Hastings Center Inc

INFORMING ETHICAL TRANSLATION OF XENOTRANSPLANTATION CLINICAL TRIALS - PROJECT SUMMARY XENOTRANSPLANTATION (XTX) IS A NOVEL EXPERIMENTAL TREATMENT THAT INVOLVES TRANSPLANTING ORGANS FROM NONHUMAN ANIMALS INTO HUMANS. DUE TO THE SCARCITY OF HUMAN ORGANS FOR TRANSPLANTATION, XTX COULD HELP ALLEVIATE THE ORGAN SHORTAGE, WHICH IS AN ONGOING PUBLIC HEALTH PROBLEM. EARLY EXPERIMENTAL XENOTRANSPLANTS WERE PERFORMED IN THE U.S. FROM THE 1960S TO 1990S, INVOLVING A CHIMPANZEE KIDNEY, A BABOON HEART, AND A BABOON LIVER. DESPITE HOLDING GREAT PROMISE, XTX EXPERIMENTS ENDED IN THE LATE 1990S DUE TO SCIENTIFIC AND ETHICAL CHALLENGES. TODAY, XTX IS UNDERGOING A RENAISSANCE. SCIENTIFIC ADVANCES IN IMMUNOSUPPRESSION AND GENOME EDITING TECHNIQUES HAVE MITIGATED THE RISK OF ZOONOTIC DISEASE TRANSMISSION. THE TRANSPLANT FIELD IS PRIMED TO CONDUCT XTX CLINICAL TRIALS AND THEN TRANSLATE FINDINGS TO CLINICAL CARE. HOWEVER, AVAILABLE GUIDELINES FOR CONDUCTING XTX CLINICAL TRIALS ARE OUTDATED, DO NOT ADDRESS ADVANCES IN THE SCIENCE OF XTX, DO NOT ACCOUNT FOR STAKEHOLDERS’ CONCERNS, AND DO NOT CONSIDER THE IMPACT ON POLICY CHANGES TO ORGAN ALLOCATION. THE OVERALL OBJECTIVE OF THE PROPOSED STUDY IS TO IDENTIFY APPROPRIATE ETHICAL AND POLICY GUIDANCE FOR TRANSLATIONAL SOLID ORGAN XTX CLINICAL TRIALS. THE RESEARCH TEAM INCLUDES NATIONAL BIOETHICS LEADERS AT THE HASTINGS CENTER, NORTHWESTERN UNIVERSITY, AND RUTGERS UNIVERSITY, WITH THE HASTINGS CENTER SERVING AS THE DATA COORDINATING CENTER. WE WILL CONDUCT IN-DEPTH INTERVIEWS WITH TRANSPLANT PATIENTS, TRANSPLANT CLINICIANS, TRANSPLANT REGULATORS, AND HUMAN SUBJECTS ETHICS REGULATORS, AND OBTAIN INPUT FROM AN ETHICS AND POLICY ADVISORY COMMITTEE COMPRISED OF EXPERTS IN TRANSLATIONAL SCIENCE AND BIOETHICS TO: (1) ASSESS XTX STAKEHOLDERS’ PERCEPTIONS AND CONCERNS ABOUT ETHICAL AND POLICY CHALLENGES FOR XTX CLINICAL TRIALS; (2) DEVELOP XTX STAKEHOLDER DECISION AIDS THAT HELP PATIENTS, CLINICIANS, AND INSTITUTIONAL REVIEW BOARDS TO EVALUATE, DESIGN, AND OVERSEE XTX CLINICAL TRIALS, RESPECTIVELY; AND (3) DEVELOP RECOMMENDATIONS FOR THE ETHICAL TRANSLATION OF XTX CLINICAL TRIALS. UPDATED GUIDANCE AND DECISION AIDS WILL FACILITATE ETHICAL DECISION-MAKING ABOUT XTX CLINICAL TRIALS. THE INNOVATIVE AND TIMELY DECISION AIDS WILL CONTAIN GENERALIZABLE ETHICAL PRINCIPLES FOR HUMAN SUBJECTS RESEARCH PROTECTIONS AND POLICY CONSIDERATIONS REGARDING ORGAN ALLOCATION THAT WILL APPLY TO XTX CLINICAL TRIALS INVOLVING OTHER ORGANS. FUTURE NEXT STEPS INCLUDE DESIGNING A STUDY TO TEST THE INFLUENCE OF THE DECISION AIDS ON THE CHOICES OF PATIENTS, IRBS, AND TRANSPLANT CENTERS ABOUT XTX KIDNEY CLINICAL TRIALS.

