we have to make sure they work and their claims are backed up by hard evidence. I know the agency is working to speed that up right now, but to me its less clear how fdas going to ensure that the sheer quantity of products that are now on the market are being validated, and wanted to you what actions fdas taking to make sure the patients and providers can put their trust in the Digital Health products . Just quickly, thanks for the question. We continue to receive adverse reports even for Software Product and Digital Products that we might exclude from regulation based on the parameters outlined in the care statute. If there was a situation when we seek an adverse reports of a recall or product that we exclude from regulation, that would be a request to then bring the product back under relation to the provisions in tears because if some adverse event or some issue with assault which of the link to adverse event, that tells us we should not have been excluded in the first place. We continue to monitor the products we are scoping out our active regulation. Okay. What is to updated. Thats going to take a lot of work in the future. Thank you. Thank you, senator murray. Senator roberts and senator young have deferred to senator cassidy. Senator cassidy, we have our hearing next wednesday and oversight of Mental Health law that you and senator murphy worked on so that will be here. Wonderful. And i i thank my colleagues for allowing me to speak now. This is not an Appropriations Committee but its a broad topic and sleep you dont mind, dr. Collins, again, Great Respect for you and for institute. But as i point out in the past we dont seem to have an nih which targets funding relative to disease burden. So when i look at nida, the budget only went up 2 last year and this remains far smaller than other institutes in which theres far less morbidity and mortality flowing from those disease conditions. So if were going to address the issues of opioids for Mental Health, both of which are playing into this, it seems like i spent greater shift in where our funding is going at nih torch of these disease conditions. In the past youve suggested we will organically grow, this one a stable and allow this one to grow, but when a look at all the institutes seem to be growing at about the same pace. I guess my question for you is, is it doesnt seem that nih is making these of priority if you look over other conditions, if you look at the relative funding increase of those institutes. You are a very thoughtful person. So please give me your thoughts on that. Senator, you point a very important issue but how do we make decisions. I i have to point out that its the congress that assigns the budget. Its a line item every year in the appropriations process to each of those institutes, as the nih director i dont get to set those numbers, and so we follow what the Congress Tells us all to be the appropriation for a given year. And then we work with great flexibility to try to be sure that when there is a Public Health need as her is now for instance, with opioids which i think you are referring to, because of course we have a big opportunity there in terms of our understanding of how the brain works. The Brain Initiative is relevant. The Neurology Institute at the gnome as investment and pain as does the National Center for consummated and integrated health. One should look at our organizational structure and say that the money actually fits precisely into those pockets. We have lots of ways that we can mix and speedy i accept that. If i me ive limited time, so you were saying that if we want more money to go to the National Institute of drug addiction we need to line item in our budget . That feeling when it happens. That said, the flexibility does seem we should be flexing things towards nida. Pain is important but pain translate into addiction. Thats a final common pathway. Its a seem as if we should be flexing towards them. Is that with a flexing is taking place . I think thats what were trying to do is to shift with the priority opportunities we have more funds into the space because we recognize this is a terrible Public Health emergency. Let me ask a different topic again trying to stay on time. There is a move afoot to suggest that marijuana usage can be used in lieu of opioids that states that have legalized marijuana more liberally have lower incidence of opioid addiction. Thats right. But then i read about the brain pain for the plastic up until age 25, and so, we all know the potted, the kid that is a Motivational Center if you will, so theres been a least one suggestion ive read that we should make a recommendation that legalization of marijuana should be restricted to those 25 and above. And i say this not because im an expert but to get the thoughts of those such as the two of you who are so expert. There is published date on the list of controversial that heavy have use of marijuana begin in adolescent does have permanent consequences in terms of intellectual performance that iq points get lost in those individuals who have been exposed to marijuana starting in adolescence. It is also true as you said that there seems to be a statistical relationship between the states that have legalized marijuana and a reduced incidence of opioid overdoses in death but one has to be careful there. Thats a correlation and not necessarily a causation. I would not want to link to that. I would go to the point that we are increasingly studying the cannabinoid receptor pathway in the brain as a potential way that we might come up with alternatives that would be effective for managing pain and depression and anxiety, not mere one and using that pathway. But for the two of you is it reasonable Public Policy considerations that perhaps the age of Legal Marijuana should be 25 and above . Were getting into difficult of Public Policy territory. I will simply say the concerns about marijuana exposure to the developing brain would have to be strongly considered in anything that made access to adolescence more readily available because we do have that concert. And the brain is developing at least 2h25 . You could say 22, you could say 25. I dont know if i have a precise speedy precise speedy my wife says its 60. Dr. Gottlieb, im out of time, im sorry, i should just back. I apologize. Thank you. Thank you, senator cassidy. Senator casey. Thank you very much. I do want to add my words of commendation to you and to the Ranking Member for the work you did to get this legislation passed. It is hard to believe it is a year and a nowin for ways to go with regard to the limitation, but in a place and in an institution where there are not many days where you have, not just bipartisanship, but a bipartisanship that undergirds a substantial matter of Public Policy of this importance, its especially great to be able to celebrate this passage and to continue to Work Together. Dr. Gottlieb, i wanted to start with you on a question regarding 503, pounders. While we are primarily been focused on the hearing, im getting new drugs to patients, im also concerned about maintaining the supply of drugs already in the market. We know that since Hurricane Maria hit puerto rico, ive heard from pennsylvania households regarding shortage of iv fluid and amino acids for injection, a critical product for patients who must receive nutrients intravenously. And while puerto ricos 1500 miles away, providers in pennsylvania now face product shortages due to challenges facing Major Medical Product Manufacturing facilities located on the island. The shortages are especially damaging because in the case of the iv fluid of amino acids, the facility on the items were the sole source of the product for the entire country. When you mentioned Continuous Manufacturing and how that