Transcripts For CSPAN3 House Hearing On Coronavirus Response

Moment and a reflection of the part we all have to play when slowing the spread of covid19. In light of this remote format i also some reminders to the members about conduct of the hearing. Members keep their video feed on as long as they are present at the hearing. Members are responsible for muting and unmuting their microphones and please keep your microphones muted when youre speaking. And finally if members have documents they wish to submit for the record please email to the committee whose email address was circulated prior to the hearing. Well, good afternoon, and well coom the First Virtual hearing of the committee on investigations and oversight. Today were discussing a critical issue. Research into repurposing existing therapeutic drugs for covid19 treatment as well as scientific basis for the federal governments evaluation of such drugs. I appreciate our witnesses being here under these unusual circumstances, but these are very important issues, and we look forward to your testimony. Todays hearing resolves around humanitys tools in the current pandemic. Repurposing therapeutic drugs. The appeal of repurposing existing therapeutics is obvious. These drugs have already been developed, already manufactured. In some cases can quickly be accessed in large quantities. For drugs that have already been approved to treat other diseases a certain amount of safety data is often available to regulators. In the absence of any covid19 vaccine on a novel treatment existing therapeutics could potentially offer critical assistance for severely ill patients and bridge the gap until more prevention and Treatment Options become available. But with great promise comes great concerns. Since existing therapeutics have demonstrated benefits in other circumstances it can be all too easy in the midst of a pandemic to cut corners and pursue shortcuts. And sanctioned on the basis of factual evidence regarding safety and efficacy in their new context. And while the process itself should be flexible and as fast as possible the integrity of the process must be firmly up held. The Research Communitys evidence based evaluation of existing therapeutics must be paramount, and Political Considerations must never enter into the equation for any specific treatment. Politics is allowed to interfere and Scientific Research may be distorted, nations may be placed at risk and the public in our Public Health mechanism may be shaped. Unfortunately were seeing some consequences of some political interference in the controversy vounldsi surrounding two existing therapeutic drugs. In march the fda issued an emergency use authorization for these drugs as covid19 treatments. The Scientific Evidence to support this decision was dangerously thin, but the Political Considerations were clear and our president became the Worlds Largest cheerleader for both drugs. Researchers, experts and former fda officials and now nearly three months later the fda just this week revoked the emergency authorization acknowledging Clinical Data showing the drugs, quote, may not be effective to treat covid19 and that, quote, potential benefits of such use do not outweigh the known and potential risks. This is the clear example of the dangers of allowing Political Considerations to distort what should be a scientific process. This hearing will explore the importance of exploring Scientific Research and repurposi repurposing existing therapeutics and the cost of resisting politics. The federal Government Supports many of these efforts, but there may be more we can do as policy makers to provide researchers who are funding and the conditions they feed to make progress. And there may also be more we can do to uphold the integrity and the role of science as the foundation for federal efforts in this area. Our witnesses bring diverse perspectives with deep experience in these areas. I look forward to learning from them about the most effective way for the federal government to support research and to repurpose existing therapeutics and for this pandemic and probably unfortunately probably for the next one. Well, thank you all. And the chair will now recognize there lucas. Thank you, chairman foster. And thank you to our witnesses for participation today. The covid19 pandemic is unlike anything weve faced since the 1918 spanish flu. In those days we had very few tools to slow the spread of the virus, develop treatments or produce a vaccine to make ourselves immune to it. Thankfully that has changed. Our nations enterprise including government, academia, and industry has the expertise and resources to fight this pandemic. We have super computers, advanced manufacturing techniques and even advanced photon sources being used to fight covid19. From ppe manufacturing to repurposing existing therapeutics americas Scientific Community has heeded the call to action. An excellent example of the publicprivate collaboration, leveraging technology to fight a common cause is the covid19 High Performance compute and sourcing. Covid19 researchers can access the worlds most powerful Computing Resources through complex models and develop large numbers of calculations at astonishing speeds. By leveraging these Computing Resources and deploying Artificial Intelligence and Machine Learning techniques researchers can determine i should say which drugs have the potential to be repurposed against covid19 at a speed and scale previously unthinkable. Technology will continue to play a Critical Role in saving lives and preventing the spread of covid19. And our federal Research Enterprise must have access to the resources and Technology Necessary to do their jobs and do it well. Thats why i introduced the Covid Research act of 2020 which would create a working group to address Infectious Diseases. This deal authorizes 50 million for Infectious Research program for the next few years. Working together with nasa and the nsf this Program Gives us the ability to utilize the federal governments Computing Resources to respond to Infectious Diseases. Our National Labs have already demonstrated the value of using High Performance computing in advance Research Facilities to model novel coronavirus, understand its effects on human cells and predict its spread. But im pleased to learn there is work under way that is particularly relevant to repurposing therapeutics to fight covid19. And thank you dr. Stevens for being here today. I look forward to learning more about this important work. And more broadly id like to extend my thanks to the entire Scientific Community, researcher after researcher, lab after lab pivoting immediately to fight covid19 when it reached our shores. I said one of our most important responsibilities is to tell the story of science and to make sure our constituents understand the tremendous research being done and why it matters to the next generation of americans thissterry in particular of how american scientists, researchers and engineers responded to covid19 is one everyone should know. With that, mr. Chairman, i yield back. Thank you. And there are members who wish to submit at this point. At this point, i would like to introduce the witnesses. Our first witness is dr. Peter lurie. Dr. Lurie is the president of the center for science and public interest, a Nonprofit Health Advocacy Group based in washington, d. C. He held several positions at the food and drug administration, including associate commissioner for Public Health strategy and analysis. He served nearly eight years as a top official at the fda. Our next witness is dr. James finnegan. Hes doctor of the respiratory centers of excellence at National Jewish health, the nations leading respiratory hospital. Hes also director of the lung Cancer Screening program. Dr. Finnegan is a pullmmonologi with a focus on lung cancer and injury. Our third witness is dr. Rick stevens, hes the associate lab director at argone national laboratory. He also serves as the leader of their computing initiative. Hes worked at argone labs since 1962. Dr. Rome is an associate professor at Brigham Womens hospital in boston, massachusetts. Hes also a Postdoctoral Research fellow at Harvard Medical School. His Academic Research focuses on the fda approval process for drugs and medical devices as well as the effect of federal policies and regulations on drug pricing and utilization. As our witnesses should know, each of you have five minutes for your spoken testimony. Your written thome will be included in the record for the hearing, and when you all have completed your spoken testimony, well begin with questions. Each member will have five minutes to question the panel. And if there is time, we may be able to have a second round of questions from those members with questions. Well start with dr. Leury. Well, thank you, chairman foster, Ranking Member lucas, and other Committee Members for inviting me to testify on this important topic. For this testimony, im defining repurposed drugs as approved drugs for second indication for covid19 and sort, some of our witnesses may use other definitions. Unfortunately, the unmistakable allure of repurposed drugs is not enough on its own. Effectiveness for one condition does not guarantee effectiveness for a second even closely related condition. Populations may be demogra demographically and medically different, so they may have limited relevance. The product may be administered in different doses and by different routes. Lets look at two repurposed drugs. Chloroquine and hydroxychloroquine, which im considering together, will likely have languished well down the list of candidates for covid19, and may not be catapulted to prominence by president trumps comments. March 21st, the president described them as, quote, one of the biggest Game Changers in the history of medicine. And later stated he was taking the drug himself. The ultimate celebrity endorsement. On march 28th, under pressure from the administration, fda granted the drugs an emergency use authorization, eua, but the evidence provided was less than that provided for many previous euas. Eventually, the scientific process played itself out. With several observation studies that showed no benefits for the drugs or even indicated that mortality rates were higher. Fda issued a warning that the drugs caused life threatening heart arrythmias. The first suggested that the product was ineffective in preventing infection among those exposed to the virus, and the second that it was also ineffective in treating covid itself. On june 15th, fda revoked the uea. What can we learn from this embarrassment . Well, first, we should adhere to accepted methods of Drug Discovery even in a pandemic. Its the painstaking process of trials even if its definitive evidence of lack of evidence. Second, the patients in the president s phrase, did have a lot to lose. Life threatening arrythmias were fairly common, even patients without covid19 suffered, as those needing hydroxychloroquine for its fdaf approved conditions had difficulty obtaining the drug. Finally, the president s announcements distorted the Overall Research effort for covid19. It is inconceivable that left to their own devices, scientists would have designed over 150 randomized control trials assessing the effectiveness of these drugs. How many more promising drugs were left unstudied or understudied as researchers pivoted to address the headlines . A second problematic repurposed drug was an over the counter heart burn drug also known as pepcid, seemingly unlikely drug for covid19. One of its primary advocates