ACTIONABLE ETHICS OVERSIGHT FOR HUMAN-ANIMAL CHIMERA RESEARCH

GOALS AND PRACTICES FOR NEXT GENERATION PRENATAL TESTING

FROM RESEARCH TO CLINIC: ADDRESSING ETHICAL AND POLICY CHALLENGES FACING THE GENE THERAPY ECOSYSTEM - PROJECT SUMMARY THE U.S. FOOD AND DRUG ADMINISTRATION HAS APPROVED GENE THERAPIES FOR SEVERAL RARE INHERITED DISEASES AND BLOOD CANCERS, AND HUNDREDS OF CLINICAL TRIALS ARE IN PROGRESS TESTING THE SAFETY AND EFFECTIVENESS OF GENE THERAPIES FOR RARE AND ULTRA-RARE DISORDERS, VARIOUS CANCERS, AND COMPLEX NEUROLOGICAL DISEASES. FOR PATIENTS WITH RARE AND SERIOUS OR DEBILITATING DISORDERS FOR WHOM EXISTING TREATMENT OPTIONS ARE LIMITED OR DO NOT WORK, THE APPROVED GENE THERAPIES AND THE PROMISE OF OTHERS ARE ENCOURAGING SIGNS THAT NEW TREATMENT OPTIONS ARE EMERGING. YET THE TRANSLATIONAL GENE THERAPY ECOSYSTEM FACES SEVERAL INTERRELATED CHALLENGES: 1) OBTAINING SUFFICIENT EVIDENCE OF SAFETY/EFFECTIVENESS FROM CLINICAL TRIALS TO JUSTIFY FDA APPROVAL; 2) ESTABLISHING COST AND PAYER COVERAGE POLICIES SO PATIENTS HAVE ACCESS TO AFFORDABLE TREATMENTS; AND 3) GENERATING SUFFICIENT SAFETY AND EFFECTIVENESS EVIDENCE OF APPROVED GENE THERAPIES WHEN USED IN THE CLINICAL SETTING. THE PROPOSED PROJECT WILL INVESTIGATE HOW GENE THERAPY CHALLENGES AND ASSOCIATED ETHICAL AND POLICY ISSUES THAT EXIST WITHIN THE TRANSLATIONAL GENE THERAPY ECOSYSTEM ARE CHARACTERIZED AND BEING ADDRESSED. WE WILL 1) ANALYZE DOCUMENTS FROM FEDERAL AND STATE POLICYMAKERS (THE FDA, THE CENTERS FOR MEDICARE AND MEDICAID SERVICES, RELEVANT STATE MEDICAID AGENCIES, THE U.S. CONGRESS) AND ORGANIZATIONS THAT PLAY A ROLE IN AGENDA SETTING AND INFLUENCING PUBLIC POLICY REGARDING THE TRANSLATIONAL GENE THERAPY ECOSYSTEM; 2) CONDUCT A SURVEY WITH PHYSICIANS FROM FOUR THERAPEUTIC DOMAINS (HEMATOLOGY, INFECTIOUS DISEASE, NEUROLOGY, ONCOLOGY); 3) CONDUCT IN-DEPTH INTERVIEWS WITH EXPERTS FROM FIVE DOMAINS (TRANSLATIONAL GENE THERAPY RESEARCH AND DEVELOPMENT; THE FDA DRUG-APPROVAL/POST- MARKETING PROCESS; HEALTH POLICY/PAYER COVERAGE; PATIENT ADVOCACY; BIOETHICS/ELSI OF GENETICS AND GENOMICS); AND 4) DEVELOP A) ISSUE/POLICY BRIEFS, B) RECOMMENDATIONS FOR ADDRESSING GENE THERAPY CHALLENGES AND ASSOCIATED ETHICAL AND POLICY ISSUES, AND C) RECOMMENDATIONS FOR FUTURE NORMATIVE AND EMPIRICAL ANALYSIS OF GENE THERAPY CHALLENGES AND ASSOCIATED ETHICAL AND POLICY ISSUES. INNOVATIVE FEATURES OF THE PROPOSED PROJECT INCLUDE BEING FRAMED BY THE PREMISE THAT GENE THERAPY CHALLENGES ARE INTERRELATED AND CO-EXIST WITHIN A COMPLEX TRANSLATIONAL SCIENCE ECOSYSTEM; EXAMINING HOW PHYSICIANS, VARIOUS EXPERTS, AND POLICYMAKERS ARE GRAPPLING WITH GENE THERAPY CHALLENGES; AND APPLYING A NORMATIVE FRAMEWORK THAT DRAWS ON IDEAS AND CONCEPTS FROM BIOETHICS AND POLITICAL SCIENCE. THE PROPOSED PROJECT WILL SYNTHESIZE THE FINDINGS FROM THE DOCUMENT/POLICY ANALYSIS, SURVEY, IN-DEPTH INTERVIEWS, AND NORMATIVE ANALYSIS OF GENE THERAPY CHALLENGES AND ASSOCIATED ETHICAL AND POLICY ISSUES TO DEVELOP RECOMMENDATIONS AND ISSUE/POLICY BRIEFS THAT WILL 1) HELP STAKEHOLDERS IN THE TRANSLATIONAL GENE THERAPY ECOSYSTEM IN THEIR DELIBERATIONS AND DECISION-MAKING ABOUT ADDRESSING GENE THERAPY CHALLENGES AND ASSOCIATED ETHICAL AND POLICY ISSUES, AND 2) IDENTIFY ETHICAL AND POLICY ISSUES WITHIN THE TRANSLATIONAL GENE THERAPY ECOSYSTEM THAT WARRANT ADDITIONAL NORMATIVE AND EMPIRICAL INVESTIGATION BY VARIOUS STAKEHOLDERS.

