>>WELCOME, EVERYBODY, TO THE
OCTOBER MEETING OF THE MUSCULAR
DYSTROPHY COORDINATING
COMMITTEE, I'M GLEN NUCKOLLS,
AND I'M A PROGRAM DIRECTOR AT
THE NATIONAL INSTITUTE OF
NEUROLOGICAL DISORDERS AND
STROKE.
WHY DON'T WE GO AROUND AND
INTRODUCE COMMITTEE MEMBERS AND
WE'LL START WITH OUR CHAIR, DR.
BIANCHI.
>>I DON'T SEE HER ON YET, GLEN.
>>HMM.
OKAY.
WE'LL COME BACK TO HER.
LET'S INTRODUCE THERESA
SANAGUSTIN.
>>GOOD AFTERNOON, EVERYONE.
I'M THERESA SAN AGUSTIN,
NATIONAL INSTITUTE ON
DISABILITY, INDEPENDENT LIVING
AND REHABILITATION RESEARCH
UNDER ADMINISTRATION OF
COMMUNITY LIVING, HHS.
THANK YOU, EVERYONE.
>>THANKS.
>>HI, CHRIS ANSELMO, MUSCULAR
DYSTROPHY ASSOCIATION, ALSO A
MEMBER OF THE MUSCULAR DYSTROPHY
COMMUNITY.
>>LINDSEY CRISWELL.
>>I'M DIRECTOR OF NATIONAL
INSTITUTE OF ARTHRITIS AND
MUSCULOSKELETAL AND SKIN
DISEASE, NIAMS, HAPPY TO BE HERE
WITH YOU TODAY.
>>GUSTAVO DZIEWCZAPOLSKI.
>>I'M SCIENTIFIC DIRECTOR AT
CURE CMD.
>>EMILY FREILICH?
EMILY FREILICH?
WE'LL GIVE HER A MINUTE.
DR. BIANCHI JUST JOINED.
>>I WAS SENT THE WRONG LINK, MY
APOLOGIES.
I KEPT GETTING DOUBLE LINKS TO
THIS MEETING, I SIGNED IN AS
ATTENDEE, NOT PARTICIPANT, SO
IT'S FRUSTRATING WHEN I'M TRYING
TO GET ON AND I CAN HEAR YOU,
BUT YOU CAN'T HEAR ME, BUT I'M
HERE NOW, WELCOME, EVERYBODY.
>>SORRY ABOUT THAT TROUBLE.
WE'LL GET THAT STRAIGHTENED OUT
FOR YOU.
GENE FREUND?
IS GENE ON THE LINE?
OKAY.
MICHAEL GOLDSTEIN.
I HOPE THEY DON'T ALL HAVE
ATTENDEE LINKS AS WELL.
ALISHA KEEHN?
>>HI, I'M HERE.
>>WOULD YOU LIKE TO INTRODUCE
YOURSELF?
>>I'M ALISHA KEEHN, BRANCH CHI.
>>JIM KILEY?
>>HE'S AWAY.
>>OKAY.
THANK YOU.
WALTER KOROSHETZ?
>>GOOD AFTERNOON, I'M WALTER,
DIRECTOR OF THE NATIONAL
INSTITUTE OF NEUROLOGICAL
DISORDERS AND STROKE.
PLEASED TO BE HERE.
>>MARIELENA McGUIRE?
YOU'RE MUTED STILL.
CAN'T HEAR YOU.
>>HOW ABOUT NOW?
>>YES, THAT WORKS.
>>SORRY ABOUT THAT, FOLKS.
I'M THE PROGRAM MANAGER FOR THE
DEE DUCHENNE MUSCULAR DYSTROPHY
RESEARCH PROGRAM, UNDER
CONGRESSIONALLY DIRECTED MEDICAL
RESEARCH PROGRAMS AT THE DoD.
THANK YOU.
>>THANKS.
DEBRA MILLER?
>>GOOD MORNING IN CALIFORNIA,
DEBRA MILLER, CEO AND FOUNDER OF
CURE DUCHENNE, I ALSO HAVE A
25-YEAR-OLD SON WITH DUCHENNE
MUSCULAR DYSTROPHY.
HAPPY TO BE HERE.
THANK YOU.
>>THANK YOU.
DENICE MILER?
>>FROM IDAHO, DISABLED ADVOCATE
HELPING THE IDAHO ENTER MOUNTAIN
AGENCY, RENTAL ASSISTANCE, ALSO
INVOLVED WITH IDAHO CAREGIVER
ALLIANCE.
I THINK THAT'S ENOUGH FOR NOW.
>>OKAY.
THANK YOU.
DAN PEREZ?
>>DAN PEREZ, CO-FOUNDER AND
DIRECTOR FSHD CODE, IN GLOCKTON,
MASSACHUSETTS.
>>NATALIE STREET?
>>HI, NATALIE STREET, HEALTH
SCIENTIST, PROGRAM ACTIVITIES IN
THE CENTERS FOR DISEASE CONTROL
AND PREVENTION.
>>ERIC LANG?
NOT ON YET.
I SEE EMILY FREILICH JOINED US.
>>HI, I'M A PEDIATRIC
NEUROLOGIST FROM FDA WITH
DIVISION OF NEUROLOGY.
>>DID GENE, MICHAEL OR ERIC
JOIN?
>>HI, GLEN, IT'S MICHAEL
GOLDSTEIN, I WAS UPGRADED TO
PARTICIPANT, THANK YOU FOR
HAVING ME.
I'M THE DIRECTOR OF THE OFFICE
OF MEDICAL POLICY AT THE SOCIAL
SECURITY ADMINISTRATION, AND OUR
OFFICE HOUSES MEDICAL LISTINGS,
SPECIFICALLY NEUROLOGICAL
LISTINGS, WHICH INCLUDE MUSCULAR
DYSTROPHIES AND ALSO ANOTHER
NUMBER OF POLICY AREAS,
INCLUDING OUR COMPASSIONATE
ALLOWANCE INITIATIVES COMPRISING
SEVERAL MUSCULAR DYSTROPHIES.
THANKS FOR HAVING ME.
>>GENE FREUND OR ERIC LANG?
>>HI, GLEN.
THERE'S A NOTE FROM GENE IN THE
Q&A HE WAS SENT AN ATTENDEE
LINK, NOT PANELLEST LINK, THAT'S
WHY HE HASN'T BEEN ABLE TO TALK.
>>SHERRY, CAN YOU SEND
APPROPRIATE LINK PLEASE?
>>TAKING CARE OF IT RIGHT NOW.
THANK YOU.
>>OKAY.
WELL, LET'S GET STARTED AND THEN
GIVE THEM AN OPPORTUNITY TO JOIN
LATER.
THIS MEETING IS CONDUCTED IN
COMPLIANCE WITH THE FEDERAL
ADVISORY COMMITTEE ACT, TO
ENSURE THAT THE COMMITTEE
PROVIDES EXPERT ADVICE AND
DIVERSE OPINIONS TO INFORM
DECISION MAKING BY OFFICIALS AND
AGENCIES IN THE EXECUTIVE BRANCH
OF THE FEDERAL GOVERNMENT IN A
MANNER THAT IS TRANSPARENT AND
FREE OF CONFLICTS OF INTEREST.
THERE IS NO CLOSED SESSION
PLANNED FOR TODAY'S MEETING.
WE DO NOT ANTICIPATE DISCUSSIONS
OR ACTIONS SPECIFIC TO THE
ORGANIZATIONS OR FINANCIAL
INTERESTS OF OUR MEMBERS.
SO THERE'S NO NEED FOR RECUSALS.
WE DID POST NOTICE TO FEDERAL
REGISTER ABOUT THIS MEETING, AND
INVITE OPPORTUNITIES FOR PUBLIC
COMMENT.
WE DID NOT RECEIVE REQUESTS TO
ADDRESS THE COMMITTEE AND DID
NOT SCHEDULE PUBLIC COMMENTS
DURING THIS MEETING.
THE MEETING IS BEING STREAMED
LIVE FOR PUBLIC VIEWING AND IS
BEING RECORDED.
THE STREAM AND RECORDING ARE
AVAILABLE AT VIDEOCAST.NIH.GOV,
WE'LL ALSO PROVIDE A LINK AT OUR
WEBSITE, MDCCC.NIH.GOV.
FOR THOSE CONNECTING THROUGH
ZOOM, THE COMMITTEE MEMBERS AND
OTHER DESIGNATED PANELISTS, YOU
CAN RAISE YOUR HAND AND UNMUTE
TO SPEAK, ASK QUESTIONS, IF
YOU'RE NOT A COMMITTEE MEMBER OR
DESIGNATED PANELIST, AND YOU'RE
A DESIGNATED PARTICIPANT YOU CAN
SUBMIT QUESTIONS VIA THE CHAT
FEATURE AND WE'LL READ THOSE OUT
FOR YOU.
I WOULD LIKE TO THANK THE NIH
AND CONTRACTOR STAFF THAT HAVE
CONTRIBUTED TO HELP PREPARE FOR
THIS MEETING.
SO UNLESS THERE'S ANY QUESTIONS
I'LL TURN IT OVER TO DR. BIANCHI
FOR YOUR CHAIR PRESENTATION
>>THANK YOU.
I'M DIRECTOR OF NICHD SHALL
SERVING RIGHT NOW AS CHAIR OF
THE MDCC.
IT'S FRUSTRATING WHEN YOU KNOW
YOU ARE CHAIRING AND HOPEFULLY
CAN'T GET INTO THE MEETING,
HOPEFULLY WE'LL FIX THAT NEXT
TIME.
I'LL GO AHEAD AND SHARE MY
SCREEN AND IT WILL BE MY GREAT
PLEASURE TO UPDATE YOU ON WHAT'S
BEEN HAPPENING SINCE WE LAST
MET.
CAN YOU SEE IT IN PRESENTATION
MODE?
WE'RE CELEBRATING OUR 60th
ANNIVERSARY, WE'LL HAVE OUR
60th ANNIVERSARY SYMPOSIUM IN
A COUPLE WEEKS.
WE'LL GIVE YOU AN UPDATE ON THE
NIH BUDGET, TALK ABOUT CHANGES
IN ARPA-H, AND SOME UPDATES ON
THE NIH DATA MANAGEMENT AND
SHARING POLICY, SOME NEWS ABOUT
THE NIH COMMON FUND ARTIFICIAL
INTELLIGENCE INITIATIVE, AND
SELECTED ADVANCES IN MUSCULAR
DYSTROPHY RESEARCH.
I'D LIKE TO THANK STAFF MEMBERS
WHO CONTRIBUTED WHAT THEY
THOUGHT WERE THE HIGHLIGHTS IN
MUSCULAR DYSTROPHY RESEARCH.
THE HEADLINE IS OF COURSE AS OF
FRIDAY, WE WERE GRANTED A
CONTINUING RESOLUTION THROUGH
DECEMBER 16, 2022.
THAT WAS BETTER THAN ALTERNATIVE
OF A GOVERNMENT SHUTDOWN, STILL
NOT AS OPTIMAL AS HAVING A
BUDGET ACT OF OCTOBER 1.
WE'RE NOW ALREADY INTO FISCAL
YEAR 2023, AND WHAT IT MEANS
WHEN WE HAVE A CONTINUING
RESOLUTION IS WE HAVE FUNDS THAT
ALLOW US TO MOVE FORWARD BUT WE
DON'T REALLY KNOW WHAT THE
BUDGET IS.
WE'RE AT A FLAT LINE, AND WE CAN
DO OUR BEST TO ESTIMATE.
BUT EVEN THOUGH WE GOT THE
BUDGET FOR THIS PAST FISCAL
YEAR, 22, ON MARCH 15, YOU CAN
IMAGINE THE AMOUNT OF WORK IT
INVOLVES TO GET WHAT WE WOULD
NORMALLY DO IN 12 MONTHS DONE IN
6 MONTHS.
SO, I'D LIKE TO EXPRESS MY
APPRECIATION FOR EVERYONE WHO
MOVED MOUNTAINS, LITERALLY, TO
GET TWICE AS MUCH WORK DONE IN
HALF OF THE USUAL TIME.
WHICH WAS SUCCESSFULLY DONE.
WE'RE KINDING IN THE SAME
SITUATION AGAIN, HOPEFUL THAT
PERHAPS AFTER THE MIDTERM
ELECTIONS THAT DECISIONS CAN BE
MADE.
AND THAT WE COULD GET A
WONDERFUL HOLIDAY PRESENT OF
HAVING A REAL BUDGET TO PLAN
ACCORDINGLY.
THERE ARE COMPONENTS OF THE
BUDGET THAT HAVE BEEN WORKED ON
ALREADY, THE PRESIDENT'S BUDGET
PROPOSED $62.5 BILLION FOR NIH.