can help reduce drug shortages, i wanted to ask you, good 503b outsourcing facilities also help in the case of drug shortages . The short answer is yes. We remain extremely concerned about the shortage situation in puerto rico, taken as a relates to the iv fluids reference in amino acids. We think the steps weve taken in concert college with the manufacturers and the authorities in puerto rico will start to alleviate the shortage situation going into next your but we saw to get through to ded we still face another hard month when his country challenges getting access to adequate supply, but we do expect us to continue to improve going forward. The issue with the 503b compound they theoretically can compound this product if they would have authority to do that. One of the issues is the products that are in shortage are not just the iv solutions themselves with the actual physical plastic bags to put the iv solutions in. The 503b, pounders also face a challenge in access to this, to the plastic bags they need to know to compound the product because is also manufactured in puerto rico. And has been a challenge and were as you would expected the fso spitler step it to supply more the smart i think theyve been limited in their ability to do that. I want to ask as well, im not a limited time, with regard to the pediatric priority review voucher program, we know that an estimated one in ten people in the United States, twothirds of whom are children had a rare disease. According to the National Organization for rare disorders. Despite the need of private companies are less likely to pursue new therapy for rare disease because it requires making an investment in products that will likely not recoup the high cost associated with the Research Development and marketing and distribution. As you will remember i worked with senator isakson, chairman alexander and Ranking Member murray to extend this review program at fda. And this particular Program Provides important incentives to companies to invest in new therapies for rare pediatric diseases. When we last spoke, the fda was still working on implementing changes that were made to the program. Most importantly, the definitn of what constitutes quote, rare pediatric disease, unquote. Can you give us a sense of the progress you have made on the update of that definition . And are you beating the statutory requirements to respond to requests for Companies Seeking designation for the products within 60 days . I know thats a lot. Im proud to say we are, senator, and we have put forward some guidance. I think theres some Additional Guidance coming out in the bidding the prb program. We continue to look at this as a potential opportunity to verify what these. I which is close by saying i think theres a lot of other things that we cant and are doing to try to great additional efficiencies to address the challenges you outlined with respect to pediatric drug depot of including one we took yesterday. I want to put a plugin for policy we put out yesterday trying to outline a more efficient pathway for drugs targeted to very rare pediatric diseases. Thank you, doctor. Senator young. Doctors, ive a lot to cover in five minutes so i i ask that you try and be concise with these questions can so thank you for your present to today. Dr. Collins, you mentioned the plan jeff and admitting the eureka competitions for a patient incurious that price program. When i was in the house of representatives i put together an amendment to cheers, a variant cures, a variant of this became the eureka prize provision i know others contribute to the effort as well. It was inspired by a neighbor of mine who is a latterday thomas edison. He develops medical devices in his garage. I consulted with eminent economists, healthcare professionals, researchers, venture capitalists, Angel Investors and all sorts of individuals in developing my form of price. And the objective was to ensure that we have objective rather than highly subjective criteria with respect to what those prices are offered for. My hope, something are taken up by one of my colleagues here today, was that we would target funding according to disease burden. And when my colleagues consulted with the nih, a were told no, they dont want to be directed. And so it effectively killed this effort, which i frankly find more meritorious than the confirmation. What criteria do you or others within an age used to determine what areas you are going to be funding . And when you see an opportunity thats particularly ripe for investment we dont want to miss that. With the prize mechanism we put out a request for ideas for alzheimers disease. Talk about an area of high disease burden. We look forward to that and we have prizes looking at stirring up interest in antimicrobial. And a test that would tell you in hours. And thats the case it will go through a lot of it and i can give you ill scrutinize that and thank you for publishing that information. Do you include or do you plan on including the private sector or outside stake holders like some of this i mentioned as we move forward in reviewing proposals, and in designing prize competitions . Yes in both cases. Our review panel, especially for high profile, and with people with expertise. In prize competitions we want to know what people think in all sectors in an alzheimers prize. Lastly, do you allow in your prize competition or have any plans to offer inkind benefits . By that i mean, the ability for a garage investor or researcher who use lab space at nih or to use equipment that we, the taxpayers, have paid for or to offer Technical Assistance to those that need it. I think weve done that, actually in a couple of the small project prizes where were particularly asking students, undergraduates that have a great idea to be able to apply and they may not have access to the equipment. Were trying to be very flexible on that. Thank you, it sounds as if the career nih folks, telling members of congress thought the idea was not thought well enough, maybe theyre on the right track. So, dr. Gottlieb, and called shooting in the dark, impacts that make a program a success with very limited data. For example, decisions including indication selection, dosage end points and inclusionexclusion criteria. You might say are mid suboperatima suboptimally. Theyre in accessible to most stake holders. They are high cost and longer time lines. Now, the fda already has much of this data, this otherwise siloed information. So, my question for you is, has the fda taken any steps in aggravating Health Care Data across silos to improve the pharmaceutical Development Process and if not, would the fda be willing to analyze the data it collects to provide further scientific insight back to the Research Community, to accelerate and derisk biomedical innovation . I appreciate the question and its a complex one and id be delighted to follow up on it. There are situations first of all, well take steps soon to take more data from the clinical portion review where it can be aggregated into the data you speak of. There are situations where we develop our proprietary data sets from data we glean across application to make decisions particularly around drug safety. But those remain proprietary to the fda because that information is commercially confidential. We are looking how we could make the data sets public, in a way without inappropriates someones data. Iffer woo he a making data that isnt accessible to the public thats probably something we should try to address. This is a complex area were actively working on. Suffice to say were trying to move in a direction that you suggest. There are legal complexities associated with that. Were out of time. I look forward to working with you. Thank you, senator young. Senator