Presentation on theme: "Professional Societies, Advocacy, and the Gov’t-How do we get along?"— Presentation transcript:
1Professional Societies, Advocacy, and the Gov’t-How do we get along? Gary D. Wu, M.DFerdinand G. Weisbrod Professor of MedicineDivision of GastroenterologyPerelman School of MedicineUniversity of Pennsylvania
2The AGA Center for Gut Microbiome Research & Education
3The Center’s Mission Statement To advance research and education on the gut microbiome in human health and disease.The Center will serve as the focus of all AGA activities and programs in this field and will be built around the pillars of the AGA Strategic Plan: Research-Education-Advocacy-Practice.
4AGA Microbiome Scientific Advisory Board Provides guidance to AGA Board on scientific matters relevant to the microbiome: strategic direction, topic and programmatic priorities, program participants. Eight members representing:Computational biologyMetagenomicsAnimal modelsMicrobiologyTranslational researchNutrition and obesityMotilityPediatricsClinical Practice (FMT)Regulatory and policy issuesMembers:Gary D. Wu, MD, SAB Chair, University of Pennsylvania, Philadelphia, PAMartin J. Blaser, MD, New York University, New York, NYGail A. Hecht, MD, Loyola University, Maywood, ILPurna Kashyap, MD, Mayo Clinic, Rhochester, MNColleen Kelly, MD, Brown University, Providence, RILee M. Kaplan, MD, PhD, Harvard University/MGH, Boston, MARob Knight, PhD, University of Colorado, Boulder, COLoren Laine, MD, Yale University, New Haven, CTMary Ellen Sanders, PhD, Consultant, Centennial, COR. Balfour Sartor, MD, University of North Carolina, Chapel Hill, NCPhillip Tarr, MD, Wash. Univ., St. Louis, MOEx officio mbrs: Council chair; GB basic science councillorQuarterly Meetings X 3 so far. At meeting 1, COI issues addressed and this was a significant discussion. Also, given the acuity of the FMT IND issue, the SAB decided to focus on this issue as a time sensitive item.
6Currently over 500 cases reported in the literature Fecal Microbiota Transplantation (FMT), a Success Story for the Treatment of Refractory CDI—But with a Note of CautionPrescreening of donors to prevent transmission of currently known pathogensHomogenization, filtration, and administration usually through a colonoscope.Success rate of around 90% when fecal microbiota transplantation (FMT) is used to treat CDICurrently over 500 cases reported in the literaturePlacebo-controlled clinical trial: Duodenal Infusion of Donor Feces for Recurrent Clostridium difficile. N Engl J Med 2013; 368:407-41
8Response of the Microbiome Center SAB to Issues Related to FDA FMT IND for CDI May 2013: Notification of AGA membership that an IND was required for FMT used for any indication including the treatment of refractory CDI. Emergency use IND hotline provided to membership.Nine member committee established (5 AGA, 2 NASPGHAN, 2 IDSA) to provide feedback to FDA regarding IND for FMT.FDA issues “regulatory restraint” on use of FMT for CDI—AGA membership notified of decision.AGA committee develops “Current Consensus Guidance on Donor Screening and Stool Testing for FMT” document for FDA together with IDSA, NASPGHAN, ACG, and ASGE.