is boston physician named Michael Callahan who is also a consultant on the start of the assistant secretary for preparedness and response, dr. Robert kadlec. Under the doctors direction, dr. Callahan, having advocated for the drug, insists a Pharmaceutical Company and a hospital to prepare an application for funding to conduct a trial. Shortly thereafter, the doctor ordered a hefty 21 Million Contract to these entities. Senior officials were cut out of the granting process. There are two other prom nnlts drugs worth mentioning here. Remdesivir is the only drug so far proved effective against covid2, but its not a repurposed drug, at least in my definition. Its an unapproved drug demonstrated to be effective in a study funded by nih. The second drug, dex amethazone is the first drug to reduce mortality in patients with covid19. Whether its a repurposed drug is a matter of definition as its long been approved but often considered as a general treatment for respiratory illness based on its inflammatory activity. But the benefits of these two drugs were demonstrated the Old Fashioned way, through rigorous randomized control trials. Interestingly, the dexa methazone results are derived from the same british study that reported the ineffectiveness of hydr hydroxychloroqui hydroxychloroquine. That trial is very large and able to test many therapies simultaneously. The testing in the United States has been fragmented, resulting in relatively small studies, often testing the same drug with some studies struggling to enroll patients. In conclusion, so far in this pandemic, effective treatments have not been identified by anecdote, by wishful thinking, by president ial pronouncement, or by questionable contracting practices. They were identified instead by the fair, transparent, and systematic application of the very scientific principles that for decades had delivered so many safe and effective treatments. But when we departed from these principles, precious time was lost, resources were squandered and some patients paid with their lives. Thank you. Thank you. And our next witness is dr. Finnegan. Now recognized for five minutes. Thank you. I would like to thank the members of the subcommittee for theviting me to speak on my experiences as a clinical investigator during the covid19 pandemic. Im a pullman air and Critical Care physician at National Jewish health in denver, colorado, where i see patients in our pullmmonary clinic. Its dedicated exclusively to medical research and to patients with respiratory, cardiac, immune, and related disorders. We work with several hospitals in colorado including st. Josephs hospital and have established respiratory institutes in new york in partnership with mt. Sinai Health System and in philadelphia with jefferson health. I have close to two decades of basic translational and Clinical Research experience and currently help lead our covid19 Clinical Research program. Responding to this pandemic has required a complete reorientation of our clinical and Research Programs at National Jewish. Clinically, we reorganized our work force and Physical Plant to diagnose and treat covid19 patients while simultaneously planning for the worst case scenario. For our Research Operations, it meant halting existing studies and starting new studies as quickly as possible all with much of our staff working remotely. Many of these are basic Scientific Investigations to identify new targets for treatment. We have gone from zero covid19 clinical studies to ten or more therapeutic trials in various stages of development over the past 12 weeks. Prior to embarking on any specific research study, each trial requires a number of time consuming steps. Including protocol review, assessment of our ability to perform the trial as designed, determination of any conflicts with ongoing trials, budget negotiation, and agreement on contracting terms. This process ordinarily takes three months or longer. During this crisis, we have been able to cut that time to a few weeks. For a Pharmaceutical Company or other study sponsor, this process must be repeated at every study site. As an example, the remdesivir study had 16 sites. Reflecting on our experience at National Jewish health during this pandemic, i believe three points should be highlighted. First, to rapidly deploy Clinical Trials of new or repurposed drugs, preexisting organized network of sites is essential. The recently announced nihled example is an example of that. That stands for accelerating covid19 therapeutics and vaccines and is a First Virtual<\/a> hearing of the committee on investigations and oversight. Today were discussing a critical issue. Research into repurposing existing therapeutic drugs for covid19 treatment as well as scientific basis for the federal governments evaluation of such drugs. I appreciate our witnesses being here under these unusual circumstances, but these are very important issues, and we look forward to your testimony. Todays hearing resolves around humanitys tools in the current pandemic. Repurposing therapeutic drugs. The appeal of repurposing existing therapeutics is obvious. These drugs have already been developed, already manufactured. In some cases can quickly be accessed in large quantities. For drugs that have already been approved to treat other diseases a certain amount of safety data is often available to regulators. In the absence of any covid19 vaccine on a novel treatment existing therapeutics could potentially offer critical assistance for severely ill patients and bridge the gap until more prevention and Treatment Options<\/a> become available. But with great promise comes great concerns. Since existing therapeutics have demonstrated benefits in other circumstances it can be all too easy in the midst of a pandemic to cut corners and pursue shortcuts. And sanctioned on the basis of factual evidence regarding safety and efficacy in their new context. And while the process itself should be flexible and as fast as possible the integrity of the process must be firmly up held. The Research Community<\/a>s evidence based evaluation of existing therapeutics must be paramount, and Political Considerations<\/a> must never enter into the equation for any specific treatment. Politics is allowed to interfere and Scientific Research<\/a> may be distorted, nations may be placed at risk and the public in our Public Health<\/a> mechanism may be shaped. Unfortunately were seeing some consequences of some political interference in the controversy vounldsi surrounding two existing therapeutic drugs. In march the fda issued an emergency use authorization for these drugs as covid19 treatments. The Scientific Evidence<\/a> to support this decision was dangerously thin, but the Political Considerations<\/a> were clear and our president became the Worlds Largest<\/a> cheerleader for both drugs. Researchers, experts and former fda officials and now nearly three months later the fda just this week revoked the emergency authorization acknowledging Clinical Data<\/a> showing the drugs, quote, may not be effective to treat covid19 and that, quote, potential benefits of such use do not outweigh the known and potential risks. This is the clear example of the dangers of allowing Political Considerations<\/a> to distort what should be a scientific process. This hearing will explore the importance of exploring Scientific Research<\/a> and repurposi repurposing existing therapeutics and the cost of resisting politics. The federal Government Supports<\/a> many of these efforts, but there may be more we can do as policy makers to provide researchers who are funding and the conditions they feed to make progress. And there may also be more we can do to uphold the integrity and the role of science as the foundation for federal efforts in this area. Our witnesses bring diverse perspectives with deep experience in these areas. I look forward to learning from them about the most effective way for the federal government to support research and to repurpose existing therapeutics and for this pandemic and probably unfortunately probably for the next one. Well, thank you all. And the chair will now recognize there lucas. Thank you, chairman foster. And thank you to our witnesses for participation today. The covid19 pandemic is unlike anything weve faced since the 1918 spanish flu. In those days we had very few tools to slow the spread of the virus, develop treatments or produce a vaccine to make ourselves immune to it. Thankfully that has changed. Our nations enterprise including government, academia, and industry has the expertise and resources to fight this pandemic. We have super computers, advanced manufacturing techniques and even advanced photon sources being used to fight covid19. From ppe manufacturing to repurposing existing therapeutics americas Scientific Community<\/a> has heeded the call to action. An excellent example of the publicprivate collaboration, leveraging technology to fight a common cause is the covid19 High Performance<\/a> compute and sourcing. Covid19 researchers can access the worlds most powerful Computing Resources<\/a> through complex models and develop large numbers of calculations at astonishing speeds. By leveraging these Computing Resources<\/a> and deploying Artificial Intelligence<\/a> and Machine Learning<\/a> techniques researchers can determine i should say which drugs have the potential to be repurposed against covid19 at a speed and scale previously unthinkable. Technology will continue to play a Critical Role<\/a> in saving lives and preventing the spread of covid19. And our federal Research Enterprise<\/a> must have access to the resources and Technology Necessary<\/a> to do their jobs and do it well. Thats why i introduced the Covid Research<\/a> act of 2020 which would create a working group to address Infectious Disease<\/a>s. This deal authorizes 50 million for Infectious Research<\/a> program for the next few years. Working together with nasa and the nsf this Program Gives<\/a> us the ability to utilize the federal governments Computing Resources<\/a> to respond to Infectious Disease<\/a>s. Our National Labs<\/a> have already demonstrated the value of using High Performance<\/a> computing in advance Research Facilities<\/a> to model novel coronavirus, understand its effects on human cells and predict its spread. But im pleased to learn there is work under way that is particularly relevant to repurposing therapeutics to fight covid19. And thank you dr. Stevens for being here today. I look forward to learning more about this important work. And more broadly id like to extend my thanks to the entire Scientific Community<\/a>, researcher after researcher, lab after lab pivoting immediately to fight covid19 when it reached our shores. I said one of our most important responsibilities is to tell the story of science and to make sure our constituents understand the tremendous research being done and why it matters to the next generation of americans thissterry in particular of how american scientists, researchers and engineers responded to covid19 is one everyone should know. With that, mr. Chairman, i yield back. Thank you. And there are members who wish to submit at this point. At this point, i would like to introduce the witnesses. Our first witness is dr. Peter lurie. Dr. Lurie is the president of the center for science and public interest, a Nonprofit Health<\/a> Advocacy Group<\/a> based in washington, d. C. He held several positions at the food and drug administration, including associate commissioner for Public Health<\/a> strategy and analysis. He served nearly