bennett. Thank you, mr. Chairman, i want to also congratulate you and senator murray on this one hadden year anniversary, one more reason to be happy to be on this committee. Dr. Gottlieb, i wonder if you update the committee on where you are with the med tech act, the bill that senator hatch and i worked on together . Well, i appreciate the question and ill try to be brief. We Just Announced major components of implementation of some of those provisions today. So, we continue to move forward with this on on schedule. I think its a good example of what were trying to do in this space. Its a good example of what were trying to do generally where were taking the provisions that congress outlined and trying to take what theyre trying to achieve. Congress set out process for the review or exclude certain supports by physicians. Were going to exclude certain Decision Support tools by patients as well as long as they meet certain parameters, thats an attempt by fda to try to take the spirit of what congress set out to do and extend it a little bit. What sorts of things do you expect to see sooner rather than later in terms of devices. I think that one area we havent seen as much of is in the area of Decision Support tools, where theres tools that take information and help support decisions without making a decision for the clinician or the patient. And i think in part, theres a lot of reasons why we havent seen as much innovation, that space as you would have thought, but regulatory ambiguity probably played a role for some period of time. Fda always intended to exercise enforcement in its space. Congress expressly outlined that in cures. And this put out a guidance that creates bright lines, what does and doesnt cross the line and what are the obligations of sponsors, even those excluded from active regulation to make sure continuing to look at the safety of those products and collect information where things can go wrong. So, im hopeful that well see more innovation in the space, tools that can sit on top of Electronic Health records and help physicians make decision froms that information. I appreciate your focus on it. I also noticed that unrelated to that, that the fda approved the first breakthrough designated diagnostic particular to detect genetic mutations for cancer, that approval came through, i think the new break tru not breakthrough therapies, but breakthrough device that we wrote for the bill last year and i was interested to see that at the same time that happened, there was simultaneous decision by cms to also cover the diagnostic test. And i wonder if you could share with committee how you and cms conducted these parallel reviews and whether we can expect to see this sort of coordination in the future . Well, i think it can, can, senator, and this is an example of a test that was a Laboratory Developed test that voluntarily came through the regulatory process. We were able to review it in six months, under the breakthrough designation, at first you said, breakthrough designated product to receive fda approval and we worked with cms to have in place simultaneous coverage at the same time and we think going forward, this is a panel of cancer markers that will help guide the treatment of cancer patients, and help guide the prescription of therapy. And this is an area of a lot of innovation right now and what cms said in their policy and ill let them articulate more clearly, is that panels that come through fda for voluntary approval will now automatically receive coverage, the National Coverage determination and its a powerful incentive i believe for more such tests to come through the regulatory process. We can provide, i hope, a greater assuredness of effectiveness of it. Thats a big step forward and i can tell dr. Collins agrees. I only have a minute left, senator rubio and i last year worked on the race act for pediatric cancers and i know you put out some guidance recently on developing drugs in rare pediatric diseases. I wonder if you could expand a little about that. We did, senator and were going to have more to say on this, on this area, but what we did yesterday was finalize some parameters, guidance that we had in draft form. That tries to look at very rare pediatric cancers, so this is pediatric diseases, excuse me, and trying to outline more efficient process for developing those products. We might not have to rely as much on placebo trials and might use modeling assimilation to represent the placebo arm and try multiple drugs in the same Clinical Trial. The reason why these kind of accommodations are important in this setting is because its very hard to enroll patients in these Rare Diseases where you literally might have dozens of patients who have a disease who are eligible to be unrolled in Clinical Trial, trying to allow sponsor to cooperate and randomize some of those to placebo for more efficient development. Mr. Chairman, im out of time, but i didnt thank the witnesses for their Great Service to this country and i deep think appreciate it. Thank you, senator bennett. Senator collins. Thank you, mr. Chairman. Dr. Collins, were always glad to see you and i still claim you as my cousin, regardless of the facts. I accept. Thank you. The state of maine is doing some really exciting medical research and i have visited a lot of the labs and medical ins institutes in our state. The Maine Medical Center Research Institute is conducting cutting edge work that researchers in maine have underway to develop medical treatments for chronic diseases, and in september, one of the researchers with whom i met, doctor lee oxberg and his team at Maine Medical Center, received an award through regenerative innovative project, using adult stem cells. Dr. Oxberg is working to develop novel therapies for chronic Kidney Disease, which is very exciting. Regenerative medicine also holds Great Potential for understanding aging and reversing diseases like macular degeneration. I understand that the chairman has already introduced doug oliver, but, he, too, is from the state of maine and grew up only 11 miles from where i did, and he shared his compelling story about losing and regaining his sight through regenerative therapy. Mdi biological laboratory in maine is leading the development of such therapies that hold significant potential for slowing the changes that occur with aging, and the diseases of aging. What especially can we do to support research into biological aging . What a great question, and thank you for pointing out a number of the applications to Regenerative Medicine. As were gathered here this morning, theres an intense discussion going on at a hotel in bethesda sponsored. On this topic of Regenerative Medicine, several hundred people in the room talking applications to Kidney Disease to hard disease to aging, to such things as Rare Diseases, common diseases, the whole landscape and its enormously exciting and when i spoke yesterday i forecasted if we do this in the way i think we could, we could cure, not just treat, but cure a disease like sickle cell in the course of the next five years. With regard to agingings were learning a lot what the process is. Ill mention one example, otherwise ill go into a long lecture. As you age there are a category of cells that are no longer able to keep going, they dont completely exit the stage, theyre still there and turns out theyre not good actors. Theyre actually making the healthy cells around them not so healthy. If we could figure out, as weve already done in mice, how those cells could basically be told, okay, youre done now, it could very significantly slow down the normal process of aging, with all that that entails in terms of frailty and chronic disease. This is a pretty exciting new development. I think it is also, and i remember visiting