,,ii #aafth ,,congress #ast ,session ,s4 #bjaj ,,in ,,the ,,senate ,,of ,,the ,,united ,,states ,june #bg1 #bjai,mr4 ,udall 7for himself and ,mr4 ,heinrich7 introduced the following bill2 which was read twice and referred to the ,committee on ,health1 ,education1 ,labor1 and ,pensions ,a ,,bill ,to increase research1 education1 and treatment for cerebral cavernous malformations4 #a4 ,short title ,this ,act may be cited as the ,cerebral ,cavernous ,malformations ,clinical ,awareness1 ,research1 and ,education ,act of #bjai or the ,,ccm-,,care ,act4 #b4 ,findings ,congress finds as follows3 7#a7 ,cerebral cavernous malformations 7referred to in this section as ,,ccm71 also known as cavernous angioma1 or cavernoma1 is a devastating blood vessel disease characterized by vascular lesions that develop and grow within the brain and spinal cord4 7#b7 ,detection of ,,ccm lesions is achieved through costly and specialized medical imaging techniques1 often not accessible or convenient to patients who need them4 7#c7 ,while ,,ccm is a common type of vascular anomaly1 many individuals are not aware they have the disease until the onset of serious clinical symptoms4 ,,ccm is often inherited unknowingly4 7#d7 ,,ccm affects an estimated #fjj1jjj people in the ,united ,states4 7#e7 ,individuals diagnosed with ,,ccm may experience neurological deficits1 seizure1 stroke1 or sudden death4 7#f7 ,due to limited research1 there is currently no treatment for ,,ccm other than brain and spinal surgery1 and only for certain patients4 7#g7 ,there is also a shortage of trained physicians to provide skilled and timely diagnosis and appropriate treatment for ,,ccm4 7#h7 ,while the hereditary form of ,,ccm may occur among any ethnicity1 the presence of a mutation called the common ,hispanic mutation1 has passed through #ad or more generations of ,american descendants from the original ,spanish settlers of the ,southwest in the #aeijs4 ,new ,mexico has the highest population density of ,,ccm in the world2 ,texas1 ,arizona1 and ,colorado also have high rates of ,,ccm due to the common ,hispanic mutation4 7#i7 ,a second mutation 7,,ccm#b ,common ,deletion7 originating in the ,southeastern ,united ,states before #ahjj has increased rates of the illness in ,south ,carolina1 ,georgia1 ,florida1 ,alabama1 ,mississippi1 ,louisiana1 ,texas1 ,oklahoma1 ,kentucky1 ,kansas1 and northern ,california4 #c4 ,expansion and coordination of activities of ,national ,institutes of ,health with respect to cerebral cavernous malformations research ,part ,b of title ,,iv of the ,public ,health ,service ,act 7#db ,u4,s4,c4 #bhd et seq47 is amended by adding at the end the following3 #dji,k4 ,cerebral cavernous malformations research activities 7a7 ,expansion and coordination of activities ,the ,director of ,,nih1 in coordination with the directors of the ,national ,institute of ,neurological ,disorders and ,stroke1 the ,national ,center for ,advancing ,translational ,sciences1 the ,national ,heart1 ,lung1 and ,blood ,institute1 and other national research institutes1 as appropriate1 for the purpose of conducting research and related activities concerning cerebral cavernous malformations 7referred to in this section as ,,ccm7-- 7#a7 shall strengthen and coordinate efforts of the ,national ,institutes of ,health2 and 7#b7 may award grants and cooperative agreements to public or nonprofit private entities 7including ,state health departments1 political subdivisions of ,states1 universities1 and other medical or educational entities74 7b7 ,activities ,the research and related activities described in subsection 7a7 shall include the following3 7#a7 ,clinical1 translational1 and basic research ,the ,director of ,,nih shall conduct or support1 through funding opportunity announcements1 grants1 or cooperative agreements1 basic1 clinical1 and translational research on ,,ccm1 including research on-- 7,a7 the identification and development of biomarkers that fulfill the requirement of the ,food and ,drug ,administration for biomarker qualification as proper measures of ,,ccm pathogenic biology or response to clinical intervention2 7,b7 safety or efficacy for new or repurposed currently approved drugs for ,,ccm treatment2 7,c7 research related to improving and measuring the quality of life for individuals with ,,ccm and their families2 7,d7 contributions of genetic variation to clinical presentation as targets for therapy2 7,e7 early detection1 diagnosis1 and treatment of ,,ccm2 7,f7 clinical training programs aimed at increasing the number of scientists and clinicians who are trained to treat patients and carry out the research described in this paragraph2 7,g7 continued development and expansion of novel animal