eight years as a top official at the fda. Our next witness is dr. James finnegan. Hes doctor of the respiratory centers of excellence at National Jewish<\/a> health, the nations leading respiratory hospital. Hes also director of the lung Cancer Screening<\/a> program. Dr. Finnegan is a pullmmonologi with a focus on lung cancer and injury. Our third witness is dr. Rick stevens, hes the associate lab director at argone national laboratory. He also serves as the leader of their computing initiative. Hes worked at argone labs since 1962. Dr. Rome is an associate professor at Brigham Womens<\/a> hospital in boston, massachusetts. Hes also a Postdoctoral Research<\/a> fellow at Harvard Medical School<\/a>. His Academic Research<\/a> focuses on the fda approval process for drugs and medical devices as well as the effect of federal policies and regulations on drug pricing and utilization. As our witnesses should know, each of you have five minutes for your spoken testimony. Your written thome will be included in the record for the hearing, and when you all have completed your spoken testimony, well begin with questions. Each member will have five minutes to question the panel. And if there is time, we may be able to have a second round of questions from those members with questions. Well start with dr. Leury. Well, thank you, chairman foster, Ranking Member<\/a> lucas, and other Committee Members<\/a> for inviting me to testify on this important topic. For this testimony, im defining repurposed drugs as approved drugs for second indication for covid19 and sort, some of our witnesses may use other definitions. Unfortunately, the unmistakable allure of repurposed drugs is not enough on its own. Effectiveness for one condition does not guarantee effectiveness for a second even closely related condition. Populations may be demogra demographically and medically different, so they may have limited relevance. The product may be administered in different doses and by different routes. Lets look at two repurposed drugs. Chloroquine and hydroxychloroquine, which im considering together, will likely have languished well down the list of candidates for covid19, and may not be catapulted to prominence by president trumps comments. March 21st, the president described them as, quote, one of the biggest Game Changers<\/a> in the history of medicine. And later stated he was taking the drug himself. The ultimate celebrity endorsement. On march 28th, under pressure from the administration, fda granted the drugs an emergency use authorization, eua, but the evidence provided was less than that provided for many previous euas. Eventually, the scientific process played itself out. With several observation studies that showed no benefits for the drugs or even indicated that mortality rates were higher. Fda issued a warning that the drugs caused life threatening heart arrythmias. The first suggested that the product was ineffective in preventing infection among those exposed to the virus, and the second that it was also ineffective in treating covid itself. On june 15th, fda revoked the uea. What can we learn from this embarrassment . Well, first, we should adhere to accepted methods of Drug Discovery<\/a> even in a pandemic. Its the painstaking process of trials even if its definitive evidence of lack of evidence. Second, the patients in the president s phrase, did have a lot to lose. Life threatening arrythmias were fairly common, even patients without covid19 suffered, as those needing hydroxychloroquine for its fdaf approved conditions had difficulty obtaining the drug. Finally, the president s announcements distorted the Overall Research<\/a> effort for covid19. It is inconceivable that left to their own devices, scientists would have designed over 150 randomized control trials assessing the effectiveness of these drugs. How many more promising drugs were left unstudied or understudied as researchers pivoted to address the headlines . A second problematic repurposed drug was an over the counter heart burn drug also known as pepcid, seemingly unlikely drug for covid19. One of its primary advocates is boston physician named Michael Callahan<\/a> who is also a consultant on the start of the assistant secretary for preparedness and response, dr. Robert kadlec. Under the doctors direction, dr. Callahan, having advocated for the drug, insists a Pharmaceutical Company<\/a> and a hospital to prepare an application for funding to conduct a trial. Shortly thereafter, the doctor ordered a hefty 21 Million Contract<\/a> to these entities. Senior officials were cut out of the granting process. There are two other prom nnlts drugs worth mentioning here. Remdesivir is the only drug so far proved effective against covid2, but its not a repurposed drug, at least in my definition. Its an unapproved drug demonstrated to be effective in a study funded by nih. The second drug, dex amethazone is the first drug to reduce mortality in patients with covid19. Whether its a repurposed drug is a matter of definition as its long been approved but often considered as a general treatment for respiratory illness based on its inflammatory activity. But the benefits of these two drugs were demonstrated the Old Fashioned<\/a> way, through rigorous randomized control trials. Interestingly, the dexa methazone results are derived from the same british study that reported the ineffectiveness of hydr hydroxychloroqui hydroxychloroquine. That trial is very large and able to test many therapies simultaneously. The testing in the United States<\/a> has been fragmented, resulting in relatively small studies, often testing the same drug with some studies struggling to enroll patients. In conclusion, so far in this pandemic, effective treatments have not been identified by anecdote, by wishful thinking, by president ial pronouncement, or by questionable contracting practices. They were identified instead by the fair, transparent, and systematic application of the very scientific principles that for decades had delivered so many safe and effective treatments. But when we departed from these principles, precious time was lost, resources were squandered and some patients paid with their lives. Thank you. Thank you. And our next witness is dr. Finnegan. Now recognized for five minutes. Thank you. I would like to thank the members of the subcommittee for theviting me to speak on my experiences as a clinical investigator during the covid19 pandemic. Im a pullman air and Critical Care<\/a> physician at National Jewish<\/a> health in denver, colorado, where i see patients in our pullmmonary clinic. Its dedicated exclusively to medical research and to patients with respiratory, cardiac, immune, and related disorders. We work with several hospitals in colorado including st. Josephs hospital and have established respiratory institutes in new york in partnership with mt. Sinai Health System<\/a> and in philadelphia with jefferson health. I have close to two decades of basic translational and Clinical Research<\/a> experience and currently help lead our covid19 Clinical Research<\/a> program. Responding to this pandemic has required a complete reorientation of our clinical and Research Programs<\/a> at National Jewish<\/a>. Clinically, we reorganized our work force and Physical Plant<\/a> to diagnose and treat covid19 patients while simultaneously planning for the worst case scenario. For our Research Operation<\/a>s, it meant halting existing studies and starting new studies as quickly as possible all with much of our staff working remotely. Many of these are basic Scientific Investigations<\/a> to identify new targets for treatment. We have gone from zero covid19 clinical studies to ten or more therapeutic trials in various stages of development over the past 12 weeks. Prior to embarking on any specific research study, each trial requires a number of time consuming steps. Including protocol review, assessment of our ability to perform the trial as designed, determination of any conflicts with ongoing trials, budget negotiation, and agreement on contracting terms. This process ordinarily takes three months or longer. During this crisis, we have been able to cut that time to a few weeks. For a Pharmaceutical Company<\/a> or other study sponsor, this process must be repeated at every study site. As an example, the remdesivir study had 16 sites. Reflecting on our experience at National Jewish<\/a> health during this pandemic, i believe three points should be highlighted. First, to rapidly deploy Clinical Trials<\/a> of new or repurposed drugs, preexisting organized network of sites is essential. The recently announced nihled example is an example of that. That stands for accelerating covid19 therapeutics and vaccines and is a Public Private<\/a> partnership to streamline Clinical Trials<\/a> using existing Clinical Networks<\/a>. Another example is the prevention and treatment of acute lung injury or ptal network. Academic medical centers dedicated to studying acute lung injury and distress syndrome. This network has been repurposed to study the clinical features and possible treatments of covid19. For the past month, the network developed and launched two Research Protocols<\/a> and both of these will likely be completed in the coming weeks. Networks like these can be used in collaboration with industry as a platform to launch quickly new studies on promising treatments. Second, we need Ongoing Investigation<\/a> of sars covid2 and covid19 to understand the virus and merckinisms of this disease. Much of this research will be what we call preclinical studies cells in animal models to expand our understanding of covid19. However, this can only exist if we maintain a Robust National<\/a> medical Research Mission<\/a> and infrastructure. Dividends from this kind of research are not always immediately apparent, however, a basic understanding of the underlying science of this disease will drive development of new therapeutics moving forward, both for this pandemic and to prepare us for the next one. These studies can help identify which new drugs are most promising and can inform Clinical Trials<\/a>. Third, another pandemic is likely in our future. What that will be, we dont know, but we should be planning now on how to incorporate a full Research Operation<\/a> into any future pandemic response. I have been impressed with the Research Community<\/a> reaction to this crisis. However, even with this effort, even with this effort, an organized National Response<\/a> was not launched until several months into the pandemic. Coordination of what research will be performed and how it will be executed, respective roles of organizations such as the fda, nih, cdc, barta, as well as industries should be considered. Research is as important to defeating this pandemic and being ready for the next one as personal protective equipment, intensive care units, and ventilators. Thank you. Thank you. That was beautifully timed. The chairman appreciates the accuracy of your time estimate. Well now recognize dr. Stevens for five minutes. Whoops. Rick, mute. Okay. I thought they were going to unmute me. So, thank you, chairman foster, Ranking Member<\/a> lucas, and members of the subcommittee for inviting me here to talk about our work related to covid19. My group and collaborator work primarily with cocomponents of this. Im going to talk a little bit about what were doing. Im speaking for argonne. My work focuses on employing High Performance<\/a> computer methods to problems in science and medicine. I irked in this combination space for over 25 years. And related to covid19, the