Harvard University and talking with researchers there about alzheimers disease, and theyre also looking at the possibility of turning proteins back on to restore cells that have been lost and neurons that have been lost. Excitement about all of those alternatives, as well as identifying drug targets we didnt know about before, by kifrl systems biology and how Understanding Networks in the brain that work and those individuals at risk of alzheimers. We have a partnership with industry you may have heard about called accelerating membership partnerships, and advancing this at a pace i wouldnt have thought possible a couple of years ago. That brings me to my question for you about that program. Which aspects of the accelerating medicine projects do you find most promising . Well, for alzheimers, there are two areas that were really pushing. One is biomarkers. We really need to find out what are the indications that a therapy is working without having to wait ten years to find out whether it was, in fact, protective against cognitive decline and theres a lot going on with imaging for cow, one of the proteins involved in this and the other is systems biology where were trying to step away from what we know already, and ask the question what else is going on in alzheimers, and how can we use that for the next generation of therapeutics, taking the areas na we know about coming up with interventions that we know work and apply those early before people succumb to the illness. Weve got to start early if we want a good effective. Thank you. Thank you, senator collins. Senator murphy. Thank you both for your service, and i know it comes at sacrifice. And doctor you serve our country and thank you to both of you. Dr. Collins, i wanted to talk about the all of Us Research Program, a program that designs a diverse medical data set for the Precision Medicine initiative. Im interested because one of the participating Health Centers, Community Health centers that is currently gathering data is based in middletown, connecticut. I think it great that youve gone out and worked with Community Health centers because these centers, you know, typically serve a Patient Population thats often underserved in Biomedical Research. So, i just want to put that question to you, which is, if you could you can at that about the importance of having fuhcs as part of this initiative and whether there are plans to expand beyond the current six Health Centers that are right now part of this initiative, Community Health center in connecticut, very pleased with their partnership with you on this and wed love to see more like them get involved. [inaudible] opening remarks i put up this visual image how it is were seek to enroll participants in this very bold, largest ever prospective study of health and illness in the United States. And we are inviting people to participate by a variety of means, but one of them is through the Community Health centers here, included in the Health Provider organizations because we have a very specific goal here of having at least 50 of the participants in all of us being individuals that are underrepresented traditionally in medical research programs. And the Community Health centers who provide care to a great number of people, particularly those in lower socioeconomic situations are very excited about being our partners and were excited about having them as partners. Were starting with the six in middletown as a place thats clearly been very successful in getting this up and going, but thats a pilot to see if we can have more. We fully expect to launch in the spring. Right now were in a beta test with 12,000 individuals. Were working to learn how the parts Work Together. Looking good. And wanted to switch to an Exciting Development out of the cures act. This is the establishment at the fda of the Oncology Center for excellence, which creates a crosscenter team to Work Together on a variety of products to treat cancer. Just an update on what youve learned thus far from this model and what do you take into account when youre thinking about creating other diseasespecific offices. Having gone to college in middletown, connecticut, i appreciate the shoutout, senator. Right. And this is an extremely important effort on the part of the agency so i appreciate your asking the question. The oncology college for exlength, trying to consolidate the review of Oncology Products into one center. This is to expedite the review of the products, for example, by consolidating this, were able to more efficiently look at by logics. Weve had them standing up and fully funding it. We believe that this is the future of the agency though, trying to get these consolidated programs in place and were looking to other therapeutic areas to do this. Before we can go on the other areas were looking at oncology setting. Were looking forward to try to move this program forward. Another reminder to us that weve got to give the funds to implement this act. Quickly back to you, dr. Collins, one more question and that is on another part of the 21st century cures act. Senator isaacson and i worked on a provision that allows for the c. D. C. To collect information on the incidents and prevalence of neurological diseases that senator alexander and senator murray helped to include in the legislation. Talk about the importance of having data on neurological diseases to Research Done at nih. Its incredibly helpful to know what incidents and prevalence is for conditions like parkinsons, but many other disorders as well. Its challenging and expensive to do that kind of analysis and to do it effectively and to keep it updated. As i understand it, while c. D. C. Was given the charts to do this, at the present time they do not have the funding to carry it out. Great. Youve got another advertisement to put the money behind the legislation we passed. Thank you very much, mr. Chairman. Thank you, senator murphy. Senator hatch, former chairman of this committee, welcome. Well, thank you so much, mr. Chairman. I appreciate it. I certainly appreciate you two gentlemen. I think youre both some of the best Public Servants ive seen in all of my 40plus years in the United States senate and im proud of both of you and hope you keep doing what youre doing. So, im going to thank you both here today. Dr. Gottlieb, last congress i joined senator bennett in authoring the path act, whiches with an included in the 21st century cures and will help advance the development of new antibiotics for multidrug resistent infections by allowing them to be studied in smaller and rapidly Clinical Trials and therefore approved more quickly for patients who need it the most. The fda was tasked for developing guidance for industry regarding this limited Population Pathway or elpad. Can you detail the way that input is being solicited and incorporated into the guidance. Thank you, senator. We plan to issue the guidance you reference in the spring and have been meeting with stake holders and interested parties in the development of that guidance consistent with good guidance practices. So we will have stakeholder meetings and development of any guidance documents. We think this is an extremely important pathway and weve had multiple ind meetings with sponsors and believe this will be a robust vehicle for trying to create new path ways for drugs targeting significant unmet medical needs. Thank you. I was pleased, dr. Collins, as a result of 21st century cures, n hiechlt h was able to start the Regenerative Medicine Innovation Project and first words gone to research on Rare Diseases. As you know, af he been a champion of the Rare Disease Community for quite some time and i applaud you recognizing how Vital Research in this area truly is. Strides in Regenerative Medicine may be truly