models for preclinical research relating to ,,ccm2 7,h7 preclinical and clinical research related to repurposing currently approved drugs for ,,ccm treatment2 7,i7 proteomic1 pharmacological1 and cell biological analysis of ,,ccm molecules2 7,j7 biological mechanisms for lesion genesis1 development1 and maturation2 7,k7 biological mechanisms for lesion bleeding and symptomology2 7,l7 novel biomedical and pharmacological interventions designed to inhibit new lesion development1 lesion growth1 and lesion bleeding2 7,m7 novel biomedical and pharmacological interventions designed to target existing lesions to reduce their size and clinical activity2 7,n7 continued research related to understanding better the natural history and clinical variation associated with ,,ccm1 particularly as it relates to the development of drug development tools and clinical outcome assessments2 7,o7 the gut-brain axis and the effects of microbiome composition on clinical symptomology2 and 7,p7 the microbiome as a therapeutic target for ,,ccm treatment4 7#b7 ,facilitation of research resources2 clinical trial preparedness 7,a7 ,in general ,the ,director of ,,nih shall award grants and contracts to public or nonprofit private entities to fund all or part of the cost of planning1 establishing1 and providing basic operating support for a network of ,,ccm ,clinical ,research ,centers1 including ,coordinating and ,participating centers regarding research on various forms of ,,ccm4 7,b7 ,clinical and research coordination centers 7i7 ,in general ,the ,director of ,,nih shall build upon the network created by the ,u#ja ,clinical ,trial ,readiness ,research ,project to identify and support the development of #b geographically distributed national clinical and research coordinating centers with unique clinical expertise and the potential for coordinating multi-site clinical drug trials with respect to ,,ccm4 7ii7 ,duties ,the coordinating centers identified under clause 7i7 shall provide a model for the participation centers described in paragraph 7#c71 facilitate medical research to develop a cure for ,,ccm1 and enhance the medical care of individuals with ,,ccm nationwide1 including by-- 7,i7 maintaining an institutional infrastructure capable of hosting clinical trials and facilitating translational research projects and collaborations for clinical trials2 7,,ii7 implementing the programs dedicated to patient education1 patient outreach1 and awareness developed by the ,cerebral ,cavernous ,malformations ,consortium under subsection 7c77#c77;,b72 7,,iii7 developing the capacity to establish and maintain communication with other major ,,ccm research and care institutions internationally for information sharing and coordination of research activities2 7,,iv7 demonstrating clinical expertise in the management of ,,ccm and appointing a director and support staff1 including a trainee and patient representative1 for ,,ccm research programming2 7,v7 treating a sufficient number of eligible patients for participation with particular focus on unique subpopulations1 such as patients with the common ,hispanic mutation1 ,ashkenazi ,jewish mutation1 ,,ccm#b ,common ,deletion1 or ,,ccm#c gene mutation carriers2 and 7,,vi7 maintaining a telehealth infrastructure to support and provide clinical consultation for remote and underserved communities4 7#c7 ,participation centers 7,a7 ,in general ,the ,director of ,,nih shall build upon the network created by the ,u#ja ,clinical ,trial ,readiness ,research ,project to identify and support the development of approximately #f to #aj clinical and research participation centers to facilitate medical research to develop a cure for ,,ccm and enhance the medical care of individuals with ,,ccm1 in partnership with the coordinating centers under paragraph 7#b7 and other national and international entities1 as appropriate4 7,b7 ,eligibility ,to qualify for selection as a participation center under subparagraph 7,a71 an entity shall-- 7i7 at the time of selection-- 7,i7 be affiliated with an established research network of the ,national ,institutes of ,health2 and 7,,ii7 have the potential to participate in a multisite clinical drug trial with respect to ,,ccm2 7ii7 demonstrate-- 7,i7 an institutional infrastructure capable of hosting a clinical trial site and facilitating translational projects and collaborations for clinical trials2 7,,ii7 the capacity to maintain communication with other major ,,ccm research and care institutions internationally for information sharing and coordination of research activities1 especially through health information technology2 and 7,,iii7 clinical expertise in ,,ccm management or complete the ,,ccm clinical training program