doe c. A. R. E. S. Act funded nine Laboratory Consortium<\/a> product that is working on molecular design for covid. As part of the effort, were looking at repurposable drugs as well as compounds. Let me tell you a little bit about the virus and why this drug search process is challenging. The virus is an rna virus. It codes for about 30 proteins. About two thirds of those proteins commandeer host cell machinery to make copies of the virus, about a third of them are involved in the virus. Of those proteins, theres perhaps ten, maybe a little more than that, in the virus, that the virus comes for that are plausible drug targets. The virus proteins also interact with the host, perhaps as many as 300 protein interactions appear to occur, and a number of those host proteins could also be drug targets. Now, its also important to know this virus is very closely related to sars1, and so since around 2003, the community has had access to information about its genome and has been working on this, and thanks to the dna sources and my sources elsewhere, we have very detailed atomic structural maps of these proteins and in the last few months, we have acquired more of these structural maps. But whats not known is essentially how existing drugs interact with these virus targets. That has not bib the subject of largescale computational work prior to now and not the study of largescale environmental work. What im working in, and my collaborators at the university of chicago and at the Nine National<\/a> laboratories that are collaborating with us, are really looking at how we can apply High Performance<\/a> computing to scan not only the 2500 or so licensed drugs worldwide and the 7,000 or so drugs that are in the pipeline, but literally billions of molecules that we know can exist. In this effort, its also critical to recognize the three main infrastructures that were using. Were using supercomputers, the fastest machines in the world that exist at the doe labs like at argonne and oak ridge. Also, machines that the nsf supports. We also use the light sources. These are critical for determining structures of proteins and for determining structure with molecules, potentially inhibitors bound into these proteins so we can understand their mechanism. And the third resource thats critical for this effort is the nih funded biocontainment laboratories, the regional biocontainment laboratories stood up after 9 11, after the scare of the anthrax scare and the emerging concern about emerging pathogens and these exist at various locations in the country. The one that is close to me is the ht rickets lab operated by the university of chicago. Were also using a laboratory at the university of Tennessee Health<\/a> sciences center. Both centers are critical because they can work on active virus, virus thats essential viruses are not alive, but viruses where we can look at the entire life cycle. So essentially, what our program is is to use the computers to search for molecules, including all the repurposing drugs that get scored on each individual molecular target. Drugs that appear to have high potential get forwarded to our experimental collaborators. Theres lots of advice we can give about future pandemics but one Thing Holding<\/a> back the Scientific Community<\/a> right now is the lack of biochemical asseys with the specific virus proteins. The National Institute<\/a> of health is investigating, the National Laboratories<\/a> are investing in that, but thats a major bottleneck. In the future, we need to invest in asas. They need to be stockpiles. They should be made available in these biocontainment laboratories so in the future rapid screening can happen on any new outbreak. Ill leave it at that. Thank you. Well, thank you. Well, at this point, well begin our first round of questions and the chair will recognize himself for five minutes here. Dr. Rome and dr. Lurie, theres been mention of what is being set up in europe and internationally. And as opposed to what has happened in the United States<\/a> in terms of the coordination of the large number of Clinical Trials<\/a>. Could either of you say a little bit about what we get right thats thats better or worse than whats done in other countries and other International Collaborations<\/a> and whether were insufficiently or sufficiently connected to those. Let me let the doctor answer. Mr. Chairman apologies. My apologies. Thank you, dr. Rome. I was fumbling multiple windows here. And thank you for that. All right. Doctor, youre now recognized for five minutes. Thank you, sorry about that. So chairman foster, Ranking Member<\/a> lucas, and members of the subcommittee, thank you for inviting me. Im a practicing primary care physician and a Health Policy<\/a> researcher at Harvard Medical School<\/a> and brigham and Womens Hospital<\/a> in boston. Im a member of the division of the program of regulation, therapeutics and law, and Interdisciplinary Group<\/a> that studies regulation, use, and cost. Im honored to be here today to talk to you about the process for studying and approving repurposed drugs during the covid19 pandemic. Drug development can be a lengthy process and repurchasing several medications with existing data about safe use in humans allowed Clinical Trials<\/a> to begin early in the pandemic. As a result, just four months after the first covid19 patient was reported in the u. S. , several highquality Clinical Trials<\/a> had provided solid evidence relating to at least four drugs, two of which have proven effective. Al lowcost generic steroid th can be readily supplies by clinicians and remdesivir that has not yet been approved by the fda but is now available under an emergency use authorization. However, we have also witnessed examples of how the process for testing and approving drugs can go awry. As exemplified by the case of hydroxychloroquine. We should learn from our past missteps as we move forward, and our experience so far suggests four key actions grisz should take. Congress should hold all Government Agencies<\/a> accountable for making statements and acting based on the best available Scientific Evidence<\/a>. Hydroxychloroquine was widely touted by President Donald Trump<\/a> and was issued an maernls use authorization by the fda based on preclinical and limited anecdotal evidence that turned out to be unreliable. These actions led to widespread use of the drug which exposed patients to risk, led to shortages at pharmacies, and diverted attention and resources that might have been dedicated to other potential therapies. Second, congress should invest heavily in highquality Clinical Trials<\/a> which are necessary for determining whether drugs are safe and effective. Notably, most of the high quality evidence generated so far during the pandemic has resulted from public funding. Including the u. S. Government in the case of remdesivir, and the United Kingdom<\/a> in the case of dexamethazone. While the pharmaceutical industry will continue to have a role to play, the federal governments leadership and involvement are crucial. Particularly for repurposed drugs which industry may have little or no financial incentive to study. However, such Public Investment<\/a> should be made with the assurance that any medications that are found effective will be priced fairly and distributed equitably to patients who need them. No american should be prevented from accessing potentially lifesaving treatment for covid19 due to cost. Third, congress should invest in a Public Health<\/a> infrastructure and National Clinical<\/a> Trial Network<\/a> that can help shape the research agenda, facilitate Research Across<\/a> multiple sites, and limit duplicative efforts. In several european countries, government and academics have collaborated on large Clinical Trials<\/a> that test multiple repurposed drugs simultaneously. Prime example is the recovery trial. Based out of the university of oxford. This trial has already provided useful information about the lack of effectiveness of hydroxy chlorakwan and the effectiveness of dexamethazone. Finally, congress should amend the process by which the fda issues euas. The level of evidence required to meet the standard of an eua should be clarified and to increase transparency, congress should compel the fda to make all data public at the time the eua is issued. The fda should be directed to apply the same standards for revoking an uea as accompanying it. It should be accompanied by a clear and transparent plan on how it drug should be fairly and equitably distributed. Something lacking for hydr hydroxychloroquine and remdesivir. Issuance should be accompanied by a collection of data about the drugs safety and effectiveness. Our experiences so far studying repurposed drugs in the covid19 pandemic have shown we need not choose between rigorous Scientific Evidence<\/a> and speed. We can have both. As our fight to control the covid19 pandemic continues, Congress Must<\/a> assure we uphold a drug approval process that upholds science. In a recent viewpoint, we argued that, quote, the health of individual patients and the public at large will be best served by remaining true to our timetested approach and Clinical Trial<\/a> evidence and drug evaluation. Thank you. Thank you. And my apologies again for having skipped your testimony in the order. I guess thats the danger that occurs when i have read your testimony in advance and feel less need to hear it directly from you. And so i guess i will repeat my question, which was largely directed at your testimony. To say a little bit more about the differences in the way things are being done internationally versus in the u. S. And what lessons we might learn from that. Thank you. Yeah. Im appreciative. So your question is a good one. We have had two successes in this pandemic so far with dexamethazone and remdesivir. One was primarily driven in the u. S. , and the other came from funding from other countries. And i can say that most of the large Clinical Trials<\/a> that are being conducted, especially the ones that were started very, very early in the pandemic and are likely to get us results in a timely fashion were led by our peers in europe and other countries. And definitely the u. S. Should and Going Forward<\/a> in this pandemic and future pandemics, use those efforts and become a leader in the world for running these sorts of Clinical Trials<\/a>. In the case of the work, the antiinflammatory that worked in england, was that funded by the manufactur manufacturer . If all of the Clinical Trials<\/a> are funded by manufacturers, they will prefer drugs for which they have an intellectual property or manufacturer position in, and that we may fo forego equally promising drugs that are off patent or generic drugs. Is that handled differently in other countries or are essentially all trials worldwide funded by the manufacturer . It was funded by the uk government. Dexamexazone is likely tabe true of many of these repurposed drugs which may be older, off patent, generic drugs which are widely available and great for patients, but not necessarily a good investment from the perspective of the manufacturer. Not only that, the Clinical Trial<\/a> for remdesivir, which is still patented drug, owned by gilead, the key Clinical Trial<\/a> upon which were using the drug was funded by the u. S. Government, by the naid. And this is a case where they should have been running the key Clinical Trials<\/a> and had a trial testing two doses of the medication against itself, leaving the key Clinical Trial<\/a> to come to the u. S. Government. They have a patent