CONSISTING OF $45.5 BILLION IN A
BASE BUDGET, $5 BILLION FOR
ARPA-H, AND SPECIFIC PROBLEMS.
THE SENATE, $48 BILLION AND LESS
FOR ARPA-H, HOUSE APPROACH
R IGS -- APPROPRIATION BILL HAS
NOT YET PASSED.
ARPA-H WAS ESTABLISHED BY
CONGRESS WITHIN HEALTH AND HUMAN
SERVICES LAST SPRING, WITH THE
BUDGET ACTIVITIES.
SOME WHAT CONFUSING TO FOLKS,
DOES IT -- IS IT AT NIH?
HOW DOES IT RELATE TO NIH?
THERE'S QUITE A BIT OF
COMPETITION AMONGST DIFFERENT
STATES AND CITIES TO HOUSE
ARPA-H.
IT IS AN INDEPENDENT ENTITY BUT
IS RECEIVING INFRASTRUCTURE
SUPPORT SUCH AS PERSONNEL
MANAGEMENT, FOR EXAMPLE, ALL
KINDS OF THINGS THAT NIH DOES,
ALREADY DOES FOR OTHER AGENCIES
AS WELL.
SO RATHER THAN START UP A
COMPLETELY NEW AGENCY, FROM
SCRATCH, IT'S GETTING A LOT OF
SUPPORT FROM NIH.
IT'S HAD AN INTERIM DIRECTOR,
DR. ADAM RUSSELL.
BUT WITHIN THE PAST MONTH DR.
RENEE WEGRYGN WAS APPOINTED THE
FIRST PERMANENT DIRECTOR, SEEMS
TO BE IDEALLY SUITED WITH A
BIOTECH COMPANY IN BOSTON,
WORKED AT DARPA AND IARPA,
FAMILIAR WITH THIS CONCEPT OF
HIGH RISK, HIGH REWARD RESEARCH,
THAT IS EXPECTED TO FAIL FAST
AND FAIL OFTEN.
AND SOMETHING THE PRESIDENT IS
HIGHLY SUPPORTIVE OF TO REALLY
GET TO CHORES AND OTHER SORTS OF
TRANSFORMATIVE SOLUTIONS FOR ALL
PATIENTS.
AND PROJECTS THAT ARE ASKING FOR
SUPPORT MUST ALL INCLUDE EQUITY
IN THEIR DESIGN, AND NIH HAS A
WEBSITE DEDICATED TO ARPA-H, NOT
SURE WHEN DR. DR.ER DR.WEGRYGN
SHOULD START SOON ON CAMPUS.
WE WANTED TO BEGINNING THIS UP,
IT'S CAUSING CONCERN AMONGST
INVESTIGATORS, THIS POLICY THAT
WILL BECOME EFFECTIVE IN
JANUARY,OF NEXT YEAR.
IT'S NOT RETROACTIVE IN THE
SENSE IF YOU HAVE A FUNDED
GRANT, YOU'RE NOT GOING TO HAVE
TO DO THIS FOR THE FUNDED GRANT.
IT'S GOING TO AFFECT ALL
APPLICATIONS GOING FORWARD.
AND IT EXPECTS INVESTIGATORS AND
INSTITUTIONS TO PLAN AND BUDGET
FOR MANAGEMENT AND SHARING OF
DATA.
AND ALL INVESTIGATORS WILL NEED
TO SUBMIT A DATA MANAGEMENT
SHARING PLAN FOR REVIEW WHEN
APPLYING FOR NIH FUNDING.
AND IT WILL BE LOOKED AT AND
EXAMINED FOR COMPLIANCE WITH THE
OVERALL NIH APPROVED DATA
MANAGEMENT AND SHARING PLAN.
THE GOAL IS REALLY TO MAKE DATA,
SCIENTIFIC DATA, AS ACCESSIBLE
AS POSSIBLE, AS SOON AS
POSSIBLE, BY THE EARLIEST OF TWO
TIME POINTS.
SO, BEFORE OR JUST BEFORE A
PUBLICATION THAT IS ASSOCIATED
WITH THIS GRANT FUNDING IS
PUBLISHED, AND OR THE END OF THE
PERFORMANCE PERIOD OF THE
EXTRAMURAL AWARD THAT GENERATED
THE DATA.
AND THERE ARE MORE DETAILS ON
THIS WEBSITE.
HTTPS//SHARING.NIH.GOV.
I'LL TELL YOU ABOUT AN EXCITING
CHALLENGE THAT IS -- THAT HAS
BEEN FUNDED NOW THAT IS -- WAS
REALLY DEVELOPED BECAUSE
CONCERNS WERE THAT MOST
BIOMEDICAL MEDICAL IS NOT
SUITABLE FOR MACHINE LEARNING
BECAUSE THEY ARE INCOMPLETE AND
GOAL OF BRIDGE2AI ADDRESSES
BIOMEDICAL AND BEHAVIORAL
RESEARCH GRANT CHALLENGES.
SO, THE GOALS ARE TO GENERATE
DATASETS THAT ARE ETHICALLY
SOURCED, TRUSTWORTHY, WELL
DEFINED, ACCESSIBLE.
TO DEVELOP SOFTWARE AND
STANDARDS ACROSS DATA SOURCES
AND DATA TYPES, TO CREATE
AUTOMATED TOOLS AND ETHICALLY
RESOURCED DATASETS.
ALSO, THE GOAL IS TO CREATE
TRAINING MATERIALS AND
ACTIVITIES FOR WORKFORCE
DEVELOPMENT THAT BRIDGES A.I.,
BIOMEDICAL, BEHAVIORAL RESEARCH
COMMUNITIES.
THE FIRST AWARDS WERE MADE IN
FISCAL YEAR 22 JUST LAST MONTH.
THIS IS $130 MILLION PROGRAM
THAT ISED -- IS ADMINISTERED
THROUGH COMMON FUND.
THE FIRST ARE THE BRIDGE AWARDS
WHICH EMPHASIZE INTEGRATION,
DISSEMINATION, EVALUATION.
CENTER AWARDS.
AND THE ONES THAT HAVE BEEN
AWARDED SO FAR INCLUDE PRECISION
PUBLIC HEALTH, THESE USE VOICE
AS A BIOMARKER FOR HUMAN HEALTH
REVEALING HOW GENOMIC VARIATION,
BEHAVIORAL, AND ENVIRONMENTAL
FACTORS AFFECT INDIVIDUAL AND
POPULATION HEALTH.
FUNCTIONAL GENOMICS, THIS IS
MAPPING SPATIOTEMPORAL
ARCHITECTURE OF HUMAN CELLS TO
INTERPRET CELL STRUCTURE AND
FUNCTION IN HEALTH AND DISEASE.
SALUTEOGENESIS, UNCOVERING
DETAILS RESTORING HEALTH AFTER
DISEASE USING TYPE 2 DIABETES
AS A MODEL, AND CLINICAL CARE
INFORMATICS FOR DIAGNOSTIC AND
RISK PREDICTION.
LET'S GET TO ADVANCES IN
MUSCULAR DYSTROPHY RESEARCH.
SO, THE FIRST PAPER WAS
PUBLISHED IN ACS CHEMICAL
BIOLOGY RECENTLY, SUPPORTED BY
NIAMS.
AND THE TITLE WAS A SELECTIVE
AGENT FOR CDG REPEATS IN
MYOTONIC DYSTROPHY TYPE 1, THE
RESEARCHERS CREATED A SELECTIVE
DNA MODIFYING SMALL MOLECULE
THAT TARGETS A DISEASE-SPECIFIC
STRUCTURE AND MISMICHIGANS
INVOLVED IN MYOTONIC DYSTROPHY
TYPE 1.
THEY INTRODUCED A SMALL MOLECULE
IN CELLS WITH DM1, THAT LED TO
DECREASED LEVELS OF THE TOXIC
TRANSCRIPT R.C.UG EXPANDED.
IT OFFERS A STRATEGY FOR ORIGINS
RATHER THAN DOWNSTREAM PROCESS.
THE NEXT STUDY INVOLVED
LONG-TERM MAINTENANCE AND
RESISTANCE TO INJURY OF SKELETAL
MUSCLE IN DMD MICE THAT HAVE
BEEN GENE EDITED.
YOU CAN SEE HOW RECENTLY IT WAS
PUBLISHED.
THIS STUDY TESTED LONGEVITY AND
DURABILITY OF CRISPR/CAS9
EDITING IN YOUNG MICE WITH
DUCHENNE, MONITORED LONGEVITY
WITH DELETION OF DMD EXON 44,
RESULTS SHOWS THERAPEUTIC
EFFECTS FROM AAV CRISPR THERAPY,
VERY HOPEFUL.
IN ADDITION WITH REGARD TO
DUCHENNE MUSCULAR DYSTROPHY
CONCERN IS THAT PATIENTS WITH
DMD CAN HAVE ARRHYTHMIAS,
CARDIOMYOPATHY, SUDDEN CARDIAC
DEATH, AND MECHANISMS
RESPONSIBLE FOR CARDIAC
COMORBIDITIES ARE POORLY
UNDERSTOOD, SUPPORTED BY NHLBI,
AND NIAMS, SNTA1 GENE RESCUES
ION CHANNEL FUNCTION.
PLURIPOTENT STEM CELLS
TRANSFORMED INTO CARDIOMYOCYTES
FROM PEOPLE WITH DUCHENNE
MUSCULAR DYSTROPHY AND
CARDIOMYOPATHY, DEMONSTRATING
DMD MUTATIONS CONTROL CARDIAC
EXCITABILITY AND CONDUCTION
VELOCITY, DETECTS COULD BE
RESCUED WITH SNTA1, PART OF
DYSTROPHIN-ASSOCIATED PROTEIN
COMPLEX.
AND ALSO, WITH REGARD TO
DUCHENNE MUSCULAR DYSTROPHY, A
NEW THERAPY WAS TESTED IN THIS
STUDY THAT WAS SUPPORTED BY
NINDS, ENTITLED EFFICACY AND
SAFETY OF VAMOROLONE VERSUS
PLACEBO AND PREDNISONE AMONG
BOYS WITH DUCHENNE.
LONG-TERM CORTICOSTEROID USE
SUCH AS TAKING PREDNISONE IS A
STANDARD OF CARE FOR DUCHENNE
MUSCULAR DYSTROPHY BUT HAS
ADVERSE EFFECTS THAT DETRACT
FROM QUALITY OF LIFE FROM PEOPLE
WITH DMD.
VAMOROLONE IS A STEROIDAL
ANTI-INFLAMMATORY DRUG THAT
BINDS THE SAME BUT SHOWS A
DISTINCT CHEMICAL STRUCTURE.
PARTICIPANTS RECEIVED A PLACEBO
DRUG, PREDNISONE, OR ONE OF TWO
DOSES OF VAMOROLONE, AND
VAMOROLONE WAS ABLE TO REDUCE
BONE MORBIDITIES COMPARED TO
PREDNISONE, WHICH IS IMPORTANT
BECAUSE PREDNISONE WILL THIN
BONES, SO THERE WAS NO STUNTING
OF GROWTH AND NO DELETERIOUS
CHANGES IN BONE MARKERS.
AND WITH FSHD PATIENTS, I KNOW
WE'VE DISCUSSED PREVIOUSLY, IN
PREVIOUS COMMITTEE MEETINGS,
ABOUT SLEEP AND THE IMPORTANCE
OF SLEEP, HIGH QUALITY SLEEP, SO
HERE'S A STUDY SUPPORTED BY
NINDS, SELF-REPORTED REDUCED
SLEEP QUALITY AND EXCESSIVE
DAYTIME SLEEPINESS IN FSHD.
SO, WE'VE DISCUSSED QUITE A BIT
THAT THE SECONDARY ASSOCIATIONS
INCLUDE ABNORMAL SLEEP PATTERNS,
INVESTIGATORS MEASURED
SELF-REPORTED SLEEP QUALITY FROM
THE PARTICIPANTS AND THEIR
DAYTIME SLEEPINESS.
66% SHOWED REDUCED SLEEP
QUALITY, 15% EXCESSIVE DAYTIME
SLEEPINESS.
SO THE RECOMMENDATION WAS THAT
CAREGIVERS SHOULD MONITOR SLEEP
QUALITY OF PEOPLE WITH FSHD AS
PART OF ROUTINE CARE, WITH
SPECIAL ATTENTION TO POTENTIALLY
MODIFIABLE FACTORS, SUCH AS
CONSIDERATION OF BIPAP, AND
ADDRESSED EFFECTS OF PAIN IN
SLEEP.