prove to be transformational in the way we understand and even treat Rare Diseases. What barriers do you forsee in expanding research into this area, as the Regenerative Medicine Innovation Project continues . Well, thank you, senator for the kind remarks, at the beginning of your time and also for the question. I think this is an enormously exciting time for Rare Diseases because we have tools now that are starting to work. Dr. Gottlieb referred a little bit ago. An advance in hemophilia using gene therapy with a viral vector, delivering to the liver and its men because its xlink condition. And remarkable over the course of many weeks. Thats a single example of whats possible in this space. I mentioned earlier, my hopes that we could cure Sickle Cell Disease taking out the bone marrow cells and correcting it and its a transplant to yourself, put it back. Its a gene editing approach which we find to be exciting. Recently this terrible disease, sma, spinal muscular atrophy, in children born seemed to be okay and develop paralysis and often dont live past their first year. With a Clinical Trial, some of these kids are making it to prekindergarten and looking pretty good again by a genetic change using either a virus or gene editing strategy. He think the big barrier right now is to push the science as hard as we can and the cures bill helps us by giving that kind of inspiration. Im glad to say, the barriers with regulation are not the issue right now, working with scott and his colleagues at fda who also have made rare disease a very high priority. Of course, there is an issue about investment. Companies may not be so interested in putting a lot of money into a very rare disease because the markets going to be small, which means nih has a stronger responsibility to derisk the project and push them as far down the road as possible. One thing that you did for us and the cures bill is make it possible for us to run phase three trials for Rare Diseases in the therapeutics and neglected disease programs and ncats, we did not have the previously doing for this purpose. One of the divisions for the 21st century cures is to provide opportunities for young and emerging researchers. And from the university of utah, received 150 million in nih grants an annually. Theyve seen an improvement in this area and for that id like to thank you and your staff and your work, in this area. My time is up so ill just thank you and tell you how much i appreciate your willingness to serve in this government and how much, how much you really mean to People Like Us who have worked all of these years in these areas. Thank you, senator. Thank you. Thank you, senator hatch. Senator baldwin. Thank you. And i want to add my words to the others of congratulations of the bipartisan work you led, mr. Chairman, and Ranking Member murray, on the 21st century cures act and thank both of you, dr. Collins and dr. Gottlieb for your service. During the Committee Deliberations on 21st century cures, i regailed the committee any number of times about being the granddaughter of nihfunded scientists and how that influenced my championing,ing strengthening our research and enterprise for the nih. But in my first year, in the United States senate, in 2013, i had a particularly powerful and inspirational meeting with a young man, a high school senior. His name is ian. And he is a bone cancer survivor from fond du lac, wisconsin. Ian told me that cancer research, no doubt, helped save his life and thats why he wanted to grow up to be a scientist, to help others with his disease. But he was concerned that it wouldnt be possible for him to break in as a new researcher, due to his awareness of nih funding cuts at the time. Ian inspired me to author the next Generation Researchers act, along with my colleague, senator collins, to fight to improve nih opportunities for new and early stage researchers. I am proud to report that ian recently graduated from college, where he was helping a researcher at the university of Minnesota Study the genetics of osteosarcoma and hes now working with a scientist at Huntsmans Cancer Institute in salt lake city, utah, on pediatric cancers. Dr. Collins, i am encouraged that the nih has begun to robustly implement the next Generation Researchers initiative, to help support future scientific leaders like ian. As they discover cures for cancer and pursue other life saving research. You announced a new policy this year to issue more awards to investigators in the earliest parts of their independent research careers, to help them sustain or achieve research independence. Id like it, dr. Collins, if you could describe how each institute and center will prioritize awards for these early and mid career investigators and how this will him improve and stabilize opportunities for our next generation of researchers. Well, thank you for the question. Youre touching on a personal passion that i feel and that many of the other Institute Directors do, as well. We actually just published about a month ago, myself and mike, and larry tabak, what this policy is and how were going to implement it, because we passionately agree with you, the next generation is critical for our future. And its been a tough with the loss of purchasing power through 2015, first time early stage investigators were having a hard time Getting Started and we cannot lose them. And we were starting to. So, each one of the institutes, depending where they fit, think they can find their flexabilities are fleeing up dollars to make it possible for those early stage investigators, who otherwise would just miss the pay line, to actually get funded. We started this quite late in fiscal year 17, but we were able to make a whole bunch of awards and were not done yet. Were trying to reach back into some of the about fiscal year 17 fund reviews. And in my committee, we have a working group, you would be interested in, it has graduate students and junior faculty not just gray eminences, but those who have the right plan in order to make this particular priority really happen. Im running out of time, but i want to just note, maybe you can answer for the record that you estimate that this new effort to prioritize more awards for early investigators will would be about 210 million in the next year and 1. 1 billion over the next five years. Does nih need Additional Resources for this policy to ensure that it fulfills promise, its promise and continue to advance all other critical nih efforts . Quickly, woo we are prioritizing this, but we can do more if the resources are available. Before we go to senator warren, let me recognize senator murray. Thank you both for your answers. And i will make more, but i have another commitment. We have another on Mental Health part of cures, its educational for all of us and appreciate both of your efforts and look forward to continuing to work with you. Thank you, senator murray. Senator warren. Thank you, mr. Chairman, so we have been talking about the cures act. It has a lot of bipartisan provisions that im really glad became law. During our recent hearing on gene editing, we talked about pricing that senator inssy and i have worked on together. Right now massachusetts Biotech Companies are benefitting from a provision that senator bennett and senator burn and senator hatch and i wrote to try to clarify fda authority relating to gene therapies for Rare Diseases and i could go on. Its a long list. But cures also fell short in a really big way, and thats on funding. I led democrats on this committee in calling for an extra 50 billion for the nih and fda and cures did know the send one single new dollar to these agencies. Instead, it only said that future congresses might spend about 10 of that amount on nih and fda. And im glad that so far, congress