on that drug and can financially benefit from it when or if and when it gets fda approved. Thank you. Any comments on whats done internationally versus the u. S. And lessons we might learn . I think what the doctor said is spot on the money. Unfortunately, things have been to a certain extent delegated to the pharmaceutical industry and individual academic institutions in this country. What we really need is somebody to coordinate the whole thing. I know that the nih would like to do that. I know the britdi ibritish gove has done so successfully, but we need a stronger hand. Somebody to prioritize the drugs, figure out the ones that matter the most, and then do proper trials on them. I guess i would add to what the doctor said in the following way. Its tempting in the setting of a pandemic to say we need to cut corners. But actually, the pandemic is almost the best place to stick with the usual game plan. Because there are so many patients, im sorry to say, and the disease makes you ill so quickly, im sorry to say, that theres more than enough statistical power for people to do the randomized control trials which we expect drug approval to be based upon. So lets stick with the methods that work. Lets not use the pandemic as some excuse for corner cutting or deregulation. All right. Yeah, thats interesting. Do you think there may be opportunities that were overlooking for sort of lightweight outpatient Clinical Trials<\/a> . You can imagine to have a quick but scientifically valid look at hydroxychloroquine, for example, if you had any one, some fraction of the large number of people who tested positive were immediately given the option of being screened and just on an outpatient basis given that we could have rapidly understood without a lot of safety concern. There are opportunities there we should think about . I think there are. But so far, if you look at the totality of the research thats been done, most of it is based on the inpatient setting. That makes a certain kind of sense. These are the sickest patients, after all. The patients on whom you can demonstrate benefit most easily. I agree theres opportunity, but i dont mean that as a criticism of the Research Enterprise<\/a> to date. All right. And that exceeds my five minutes. So i would like to recognize representative lucas. Chairman lucas, for five minutes. Thank you, mr. Chairman. Dr. Stevens, could you provide us with an example of cuttingedge Research Capability<\/a> unique to the Argonne National<\/a> lab and how researchers work toward repurposing existing drugs to treat covid19 . Probably the best example is the use of the advanced photon source to quickly within a few days assuming you can get it, produce a new structure of a viral protein bound to a drug. This is critical to understand whether or not the target is in fact a target that the drug is working on to understand how to use the structure of the protein to interrupt its function. Thats a pretty unique capability. Theres only a handful of places in the u. S. And the world that can do that and do it quickly, and after the pandemic became apparent, argonne had a level of operation. We kept the advanced protonsource up and kept working on determining the structure of the virus intact. Thats a really good example. Could you, along those lines, explain how Argonne National<\/a> lab is working collaboratively with other Research Entities<\/a> towards identifying covid19 drug candidates . So we have a ninelab consortium that includes argonne, oak ridge, brookhaven, livermore, National Laboratories<\/a>, slack, and Pacific Northwest<\/a> labs. Nine labs all working together. We are using large scale computation to computationally screen drugs, billions of drugs. Billions of potential drugs. All existing drugs and billions of molecules that can be potential drugs. The drugs what is most interesting from the computation is immediately procured. Some cases, you cant get them fast enough. For things that succeed in that, you can get a wide application, things we see there we can pass on to animal models and then pass on to clinical cases. It takes a large team to do this. Virologists, physicians, chemists, computer scientists and so on. Because of that large team, in fact, even indications of interesting compounds or drugs were discussed with physicians that were on clinicals, so were benefitting from your advice. As i mentioned earlier, my bill hr6599 focuses on collaboration among federal agencies and aims to create a National Strategy<\/a> for any Infectious Disease<\/a> outbreaks in the future, and certainly well face them in the future again, as the chairman alluded to. Are there any other collaborations were not thinking about that would help you, dr. Stevens. Early on, we established a collaboration between the Doe National Lab<\/a> and the nih, which has Laboratory Activities<\/a> and research groups, so theres linkage. I think whats needed in the framework of your bill is a sustained ongoing network of Research Collaborations<\/a> thats consistently working on problems and sharing data, sharing research, sharing asseys, sharing information, and it involves doe, the nih, probably nsf resources in some cases, the dod, all of the players that are necessary for integrated Public Health<\/a> in this country. In this ongoing collaboration around emerging threats. One last question, dr dr. Stevens. Is there Anything Congress<\/a> can do to help scientists and researchers like yourself do their jobs more efficiently during this pandemic and bring us one step closer to ultimately a cure . I believe that the current activity is exactly what is needed. The funding, the ongoing funding support for these new efforts is of course critical to extend that longer. Were not out of this pandemic yet. I believe the interagency coordination process is working quite well. I believe that the institutions have put together structures to support this within the department of energy, for example, they created the National Virtual<\/a> biotechnology lab, a coordination process across all of the National Labs<\/a> in the u. S. To drive toward a coherent covid19 strategy. Thats working. Continued support of that level of activity is what i recommend. Thank you, doctor. Thank you, mr. Chairman. I yield back. Thank you, and i will now recognize representative bone amaechi for five minutes. Thank you, mr. Chairman. Can you hear me . Yes. Terrific. Well, thank you to chair foster and Ranking Member<\/a> lucas and really to our witnesses today. Thank you for your expertise. We know that covid19 is disproportionately affecting black, latinx, indigenous, and other people of color and theyre contracting the disease and dying at alarming rate. As researchers develop studies and carry out trials, the administration and congress can and must address these disparities and do all we can to encourage or require research that deliberately is inclusive of all demographics and effectively addresses these inequitable outcomes. Recruiting patients to participate in research can be challenging even under ideal settings, but trials can fail if theres a lack of patient enrollment. There are valid reasons why a patient invited to take place in a study may not trust medical researchers or feel comfortable participating and even once a willing participant is identified, there can be barriers to their inclusion. A recent politico article talked about physicians who are conducting nihfunded Clinical Trials<\/a> for remdesivir at sites in boston, new york, and atlanta. They face language barriers in recruiting patients with limited english proficiency. They didnt have consent forms in spanish. They had to work with translartds by phone to explain the study and get consent, and it took extra hours for patients. I know dr. Lurie, you mentioned this, do the witnesses all agree that its important to have diverse representation in studies and trials . Do you all acknowledge thats important . If i may go, i most certainly do. I have not seen specific information about recruitment and how it may vary by ethnicity so far in this pandemic, but i do know that this is not an equal opportunity virus. In all stages of this disease, africanamericans and people of color are at a distinct advantage. Theyre more likely to be exposed to the virus in that theyre more likely to be living in crowded living conditions, more likely to be working in mae meat packing presents, more likely to be Health Care Workers<\/a> on the front lines of the virus. After that, you very often have difficulty gaining access to treatment, in part because of lack of health insurance, and then, within the hospital, you know, the outcomes have not been equal across ethnic groups. Perhaps because of significant Underlying Health<\/a> conditions as well. So all the way across i appreciate that. I dont mean to interrupt, but im also going to ask you and dr. Finigan, are there strategies to get diverse representation in testing and trials . If not, what could not only the government but the medical community do, just on how to build trust in the communities that may have been historically excluded from governmentfunded research . I want to get your thoughts and dr. Finigan. Dr. Finigan, go ahead. Thank you. First off, youre correct. I have seen firsthand in the covid19 pandemic where there have been examples of people who were not recruited adequately or were not recruited because there was a language barrier, there was not an appropriate consent form, that was particularly challenging for people who only spoke spanish. One important thing to note is that theres always a time window in which you can recruit somebody. So typically, you cant recruit somebody into a study in an unlimited time window. You may have to do it within 24 or 48 hours of them being positive, so theres a little bit of a race against the clock in this. So those kinds of barriers really can have significant meaning. I think those things need to be taken account of ahead of time. Its relatively common that africanamericans, latinos, nonwhites are sort of underrepresented in studies. So being ready for that kind of thing ahead of time to make sure they can get adequately enrolled, all the resources are available to them, those things are critical. I know of studies where they got those kinds of resources, those consent forms, but it happened weeks into the rile. So you lost time, you lost patients, and the other critical piece there i think youre getting at is thats a lost opportunity for that person to be in a trial. Our goal is to give every patient the opportunity to enroll in a trial if they want to. And if you cant enroll them because theres not an adequate consent form, lets say, thats a missed opportunity for that patient, and they may lose the chance of being in a trial say, on remdesivir, where theres a benefit. I appreciate that. There was an article this morning, active health newsletter, theres this talk this week this week about a steroid thats being hailed as a breakthrough treatment, but theres also evidence, according to the chair of pharmacology that africanamericans may respond differently to this steroid. As we know, covid19 doesnt discriminate based on somebodys race. Its different unfortunately, but real quickly, we know repurchasing existing drugs is an exactive option because medications have already gone through testing. Can you tell us more about how preclinical testing and Clinical Trial<\/a> phases can be safely accelerated if the drug has already been approved for another use . So there are so there are different ways this can be done, but i think