under subsection 7c77#d72 and 7iii7 have a sufficient number of eligible patients with ,,ccm4 7,c7 ,duration of support ,the ,director of ,,nih may provide support for participation centers under this section for a period not to exceed #e years4 ,the ,director of ,,nih may extend the period of support for a center for #a or more additional periods1 not to exceed an additional #e years1 if the operations of such center have been reviewed by an appropriate technical and scientific peer review group established by the ,director of ,,nih and if such group has recommended to the ,director that such period should be extended4 7c7 ,cerebral cavernous malformations consortium 7#a7 ,in general ,the ,director of ,,nih shall build upon the network created by the ,u#ja ,clinical ,trial ,readiness ,research ,project to convene a ,cerebral ,cavernous ,malformations ,research ,consortium 7referred to in this section as the consortium74 7#b7 ,membership ,the consortium-- 7,a7 shall include representatives of-- 7i7 the coordinating centers selected under subsection 7b77#b72 and 7ii7 at least #a national ,,ccm patient advocacy organization1 which may be an entity that receives a grant or contract under subsection 7b77#b77;,a72 and 7,b7 may include representatives of the ,national ,institutes of ,health or the ,food and ,drug ,administration1 in an advisory or ex officio role4 7#c7 ,responsibilities ,through a consensus based decisionmaking model1 the consortium shall divide assignments and be responsible for-- 7,a7 developing and implementing training programs for clinicians and scientists in accordance with paragraph 7#d72 7,b7 developing patient education1 outreach1 and awareness programs and materials1 which may be tailored for specific regional needs at coordinating centers1 including-- 7i7 a regional multimedia public awareness campaign2 7ii7 patient education materials for distribution by regional physician and surgeon offices2 7iii7 an education program for elementary and secondary school nurses to facilitate early detection and diagnosis of ,,ccm in areas in which there is a high density of cases of ,,ccm2 7iv7 regular regional patient and family-oriented educational conferences2 and 7v7 nationally relevant electronic health teaching and communication tools and a network of professional capacity and patient and family support2 and 7,c7 preparing a biannual report to ,congress1 in accordance with paragraph 7#e74 7#d7 ,training program for clinicians and scientists 7,a7 ,in general ,the consortium1 in cooperation with the coordinating centers1 shall establish or expand a physician training program1 including information and education on advances in the diagnosis and treatment of ,,ccm1 and training and continuing education through programs for scientists1 physicians1 medical students1 and other health professionals and care coordinators who provide care for patients with ,,ccm1 telehealth1 and research relevant to ,,ccm1 for the purpose of supporting the development of new participation centers through educational programming to gain the expertise needed to become clinical and research participation centers with the potential to participate in clinical drug trials4 7,b7 ,stipends ,the ,director of ,,nih may provide stipends for health professionals who are enrolled in the training programs described in subparagraph 7,a74 7,c7 ,eligibility ,to be eligible to participate in the training program1 an individual shall be affiliated with an entity that is in an existing clinical research network of the ,national ,institutes of ,health4 7#e7 ,report to ,congress ,the consortium shall biennially submit to the ,committee on ,health1 ,education1 ,labor1 and ,pensions of the ,senate and the ,committee on ,energy and ,commerce of the ,house of ,representatives a report that describes the research1 education1 and other activities on ,,ccm conducted or supported through the ,department of ,health and ,human ,services4 ,each such report shall include-- 7,a7 a research plan2 7,b7 provisions specifying the amounts expended by the ,department of ,health and ,human ,services with respect to various forms of ,,ccm1 including those affected by the common ,hispanic ,mutation1 ,ashkenazi ,jewish mutation1 ,,ccm#b ,common ,deletion1 ,,ccm#c gene mutations1 and other familial and sporadic forms of cerebral cavernous malformation2 and 7,c7 recommendations for particular projects or types of projects that the national research institutes or other entities in the field of research should conduct on inherited or non-inherited forms of ,,ccm4 7d7 ,prioritize ,,ccm funding for biotech ,the ,director of ,,nih1 in coordination with the directors of the ,national ,institute of ,neurological ,disorders and ,stroke1 the ,national ,center for ,advancing ,translational ,sciences1 the ,national ,heart1 ,lung1 and ,blood ,institute1 and other national research institutes1 as appropriate1 shall prioritize the provision of grant funding for small biotechnology entities that are working to develop treatments for ,,ccm4 4 #d4 ,centers for ,disease ,control and prevention cerebral cavernous malformations surveillance and research programs ,part ,b of title ,,iii of the ,public ,health ,service ,act 7#db ,u4,s4,c4 #bdc et seq47 is amended by inserting after section #cag,t the following3 #cag,u4 ,cerebral cavernous malformations surveillance and research programs 7a7 ,in general ,the ,secretary1 acting through the ,director of the ,centers for ,disease ,control and ,prevention1 may award grants in such sums as may be necessary and cooperative agreements to public or nonprofit private entities 7including ,state health departments1 political subdivisions of ,states1 universities1 and other medical or educational entities7 for the collection1 analysis1 and reporting of data on cerebral cavernous malformations 7referred to in this section as ,,ccm74 7b7 ,national cerebral cavernous malformations epidemiology program ,the ,secretary shall award grants and cooperative agreements1 including technical assistance1 to public or nonprofit private entities for-- 7#a7 the collection1 analysis1 and reporting of data on ,,ccm2 and 7#b7 epidemiological activities1 including encouraging consistency in ,,icd-#aj coding1 collecting and analyzing information on the number1 incidence1 correlates1 and symptoms of cases and the clinical utility of specific practice patterns4 7c7 ,national surveillance program ,the ,secretary shall-- 7#a7 provide for a national surveillance program for the purpose of carrying out epidemiological activities regarding ,,ccm1 including collecting and analyzing information on the number1 incidence1 correlates1 and symptoms of cases of ,,ccm and the clinical utility 7including costs and benefits7 of specific practice patterns2 and 7#b7 wherever possible1 ensure that the surveillance program is coordinated with the data and sample collection activities of the ,national ,institutes of ,health under section #dji,k4 7d7 ,technical assistance ,in making awards under this section1 the ,secretary may provide direct technical assistance1 including personnel support4 7e7 ,coordination with clinical centers ,the ,secretary shall ensure that epidemiological information is made available to clinical centers as supported by the ,director of the ,national ,institutes of ,health under section #dji,k4 7f7 ,authorization of appropriations ,there are authorized to be appropriated such sums as may be necessary to carry out this section4 4 #e4 ,food and ,drug ,administration cerebral cavernous malformations clinical trial preparedness and support program 7a7 ,biomarker qualification program ,the ,secretary of ,health and ,human ,services1 acting through the ,commissioner of ,food and ,drugs1 shall coordinate with clinical centers1 investigators1 and advocates to support the qualification of appropriate surrogate biomarkers in an effort to hasten the pace of clinical trials for cerebral cavernous malformation4 7b7 ,clinical outcome assessment qualification ,the ,secretary of ,health and ,human ,services1 acting through the ,commissioner of ,food and ,drugs1 shall coordinate with clinical centers1 investigators1 and advocates to support the qualification of newly developed patient reported outcome measures for quality of life as a clinical outcome in an effort to hasten the pace of clinical trials for cerebral cavernous malformation4 7c7 ,investigational new drug application ,the ,secretary of ,health and ,human ,services1 acting through the ,commissioner of ,food and ,drugs1 shall coordinate with clinical centers1 investigators1 and advocates to support appropriate investigational new drug applications under section #eje7;i7 of the ,federal ,food1 ,drug1 and ,cosmetic ,act 7#ba ,u4,s4,c4 #cee7;i77 in an effort to hasten the pace of clinical trials for cerebral cavernous malformation4 7d7 ,adaptive trial design and expedited review pathways ,the ,secretary of ,health and ,human ,services1 acting through the ,commissioner of ,food and ,drugs1 shall coordinate with clinical centers1 investigators1 and advocates to support appropriate adaptive trial designs for rare disease research and expedited peer review mechanisms for including ,orphan ,drug ,designation1 ,fast ,track1 ,breakthrough ,therapy ,designation1 ,priority ,review or ,accelerated ,review1 where appropriate1 in an effort to hasten the pace of clinical trials for cerebral cavernous malformation4