has been increasing nih funding. But i dont think its time for us to pat ourselves on the back yet over where we are in funding the nih. So, dr. Collins, let me just go through this a little bit. Does the nih fund most of the grant applications that it receives from scientists . No, we certainly arent able to do that. We fund about 19 of those because thats the way it comes out after we do the priority scoring and see how much money we have. Okay, out of every 100 applications you get youre funding about 19 of them. Is that because the other 81 would have been bad investments na would not have helped us make biomedical breakthroughs to advance science . If we look back in history, 2000 and 2001, we were funding 30 and maybe even 35 because the funds were more available. Weve looked at those to see, did a grant that scored at 25th percentile actually turn out to be less productive than one at the 15th percentile, the answer is no, we cant tell the difference up to 30th percentile, even though peer review is trying to draw distinctions, its hard to do so in the top third. In other words, roughly using the numbers you have here, if weve doubled, for example, the number of grants that we were able to fund, you think theres still a lot of good science to be had out there . I think there would be fantastic science. Okay, thats powerfully important. I want to follow up on a point that senator baldwin made and the discussion you all had about researchers in the early part of their career. You know, getting that first nih grant can make or break an academic career, it can be the difference between whether the scientists stays in the fight or whether the scientist has to leave academic medicine and go somewhere else. So, i just want to ask more about the details here. Where are we right now on early career researchers . What percentage of the grants are they able to get . Well, beginning in 2008, we actually instituted a policy so that those applicants who came to us for the first time as a Principal Investigator got a bit of a boost. They competed against each other, essentially, as opposed to against the most experienced ones, which meant effectively in priority score terms, they got a few extra points, but thats not good enough. Were still losing lots of those, their success rates for early stage investors were still well below what youd want to see. Ultimately. We think it would be most healthy if at least, say, 25 of those applications were going to get funded and thats what were trying to do with this new initiative, the next Generation Research initiative which is named specifically for the words that were used in this bill. Thank you, senator baldwin for that encouragement. But i understand right now, weve been at about 16 , is that right . And youre saying at a minimum we ought to be boosting that to about 25 . And weve looked closely at every institute successes and try to figure out how to get there with this new policy, yes. I know that nih has done what it can in this area, but nih funding is still down about 15 of where it was a decade ago. Back when we had a 50 higher success rate for the proposals that were coming across reviewers desks. The cures act did not solve this problem, frankly, it didnt come close, and thats why today were reintroducing the national Biomedical Research act, which provides 50 billion dollars in new funding for the nih and for the fda. I see youre sitting up straighter there, dr. Gottlieb. This legislation is cosponsored by senator sanders, casey, franken, bennett, whitehouse, baldwin, murray, cane, hassan and members of this committee as well as several democratic colleagues who are not on the committee. Families across this country are waiting for medical breakthroughs and researchers are waiting for the money to fund their work so they can make those breakthroughs. Its time for us to step up and put more money into nih. Thank you. Thank you, mr. Chairman. Thank you, senator warren. Senator hassan. Thank you, mr. Chair and ill add my thanks to you and the Ranking Member for this hearing and for your work on the cures act, to doctors collins and gottlieb, thank you for being here and would you please, along with us thanking the two of you for your service and leadership, please thank the men and women who work in your agencies for the work that they do on behalf of the United States. Dr. Gottlieb, i wanted to ask a question of you. We discussed the Opioid Epidemic in New Hampshire and across the country. One of the tools in combatting the epidemic is medication assisted treatment. It plays an Important Role in recovery, along with access to other services and supports. And we also, both of you, i think, mentioned in your opening comments the possibility that we will develop nonaddictive pain products that will help prevent addiction when somebody, for example, gets in an accident and is prescribed an opioid and becomes addicted. The 21st century cures act took some important steps on focused Drug Development, including requiring guidance on Patient Experience data. So, dr. Gottlieb, can you discuss how patient focused Drug Development initiatives could be used in relation to new medication assisted treatment and the development of new, nonaddictive pain treatments . I appreciate the question. The bottom line is, they can be a very important tool and i think the provisions that are in the cures act are going to help inform about how we go about thinking about the parameters that we use to encourage the development of products, both kinds of products, both nonaddictive to some of the opioid products, but in particular, medication that can assist people to live life through sobriety. We have committed to publish, to develop new guidance documents, for outlining the pathway for the development of medically assisted therapy. We want to create incentives for sponsors to come in and try to develop those products and part of that is making sure we have very clear guidelines. As part of that, were looking at alternative end points we havent looked for in the past. Issues like craving. We know craving is a factor that leads people to continue to use opioids, if this can be an end point in the trial that we use to assess new products, it might have a more efficient pathway. Thats is with the work we do with patients and patients informed end points. Thank you, and dr. Collins, i wanted to talk to you, too, but you made a comment in a response i think to senator alexander about the impact of the other Transaction Authority that you now have and can you comment a little bit about how that could be helpful in the opioid space . You said it would be, but how specifically would ota be useful to the nih and its work in doing opioid Disorder Research . So, the plan that we have put in place, which is going to be fleshed out in more detail next week in an intense twoday meeting, will involve a lot of rapid action, both to come up with new ways to treat addiction, cause we need more options to treat overdoses that dont respond as well as they might to fentanyl and thats going to require partnerships between academic institutions that have the appropriate science skills, with industry that may have formulation capabilities, or Drug Development path ways. If we have to build that on the process of issuing grants and contracts and the traditional way, its going to take a long time. Other Transaction Authority allows us to do something in maybe six weeks that might have otherwise taken nine months. Weve learned how to use this effectively and responsibly for the all of us program, for the common fund. And we think this would be a great place for it to be available. We will be careful about how to use it, but it could help us a lot. Well, thank you. And finally, i wanted to talk a little