NOW, AN NIAID TRAINING GRANT
SUPPORTED THIS STUDY WHICH WAS
ENTITLED INVESTIGATING ATTITUDES
TOWARDS PRENATAL DIAGNOSIS AND
FETAL THERAPY FOR SPINAL
MUSCULAR ATROPHY.
I HAVE TO CONFESS I SELECTED
THIS ARTICLE BECAUSE ONE OF MY
PROFESSIONAL INTERESTS IS
PRENATAL THERAPY.
SO THIS WAS ACTUALLY A
QUESTIONNAIRE-RELATED STUDY.
LOOKING AT HOW AFFECTED FAMILIES
WOULD RESPOND TO THE POSSIBILITY
OF SPINAL MUSCULAR ATROPHY
TREATMENT IN UTERO.
AND IF TREATMENT IN UTERO CAN BE
GIVEN, IT COULD IMPROVE SURVIVAL
AND NEUROLOGIC OUTCOMES,
INVESTIGATING ATTITUDES OF
PATIENTS AND PARENTS WITH SMA
REGARDING PRENATAL DIAGNOSIS,
FETAL THERAPIES, CLINICAL
TRIALS.
AND THIS QUESTIONNAIRE WAS
DISTRIBUTED BY CURE SMA, 114
RESPONDENTS, 60% WERE PATIENTS
OVER AGE 18, 40% CAREGIVERS.
91 SUPPORTED PRENATAL TESTING,
61% WOULD ENROLL IN FETAL GENE
THERAPY TRIALS, 7% WOULD CHOOSE
FETAL GENE THERAPIES.
IT'S ALWAYS IMPORTANT TO
CONSIDER BOTH ENDS OF THE
LIFESPAN.
SO THERE IS PARTICULARLY IN THE
INTERNATIONAL SOCIETY FOR
PRENATAL DIAGNOSIS, AND PRENATAL
DIAGNOSIS, WHICH IS OFFICIAL
JOURNAL OF THAT SOCIETY, A LOT
OF INTEREST ABOUT EXPLORING
PRENATAL THERAPIES.
THE SENIOR AUTHOR HERE IS
McKENZIE, DO A PRENATAL
TREATMENT STUDY FOR ALPHA
THALASSEMIA, QUITE EXPERIENCED
WITH PRENATAL THERAPIES.
I WANT TO CLOSE WITH SOMETHING
VISUAL.
I CAME ACROSS THESE PHOTOS IN AN
AD FOR GENENTECH AND THOUGHT,
YOU KNOW, I THOUGHT THEY WERE
INCREDIBLY COOL.
HERE WAS A FASHION SHOW THAT
FOCUSED ON PEOPLE WITH SPINAL
MUSCULAR ATROPHY, AND THEY JUST
ARE ALL LOOKING FABULOUS.
I JUST WANTED TO END WITH JUST
SOMETHING VERY POSITIVE AND
VISUAL.
THAT'S THE END OF MY PREPARED
REMARKS.
I'M GOING TO STOP SHARING SO I
CAN SEE YOU ALL AND I'M HAPPY TO
TAKE QUESTIONS.
WE'VE GOT TEN MINUTES FOR
QUESTIONS.
IF THERE ARE NO QUESTIONS I'LL
GIVE YOU A POP QUIZ.
THE NOBEL PRIZE WENT THIS
MORNING FOR A ROLE IN
PALEOGENOMICS, HE WAS ONE OF
THREE PARENT-CHILD COMBOS WHO
WON THE NOBEL PRIZE.
SO HE AND HIS FATHER PREVIOUSLY
WON THE NOBEL PRIZE.
WHO ARE THE OTHER TWO?
PARENT-CHILD COMBOS.
I DON'T KNOW IF DR. KOROSHETZ OR
DR. CRISWELL WOULD LIKE TO
COMMENT ON THE STUDIES WE
HIGHLIGHTED.
>>WELL --
>>GO AHEAD.
>>WE WANT TO KNOW THE RESPONSE
TO YOUR QUESTION.
>>NO CHEATING ON GOOGLE.
>>I'M JUST LOOKING.
>>ARE YOU GOING TO GIVE THE
RESPONSE FIRST?
>>I CAN, IF NOBODY HAS THE
ANSWER.
I'LL CHECK THE CHAT BOX TO SEE
IF ANYBODY CAME UP WITH IT.
>>ONE IMMEDIATELY, THE OTHER
WAS HARDER.
MARIE CURIE, HER DAUGHTER IRENE
ALSO WON THE NOBEL PRIZE.
AND THEN ARTHUR CORNBERG, I
SHOULD HAVE KNOWN BECAUSE I WENT
TO STANFORD, AND HIS SON ROGER
ALSO WON THE NOBEL PRIZE.
THAT WAS MEANT TO WAKE EVERYBODY
UP SO YOU COULD HAVE QUESTIONS.
>>I'M HAPPY TO TAKE YOUR OFFER
TO SHARE A COUPLE OF EXPRESSIONS
OF ENTHUSIASM FOR THE RESEARCH
HIGHLIGHTED SO IT'S GREAT TO SEE
ALL THE PROGRESS.
WE WERE PLEASED YOU HIGHLIGHTED
THE ARTICLE BY LEE AND THERE WAS
ANOTHER BY KRUEGER, WITH STEPHEN
ZIMMERMAN AS SENIOR AUTHOR ON
SOME OF THE MYOTONIC DYSTROPHY
RESEARCH AND REALLY HAPPY TO SEE
KIND OF PROGRESS IN THAT AREA
USING A SMALL MOLECULE THAT
TARGET DNA SEQUENCE, THAT SEEMS
REALLY EXCITING.
AS WAS, AMONG OTHERS, THE
ARTICLE THAT WAS HIGHLIGHTED
ABOUT USING A microRNA TO
INHIBIT DUX4 EXPRESSION IN
CONTEXT.
REALLY EXCITING TO SEE ALL THIS
PROGRESS.
THANK YOU FOR HIGHLIGHTING THOSE
IN THIS SESSION.
>>THANK YOU FOR YOUR COMMENTS.
WALTER?
>>YES, THANK YOU, DIANA.
I WONDERED, DO YOU HAVE ANY
CHILDREN IN SCIENCE THAT COULD
WIN THE NOBEL PRIZE WITH YOU?
[LAUGHTER]
>>I DO NOT.
>>YES, SO I GUESS I JUST WANTED
TO THROW OUT TO THE GROUP THIS
PAPER POINTED OUT ABOUT THE
LONG-TERM MAINTENANCE OF
EXPRESSION AND RESISTANCE,
INJURY.
THIS IS USING THE CRISPR/CAS9
GENE EDITING TOOLS THAT EXPLODED
ON THE SCENE IN THE LAST TEN
YEARS, ANOTHER NOBEL PRIZE WENT
TO THE DISCOVERY THERE.
AND THIS ENABLES -- REALLY WILL
ENABLE A CORRECTION OF GENE
DEFECTS BECAUSE YOU CAN GO IN
PRECISELY FIND THE MUTATION AREA
AND CUT IT OUT OR MAYBE EVEN
REPLACE IT WITH NORMAL CODONS.
AND SO, YOU KNOW, I THINK FOR A
LOT OF GENETIC DISEASES IT'S
KIND OF THE -- YOU KNOW, IT'S
GETTING RIGHT AT THE TARGET OF
THE PROBLEM, GOT TO BE DONE
EARLY.
BUT TO SAY THAT THE COMMON FUND
AT NIH, WHICH IS MONEY THAT
COMES TO THE DIRECTOR, ONE OF
THE BIG PROGRAMS IN THE COMMON
FUND IS ON SOMATIC CELL GENE
EDITING, IT STARTED OUT FIVE
YEARS AGO DEVELOPING THE TOOLS
BUT AS I SAID, THE FIELD IS
EXPLODING.
AND THERE'S A SENSE THAT SOME OF
THESE TOOLS WITHIN THE NEXT FIVE
YEARS WILL BE READY TO BE USED
IN PEOPLE.
THERE HAVE BEEN SOME WORK DONE
ON GENE EDITING OF CELLS TAKEN
OUT OF THE PERSON, AND EDITED
AND GIVEN BACK, OF COURSE WITH
DUCHENNE'S MUSCULAR DYSTROPHY,
IN THIS CASE IT WAS A VIRAL
VECTOR TO DELIVER THE
CRISPR/CAS9 MACHINERY, AND BUT
IN SOMATIC GENE EDITING PROGRAM
THERE'S A CALL FOR ACTUAL GRANTS
THAT GO INTO PATIENTS BY THE END
OF THE PROGRAM, SO THIS IS, YOU
KNOW, KIND OF FUTURISTIC BUT THE
FUTURE IS HERE ACTUALLY.
>>THANK YOU, WALTER.
I SHOULD ALSO SAY THAT LATER
THIS WEEK, I'LL BE ATTENDING AND
PRESENTING AT THE FIRST
INTERNATIONAL CONFERENCE ON
NEWBORN SEQUENCING, WHICH IS
GOING TO RAISE A LOT OF VERY
INTERESTING QUESTIONS.
NEWBORN SEQUENCING IS
INCREASINGLY BEING USED
CLINICALLY IN MANY NEWBORN
ICUs AROUND THE COUNTRY.
AND IN FACT I THINK THERE ARE
NOW FIVE STATE MEDICAID PROGRAMS
THAT ARE PAYING FOR IT.
BUT THE QUESTION IS WHETHER TO
OFFER THIS TO INFANTS WHO ARE
HEALTHY AND WHETHER IT SHOULD BE
ADDED ON TO EXISTING STATE-BASED
NEWBORN SCREENING PROGRAMS.
AND SO IT'S DEFINITELY GOING TO
INTERSECT WITH THE WORLD OF
MUSCULAR DYSTROPHY BECAUSE
EITHER THERE WILL BE ADDITIONAL
DIAGNOSES OF WELL-KNOWN
CONDITIONS OR IT'S POSSIBLE THAT
ADDITIONAL GENE MUTATIONS WILL
BE FOUND THAT WILL BE ASSOCIATED
EVENTUALLY CLINICALLY WITH
CONDITIONS THAT PERHAPS ARE NOT
RIGHT NOW RECOGNIZED AS BEING
PART OF THE FAMILY OF MUSCULAR
DYSTROPHIES.
BUT THAT AREA IS PROGRESSING
VERY QUICKLY AS WELL FROM
RESEARCH THAT HAS BEEN SUPPORTED
BY NIH TO CLINICAL
IMPLEMENTATION IN MANY NEWBORN
ICUs IN THE COUNTRY.
PEOPLE ARE A LITTLE QUIET TODAY.
I DON'T KNOW, COLD WEATHER?
WE'LL GIVE YOU THE THREE MINUTES
BACK IF YOU DON'T HAVE
QUESTIONS.
ONE THING IN THE CHAT BOX?
NO, JUST INSTRUCTIONS YOU CAN
RAISE YOUR HAND OR ASK A
QUESTION.
>>WE'VE HAD TWO COMMITTEE
MEMBERS THAT HAVE JOINED SINCE
THE INTRODUCTION SO WE'LL GIVE
ERIC LANG AND OPPORTUNITY TO
INTRODUCE HIMSELF.
>>THIS IS ERIC LANG, MY DAY JOB
IS ASSOCIATE PROFESSOR AT
UNIVERSITY OF FLORIDA, I STUDY
ASPECTS OF GENE REGULATION AND
NEUROMUSCULAR DISEASE WITH FOCUS
ON MYOTONIC DYSTROPHY, AND WHAT
INITIALLY BROUGHT ME INTO THIS
SPACE WAS HAVING FAMILY MEMBERS
AFFECTED AND SO I'M ALSO AN
ADVOCATE FOR THE MYOTONIC
DYSTROPHY FOUNDATION, SERVE ON
SCIENTIFIC ADVISORY COMMITTEE
WITH THEM AND PARTICIPATE IN A
VARIETY OF WAYS TO PUSH MYOTONIC
DYSTROPHY RESEARCH AND PATIENT
CARE TOPICS FORWARD.
>>YOU'RE IN GAINESVILLE, RIGHT?
YOU WERE AFFECTED?
>>COMPLETELY UNSCATHED
FORTUNATELY, YEAH.
>>THANKS, ERIC.
GLAD YOU'RE WELL.
GENE FREUND?
>>GENE FREUND, MEDICAL OFFICER
WITH THE CENTERS FOR MEDICARE
AND MEDICAID SERVICES.
ACTUALLY IN CINCINNATI VISITING
MY MOM, THIS WEEK, SO BACK ON
DUTY FOR AN AFTERNOON TO VISIT
WITH YOU, AND HAPPY TO DO THAT.