STANDARD GRANT: PUBLIC DELIBERATION ON GENE EDITING IN WILD POPULATIONS

THE ETHICS OF DELIBERATE EXTINCTION -GENOME EDITING PROVIDES NEW TOOLS FOR CONTROLLING WILD ORGANISMS--MAYBE BY SUPPRESSING OR ERADICATING POPULATIONS, AND EVEN IN PRINCIPLE BY DRIVING ENTIRE SPECIES EXTINCT. CANDIDATE SPECIES INCLUDE THE NEW WORLD SCREW WORM, WHICH EATS THE LIVING FLESH OF ANIMALS INCLUDING HUMAN BEINGS; MOSQUITOS THAT TRANSMIT INFECTIOUS DISEASES SUCH AS MALARIA; AND RATS, WHICH POSE PUBLIC HEALTH AND ENVIRONMENTAL THREATS TO THREATENED AND ENDANGERED SPECIES IN MANY PLACES. NONETHELESS, THE PROSPECT OF USING GENOME EDITING TO EXTINGUISH A WILD SPECIES IS INHERENTLY TROUBLING FOR MANY PEOPLE. THIS PROJECT AIMS TO BRING ATTENTION TO THIS POSSIBLE USE AND PROPOSE RECOMMENDATIONS FOR HOW DECISIONS ABOUT IT SHOULD BE MADE. THE PROJECT WILL THEREBY SUPPORT REGULATORY OVERSIGHT AND PROMOTE BROAD PUBLIC DELIBERATION ABOUT GENOME EDITING. THE WORK WILL BE SHARED THROUGH AN OPEN-ACCESS REPORT AND PUBLICATIONS FOR PROFESSIONAL AND NONPROFESSIONAL AUDIENCES. THE PROJECT WILL ALSO BUILD SCHOLARSHIP ON THESE ISSUES, BY ENLISTING A GROUP OF SCHOLARS IN THE DEVELOPMENT OF THE REPORT AND BY PROVIDING TRAINING IN VALUES-ORIENTED RESEARCH TO A GRADUATE STUDENT IN ECOLOGY OR CONSERVATION BIOLOGY. THE SCHOLARLY FOCUS OF THE PROJECT IS ON PHILOSOPHICAL AND ETHICAL QUESTIONS RAISED BY THE IDEA OF EXTINCTION VIA GENOME EDITING. WHY, EXACTLY, MIGHT THAT IDEA BE TROUBLING? SOME OF THESE QUESTIONS ARE ABOUT THE VALUE OF SPECIES, BIODIVERSITY, AND THE HUMAN RELATIONSHIP TO NATURE GENERALLY, WHETHER HUMANS OUGHT TO REDUCE THE SUFFERING OF WILD ANIMALS, AND HOW TRADE-OFFS SHOULD BE MADE BETWEEN PUBLIC HEALTH, AGRICULTURAL, ANIMAL WELFARE, CONSERVATION, VALUES, AND OTHER GOALS. OTHER QUESTIONS ARE ABOUT THE NATURE OF GENOME EDITING AND HOW IT DIFFERS FROM OTHER WAYS OF CONTROLLING SPECIES. YET OTHER QUESTIONS HAVE TO DO WITH HOW THE PUBLIC SHOULD BE ENGAGED. THE WORK WILL CONTRIBUTE TO ENVIRONMENTAL ETHICS, CONSERVATION BIOLOGY, SCIENCE AND TECHNOLOGY STUDIES, AND POLITICAL SCIENCE. THIS AWARD REFLECTS NSF'S STATUTORY MISSION AND HAS BEEN DEEMED WORTHY OF SUPPORT THROUGH EVALUATION USING THE FOUNDATION'S INTELLECTUAL MERIT AND BROADER IMPACTS REVIEW CRITERIA.