bit about our new generation of scientific researchers because both senators baldwin and warren were talking about that. Cures took an important step for the next generation of researchers to by helping it make it more affordable for students to pursue their graduate degrees. And nih has been special funding consideration for graduate students. In recent weeks ive heard from a number of graduate students, dr. Collins, who are fearful of how the republican tax legislation, particularly the house version of it, could impact their ability to pay back their student debts and whether, it can even force them to drop out of their programs. One particular provision is in the house bill would require that graduate waived tuition is taxed with their stipends. A change that ive heard from ph. D. Candidates could really impact one wrote, this would triple my taxable income and increase my yearly taxes by more than 10,000. It would force me to drop out of school because i wouldnt be able to afford rent and groceries while earning below the poverty line. So, can you comment, dr. Collins, on what you think this provision would mean for the future of our young researchers and Biomedical Research . Quickly, because of the time, these are our future graduate students that are learning to be the next generation of leaders in science across many disciplines, but certainly, i think of life sentences, needing those individuals to be the ones who are going to make the next breakthroughs. Anything that happens to discourage the best and brightest from taking that track or to feel that they cant afford to do so is something that we should approach with great concern. Thank you very much. Thank you, senator. Thank you, senator hassan. Senator whitehouse. Thank you, chairman and i join my colleagues on congratulating you and we hope we have more to come. One thing in the cures act, the request that you reduce the burden of what we called low risk subrecipient monitoring. I just left brand universitys director of research, a moment ago and this was the university of Rhode Islands request, you get things Like Brown University and university of rhode island working together on a project, and the supposed obligation to monitor a subcontractors, now applies to each of them. So you have uri, and brown monitoring, and both monitored by omb. Can you help reduce the bureaucratic and reporting burden to your subrecipients . Senator, we dont particularly enjoy doing that kind of low risk monitoring either and we have, in fact, thank you to the cures bill, put together a proposal of a way that we might reduce the amount of low risk subrecipient monitoring. There are certain situations that dont quite need that. Many of them do, those are would you descriinclude us i cycle and be helpful in giving advice making sure that goes forward at a good pace. Be happy to. Doctor gottlieb, youve done training to connect two. But the original testimony that we had from fda from the drug and device sides, what you needed was a third pathway for drug device combinations. Would you assure us that if it turns out that the hybrid effort that the cures act established, isnt doing the job, that you will let us know so we can take a second crack at it legislatively . Absolutely, senator. This has been a challenging area over a period of time. We think the provisions and the cures act give us a lot of tools. There will be some guidance soon that we think will articulate a better pathway. But if it doesnt resolve the challenges you have identified in the past, ill be delighted to talk to you about alternatives. Thank you, as long as were staying in touch, in the loop and not wasting time if it turns out not to be productive. Dr. Collins, there have been some very everyday moments that are very significant. 1876, a gentleman called his assistant watson to come into the room, and in 2012, a lady named kathy hutchinson, minor thanks, except for technology. Come here, watson, i need you Alexander Graham bell first using the telephone to summon his assistant and miss hutchinson picked up a cup of coffee and brought it to her lips through at what Brown University they called a brain gate, electrodes in the brain by mere thought she could control the robotic arm. The funding at nih is terrific. Are you satisfied youre adequately connected to the brain gate to make sure that everybodys pulling in the same direction . Were enormously excited about that and weve worked closely with darp closely, how you can work with people who are paralyzed with a robotic arm to carry out sophisticated activities including the one you mentioned. This is part of the initiative, involving darp, department of energy, and International Partners aims to do to figure out how the 86 billion neurons between your ears do what they do in these complicated circuits that were beginning to take apart and understand better. Because we would like to go from where we are now, which is sort of an empirical effort to get this to work to understand it so well that you know exactly where to place the electrodes to get the maximum sophisticated of the robotic arm. And has topic. Weve done legislation on plastics in the senate. The u. S. Has issued, i think, a unanimous statement of concerns about plastic. Plastic doesnt biodegrade, it breaks down into smaller, smaller, smaller points and microscopic creatures can consume it and begins the track up the food chain. Never in Human History have we had to experience that kind of plastic loading into our diet, its now found in tap water, its found all over the place, its obviously going to be in our food. Is this something that the National Institute of health should begin doing basic research on so that if this turns out to be a problem, its certainly a new experience of human kind to have to digest and process that kind of microskcopic plastic in the food chain that youre alerted to it. One of our 27 institutes, one located in north carolina, Research Triangle park, is already looking at this. I can give you a summary where we currently stand in terms of the research currently conducted. Id appreciate that, we can do that off line and through your thank you. Thank you, chairman. Thank you, senator whitehouse. Thanks to both of you for being here today. I hope youll follow up with the memo on Regenerative Medicine sometime in the next few weeks, that i can give to senator mcconnell and other senators who are interested in that. You heard several senators mention that today and you have quite a story to tell, i think. Also, well be interested as we look forward the second anniversary of the cures act in a year, to, especially how were taking that 10 or 12 years between idea and something in the medicine cabinet, something in the Doctors Office, how were compressing that, how were setting priorities and how fda, nih and cms are working together to do that. I salute you for the steps youve already taken, but that would be a very promising way to do things and really, you have to do that more than we. I mean, we can do some things in legislation, but that we really cant do as well. We can order you to do that, but that wouldnt make you do. You have to do what youve already started to do, which is to Work Together to speed that up and still doing it in a way that provides safety and efficacy. Without getting you in the middle, dr. Collins, i sometimes worry that the messages that come out of washington arent you know, are heard by the graduate students and the researchers across the country and they worry that were not funding their work. If the president s budget, for example, says one thing, and everybody pays a lot of attention to it and then that really doesnt happen, nobody knows it doesnt happen. I remember that in president obamas last year, he actually