the key is to have sort of an integrated network so you can hit all the phases at once. As has been described, there are things you can do in a computer where you can try to rationally identify drugs. For example, i was a part of a study where one of our investigators builds essentially a Google Program<\/a> where you could put in drugs and then put in the kind of drug you wanted, or the kind of protein you wanted to target, and this Computer Program<\/a> would sort of spit out the drug that you wanted. Then you could marry that to an acid, you could do in a lab where you might have, lets say 500 little wells and you could test different drugs in each one of those wells. So being able to marry those Different Things<\/a> together and being able to do that and rapidly move that into an animal model, those things are important to have that whole spectrum represented, whether thats requires one institution or multiple institutions is important. And i think as was said earlier, having these asas ready to go is important, so thinking about what these might be, whether or not they kill cells or Something Like<\/a> that, those are the things that need to be thought about ahead of time. Im afraid i have to my time is expired. I yield back. Thank you. And well have a little bit of forbearance with representatives who are coming ipon the telephone because they cant see the timer. And well now recognize representative biggs for five minutes. Thank you, mr. Chairman. And thanks, Ranking Member<\/a> lucas, and thank you to each member of the panel. This has been very interesting. As were trying to develop a vaccine and cures for the covid, i see were moving fairly rapidly. It looks like were moving rapidly, and i appreciate dr. Lurie talking about through this maintaining some standards and normalcy, but i guess my question that i want to ask here is, as we go through this and we accelerate these processes, can you address, and i guess ill just open it up to whoever wants to answer this, how can we maintain scientific rigor while we accelerate the development of vaccines and curatives . And each one of you kind of nibbled around the edges here, but im wondering if theres any way that you see that we can maintain that scientific rigor thats so necessary, to really get a handle on this. Well, you know, i think the playbook is clear. The playbook is the playbook we had for decades. The playbook that has produced effective therapy through following that very playbook, through keeping to strong standards. All i think we really need to do is coordinate better, obviously speed things up the way researchers collectively have decided to do by turning their attention to this, and if we keep our standards up, i would like to think that ultimately well have the products that we need. In so that gets me to dr. Rome, who i think mentioned something im in total agreement with. If you could maybe expand that. In euas, one of the things we need to do is be more transparent. If you could address how we do that, how could we best be more transparent . Thank you. I totally agree. Transparency is key with euas. We had two examples of euatutns emergency use authorizations so far. Hydroxychloroquine and chloroquine was the first one. That was based on very little evidence. When it came out, it wasnt clear what evidence the fda had considered and it sort of only later did we learn a little bit about what was going through the minds of the folks at the fda. With remdesivir, we had a topline result published by a Clinical Trial<\/a>, but not until three weeks later did we have the full data released. It was already being shipped out to hospitals and being used and we didnt know necessarily how to best target the drug towards particular patients and we had a limited supply. So absolutely, transparency is key. The fda should make decisions in a consistent way that meet the standard. The standard for an eua is it is reasonable to believe based on the totality of evidence that the drug is likely to be effective. So that reason to believe standard needs to be enforced. When new data comes out, we need to reassess, and we need whatever the data the fda is using to make those decisions to be public at the same moment the eua is issued. Great. Thank you. And im just going to go to dr. Stevens. Dr. Stevens, you mentioned that although repurposing existing drugs may be a fast route to possible trumenteatments, its y likely well need purpose built drugs. Can you expand on how the work youre doing to build purposebuilt drugs specifically . Yeah, so what the team is doing is were trying to produce a set of qualified leads. Compounds that show some promise in the computational work, show some promise in initial functional asseys but are not fully refined as drugs. These would be compounds we would hand over essentially to the pharmaceutical industry and say, heres all the data that we have computed and that we have measured on these compounds. And let them take it from there. And this that kind of handoff has been discussed between labs and pharma. Its the kind of thing that pharma is very interested in because you think of the drug process is a giant funnel. At the top of the funnel, youve got billions of possible molecules out of the all of the possible drug molecules we know of a few billion of them that we thought about in some sense, and we have to narrow that down to handfuls, tens or 20s of compounds that pharmaceuticals can take and do more advanced studies on, can refine and improve the molecules, improve their safety, their effectiveness, the therapeutic window. So what were doing in the Public Sector<\/a> is essentially that big top part of the funnel, and reducing it down in a very public way and open way, set priorities they can then take and invest privately into reforming into drugs. Thats the strategy. Great. I thank you. With that, mr. Chairman, ill yield back. Thank you. And i will now recognize mr mr. Byer for five minutes. Thank you, mr. Chairman, and thank you all of you for being with us. Let me begin with dr. Rome. One of the things in your testimony, you said its imperative we establish a Clinical Trial<\/a> network. Does the one not already exist, and isnt that part of the folks of nih to have established that over the years . Thank you for the question. Yeah, so certainly, we have Small Networks<\/a> of Clinical Trial<\/a>ists, and i think that dr. Finigan can speak to this more, but i would say that the nih does in fact do direct research itself in some cases, as was the case in remdesivir. But in other cases, it will outsource to academics. As was already mentioned, when a study is done at multiple sites, theres a lot of regulatory things that need to happen. You have to assure safety of the Clinical Trial<\/a> through institutional review boards, and that can take a long time. And so look, where i think the efforts need to be is Clinical Trial<\/a>ists and scientists are ready to go and want to act. What needs to be cut down are the things that are super important like maintaining patient safety, but the time to do those things and the time to coordinate across different sites can definitely be cut down on by investing further in those infrastructures. The vision has to be that there is an existing National Network<\/a> of clinical sites, say 50, 100, 300. And in the future crisis go ahead, turn it on. Dr. Finigan, you mentioned at National Jewish<\/a> health, youre working on delineating the structure of the protein. Why would an individual hospital do that rather than the National Labs<\/a> that have all of the big computing machines and the neutron devices and the like devices . You know, so it has to do with a couple things. Number one, ability and interest. We have people who have that ability and can do it, and as i said, everything sort of reoriented towards covid19, so everybody in the hospital dropped what they were doing and started to do new things directed towards covid19. So people who had that ability here worked on that. I think it also speaks to a little bit of a lack of coordination of how this would be attacked from the beginning. So from the beginning, there was not a sort of at least not a publicly announced kind of strategy that was clear to everybody in terms of how things were going to happen, how things were going to get laid out from sort of basic science, understanding some of those basic facts to driving it into Clinical Trials<\/a>, and that creates a fair amount of duplicati duplication, and an example of that, just to answer the question you brought up, there are Clinical Networks<\/a> that have existed and there are lots of them that still exist. Its just that it took several months to utilize those for covid19. They sat not being used for covid19 trials for a period of time, and now theyre starting to get used. And so it may not be creating a new network. It just means understanding that these things exist and you have a strategy ready to go that youre going to use them. Thank you. Dr. Stevens, i was fascinated by the notion that the covid the rna translates into 30 specific proteins. You understand the structure of how theyre folded, and 10 to 20 of them are what creates this issue. And you talk about purpose built. Are you thinking its possible to think, and i think mathematically with your supercomputers, how to tear apart one of those 20 proteins . Well, were building physics based models and aibased models to custom design inhibitor molecules for each of those proteins using the power of supercomputing. Thats what the community that can do this type of biophysical modeling and ai is working on. Theres many groups that are collaborating on this task. And i believe in the near future, i cant say exactly how long this will take, we will have new compounds that are the result of this process that will go into the experimental screening pipelines. Do you throw out more than one of those proteins . You have to. If you look at state of the art drugs, often theyre a cocktail of drugs. We think the best strategy is probably a multiple therapeutic mix that would go after multiple targets, maybe a target that would help in blocking viral entry, one that might block replication, one that might block some host process that is a problem, and so forth. So you would probably end up at the end of the day with a mixture of compounds in a future drug. A future drug treatment. I think its really important, though, to say that to develop the kind of drugs that were imagining will take a long time. If you think about in the hiv timeframe, it took many, many years before there were effective hiv therapies, over a decade. And while were moving faster, we have better tools, this is a very hard problem. And while the community has been working on kind of crisis mode in this, they cant work in crisis mode for years. So we have to put institutional structures around this to get it done. Thank you very much. I yield back, mr. Chairman. Thank you. Ill recognize representative wexton for five minutes now. Mute. Whoops. Microphone. Mute. Youre muted. Shame on me. Hi. Thank you, mr. Chairman, for yielding and for not charging me my five minutes quite yet. And to the panelists for joining us today, this is a really fascinating discussion and im glad to be here for it. You know, the controversy surrounding the fdas eua for hydroxychloroquine has caused a lot of people to question the scientific integrity of the fdas process. And so the policy making, especially during this pandemic. Dr. Lurie, dr. Rome, could you please give us your general assessment of the rigor of fda policy making