UNDERSTANDING ALL OF US ENROLLEES AND DECLINERS ?? MOTIVATIONS TO ENHANCE RECRUITMENT AND RETENTION: FQHC'S BARRIERS TO CARING FOR PATIENTS WITH CLINICALLY ACTIONABLE GENETIC RESEARCH RESULTS

THE HASTINGS CENTER HUMANITIES RESEARCH INITIATIVE

VALUES IN IMPACT ASSESSMENT

SHAPING HUMANS: A DISCUSSION SERIES ON TECHNOLOGY, DISABILITY, AND HUMAN FLOURISHING

GENERATIVE AI AND THE FUTURE OF HUMAN CONNECTION [THIS COLLABORATION BETWEEN THE HASTINGS CENTER AND THE DIVISION OF MEDICAL ETHICS AT NYU SEEKS TO PREPARE A MANUSCRIPT FOR A THEMED ISSUE OF THE PROMINENT BIOETHICS JOURNAL&NBSP;<EM>THE HASTINGS CENTER REPORT</EM>&NBSP;CALLED ?GENERATIVE AI AND THE FUTURE OF HUMAN CONNECTION.? THIS SPECIAL ISSUE WILL ASK A QUESTION THAT ONLY ARISES AT THE INTERSECTION OF THE HUMANITIES AND AI??WHAT ARE HUMANS GOOD FOR?? WHAT, IN OTHER WORDS, DO HUMANS OFFER EACH OTHER THAT GENERATIVE AI MAY BE ABLE TO MIMIC BUT NEVER REPLACE? THE ARTICLES IN THIS SPECIAL ISSUE WILL CRITICALLY EVALUATE EIGHT CANDIDATES?EMPATHY, CARE, TRUST, MORALITY, EMOTION, ATTENTION, HUMAN EXCEPTIONALISM AND FLOURISHING?USING EXAMPLES OF AI IN HEALTHCARE TO MAKE THE QUESTIONS MORE CONCRETE. WE HOPE THAT THIS COLLABORATION WILL SET A NEW TONE FOR AI ETHICS AND PUSH HUMANITIES RESEARCH IN NEW DIRECTIONS. OUR LONG-TERM VISION IS TO FORM A FOUNDATION FOR SCHOLARSHIP THAT WILL ENSURE A FUTURE FOR HUMAN CONNECTION IN A WORLD OF AI.]

PHARMACOLOGICALLY TREATING BEHAVIORAL DISTURBANCES IN CHILDREN: ENGAGING THE CONT

CREATING AN INITIAL ETHICS FRAMEWORK FOR BIOMEDICAL DATA MODELING BY MAPPING AND EXPLORING KEY DECISION POINTS

THE MEANINGS OF DEMENTIA: INTERPRETING CULTURAL NARRATIVES OF AGING SOCIETIES [THE MEANINGS OF DEMENTIA: INTERPRETING CULTURAL NARRATIVES OF AGING SOCIETIES IS AN 18-MONTH PROJECT TO PRODUCE NEW CRITICAL WRITING ON MEANINGS OF DEMENTIA IN DIVERSE SOCIAL GROUPS IN THE UNITED STATES AND OTHER AGING SOCIETIES. DEMENTIA REFERS TO A GROUP OF COMMON, AGE-ASSOCIATED, PROGRESSIVELY DEBILITATING, ULTIMATELY TERMINAL CONDITIONS AFFECTING THOUGHT, MEMORY, SPEECH, AND BEHAVIOR. HUMANITIES SCHOLARSHIP HAS LONG STUDIED PERSONAL NARRATIVES; THIS HUMANITIES-SOCIAL SCIENCE COLLABORATION WILL CONSIDER HOW GREATER ATTENTION TO CULTURAL NARRATIVES ? CONCEPTS EXPRESSED THROUGH METAPHORS, TROPES, IMAGES, AND OTHER REPRESENTATIONS THAT CIRCULATE THROUGH A SOCIETY TO MAKE MEANING OUT OF EXPERIENCE ? CAN TRANSLATE INTO PUBLIC HUMANITIES WORK FOSTERING GREATER INCLUSION FOR FELLOW CITIZENS LIVING WITH DEMENTIA OR PROVIDING DEMENTIA CARE. WE WILL PRODUCE A PRINT AND OPEN-ACCESS DIGITAL VOLUME OF 18 ESSAYS FOR PEER REVIEW AND PRINT PUBLICATION AS A SUPPLEMENT TO A SCHOLARLY JOURNAL.]