reduced recommended funding, discretionary funding for the National Institutes of health and he recommended big increase in mandatory funding for the National Institutes of health. Now, this isnt too hard to for people to understand. This is the authorizing committee. We dont appropriate money, usually. Or we cant appropriate money. And we have another committee, which senator murray is the Ranking Member of and senator blunt is the chairman of, thats the money committee. So, for us to appropriate, say, 50 billion in new funding for National Institutes of health is a wonderful aspiration, but thats not what we do. We decide, for example, whether dr. Gottlieb should have a new breakthrough path for medical devices. If the Appropriations Committee were to decide that dr. Gottlieb should have a breakthrough device pathway medical devices we would would be upset. We would say thats our probable and try to appropriate another 50 billion for you, the Appropriations Committee would be upset theyd say thats our job. Let me ask you this, we have discretionary funding, thats the Appropriations Committee. We have mandatory funding, which this committee could do. Whats the size of the nih budget this year . Whats your total funding . 34 billion. How much of that is Biomedical Research . Virtually all of it. And to be clear, more than 80 of that goes out to all of those institutions all over the country that do that. And how much of that 34 million is mandatory funding . I think theres 150,000 in there, almost all of it is money thats supplied by the 150 million for type one through the subcommittee that senator blunt and senator murray. Now, two years ago, if im correct, senator blunt and senator murray recommended and Congress Approved a 2 billion funding increase for the nih. Yes. Last year they recommended and congress agreed and president signed another 2 billion increase for nih. Thats right. If im not correct, i believe the Committee Recommended another 2 billion for a third year in a row and the congress hasnt yet acted. And the way we normally do things here, once we put something in the budget we count for ten years. First year is 2 billion, thats 20 billion over ten years, second year, 2 billion, another 20 billion over it years, third one if we do it this year, another 20 billion over ten years, thats not guaranteed beau but thats usually what we do. We put it in the base, what we expect. With the priorities on this committee and the Appropriations Committee. I expect that to be the case. Something unusual in the cures bill. We took 4. 8 billion created a hybrid sort of funding that created all kinds of consternation with the house of representatives and our Appropriations Committee and special funding to the Precision Medicine and cancer moon shot, the Brain Initiative and some other things. But, the chances of that happening again are close to zero. The real money that is supposed to go to the National Institutes of health and nih is Appropriations Committee. Theyve done a tremendous job, im a member of it myself. Ill give senator blunt and murray, great credit for squeezing out of the budget, resources a good deal larger than in the last few years, nothing wrong with aspiring for more, theres nothing wrong with looking back 15 years and saying that if we had gone up at the same rate we had been going up, it would be even higher today, but i think its important for researchers across the country to know that this congress in a bipartisan way for the last three years has been extraordinarily committed to significant increases in funding for the National Institutes of melt and i think its made a difference. Senator, i really appreciate your taking the time to explain all of that, because i think there are people watching who are wondering how these decisions get made and where we are, and certainly, there have been a lot of anxieties in the Biomedical Research community, particularly from young investigators what is going on and whats the likelihood of the pathway. You have pointed out theres a great deal of reason to be excited and optimistic about a career in Biomedical Research, first of all, because the science now is so incredibly promising and exciting, but second of all because the support as youve outlined has been on upward trajectory with two years already with the 2 billion increase already happening and a significant promise that it may happen for the third, if that were to be the case, that would be about a 20 increase for nih over the course of three years, which is a very encouraging sign and again, im grateful in this area a where so few things seem to be bipartisan, medical Research Continues to be so and much credit to you and your colleagues for keeping that alive. And ill ask one last question of dr. Gottlieb and you, with all of the excitement and breath taking by medical advance, do you see any as you talk to High School Students or College Students, do you see any increase in interest in biology . I dont talk to high school and College Students that much. I will tell you my girls and eight and four. I think that theres an increase excitement among those training in medicine right now about what the future holds, i will affirm that. I have a lot of contact with residents and medical students and i see an increased excitement about what theyre going to be able to accomplish over the course of their careers that i couldnt complirn accomplish over my medical career. Dr. Collins. When i go to university and talk and meet with students, thats the best part of any visit to an academic students. I want to meet with the students and dont want anybody else in the room because i want to hear from them. And hear anxiety, and that things are brighter the sense of trouble is probably beyond what maybe it ought to be considering the path that were on. Boy, do i hear excitement about the scientific opportunities. If you can quickly switch to that topic, then the spark goes into the conversation and the eyes light up and this graduate students tells you about the experiments theyre doing that week and how excited they are about what they can do. There are things that a single student can do right now that might have taken a team of ten people five years to do. The technology has come along so quickly and the use of big data acomputational. If somebody wants a time in science. I hope that the one that senator baldwin is talking about will be. We want the best and brightest to join us so this can happen. Thank you. The hearing record will be open for ten days and members can submit additional within that time if theyd like. The committee will meet on tuesday 20es 12th. Cost of Prescription Drugs and National Academy of sciences, engineering and medicine report. Making medicines affordable a national imperative. The third in the hearing on drug prices which has been requested by both democratic and republican members of our committee and next wednesday we have our oversight hearing on the Mental Health aspects of the cures act. Thank you for being here today. The committee will stand adjourned. Adjourned. [inaudible conversations] [inaudible conversations] [inaudible conversations] [inaudible conversations] this news item from just a short time ago on the hill. The Congressional Budget Office has drastically lowered its estimate of the cost to renew Health Insurance program for low income children. Likely making it easier for lawmakers to agree on a plan for extending the program. In the letter sent to Senate Finance Committee Chair orrin hatch, cbo said that financing the childrens Health Insurance program or chip would cost about 800 million over the next ten years. And thats far lower than analysts original estimate of 8. 2 billion. Funding for low income 9 the million income children, in the