and Public Communications<\/a> regarding the repurposing of therapeutic drugs during this pandemic and then what needs to be done better, if anything . Well, i certainly agree it has been a disappointment. And i dont think its because of the career officials in fda who i believe are completely committed to scientific integrity and proper regulatory procedures in this pandemic. But i do think that people have turned out to be susceptible to political pressure. The hydroxychloroquine example is frankly an embarrassment. The standard for approving the eua was considerably below what it was in previous euas, and i say this based on talking to people who granted euas in previous administrations. So in the end, that turned out to be a black eye for the agency. Another embarrassment, i think, has turned out to be htantibod tests where for a while the agency allowed these products to come on market without even an eua. And then, that turned out to be a disaster when it turned out they were playing by false positives. So now they have an eua. What i hope is that from the combination of those two experiences, well get a proper use of the eua process, which i think were now seeing for remdesivir. And i sincerely believe and hope that my former colleagues at fda will be able to stand up to the political pressure because it is certainly searing. Dr. Rome, how about you . Yeah, thank you for the question. I think what youre getting at is actually an issue that has come up again and again, which is sort of the standards of evidence sort of required for any drug approval, even before covid19, which traditionally were stat torally supposed to be based on traditional evidence. That meant two Clinical Trials<\/a>, two large randomized Clinical Trials<\/a> to make sure if one trial got the answer wrong, we wouldnt get the answer wrong twice. That has changed over time. There are many drugs now expedited through the fda process, and thats something that needs to be consider and the background for when covid19 came, we had already experienced the fact that 80 plus percent of drugs are approved through some expedited pathway, maybe based on more limited evidence than that two Clinical Trials<\/a>. During covid19, we relied on the eua to cut off the fda approval process and act before the fda carefully considers all of the evidence. Makes total sense, and certainly time is of the essence. But to your point, we actually have very little experience using euas for drugs. It was done during a swine flu pandemic, 2009, 2010, there a drug was issued on eua, and the data that later came out from the Clinical Trials<\/a> showed that the drug was not actually effective for the type of patients the eua was issued for. Now we have hydroxychloroquine and remdesivir. We maybe hit one out of three potentially, though we dont know the whole story on remdesivir. Certainly, this is a time for congress to take a look at the way the euas have been utilized and tune up the regulations on the fda to make sure its done appropriately in the context of the speediness needed. So in this final minute, i guess, my question is also, theres going to be a lot of financial incentive for various firms to get their drugs through this eua process and get them approved. How does the fda eliminate conflicts of interest in the drug approval process . Make sure theres no conflicts in the Decision Making<\/a> process . Quite frankly, the process is infected with conflict of interest, and theres not very much that can be done about it in the following sense. We accept the idea that drug trials, trials of diagnostics or vaccines, are conducted in general by the manufacturers themselves. And so its a given that there will be that kind of conflict of interest and companies will come in with an interest in depicting the data that best suits them. Thats where the fda comes in. Thats where the fdas review of the actual data itself, which no other country in the world claims to do, thats where that kind of review, that kind of insulating of the reviewers from the manufacturers is so important. And thats the way its managed. But its a given that most of the time the studies will have been done by the manufacturers themselves. Thank you very much. Where see my time has see my t yield back. Thank you. I now recognize representative unmute. Thanks, chairman and panelists. Thank you. Watching your testimony, listen and watch each other and its been interesting. So the first question i have and dr. Finnegan you brought up a couple network, there are networks if place but really didnt get activated promptly. We talk and active and petal, the acronym, to everybody but start with you dr. Finnegan. A pandemic comes. You see this thing starting to roll. Is there some lead agency, is it cdc, nih, barta, who is it that says to these networks, okay. Everybodys got to jumpto. Whether its the hospitals or the laboratories or who says, get going . So, i think to a certain degree of exact agency that does it doesnt matter. It just needs to be understood ahead of time. Whether or not it is the nih or barta, you know, or another agency, i dont think really matters. Its just a function of thinking ahead of time and knowing ahead of time that these networks exist and that you want to put them into action, and especially in a situation like this where you actually have some lead time. So we knew about this pandemic for some time, and we could have been planning it, and so it doesnt necessarily matter that its the cdc or a different agency. Whichever agency funds that network or if you need to bring in more than one network, crossagency, those things just need to be thought of ahead of time. Other aspects, like how you do incensing for patients and ahead of time thought about also to be streamlined as quickly as possible for when you need to utilize those networks. So, dr. Stevens, when the labs kicked into gear on these things . Lab the started to selforganize around the 1st of march, ahead of the official proclamation. We have a little bit of internal flexibility at the lab. Thats why the labs exist. Largescale scientists and disciplinarians and used to taking initiatives on our own. Taking on our own initiatives. Labs talking to each other, arranging computer time. Pulling together actually long before the pandemic was declared, and at headquarters, very supportive we were already moving. So i think the community i think the balance of the panel will agree, saw what was coming and to a degree with degrees of action and the agencies then came up to start resourcing things. So i think it all sort of happened in parallel so to all of you, to our science committee, we have a little bit of jurisdiction with respect to hospitals but not a lot, but we definitely have jurisdiction over the laboratories. Is there any connection that we, networks that you talked about, dr. Finnegan or that we talked about the nine labses that youre collaborating with, doctor. Any connection between the Hospital Networks<\/a> and our laboratories . Are you guys talking to each other . Not so much. The department of energy typically doesnt get involved in Clinical Research<\/a>. Laboratories dont have ongoing clinics. The way it works largely due to the distinction between the different agencies on network. We do have a lot of collaborators in universities. The way in which we, and i personally have a joint appointment at the university of chicago where i have colleagues in Clinical Trials<\/a> and i have well, talking to those people. Personally, we have contacts, but institutionally, the department of energy dtypically the laboratories they support arent involved in clinical work. And turn it back to ron for my last 45 seconds. So at harvard, so National Jewish<\/a> collaboration, lots of hospitals, university of colorado, a bunch of other stuff. Harvard obviously collaborates with everything around the world. When did your medical school and when did you sort of get engaged in this thing . Now, the minute we heard about it from china . Or how did that go . I i really say the Scientific Community<\/a> acted early, but acting early involved having information and i think information comes from the top in this case. The information out of china was challenging i think for medical professionals to understand. So the by time, march, people started to gear up here that might have been unfortunately, much earlier had the administration and everyone else in the government sort of set the ball moving and pushed for action earlier on. And i just, i was remiss to say dr. Finnegan helped me on a town hall with 10,000 people on the line. I just wanted to mention that and thank all of you for the testimony today. I really appreciate it. Thank you all. At this point i guess theres probably enough member interest for another round of questioning for those members who wish, and so we can quickly already. This may about brief round of questions here. But i would like to followup on a kwucouple of points. Dr. Finnegan, you sort of mentioned the idea, the concept, the replicate, approval of the remedidesivir trial at 60 diffet locations, that there could be some single point of approval. Is it realistic to expect an individual stu individual institutions will buy into that . A Clinical Trial<\/a> that may or may not you know, be safe . Which is one of their concerns. So it the answer is, no. Theyre not going to give it up but i think there are things you ask do ahead of time to make it go much faster. What happens with a trial like the rem says veer trial or other trials we have going on, in the industry sponsor in these instances reaches out to us. Asks if we want to be a part of it. We say, yes. At that point the back and forth, protocol, read it, approve it, make its its safe, discuss the budget, make sure we have to do it. While were doing that theyre do it individually to all different sites. Spend three weeks decide we cant do it, thats wasted time for everybody. So if you have a network like, lets say, the petal network i mentioned, this exists already in place. A lot of that work has been taken care of already. A lot of that immediate work and leg work in terms of getting things approved and contracting and budgets, that stuff might be taken care of. You can imagine a situation where a drug Company Might<\/a> say i have a drug i think its promising. I want to use this federally funded network and a mechanism they have to pay in to help keep that funded but allows them to rapidly get their drug out there and not have to go through the process every time. All right. And so, yeah. Youve touched on the issue of getting the commercial incentives right. Because that must be very delicate in this. Because you know, obviously, you know, Drug Companies<\/a> can get the federal taxpayers to pay for a Clinical Trial<\/a>, for a drug that theyll eventually make money on. You know . Say this is something currently unapproved for use. You think there ought to be a mechanism in place somehow to have the federal taxpayer have a benefit for the fact they pay for this trial. Are there countries anywhere that have a different model that might be more effective for dealing with the, you know, the commercial interests . To fund trials . Or do they just fully federalize it and theres a big pot of money and a group of scientists who decide what is the most scientifically promising and allocate Clinical Trials<\/a> that way . So i cant speak to what happens very knowledgeably in other countries. Ill let others address that if they know that. Briefly ill say there are examples of, i dont know if its quite Public