ONE OF THE NICE THINGS OR ONE OF
THE SIDE EFFECTS OF HAVING A
NAME LIKE GENE IS IF MY
ATTENTION WANDERS I GET SNAPPED
BACK INTO THE CONVERSATION
FREQUENTLY WHEN YOU START
TALKING ABOUT THAT.
I'VE HAD COLLEAGUES DO GENE
EDITING BUT NOT THE KIND DR.
BIANCHI WAS TALKING ABOUT.
GOOD TO BE HERE, ALWAYS
INTERESTING TO HEAR WHAT'S GOING
ON.
>>GENE, YOU'VE BEEN EXTREMELY
HELPFUL INFORMING US ABOUT CMS
COVERAGE FOR BIPAP AND OTHER
ASSOCIATIVE DEVICES FOR
BREATHING.
WE APPRECIATE YOUR PRESENCE AND
ATTENTION.
>>COVERAGE AND DRUG PROVISIONS
OF DRUG REDUCTION ACT ARE BEING
FORMED BUT AT A FUTURE
PRESENTATION I SUSPECT THAT
MIGHT BE -- FUTURE MEETING, THAT
MIGHT BE SUBJECT FOR
PRESENTATION TO THIS GROUP.
>>THAT WOULD BE GREAT.
>>QUITE PREMATURE NOW BUT IT
COULD BE WORTH GOING TO THE
GROUP LATER.
>>RIGHT.
THANK YOU SO MUCH.
GLEN, WE'RE EXACTLY ON TIME, IF
YOU'RE OKAY WITH MOVING FORWARD.
>>PLEASE DO.
THANK YOU.
>>THANK YOU ALL.
EACH OF THE NIH INSTITUTES AND
CENTERS HAVE A STRATEGIC PLAN
THAT IS PERIODICALLY REVIEWED
AND UPDATED, ACTUALLY SPECIFIED
IN THE 21ST CENTURY CURES ACT.
THE NATIONAL INSTITUTE OF
ARTHRITIS AND MUSCULOSKELETAL
AND SKIN DISEASES WILL BE
RENEWING THEIR STRATEGIC PLAN
FOR 2025-2029 AND DR. LINDSEY
CRISWELL, DIRECTOR OF NIAMS,
WILL DESCRIBE TO US HOW YOU ALL
CAN PROVIDE INPUT.
LINDSEY, OVER TO YOU.
>>THANK YOU.
LET ME START BY SHARING MY
SCREEN.
CAN YOU ALL SEE THAT?
OKAY.
ALL RIGHT.
SO THANK YOU FOR THE
INTRODUCTION.
IT'S REALLY A PLEASURE TO BE
HERE.
SO AS I JUST HEARD, YES, WE'RE
BEGINNING TO THINK ABOUT OUR
STRATEGIC PLAN FOR FISCAL YEARS
2025 TO 29, I'D LIKE TO DESCRIBE
HOW THIS WILL DIFFER FROM
CURRENT PLAN AND HOW YOU CAN
CONTRIBUTE.
SO, AS YOU HEARD ALSO, ALL
INSTITUTES ARE REQUIRED TO HAVE
A STRATEGIC PLAN BY LAW, THEY
HAVE GREAT VALUE AS A WAY OF
COMMUNICATING THE INSTITUTE'S
INTEREST TO THE PUBLIC, TO THE
RESEARCH COMMUNITY, ALSO TO THE
NIH.
SO, THIS WILL REPRESENT A PUBLIC
STATEMENT OF WHERE NIAMS CAN BE
BEST POSITIONED OVER THE NEXT
FIVE YEARS, TO MAKE A DIFFERENCE
IN THE LIVES OF ALL AMERICANS.
BUT IMPORTANTLY THE PLAN ALSO
SERVES AS GUIDE POST FOR
RESEARCHERS, SO IT NEEDS TO
COVER THE INSTITUTE'S BROAD
MISSION AREAS OF ARTHRITIS,
MUSCULOSKELETAL AND SKIN
DISEASES.
SO, WITH INPUT FROM NIAMS
ADVISORY COUNCIL AND PUBLIC,
NIAMS DEVELOPED CURRENT
STRATEGIC PLAN COVERING FISCAL
YEARS 2020 TO 24, AND THE
ULTIMATE GOAL TO DEVELOP PATIENT
CENTERED WAYS TO IMPROVE
OUTCOMES IN FIVE CORE AREAS,
LISTED ON THE SLIDE, RHEUMATIC
AND AUTOIMMUNE DISEASES, SKIN
BIOLOGY AND DISEASES, BONE
BIOLOGY AND DISEASES, MUSCLE
BIOLOGY AND DISEASES, JOINT
BIOLOGY AND DISEASES AS WELL AS
ORTHOPEDICS.
NOW, CONSIDERING THE AREAS
WITHIN THIS BROAD PURVIEW, I
UNDERSCORE THE TREMENDOUS
BURDEN.
, AFFECTING PEOPLE OF ALL AGES
AND ALL BACKGROUNDS, COMBINED
AFFECT TENS OF MILLIONS OF
AMERICANS, CAUSE TREMENDOUS
SUFFERING, AFFECT U.S. ECONOMY
THROUGH IMPRESSIVE HEALTH CARE
COSTS AS WELL AS LOST
PRODUCTIVITY.
MOST ARE CHRONIC, MANY
ASSOCIATED WITH CHRONIC PAIN AND
DISABILITY, MANY WHETHER COMMON
OR RARE AFFECT WOMEN AND
MINORITIES DISPROPORTIONATELY,
BOTH IN TERMS OF INCREASED
NUMBERS, AS WELL AS INCREASED
SEVERITY.
THE CURRENT STRATEGIC PLAN PLAN
HIGHLIGHTS SEVERAL SCIENTIFIC
THEMES THAT CUT ACROSS ALL OUR
MISSION AREAS, NEW TECHNOLOGIES
TO IDENTIFY SHARED MECHANISMS IN
HEALTH AND AMONG DISEASES,
ADVANCING PATIENT-CENTRIC
APPROACHES, ENABLING PRECISION
MEDICINE TO TAILOR CARE,
ADDRESSING HEALTH NEEDS OF
DIVERSE POPULATIONS.
THESE WERE TOPICS THAT EMERGED
FROM NIAMS LISTENING SESSIONS
HELD IN EACH OF OUR DISEASE AND
TISSUE-SPECIFIC AREAS.
WHEREAS THE MAJORITY OF CURRENT
PLAN CONSISTS OF OUR FIVE
DISEASE AND TISSUE-SPECIFIC
INTERESTS, THE NEW PLAN WILL
FOCUS MORE ON THE CROSS-CUTTING
THEMATIC RESEARCH OPPORTUNITIES
THAT TOUCH ON ALL OF OUR DISEASE
AREAS.
WE STILL WANT TO REFERENCE OUR
DISEASE AND TISSUE-SPECIFIC
INTERESTS BUT WILL SHORTEN THIS
PART OF THE PLAN AND MAKE SURE
THE SECTIONS ARE CONSISTENT WITH
REGARDS TO LEVEL OF DETAIL
INCLUDED.
BUT WE ALSO WANT TO HIGHLIGHT
IMPORTANTLY OUR INTRAMURAL
RESEARCH PROGRAM, SO IT WILL
RECEIVE ITS OWN TWO-PAGE SECTION
IN THIS NEW PLAN.
NIAMS IS REQUESTING FEEDBACK ON
TOPICS INCLUDED IN THE PLAN FROM
INTERESTED MEMBERS OF THE PUBLIC
INCLUDING RESEARCHERS IN
ACADEMIA AND INDUSTRY, HEALTH
CARE PROFESSIONALS, PATIENT
ADVOCATES, HEALTH ADVOCACY
ORGANIZATIONS, SCIENTIFIC OR
PROFESSIONAL ORGANIZATIONS, AS
WELL AS FEDERAL AGENTS.
AND WE'RE SEEKING INPUT BOTH
ABOUT CROSS-CUTTING THEMES AS
WELL AS BOLD ASPIRATIONS.
AND BROAD COMMUNITY INPUT IS
ESSENTIAL TO NOT ONLY IMPROVE
RESEARCH BUT ALSO TO ENSURE
REPRESENTATION FOR ALL AND
ADDRESS HEALTH DISPARITIES AND
HEALTH EQUITY.
I HOPE YOU'LL SHARE IDEAS AND
SHARE THIS ANNOUNCEMENT.
NOTICE THE VIDEO REFERENCE
NUMBER AT THE TOP OF THE PAGE,
WHERE YOU CAN FIND INFORMATION
ABOUT OUR RFI.
SO YOU CAN RESPOND TO THE RFI BY
SEARCHING ON THAT NOTICE NUMBER
THAT I SHARED WITH YOU, OR BY
GOING TO THE NIAMS HOME PAGE,
YOU'LL BE ASKED TO PROVIDE FOUR
PIECES OF INFORMATION.
CROSS-CUTTING RESEARCH
OPPORTUNITIES THAT NIAMS SHOULD
CONSIDER, SECOND, BOLD
ASPIRATIONS NIAMS-SUPPORTED
RESEARCH COULD ACCOMPLISH, YOUR
NAME AND YOUR ORGANIZATION.
INDIVIDUALS ARE WELCOME TO
RESPOND BUT ORGANIZATIONS ARE
ALSO WELCOME TO RESPOND ON
BEHALF OF THEIR GROUPS.
AND THE RESPONSES WILL BE DUE BY
THE END OF NOVEMBER OF THIS
YEAR.
AS THE NEXT STEP WE'LL ANALYZED
RESULTS AND PORTFOLIO ANALYSIS
THAT WE'RE ALSO UNDERTAKING.
WE WILL DISCUSS THE FINDINGS
WITH OUR ADVISORY COUNCIL, AND
HOLD LISTENING SESSIONS TO
REFINE THEMES WE HEARD,
INCLUDING REPRESENTATIVES FROM
BOTH SCIENTIFIC AND PATIENT
COMMUNITIES AND WILL BE HELD
DURING THE NEXT CALENDAR YEAR.
AS A FINAL STEP WE'LL POST NEAR
FINAL VERSION OF THE PLAN FOR
PUBLIC COMMENT AND AGAIN INVITE
FEEDBACK THROUGH RFI.
SO, IN CLOSING I'D LIKE TO THANK
YOU IN ADVANCE FOR YOUR
THOUGHTFUL INPUT ON WAYS TO
COVER EMERGING SCIENTIFIC
OPPORTUNITIES AND BE RELEVANT TO
RESEARCHERS ACROSS OUR NIAMS
MISSIONARIES, THANK -- MISSION
AREAS.
LET ME STOP SHARING.
>>THERE WAS A QUESTION ABOUT
SHARING THE NUMBER AGAIN.
>>ARE THESE SLIDES POSTED
FOLLOWING THE MEETING?
IF NOT I WILL PUT THAT NOTICE
NUMBER IN THE CHAT SO EVERYBODY
CAN SEE THAT.
SORRY THAT FLEW BY QUICKLY.
YOU CAN FIND THE INFORMATION AT
OUR HOME PAGE BUT I WILL PUT
THAT IN THE CHAT IN JUST A
MINUTE.
I HOPE THAT MEANS THERE WAS
SERIOUS INTEREST IN RESPONDING,
THAT'S A GOOD SIGN.
>>THANK YOU, LINDSEY.
OTHER QUESTIONS?
>>IS THIS PRETTY COMMON TO
SOLICIT INPUT FOR THESE INTEREST
PLANS?
AND HOW OFTEN DO YOU GET
FEEDBACK FROM -- HOW MUCH
FEEDBACK DO YOU GET FROM
INVESTIGATORS?
MAYBE FOR MYSELF, I'VE BEEN
UNAWARE OF THIS MECHANISM.
>>WE HAD A MEETING THAT TOUCHED
ON THAT A COUPLE HOURS AGO, AND
WE'RE TRYING TO -- THE SHORT
ANSWER IS YES, THIS IS VERY
COMMON.
I KNOW IT WAS A VERY IMPORTANT
COMPONENT OF THE LAST NIAMS
STRATEGIC PLAN, I WASN'T
INVOLVED IN THAT.
AND ONE OF THE THINGS WE'VE BEEN
THINKING ABOUT IS HOW EXACTLY TO
GET THE WORD OUT TO THE
INVESTIGATOR COMMUNITY.
IN GENERAL, IT'S A CHALLENGING
COMMUNICATION ENVIRONMENT RIGHT
NOW.