9Enhanced Pathogenicity “You Shouldn’t Do it Just Because You Can—Caution about FMT and the Need for RegulationAlthough the short-term infectious risks of FMT seem to be definable and quantifiable, we should remember the entire generation of patients infected with HCV by blood transfusion before this pathogen was identified.The field should move cautiously because the long-term consequences of FMT in humans are unknown. The gut microbiome contains a highly complex and dense community of microbes that include bacteria, fungi and viruses, many of which have not been fully characterized.It is a dynamic and living consortium that can change over time in ways that scientists cannot currently fully predict.Animal model data suggests that the gut microbiome may play a role in the pathogenesis of several human diseases.BacteriaVirusesFungiArchaeaCompetitionSyntrophyEnhanced PathogenicityPredator-PreyRelationshipNormon et al. Gastro 2014
10AGA-Sponsored Webinar: In planning stages Publications on FMT for the Clinician“A How to Guide: Investigational New Drug Application for Fecal Microbiota Transplantation”Colleen R. Kelly, MD; Sachin S. Kunde, MD, MPH; Alexander Khoruts, MDClinical Gastroenterology and HepatologyWhat's the Value of an FDA IND for Fecal Microbiota Transplantation in Clostridium difficile Infection?Gail A. Hecht, MD, MS and Members of the SAB for the AGA Center for Gut Microbiome Research and EducationAGA-Sponsored Webinar: In planning stages
11The Scientific Value of FMT FMT and the Treatment of Type 2 DiabetesThe success of FMT in the treatment of CDI is “proof of principle” that the dysbiotic human microbiota can be modified to treat disease.Emphasizes the importance of using a resilient microbial community to modify dysbiosis.FMT is a window into the biology of the gut microbiome in humans:Translation of findings in animal models into human biology.Understand the long term consequences of manipulating the gut microbiota in humans
12The Future of FMT: Transplantation of Defined Microbial Communities Customization of consortium membership of bacteria with specific biological properties to produce predictable responses and reduce both short- and long-term adverse outcomesLaboratory defined conditions prevent pathogen transmissionDevelopment of standardized conditions for the transplantation (inoculation) and maintenance of the communityDurable communities that are resilient to change
13Evolution of Microbiome Research Past/Current Status of the field: “Safe” traditional view.Animal Models(functional data)Human Association StudiesEvolution of the microbiome fieldHuman Intervention StudiesNovel TherapeuticsNext generation pre-, pro-, synbioticsFMT for CDIFuture status of the field: Higher risk but higher reward.
14Goals of the FMT Registry The Progression of Science, Reduction to Practice, and Development of New Gut Microbiota-Based ProductsFMTProcessed Fecal ProductsDefined Microbial ConsortiaEvolution of Scientific and Product DevelopmentInitiationSustainabilityYesLikely YesPossibly YesLawley TD PLoS Pathog. 2012;8(10):ePetrof EO. Microbiome Jan 9;1(1):3CDI?Other diseasesFocus of technology development++++++SafetyWe used this model to identify a simple mixture of six phylogenetically diverse intestinal bacteria, including novel species, which can re-establish a health-associated microbiota and clear C. difficile 027/BI infection from mice. Thus, targeting a dysbiotic microbiota with a defined mixture of phylogenetically diverse bacteria can trigger major shifts in the microbial community structure that displaces C. difficile and, as a result, resolves disease and contagiousness. Further, we demonstrate a rational approach to harness the therapeutic potential of health-associated microbial communities to treat C. difficile disease and potentially other forms of intestinal dysbiosis.Thirty-three isolates were recovered from a healthy donor stool sample. Two patients who had failed at least three courses of metronidazole or vancomycin underwent colonoscopy and the mixture was infused throughout the right and mid colon.Goals of the FMT RegistryTo gather information on practice in the U.S. and assess effectiveness of the intervention.To assess short-term and long-term safety.To aid practitioners and sponsors in satisfying regulatory requirements.To promote scientific investigation.
15Penn-CHOP Microbiome Initiative A National FMT RegistryAGA Microbiome Center Scientific Advisory BoardInfectious Disease Society of America (IDSA)NASPGHANCCFAAGARegistry expertise with a CRO (ACI Clinical)Penn-CHOP Microbiome InitiativeFMT RegistryNIH NIAID Application for a R24 (resource related research project)BiobankStool/microbial productsAcademia, CDC, NIH and Other (i.e. Industry)Basic and clinical investigation, product developmentFDAOversight of FMT, Stool-based products, and “next generation” probioticsProfessional SocietiesClinical practice standards (efficacy/safety), liability, reimbursementU biome vs. American Gut