Private<\/a> partnerships. For instance, cystic fibrosis, regulates a lot of trials that happen in siskic fibrosis in kids and adults sponsored new drugs to rapidly get those drugs sort of tested and those that were successful and approved so the drug company ends the cystic fibrosis. That can be replicated in other instances. Ill let others talk about other countries. Any comments . Yeah. I guess i would say that, i dont know of another country, to your question sort of how that balance is made other than other countries do a much better job negotiating for valuebased prices of drugs. So that we do not sort of double pay. Paying through the roof for Clinical Research<\/a>, to develop the drug and secondarily for a crisis. Thats one comment. The other, not just in covid19. Again, i mentioned the example of remdesivir, which as you said, the government is funding the latestage clinical development. That occurs in one in four drugs that have been developed over the last decade, where the federal government is involved late in the development of the drug. Almost every drug has some sort of federal involvement in the early stages of development. So this is absolutely a problem. Its going to be highlighted in covid19, and its going to affect how the drugs are able to be active for patients once Insurance Companies<\/a> have to pay for them. Definitely it needs to be addressed. Thank you. I think one of the most potentially tragic outcomes is that promising drugs just wont get looked into. That should. If we dont set this up right. All right. Im happy to recognize chairman lucas for five minutes with additional questions. Mr. Chairman, i will yield back but simply note our constituents on the countryside are frantically looking for ways to protect themselves and cures to address it. Id like to think all the discussion today about the challenges we face to this point still the underlying issue is that were making progress, diligently working to address needs of our constituents and they should have faith in the institutions with inside and outside the federal government, working together, Care Industry<\/a> included to address their needs. Needs of issues that through by know fault of their own, just where we live at this time. With that, mr. Chairman, i yield back. Thank you. And ill now recognize representative beyer for five minutes. Thank you, mr. Chairman, very much. Dr. Stevens, in your testimony you talked about us paying attention in the long term to emerging pathogens. How do you define emerging pathogens . Some sd does someone have to get sick before we do it . And due to the billions of viruses out there, what constitutes as an emerging one . The one most agree with pathogens relatively new to science. It could be pathogens that are endemic in wild animals. Maybe in places people dont normally live, and a huge development, Economic Development<\/a> pushes large numbers of people closer to these preexisting wild areas, theres lots of opportunity for contact with these animal species, and new pathogens emerge that way. Thats the primary mechanism. If you think over the last decades of viral pathogens, ebola, ezikea, sars, covid19. These all emerge from animal reservoirs. My recommendation, we amount a scientificallybased International Program<\/a> to survey all wild populations, understand their microbios, natural viruses that coexist with them and study them. We have the technology to do that and could easily sequence these things, produce structures if we can get ahead of the curve. We could understand the reservoirs much better than we do currently, and that would leave us more time to be ready for the next one. Thank you. You also mentioned that theres 10 million molecules available for experimental validation. Yes. Are you you talked about the weathering, the funnel. The first funnel, is it going to be mathematic and physical rather than experimental . Top of the funnel, of course, theoretical sense, every molecule 10 to the 60th. The Drug Companies<\/a> and Economy Community<\/a> have understanding of maybe 4 to 5 billion molecules of that. Maybe 10 million are something i can get my hands on in a couple of weeks. Of course a better chemist can make things in roughly that time frame as well. Its conceivable to create ahead of time panels that is, collections of molecules essentially frozen in the freezers and if you have an emerging outbreak and it happens quickly you could screen a very large set of molecules in umpteen months and have a lot of possible leads to chase down and combining that computation, we would create a much better situation in terms of future therapeutic development. Thats something i think the community will be excited to work towards. Thank you. It is an amazing hard to get your arms around the 100 million molecules. One last question. Dr. Rome, your fourth point was making improvements to fdas eua process. And you talkedh clarifying, transparency, equitable distribution and Patient Outcome<\/a> data. Is this something that should be done regularly or is this a Perfect Piece<\/a> of legislation through the Health Science<\/a> community . So fda has the ability to do some of these things, but have not done so. They have the ability to collect information about the drugs but theyre not required to, and other than adverse events or safety reporting of sort of major events like deaths that occur from the drug, in a has happened, but further data has not been required as part of the uas. The fda brought authority to the write into the ua what it wants in terms of requirements but certainly those requirements, that sort of Broad Authority<\/a> could be better regulated by congress, by sort of more directing and saying, when you issue an eua, these are the things we think are necessary and weve learned a great deal about what would be helpful. I would say, again, more transparency as the outset so physicians using drugs from the ua have access to data. Not just the data thats you know, on the internet but actually, like, the replica and published studies, really helpful. You wouldnt think we are guilty of micromanagement if we led that . I mean, i i think that i think that it needs to happen. So i think if Congress Wants<\/a> to step up for the future of euas, these are tweaks we think are necessary. Thats reasonable. I would say the eua is not just the drugs. Applying to diagnostics, testing equipment mentioned before. Ventilators, other things. Again, drugs are a minority of this over the history of the eua that have been where its been used. So we only have, really, three examples. Two of which, you know, are pandemics alone. We are, i do think its time to reevaluate how it was used and decided change, small legislative changes need to be made. Thank you very much. Mr. Chairman, i yield back. Thank you. Ill recognize the representative. One question. Start with you, dr. Rome. Anybody can jump in. Serologic tests, Antibody Test<\/a>s i guess. A whole bunch. Some approved, i guess, and some not approved. So going to the diagnostics, that you were talking about. Isnt it right, or not, or is there now sort of doubt about these tests and their validity . Well, referring to the underlying test specifically, i dont think that has been well handle by fda. I think feeling the pressure to press ahead, they gave the Antibody Test<\/a> a pause to begin with and not even inquiring to uea for them. Serm these tests could produce more false positives than true positives and i think that first the agency to take a look at what theyve done and then slapped an eua upon them giving Companies Ten<\/a> days to comply. I dont know how many of them have met theuae requirements, but i suspect many disappeared because they couldnt meet the standards. Sorry to say what happens is fda has been flipflopping, if you like, course correcting to try to get this exactly right. Theyve made mistakes. Hopefully it will be better Going Forward<\/a>. Okay. Thank you. I dont know if anybody else has any comments. I just want to thank the panel and happy to yield back to you, mr. Chairman. Thank you. And i, yes. I have to say i was a little surprised when the Antibody Test<\/a>s came out so flawed. That there was no one responsibility for making, for, in the government for establishing a test panel that you run every one of the proposed tests against. Just a sample, positives and negative people, would be prepared and at least given to every manufacturer to test against and report their results. And you know, that seems like the sort of infrastructure that should exist somewhere in the future when this sort of thing happens. And also best laid by representative buyers legislation coming out of this. Something sensible to be done there. And now can i have about one remaining minute for the representative. Dr. Stevens, how is the funnel, how often do you see a drug works wonderfully in practice and not at all in theory . Well, usually either theory is wrong and we have to go back and fix the theory if that happens. The funnels pretty leaky in the sense that things fall out that we have to filter out, because were using approximate rules often to do this. But, you know, most of what we look at doesnt work. I mean, thats the reality of developments. Most compounds dont work. So it is a needle in a haystack type of problem, and occasionally youll find drugs that defy our, you know, initial view, but those usually dont come on the competitional process because filtered out, they come to physical screens on international products, for example, and then you have to go back and repeat them. So unique combinations of both. It cant all be computationally driven. I mentioned before, large chemical libraries screened in public i think is another resource we need as infrastructure. All right. I just want to thank all of our witnesses. At this point. Before bringing the hearing to a close. Very important, and keep thinking about youre doing your daytime job here what changes youd like to see in place for the next pandemic . Because i think thats going to be a big part of our job. As we try to preserve the Attention Span<\/a> of congress. So that were better prepared. Someone smart once said you go to war with the army you have, and next time, next pandemic likely better army. Thank you all for being a part of the army we have. The record will remain open two weeks for additional statements from members for additional questions that the committee may ask the witnesses, and the witnesses are now excused and the hearing is adjourned. Tonight on American History<\/a> tv our series landmark cases. Produced in cooperation with the National Constitution<\/a> center we explore the issues, people and places involved in some of the most Significant Supreme Court<\/a> cases in our nations history. 8 00 eastern, Youngstown Company<\/a> versus versus sawyer. Then at 9 30 peereastern, 1954 holding segregated schooling violates the equal protection clause of the 14th amendment because segregated schools could never be equal. Watch landmark cases tonight on cspan3 and anytime at cspan. Org. Treasury secretary Stephen Mnuchin<\/a> appears before the House Small Business Committee<\/a> on oversight of the Small Business<\/a> administration and department of treasury pandemic program. Live coverage begins friday at 10 30 a. M. Eastern on cspan. Later in the month, u. S. Attorney general william barr appears before the house judiciary general oversight on the justice department. Tuesday, july 28th. Mnuchin coverage friday on cspan. Watch anytime on cspan. 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