WE DON'T WANT TO OVERWHELM FOLKS
BUT WE'RE SERIOUSLY INTERESTED
IN RECEIVING FEEDBACK, AND WE
HOPE THAT YOU ALL CAN HELP US
SPREAD THE WORD SO WE'RE
CONTINUING TO THINK ABOUT HOW TO
BE EFFECTIVE ON THAT FRONT AND I
WOULD WELCOME ANY SUGGESTIONS
YOU HAVE OR OTHER INVESTIGATORS
THAT MIGHT BE LISTENING IN TO
THIS MEETING.
>>WALTER, DO YOU WANT TO
COMMENT ON YOUR EXPERIENCE WITH
RFIS AT NINDS?
>>SURE.
YES, I THINK IT'S PRETTY COMMON
THAT WE DO THAT, IN A WHOLE
BUNCH OF DIFFERENT AREAS WHERE
WE'RE LOOKING TO DEVELOP OUR
PLANNING.
RFIS OUT OF NIH ARE VERY COMMON.
AND, YOU KNOW, I THINK WE WANT
BROAD INPUT, SO THAT INDIVIDUALS
SENDING IN THEIR INFORMATION, WE
USUALLY, YOU KNOW, BUNDLE THEM
INTO CATEGORIES AND THEY INFORM
WHAT WE DO.
WE HAVE LIKE A WORKING GROUP OF
COUNCIL THAT'S WORKING ON THE
RECOMMENDATIONS.
THEY WILL BE SENT ALL THE RFI
COMMENTS.
AND THE LAST THING I'D SAY IS
THAT SOMETIMES THE MOST
THOUGHTFUL RFI RESPONSES COME
FROM ORGANIZATIONS THAT ARE
INTERESTED IN THE WORK THAT WE
DO HERE IN ONE OF THE
INSTITUTES, AND THEY OFTENTIMES
INFORM A LITTLE COMMITTEE AND
THEY WRITE OR, YOU KNOW, A SIX,
SEVEN-PAGE REPLY TO THE RFI.
THEY ARE VERY IMPORTANT IN
MAKING SURE THAT NIH IS
RESPONSIVE TO THE WIDER
COMMUNITY, BOTH PATIENTS AND
INVESTIGATORS AND CAREGIVERS.
>>I WOULD JUST ADD FROM THE
NICHD PERSPECTIVE, ERIC, THAT WE
DIDN'T HAVE A STRATEGIC PLAN FOR
20 YEARS.
SO THERE WAS A LOT OF PENT UP
DEMAND AND EMOTION FOR INPUT.
AND WHEN WE -- WE HAD A DRAFT
STRATEGIC PLAN, WHEN WE ASKED
FOR COMMENTS ON IT, WE DID GET
HUNDREDS, NOT ONLY FROM
INDIVIDUALS BUT FROM THE
PROFESSIONAL SOCIETIES AS WALTER
SAID.
IT'S A VERY USEFUL MECHANISM TO
REALLY PUT YOUR FINGER ON THE
PULSE, AS TO WHETHER WE'RE
GETTING IT RIGHT, DID WE FORGET
SOMETHING, AND WE ALSO PRESENTED
THE DRAFT TO OUR ADVISORY
COUNCIL, WHO ALSO HAD SOME VERY
IMPORTANT COMMENTS.
I'M GOING TO ACKNOWLEDGE
GUSTAVO'S HAND IS UP.
>>THANK YOU.
THIS IS A COMMENT AND QUESTION.
WE SHARED THE NEW IMPORTANT HIGH
FOCUS AND PATIENT-CENTRIC
HEALTH, PATIENT-CENTRIC
RESEARCH.
IN OUR ORGANIZATION, IT'S
IMPORTANT TO HELP EDUCATE
AFFECTED INDIVIDUALS AND
FAMILIES.
SO, THE QUESTION IS FUNDING
THROUGH NIH OR WE STILL SHOULD
GO THROUGH PCORI OR THOSE KINDS
OF ORGANIZATIONS.
>>WELL, ONE OF THE THINGS I'LL
SAY, MY COLLEAGUES MIGHT WONT TO
ADD, CERTAINLY SINCE I'VE
ARRIVED AT THE NIH THERE'S A LOT
OF DISCUSSION ABOUT THE
IMPORTANCE OF PATIENT
ENGAGEMENT.
AND EDUCATION AND HEALTH
LITERACY IS A VERY CRITICAL
PIECE OF THAT.
IT'S IMPORTANT FOR UNDERSTANDING
THE FULL IMPACT OF DISEASES AND
CONDITIONS ON INDIVIDUALS AND
THEIR FAMILIES, FOR ENSURING
THAT RESEARCH OF EFFORTS INVOLVE
PATIENTS AND FAMILIES IN
IMPACTFUL AND APPROPRIATE WAYS,
AND IN DISSEMINATING THE
RESEARCH, ET CETERA, ET CETERA.
I SEE A LOT OF EMPHASIS ON THAT.
I CAN'T SPEAK SPECIFICALLY TO
PATIENT EDUCATION EFFORTS AND
HOW THEY ARE FUNDED THROUGH THE
NIH, EXCEPT TO SAY IT'S CLEARLY
PART OF THE IMPORTANT MISSION OF
THE NIH.
I DON'T KNOW IF DIANA OR WALTER
WANT TO ADD TO THAT.
>>THERE ARE DEFINITELY SOME
THINGS THAT MIGHT BE OF
INTEREST.
SO THE NIH'S MISSION IS
RESEARCH.
SO, WE'VE SEEN RESEARCH GRANTS
TO TEST DIFFERENT WAYS OF
EDUCATING AT-RISK INDIVIDUALS,
SAY, ON HOW TO IMPROVE THEIR
HEALTH, WHERE THE OUTCOME IS,
YOU KNOW, TOOL AND IMPROVEMENT
IN HEALTH.
I THINK ON THE RESEARCH SIDE,
DEPENDING ON WHAT THE DISEASE
IS, AN INSTITUTE WOULD FUND --
WOULD TAKE IN GRANTS THAT WOULD,
YOU KNOW, DO RESEARCH ON HOW
BEST TO EDUCATE.
I DON'T THINK THAT NIH FUNDS
ACTUAL, YOU KNOW, ONGOING
DAY-TO-DAY EDUCATION, IF THAT
WAS THE QUESTION.
DOES THAT MAKE SENSE?
>>YES, AND I THINK THAT AS WE
HAD COORDINATING COMMITTEE AMONG
ALL THE FEDERAL BRANCHES OF THE
GOVERNMENT RELATED TO THESE
PROGRAMS, IF IT'S NOT THROUGH
THE -- THROUGH WHAT WAS
MENTIONED, TO HAVE, I DON'T
KNOW, KIND OF A DOCUMENT OR
IDEAS PUT TOGETHER TO INCREASE
FUNDING FROM FEDERAL
ORGANIZATIONS, FOR EDUCATING
PATIENTS.
I THINK IT'S SOMETHING THAT IS
LACKING.
WE STRUGGLE WITH EDUCATING
PATIENTS AND FAMILIES.
>>I THINK -- ARE YOU TALKING
ABOUT INCREASING THE ROLE OF
AFFECTED INDIVIDUALS AND
FAMILIES INTO ADVOCATING FOR
MORE MONEY FOR RESEARCH ON THE
CONDITION?
IS THAT WHAT YOU'RE --
>>NO, BECAUSE -- NO.
WE'RE TALKING ABOUT MAKING
PATIENT-CENTRIC RESEARCH OR
PATIENT-CENTRIC OUTCOMES, SO WE
NEED THE PATIENT INVOLVED, AND
FOR THE PATIENTS BEING INVOLVED
WE NEED THE EDUCATION.
>>I THINK THAT'S RECOGNIZED AS
A CRITICAL COMPONENT OF PATIENT
ENGAGEMENT, FOR SURE.
ANOTHER THING TO ADD, ALL OF THE
INSTITUTES HAVE COMMUNICATION
PROGRAMS AND DEPARTMENTS THAT
FOCUS ON, YOU KNOW,
APPROPRIATENESS OF LANGUAGE AND
OUTREACH AND DISSEMINATION.
I THINK WE GET AT MANY ASPECTS
OF WHAT YOU'RE RAISING, WHICH IS
VERY IMPORTANT OF COURSE.
>>I WOULD ADD THAT AT EACH
ADVISORY COUNCIL MEETING, WE
ALWAYS HAVE A SECTION CALLED THE
VOICE OF THE PARTICIPANT, IN
WHICH WE INVITE SOMEONE WHO IS
EITHER AN ACTIVE PARTICIPANT OR
PAST PARTICIPANT IN OUR
RESEARCH, TO TELL US, YOU KNOW,
HOW WAS THAT EXPERIENCE.
WHAT CAME OUT OF THE RESEARCH,
ET CETERA.
AND WHEN WE HAVE WORKSHOPS,
WHICH EFFECTIVELY PLAN FOR
FUTURE RESEARCH INITIATIVES, WE
FREQUENTLY INVOLVE PEOPLE WHO
HAVE THE LIVED EXPERIENCE.
SO, THAT'S ANOTHER WAY THAT WE
GET IT.
JUST SO WE DON'T GET TOO FAR OFF
SCHEDULE, DAN.
>>A GENERAL QUESTION.
I'VE PARTICIPATED MYSELF IN
(INDISCERNIBLE) TWO OR THREE
GENERATIONS OF MUSCULAR
DYSTROPHY.
I GUESS THE QUESTION IS, HOW IN
THE ANALYSIS, HOW DO YOU ANALYZE
OR DO YOU USE OR HOW MEASURED,
THE PROCESS, TALKING ABOUT
MUSCULAR DYSTROPHY PLAN, A
HUNDRED AREAS, GOOD AREAS TO
WORK ON, WHETHER YOU'RE
SUCCEEDED OR NOT, 100
RESEARCHERS, 600 PATIENTS,
THREE-YEAR PROCESS, 100 OTHERS,
DO YOU GO BACK AND SAY CHECK,
CHECK, CHECK, CHECK, WE
SUCCEEDED, WHERE DOES THIS GO?
HOW DO YOU AT THE NIH MEASURE
YOUR SUCCESS AGAINST THIS PLAN?
IS IT TIED TO PERFORMANCE REVIEW
AS A DIRECTOR, PROGRAM STAFF?
I MEAN, WHAT DOES IT DO?
>>I THINK THAT'S A GREAT
QUESTION, DAN.
AND CERTAINLY SINCE WE WILL
BEGIN OUR STRATEGIC PLANNING
PROCESS FOR THE NEXT ROUND,
THAT'S A BIG PART OF WHAT WE'RE
DOING IS WE'RE REVIEWING WHAT WE
SAID WE WERE GOING TO DO AND
LOOKING DID WE ACTUALLY DO IT.
ONE OF THE AREAS WHERE WE
SUCCEEDED AND ONE OF THE AREAS
WHERE EITHER WE FAILED OR WE
HAVEN'T APPROACHED IT YET, SO I
THINK FROM MY PERSPECTIVE IT'S
UP TO OUR INSTITUTE, IT'S NOT
LIKE NIH NECESSARILY IS LOOKING
AT WHETHER WE DID WHAT WE SAID
WE WERE GOING TO DO.
BUT CONGRESS DOES.
SO IF CONGRESS HAS APPROPRIATED
MONEY AND HAS SAID YOU MUST DO
A, B, C, D, ESSENTIALLY WE NEED
TO REPORT TO CONGRESS EITHER IN
PERSON OR IN WRITING THAT WE
HAVE DONE THAT.
AND IF NOT, THEY WANT TO KNOW
WHY.
AND THAT'S ANOTHER AREA WHERE
ADVOCACY GROUPS CAN GET INVOLVED
AND PUT THE PRESSURE ON NIH TO
ACCOMPLISH CERTAIN GOALS.
LINDSEY AND WALTER, DO YOU WANT
TO WEIGH IN?
>>I WOULD JUST SAY THANK YOU
VERY MUCH FOR THE QUESTION, DAN.
AND AT LEAST WITH RESPECT TO
STRATEGIC PLANNING, WE HAVE
TALKED ABOUT EXACTLY THE ISSUE
RAISED, THAT IS WHETHER YOU WANT
TO CALL IT STEWARDSHIP OR
ONGOING ASSESSMENT, AND WE'RE
DEFINITELY INTERESTED IN AS WE
DEVELOP THIS NEXT STRATEGIC PLAN
DEVELOPING METRICS OR HAVING A
SYSTEMATIC APPROACH TO
EVALUATING OUR PROGRESS.
THERE ARE TOOLS THAT CAN HELP US
DO THAT, IN THE OVERALL CATEGORY
OF PORTFOLIO ANALYSES, THOSE
AREN'T PERFECT, BUT WE ALSO
RECOGNIZE THAT WE CAN'T
ANTICIPATE TODAY SOME OF THE NEW
OPPORTUNITIES THAT WILL EMERGE
THREE YEARS FROM NOW SO WE NEED
TO MAKE SURE WE'RE NIMBLE,
OPPORTUNISTIC IN A SENSE LOOKING
FORWARD SO WE DON'T MISS NEW
OPPORTUNITIES THAT ARISE THAT WE
DIDN'T CONCEIVE OF AT THE OUTSET
OF THE PLAN.
SO, I THINK MOST IMPORTANTLY,
WHAT YOU'RE SPEAKING TO IS THE
TAKING SERIOUSLY THE PROCESS OF
SEEKING INPUT, DEVELOPING PLANS,
THEN MONITORING OUR PROGRESS
TOWARDS THOSE.
I DON'T KNOW IF WALTER HAS
ANYTHING ELSE TO SAY IN RESPONSE
FROM HIS EXPERIENCE.
>>OKAY.
THANK YOU.
>>THANK YOU.
>>THANKS FOR YOUR QUESTION,
DAN.
IN THE INTEREST OF TIME LET'S
MOVE ON.
WE'VE GOT TWO SUMMARY REPORTS,
TWO RECENT MUSCULAR DYSTROPHY
CONFERENCES, SO DR. GUSTAVO
DZIEWCZAPOLSKI WILL TELL US WILL
THE SCIENTIFIC AND FAMILY
CONFERENCE HELD IN JULY.
GUSTAVO, OVER TO YOU.
>>THANK YOU.
CAN YOU SEE MY SLIDES?
OKAY.
SO, WE THANK THE ORGANIZERS AND
FELLOW MEMBERS OF THE COMMITTEE
FOR GIVING US THIS CHANCE TO
SHARE WITH YOU.
OUR RECENT SCIENTIFIC AND FAMILY
CONFERENCE HOSTED IN NASHVILLE,
TENNESSEE, FOURTH OF JULY
WEEKEND, THE ONLY OPTION, IN THE
POST-PANDEMIC YEAR, POSTPONED
IN-PERSON MEETINGS, AND
EVERYBODY SEEMS TO WANT TO DO
THE CONFERENCES MISSED DURING
THE SUMMER, SAME AS US.
BUT IT WAS SUCCESSFUL.
IT WAS A FOUR-DAY MEETING,
TOTALLY HYBRID, MADE POSSIBLE IN
LARGE PART BY THE FINANCIAL
SUPPORT OF A FEW BUT VERY
IMPORTANT SPONSORS.
NIAMS WAS ONE OF THEM.
AND A PROGRAM BY THE INITIATIVE,
ONE COMPANY WORKING IN OUR
UMBRELLA, MDA, ANOTHER IN
FRANCE, A GROUP OF SPONSORS.
(INDISCERNIBLE) PATIENT
ORGANIZATIONS
[AUDIO DISTORTION]
COVERS FIVE DYSTROPHIES.
WE WERE JOINED BY A SMALL
ORGANIZATION JUST LAST WEEK,
NON-PROFIT ORGANIZATION STATUS
COVERING TITINOPATHYS.
WE JOINED FORCES, MADE STRONGER
FOR DIFFERENT PATIENTS.
ALL READINESS FOR ALL THESE RARE
CONDITIONS, COMMON STRATEGIES,
WHICH LEAVES POTENTIAL
ESTABLISHING RESEARCH PLATFORMS
WHERE MORE THAN ONE DISEASE
COULD BE MOVED FORWARD IN THE
SAME PIPELINE.
WE'VE BEEN COLLABORATING,
PROVIDING RESEARCH TO CMD
INTERNATIONAL REGISTRY, ALSO
TISSUE REPOSITORY.
THEN WE HAVE EXPERIENCE
ORGANIZING SCIENTIFIC CONFERENCE
IN 2019, SO WE'RE VERY FRIEND
ORGANIZATIONS.
ALSO THE FACT THAT MOST OF THE
EXPERTS IN THIS CMD SEE PATIENTS
(INDISCERNIBLE) SAVING TIME BY
ASKING THEM TO ATTEND ONLY ONE
CONFERENCE INSTEAD OF THREE
DIFFERENT ONES.
THE CONFERENCE THEMES WERE NOT
THAT ORIGINAL BUT VERY IMPORTANT
IN OFFERING RESEARCHERS AND
CLINICIANS THE OPPORTUNITY TO
LEARN FROM EACH OTHER AND
ENHANCE ONE ANOTHER'S WORK.
THIS ARENA ANALYZES POSSIBILITY
TO DETECT RESEARCH AND CARE
PRIORITIES FOR EACH SPECIFIC
DISEASE AS WELL AS POSSIBILITIES
FOR PLATFORMS OR PROJECTS
TOTALING MORE THAN ONE DISEASE
AT A TIME.
AND AS IT HAPPENED IN PAST
CONFERENCES, CONCLUSIONS OF THE
SCIENTIFIC CONFERENCE GUIDE US
TO FOCUS FUTURE FUNDING IN OUR
GRANT PROGRAMS.
AND LAST BUT NOT LEAST,
PROVIDING THE OPPORTUNITY OF
GATHERING AFFECTED INDIVIDUALS
WITH EACH OTHER AND WITH
CLINICIANS AND RESEARCHERS,
EXPERTS IN THESE DISEASES, THAT
HELP US IN OUR MISSION OF
CRAFTING THE MOST RELEVANT
PATIENT-FOCUSED APPROACHES POSS.
THE CONFERENCE STRUCTURE
THURSDAY AND FRIDAY MORNING WAS
SCIENTIFIC SYMPOSIUM.
RESEARCH FUNDING BY THE THREE
ORGANIZING GROUPS AS WELL AS
INVITED GRANTEES FROM
PATIENT-ADVOCACY PARTNERS, SO
CONSISTED OF 31 INDIVIDUAL TALKS
BY GRANTEES, GROUPED IN BLOCKS
BY POTENTIAL THERAPEUTIC
MODALITIES, AND OF COURSE ALSO
POSTER SESSIONS.
HERE AT DIFFERENT STAGES OF
PROJECT DEVELOPMENT, SOME OF
THEM HAVE PLANS, OTHERS WERE IN
BETWEEN, WE WANTED TO MAXIMIZE
CHANCES TO OBTAIN FEEDBACK FROM
PEERS AND OTHER STAKEHOLDERS, BY
HAVING PLATFORM TALKS, POSTERS
AND DISCUSSION.
ALL THE PRESENTERS, WE ASK THEM.
WE ALSO HAD ONE PRESENTATION BY
A COMPANY WORKING, A PLENARY
TALK, ONE OF THE HIGHLIGHTS WAS
TO HAVE THE PATIENT FOCUS WITH
FDA, PLANNING SIX MONTHS IN
ADVANCE, ALMOST A YEAR IN
ADVANCE, GRANTED THIS
OPPORTUNITY, THE FDA
INDIVIDUALLY AND ACCORDING TO
OUR FDA PROGRAM OFFICER 20
ATTENDED LIVE, OTHERS HAD THE
CHANCE OF WATCHING THE
RECORDINGS ON DEMAND.
TO US, IT WAS A SUCCESSFUL
MEETING.
WE WERE ABLE TO SHOW AND WE HAD
A LOT OF PATIENTS AND FAMILIES
AND WE CREATED A SHORT THEME TO
SHOW DAY-TO-DAY STRUGGLES AND
HOPES FOR PATIENTS, LAST TWO
DAYS DEDICATED TO THE DEEP
INTERACTION OF AFFECTED
COMMUNITIES, WITH RESEARCHERS
AND CLINICIANS, TOPICS AND ALSO
INDIVIDUAL BREAKOUT SESSIONS,
RESEARCH UPDATES, CARE UPDATES,
PROFESSIONAL SUPPORT, HOW TO AND
NAVIGATE LIFE WITH DISORDERS,
MENTAL HEALTH SUPPORT TO
UNAFFECTED SIBLINGS, NAVIGATED
CARE BENEFITS, FINANCIAL ADVICE,
ET CETERA.
FUNDED RESEARCH, IT WAS VERY
BROAD.
WE HAD VERY DIVERSE
PRESENTATIONS, THIS IS USING
DIFFERENT DISEASE MODELS FROM
ZEBRAFISH TO MOUSE MODELS,
ANIMAL MODELS.
AND PATIENT DERIVED iPSCs
AND 3D MUSCLES, ALSO VERY
DIVERSE EXPERIMENTAL THERAPEUTIC
MODALITIES, SOME PROJECTS
ATTEMPTING DRUG REPURPOSING,
USING HIGH-THROUGHPUT
METHODOLOGY, ALL KIND OF GENETIC
MANIPULATION, TRANSCRIPT
ACTIVATION, SPECIFIC GENE
ACTIVATION, SPECIFIC TRANSCRIPT
ACTIVATION, GENE EDITING AND
BASE EDITING.
ALSO SOME COUPLE OF GRANTEES
WORKING ON IMPROVING THE TOOLS.
>>WE HAVE ALLOTTED TEN MINUTES.
THERE'S A TIMER.
TEN MINUTES IS OVER, IF YOU
COULD BEGIN TO WRAP IT UP
BECAUSE WE'RE QUITE A BIT OVER
TIME RIGHT NOW.
>>YES.
SORRY.
ALSO MECHANISM OF POTENTIAL
TARGET DISCOVERIES.
SINCE I'M A MEMBER OF THE MBCC I
HAVEN'T SEEN A PAPER BEING
HIGHLIGHTED MAINLY BECAUSE
UMBRELLA USED TO BE BEHIND OTHER
MORE RARE, IT IS EXCITING TO SEE
HOW THE SAME TECHNOLOGY AND
APPROACHES ARE BEING USED IN
RESEARCH.
IT WAS ATTENDED BY 400 IN
PERSON, 150 ONLINE, 89 STATES,
IF YOU WANT TO LEARN MORE -- 18
COUNTRIES, 39 STATES.
THAT'S IT.
THANK YOU VERY MUCH.
[AUDIO DISTORTION]
>>THANK YOU.
IT WAS MY FAULT FOR NOT POINTING
IT OUT.
BUT WE THANK YOU FOR NOT ONLY
ORGANIZING THIS CONFERENCE BUT
GIVING US A THOROUGH REPORT ON
IT.
I THINK SINCE WE'RE ALREADY 11
MINUTES OVER SCHEDULE, I DON'T
WANT TO CUT INTO THE BREAK TOO
MUCH SO IF WE HAVE PRESSING
QUESTIONS PLEASE ASK THEM IN THE
Q&A OR THE CHAT BOX.
I ALSO WANT TO POINT OUT THAT
DR. CRISWELL PUT THE INFORMATION
ON THE REQUEST FOR INFORMATION
FOR THE NIAMS STRATEGIC PLAN IN
THE CHAT BOX.
NEXT A REPORT FROM DR. NANDI, HE
AND HIS COLLEAGUES HELPED
ORGANIZE A CONFERENCE ON CARDIAC
CARE FOR BOYS WITH DUCHENNE
MUSCULAR DYSTROPHY, SUPPORTED BY
PART PROJECT MUSCULAR DYSTROPHY.
WELCOME, DR. NANDI.
I DON'T SEE YOU BUT I'M HOPING
YOU'RE THERE.
>>I AM.
THANK YOU FOR HAVING ME.
I MUCH APPRECIATE IT.
I'LL BE PRESENTING ON ON BEHALF
OF THE ACTION NETWORK, A GROUP
THROUGHOUT THE NATION AND WORLD
GROWING IN SIZE, I'LL EXPLAIN
WHY, ON BEHALF OF MY CLEGS,
CHAT, AND LINDA, AND NETWORK OF
CARDIOLOGISTS TAKING CARE OF
FAMILIES.
AS WE HAVE DONE BETTER AND
BETTER WITH, THE BURDEN OF
MORTALITY HAS ACTUALLY SPREAD
INTO THE CARDIAC WORLD WHERE
CARDIAC DEATHS NOW MAKE A
MAJORITY OF WHERE WE LOSE OUR
PATIENTS, WHY OUR CARDIOLOGY
POPULATION HAD INCREASING CARE
TAKEN OVER IN THESE GROUPS.
SO, WITH THE HELP, WE
ORCHESTRATED A CONFERENCE IN
CHARLESTON THIS YEAR TAKING CARE
OF CARDIAC SIDE OF THINGS, WELL
ATTENDED FOR THE CARDIOLOGY
WORLD IN PEDIATRICS, 80
ATTENDEES, HALF WERE
CARDIOLOGISTS, ALSO
REPRESENTATIVES FROM
NEUROMUSCULAR, PULMONARY
COLLEAGUES, REPRESENTATIVES FROM
SEVERAL INDUSTRY FOLKS AS WELL
AS MEMBERS OF FDA AND NHLBI.
THE POINT OF THE CONFERENCE WAS
TO TRY TO MOVE FORWARD WITH
FURTHER CARE IN THE CARDIAC
SPEAR, LUCKY TO HAVE DR. SANTORE
FROM THE FDA SPEAK WITH US ON
ENDPOINTS AND CLINICAL TRIALS,
REITERATING FETAL FUNCTION, END
POINTS FOR RARE DISEASES.
TO SPEAK ON THOSE, THE FIELD IS
DIFFICULT IN CARDIAC PATIENTS
WITH NEUROMUSCULAR ISSUES, WHERE
WE HAVE A HARD TIME
UNDERSTANDING WHAT THEY MAY LOOK
LIKE, FUNCTION IS ALSO DIFFICULT
TO ASSESS, AND MORTALITY IS POOR
IMPROVED OUTCOME WHICH MANY
FAMILIES CANNOT WAIT, SURROGATE
ENDPOINTS ARE OFTEN NEEDED,
WHILE THEY ARE IMPORTANT AND CAN
BE BENEFICIAL THEY ARE ALSO
FRAUGHT WITH MANY ISSUES LEADING
TO CHOOSING IMPROPER ENDPOINTS
WHICH MAY BECOME PROBLEMATIC.
NOW, WE WERE VERY LUCKY TO
DISCUSS, DR. BOB SHATY AT USC, A
FORMER MENTOR OF MYSELF, THE
FIRST OF ITS KIND TRIAL OF A
MAJOR NEW DRUG WHICH APPROVED
FDA -- RECEIVED FDA APPROVAL IN
OCTOBER OF 2019, THE ONLY REAL
DRUG WE HAVE AN ACTUAL
INDICATION FOR.
IT'S VERY IMPORTANT TO NOTE
HOWEVER ENTRESTO WAS APPROVED ON
THE BASIS OF A SURROGATE MARKER,
ON PAR WITH WHAT WAS SEEN IN
ADULTS, HELPFUL TO FDA IN MAKING
APPROVAL DECISION WHICH AGAIN
SHOWS YOU THAT THE SURROGATE
MARKERS WHEN CHOSEN
APPROPRIATELY CAN BE THE KEY TO
GETTING THESE APPROVALS.
SO, KNOWING WE HAVE A GOAL OF
TRYING TO FIGURE OUT THOSE
MARKERS HOW DO WE UNDERSTAND
WITHIN THAT THE CURRENT CARDIAC
PROGNOSIS FOR OUR PATIENTS, AND
TREATMENTS THAT WE HAVE FOR
THEM.
THESE NEXT SLIDES ARE ON BEHALF
OF THE -- COURTESY OF A
PATHOLOGIST AT CINCINNATI
CHILDREN'S WHO WITH COLLEAGUES
UNDERTOOK PATHOLOGIC REVIEW OF
TEN PATIENTS, INCLUDING NINE
MALES, ONCE CINCINNATI CARRIER
FEMALE.
THIS IS THE HEART, YOUNG
36-YEAR-OLD MAN, DUCHENNE
MUSCULAR DYSTROPHY ON STEROIDS
FROM YOUNG AGE, FOUND DECEASED
AT HOME.
STRIKINGLY YOU CAN SEE HOW MUCH
FAT THERE IS THROUGHOUT THE
EPICARDIAL SURFACE, SIGNIFICANT
INFILTRATE.
LOOKING TO THE BACK, THIS IS THE
RIGHT ATRIUM, AND THE ATRIUM
THERE IS JUST VERY TRANSLUCENT
AND JUST SHOWS HOW MUCH
DESTRUCTION MYOCYTES OF GONE ON
THERE.
MOVING MORE CLOSELY, MICROSCOPIC
CLOSE-UP OF THE RIGHT ATRIUM,
WE'RE SEEING SIGNIFICANT
MYOCARDIAL REPLACEMENT, 5% OF
MYOCYTES REMAIN, AT INTEGRALS
YOU SEE ON THIS EPICARDIAL
SURFACE MORE INFILTRATE WITH
MORE REPLACEMENT OF MYOCYTES AS
WELL.
THIS HELD TRUE IN ALL OF THE
PATIENTS ESSENTIALLY, SAMPLES
TAKEN FROM AUTOPSY, SHOWING THAT
FAT AND INFILL INFILTRATE IS SO
DIFFICULT TO ASSESS WITH
EXTERNAL VIEWS OF OUR PATIENTS.
HOW DO WE UNDERSTAND THAT
DISEASE PROGRESSION WITHOUT AN
AUTOPSY, WITHOUT PATHOLOGIC
SAMPLES?
THE ANSWER IS, OF COURSE, VERY
POORLY.
THESE ARE FROM VANDERBILT
UNIVERSITY.
WE LOOKED AT BIOMARKERS, NO
CORRELATION WITH LD EJECTION
FRACTION, DO NOT CORRELATE
FUNCTION WITH THESE BLOOD
BIOMARKERS.
THIS IS -- WE BEGAN TO
UNDERSTAND BACK IN EARLY 2000s
HOW MRI COULD BE A SIGNIFICANT
BENEFIT, SPECIFICALLY WITH
REGARDS TO GADOLINIUM
ENHANCEMENT, CALLED FIBROSIS,
INCREASING ENHANCEMENT
ASSOCIATED WITH WORSE EJECTION
FRACTION AND INCREASED RATES OF
MORTALITY.
HOWEVER, IT'S A BLUNT TOOL.
ISN'T NECESSARILY THE MOST CLEAR
OUTCOME.
FIBROSIS IS SEEN ON THE LEFT
IMAGE, CORRELATING WITH PERHAPS
THE FATTY INFILTRATE, IT'S NOT
ALWAYS 1:1 AND CAN BE DIFFICULT
TO ASSESS.
THE LEADING NIH FUNDED R01
CENTER STUDY LOOKING AT MRI AT
LATE GADOLINIUM ENHANCEMENT, T1
TIMES, EXTRACELLULAR VOLUME,
NORMAL PATIENTS CAN HAVE
DIFFERENT LGE PATTERN, HOW DO WE
UNDERSTAND THIS AS ACTUALLY WHAT
IS GOING ON IN MYOCARDIAL
TISSUE.
THIS IS A THOUGHT EXPERIMENT HOW
YOU TAKE EXTRACELLULAR VOLUME,
NATIVE T1 AND PLACE THEM ON
DIFFERENT PARTS OF THE SCALE,
UNDERSTAND FIBROSIS, EDEMA,
FATTY INFILTRATE.
DR. SASLOW WAS ABLE TO EVALUATE
MANY PATIENTS, FINDS THIS
SETTLES OUT WHERE LARGER VOLUMES
SETTLE OUT AS LARGER DOTS AND
CAN SPREAD PATIENTS ALONG T2 AND
T1 TIMES.
BY TAKING THOSE TIMES WE CAN
POTENTIALLY LOOK AT EJECTION
FRACTIONS, CHARACTERIZING NORMAL
HEART, PERHAPS HIGHER EJECTION
FRACTION, TIMES INCREASE,
PERHAPS AS MORE FAT OCCUR,
DECREASING EJECTION FRACTURE.
THIS IS PRELIMINARY DATA.
IT DOES PROVIDE MECHANISM TO
POTENTIALLY HAVE A REALLY USEFUL
SURROGATE ENDPOINT TO FOLLOW
MUCH MORE CLOSELY THAN
MORTALITY.
HOW CAN WE ASSESS?
WHAT PREVENTIVE TREATMENTS ARE
BEING USED?
THIS IS A FRENCH STUDY
DEMONSTRATING USE OF ACE
INHIBITORS ON MORTALITY IN
DUCHENNE, INCREASED HAZARD OF
MORTALITY, DATA FROM OHIO FROM
MY COLLEAGUES, LOOKING AT USE ON
EJECTION FRACTION, IN WHICH
EPLERONONE TENDS TOWARD
DECREASED CHANGE IN EJECTION
FRACTION BASED ON STUDIES SUCH
AS THESE WE HAVE COMMENTS FROM
THE AMERICAN HEART ASSOCIATION,
TELLING US WE CAN USE WITH
DECREASED FUNCTION.
THIS DATA IS INCONSISTENTLY
USED AND HARD TO TEASE OUT.
WE HAVE QUERIED NUMBER OF
MUSCULAR DYSTROPHY CARDIOLOGISTS
IN THE UNITED STATES, AND
DEMONSTRATED GREAT VARIABILITY.
ON THE LEFT INDICATIONS, 68%
HAVE USED ACEs AND ARBs, 10
OR GREATER, MILD SYSTOLIC
DYSFUNCTION, 23% FOR THOSE WITH
LATE GADOLINIUM ENHANCEMENT, AND
MANY INDICATIONS AND NOT ALWAYS
PURELY BASED ON AGE RELATION.
SO, WITH ALL OF THAT IT'S
DIFFICULT TO DECONSTRUCT WHAT
PATIENTS ARE ON WHAT MEDICINES,
WHAT EFFECTS ON HEARTS, AND HOW
WE CAN ASSESS TREATMENT DOSE OR
NEW THERAPIES.
WHERE ARE WE GOING AND HOW DO WE
GET THAT DATA?
SO THE MEETING ACTUALLY SPENT A
FAIR AMOUNT OF TIME TALKING
ABOUT THIS AND WE ENDED FOCUSING
ON THREE ASPECTS OF CARE,
COLLABORATION THROUGH THE ACTION
NETWORK, HARMONIZATION OF CARE,
THE OTHER BEING ENDPOINTS, WHICH
WE NEED TO FOLLOW.
REGARDING COLLABORATION, SO
ACTION, THE ADVANCED CARDIAC
THERAPIES IMPROVING OUTCOMES
NETWORK FOUNDED IN 2017 WITH
IDEA THAT ARE DIVERSITIES IN
CHILDREN WITH NO STANDARD OF
CARE.
WE BEGAN WORKING WITH PATIENTS
WITH CARDIOMYOPATHY
MYOCART ITIS, THERE'S A
COMPONENT FOCUSED ON PATIENTS,
NOT STUDIED IN PEDIATRICS OR
DISEASES WE TREAT.
OUR DATA IS LARGELY EXTRAPOLATED
FROM ADULT STUDIES THAT THE
MEDICATIONS MONITORING
REHABILITATION, AND THUS WE HAVE
LESS KNOWLEDGE OF HOW TO USE
THESE DEVICES AND THERAPIES IN
THESE SPECIAL POPULATIONS.
SO, ACTION WAS FOUNDED IN 2017,
60 CENTERS NOW, THESE ARE ACROSS
NORTH AMERICA AND EUROPE, WHICH
HAVE SHOWN SIGNIFICANT ABILITY
TO GET WORK DONE.
FOR INSTANCE, WE USE COMMONLY
THE BERLIN X CORE, KEPT FOR
SMALL CHILDREN, AND INFANTS
UNABLE TO GET LARGER DEVICES,
HISTORICALLY HIGH STROKE RATE OF
25% IN PRIOR REGISTRY DATA.
HOWEVER, WITH HARMONIZING CARE
CUT TO 13% ALLOWS US TO USE THAT
DEVICE FOR MANY PATIENTS.
WE'RE ABLE TO ALSO COLLABORATE,
THE ONLY DISCHARGEABLE LVAD THAT
EXISTS, TWO-YEAR POST
SURVEILLANCE IN PEDIATRIC REALM,
DATA TO FDA COLLABORATION AND
HAVE A PEDIATRIC LABELING WHICH
IS VERY RARE IN PEDIATRICS THAT
WE'RE ABLE TO GET DATA LABELING
FOR OUR THERAPIES.
SO, ACTION ALREADY HAS AN IRB
AND INFRASTRUCTURE IN PLACE TO
CORRECT DATA, INHOUSE REVIEW, A
PROVEN RECORD WITH THE FDA
REGARDING DEVICES, BRANCHING OUT
MORE AND MORE SIGNIFICANTLY AND
BRANCHING OUT.
HARMONIZATION IS REALLY
IMPORTANT PART OF THIS.
WE HAVE GREAT GENETIC
HETEROGENEITY, PHENOTYPIC
HETEROGENEITY AND LACK OF
GUIDELINES, IT'S DIFFICULT TO
UNDERSTAND EFFECTS OF OTHER CARE
AND PROTOPLASM.
THERE IS NO DATA, LARGELY
CONSENSUS DRIVEN.
THESE THERAPIES HAVE ALSO BEEN
HARMONIZED WITH DUCHENNE
POPULATION, ON VERSE 3 OF THE
HARMONIZATION OF BOTH
PROPHYLACTIC AND THERAPEUTIC
TREATMENTS FOR THE MUSCULAR
DYSTROPHY POPULATION, WITH THESE
WE WERE HAVING INCREASING UPTAKE
ACROSS MANY CENTERS, NOT JUST
THE LARGEST CORE CENTERS OF THE
ACTION COMMUNITY.
HOWEVER, IN THE END WHAT WE
NEED, ENDS POINTS AND DATA,
MODERN HISTORY STUDY WITH
STANDARDIZED BACKGROUND
THERAPIES, NEED TO UNDERSTAND
CARDIAC MRI DATA BETTER AND
STILL NEED TO GO AFTER FUNCTION
AND HOW PATIENTS ARE FEELING,
WHAT ARE PATIENT-REPORTED
OUTCOMES.
SO IN PARTNERSHIP, WE HAVE BEEN
GRANTED A GRANT TO FACILITATE
BROAD DATA ENTRY, WE'RE HOPING
TO EXPLOIT THESE INCREASING
STANDARDIZATION OF BACKGROUND
THERAPIES, WE HAVE THE MEDICINES
AND WE'RE NOT SURE HOW MUCH THEY
ARE BENEFICIAL TO OUR PATIENT
POPULATION BUT FEEL THEY MAY BE.
WE HAVE ENTRESTO, INHIBITORS,
AND FURTHER USE OF GENE
THERAPIES, VECTOR DRIVEN OR EXON
SKIPPING, ALL OF THOSE HAVE
VARYING EFFECTS ON CARDIAC CARE
AND WE DO NOT UNDERSTAND THEM
FULLY BUT BY WORKING TO CREATE A
BETTER NATURAL HISTORY STUDY AS
WELL AS CARVEOUTS FOR
UNDERSTANDING NEW THERAPIES, WE
VERY MUCH HOPE TO UNDERSTAND
WHAT THAT CARDIAC PROCESS IS
GOING TO BE, WE'RE HOPING TO
LAUNCH BROAD DATA COLLECTION
STARTING NEXT QUARTER, AFTER
HAVING STARTED PILOT SITES
ALREADY.
MRI DATA IS GROSSLY NEEDING TO
BE STANDARDIZED.
WE BELIEVE THIS IS GOING TO BE
THE SURROGATE OUTCOME WITH WHICH
WE'LL BE ABLE TO UNDERSTAND MORE
READILY HOW OUR PATIENTS ARE
DOING.
WE'RE CONTRIBUTING TO MRI
STANDARDIZATION FOR DIFFERENT
DEVICES AND DATA ACQUISITION AS
WELL AS STANDARDIZING DATA
REPORT AND INTERPRETATION SO
WHEN THE MRI DATA BECOMES MORE
PRIME TIME FOR USE AS A
SURROGATE MARKER, WE'LL BE ABLE
TO QUICKLY ADOPT TO USING THEM
AS SUCH.
LASTLY PATIENT-REPORTED
OUTCOMES, ACTION HAS DEVELOPED
PEDIATRIC RELATED PATIENT
REPORTED OUTCOMES AND WE'RE
ROLLING THOSE OUT CURRENTLY.
WE'RE ACTUALLY WORKING THIS
COMING MONTH TO START
DYSTROPHINOPATHY.
WE'RE POISED WITH A ROAD MAP FOR
WHERE WE ARE AND WHERE WE'RE
GOING, IMPROVING CARDIAC CARE IN
THIS POPULATION.
WE THANK MY COLLEAGUES AND
COLLABORATORS CHET AND LINDA,
COLLEAGUES, FAMILIES, PATIENTS
WORLDWIDE.
WE DO THIS WORK THROUGH THE
UMBRELLA OF ACTION AND GENEROUS
FUNDING OF MUSCULAR DYSTROPHY TO
UNDERSTAND NEXT STEPS.
THANK YOU VERY MUCH, BACK ON
TIME.
>>A GREAT PRESENTATION.
REALLY IMPORTANT TO SHINE A
SPOTLIGHT ON THIS PROBLEM, NOW
THAT BOYS WITH MUSCULAR
DYSTROPHY ARE LIVING LONGER FROM
A RESPIRATORY PERSPECTIVE THAT
CARDIAC COMPLICATIONS ARE MORE
SIGNIFICANT, OR BEING
RECOGNIZED.
EXCELLENT WORK.
BECAUSE YOU WERE ON TIME WE'LL
LET YOU HAVE A COUPLE QUESTIONS
IF ANYBODY HAS QUESTIONS FOR DR.
NANDI?
DON'T BE SHY.
I GUESS YOU MUST HAVE ANSWERED
THEM OR ADDRESSED THEM ALL IN
YOUR PRESENTATION WHICH I
THOUGHT WAS VERY CLEAR.
IT'S GREAT TO HEAR ENTRESSTO IS
GETTING APPROVED FOR CHILDREN, I
KNOW SEVERAL ADULTS ON IT WHO
SAY IT'S A MIRACLE DRUG.
>>IT IS GREATLY HELPING
PATIENTS, IT WOULD BE NICE TO BE
MORE THAN ANECDOTAL.
>>WE'LL TAKE A SHORT BACK.
GLEN, 15-MINUTE BREAK OR STICK
TO SCHEDULE AND GIVE 10-MINUTE
BREAK.
>>UP TO YOU.
WE COULD AFFORD A 15-MINUTE
BREAK IF YOU'D LIKE.
WE'LL COME BACK AT 2:50.
>>WE'LL SEE YOU THEN.
THANK YOU.
>>WELCOME EVERYONE BACK.
THE MAIN TOPIC IS INNOVATIVE
OUTCOME MEASURES FOR MUSCULAR
DYSTROPHIES.
I'LL TURN THE MEETING OVER TO
GLEN TO INTRODUCE THIS SESSION.
>>I WANTED TO TAKE A COUPLE
MINUTES TO SET THE STAGE FOR OUR
NEXT SET OF PRESENTATIONS ON
INNOVATIVE OUTCOME MEASURES AND
INTRODUCE CONCEPTS THAT WE'RE
LIKELY TO BE DISCUSSING TODAY.
NIH SELECTED THIS TOPIC, IT DOES
NOT NECESSARILY MEAN THAT WE
INTEND TO DEVELOP NEW
INITIATIVES ON THIS TOPIC, AND
IF YOU'RE INTERESTED IN GUIDANCE
IN SUPPORTING RESEARCH IN THIS
AREA, PLEASE CONTACT ME, THERE
ARE A NUMBER OF EXISTING FUNDING
OPPORTUNITIES THAT I CAN SUGGEST
FOR YOU.
AS DEFINED IN THE RESOURCE ON
BIOMARKERS, ENDPOINTS AND TOOLS,
COAs ARE MEASURES THAT
DESCRIBE OR REFLECT HOW AN
INDIVIDUAL FEELS, FUNCTIONS,
SURVIVES, IN THE CATEGORIES OF
CLINICIAN OR OBSERVER REPORTED,
PATIENT REPORTED, ACTUALLY A
TOPIC WE DISCUSSED IN JUNE OF
2020 OR MORE OF WHAT WE TALK
ABOUT TODAY, PERFORMANCE
OUTCOMES, MEASUREMENTS OF
PATIENTS UNDERTAKING
STANDARDIZED TASKS.
SOME EXAMPLES ARE ALSO NOT SO
MUCH DIRECT MEASURES OF FUNCTION
BUT MORE INDIRECT MEASURES OF
FUNCTION, THEY MAY FIT INTO A
CATEGORY CALLED DIGITAL
BIOMARKERS RATHER THAN CLINICAL
OUTCOME MEASURES, MUCH OF THE
SAME APPLIES.
WE HEARD FROM DR. NANDI ABOUT
MEASURES OF CARDIAC PERFORMANCE
IN DUCHENNE, WHICH COULD BE USED
IN CLINICAL TRIALS THAT ARE
TARGETING THE HEART.
MANY OF THE CLINICAL TRIALS
TARGET SKELETAL MUSCLE.
I WANTED TO BRIEFLY REVIEW THE
CLINICAL OUTCOME ASSESSMENTS
USED IN THOSE TRIALS.
SO, COMMONLY USED MEASURES
INCLUDE MUSCLE STRENGTH TESTING,
TIMED FUNCTION TESTS, RATINGS
SCALES SUCH AS NORTH STAR AND
LET'S INCLUDE RESPIRATORY
OUTCOME MEASURES WHICH WE ALSO
DISCUSSED IN JUNE OF LAST YEAR
AT THE MDCC MEETING, AND
DIAPHRAGM AND MUSCLES OF
RESPIRATORY OR SKELETAL MUSCLES.
DIRECT MEASURES CAN STAND AS
PRIMARY OUTCOME MEASURE IN
CLINICAL TRIALS AND HAVE IN MANY
CASES, BUT CAN ALSO BE AFFECTED
BY OTHER FACTORS SUCH AS
MOTIVATION OF THE PATIENT OR
PERHAPS SUBCONSCIOUS BIAS OF
CLINICAL INVESTIGATOR, LEADING
TO VARIABILITY IN THE MEASURES.
ONE THING WE'RE STRIVING FOR IS
OUTCOME MEASURES THAT HAVE LESS
VARIABILITY AND ALSO ARE QUITE
SENSITIVE.
I WANTED TO POINT OUT THERE'S A
MEASURE THAT'S BEEN DEVELOPED,
DIGITAL MEASURE, THE FASTEST 5%
OF STREETS, MEASURED WITH A
VALIDATED ANKLE WORN
ACCELEROMETER, QUALIFIED BY THE
EMA AS A SECONDARY END POINT IN
DUCHENNE CLINICAL TRIALS, UNDER
REVIEW FOR QUALIFICATION FOR
FDA.
THIS IS A FIRST STEP TOWARDS
MORE TECHNOLOGICALLY ADVANCED
MEASURES AND BIOMARKERS FOR
PHYSICAL FUNCTION.
WE NEED OUTCOME MEASURES TO BE
ANALYTICALLY VALIDATED, KNOWN TO
MEASURE INTENDED FUNCTIONAL
STATE, NEED MEASUREMENTED THAT
COORDINATE WITH DISEASE STATE,
SENSITIVE TO CHANGES IN DISEASE
PROGRESSION THAT MAY OCCUR OVER
THE TRIAL DURATION WHICH IS
USUALLY ABOUT 1 TO 2 YEARS
DEPENDING ON THE TYPE OF
MUSCULAR DYSTROPHY.
WE NEED LOW VARIABILITY, LIMITED
EFFECT OF EXTERNAL FACTORS.
IF WE COMBINE SENSITIVITY AND
LOW VARIABILITY, IT MEANS THAT
WE CAN DESIGN CLINICAL TRIALS
THAT HAVE APPROPRIATE
STATISTICAL POWER WITH FEWER
PARTICIPANTS OR SHORTER
DURATION.
MEASUREMENTS NEED TO BE RELEVANT
TO QUALITY OF LIFE AND OVERALL
WELL-BEING.
IF THERE'S A LOT OF PATIENTS AND
A LOT OF SITES, THEN COST OF
EQUIPMENT AND AMOUNT OF TIME IT
TAKES TO TAKE THE MEASUREMENT
ALSO BECOME CONSIDERATIONS.
WE WOULD LIKE TO HAVE OUTCOME
MEASURES APPLICABLE TO BOTH
AMBULATORY AND NON-AMBULATORY
INDIVIDUALS WHEN POSSIBLE.
AND IF IT'S POSSIBLE WE WOULD
LIKE TO COLLECT DATA REMOTELY,
THIS CERTAINLY DECREASES THE
BURDEN OF STUDY PARTICIPATION
AND ALSO PROMOTES EQUITY, SO AS
WE DISCUSSED IN THE DECEMBER
MDCC MEETING LAST YEAR, BY
REDUCING THE BURDEN OF STUDY
PARTICIPATION WE CAN BETTER
ENSURE THE APPROPRIATE DIVERSITY
OF THE COHORTS.
SO, OUTCOME ASSESSMENTS CAN BE
USED AFTER THE DRUG IS APPROVED,
FOR EXAMPLE IN STUDIES OF
COMPARATIVE EFFECTIVENESS TO
DETERMINE IF ONE OF SEVERAL
TREATMENTS IS DESIRABLE OVER THE
OTHERS.
AND THEN IN SOME CASES WE FIND
INSURANCE COMPANIES REQUIRE
EVIDENCE THAT A DRUG CONTINUES
TO HAVE THE DESIRED EFFECT, FOR
THEM TO MAINTAIN COVERAGE FOR AN
INDIVIDUAL.
SO WE'D LIKE TO HAVE BIOMARKERS
OR OUTCOME MEASURES THAT COULD
ALSO BE USEFUL FOR THAT PURPOSE.
SO, A GOAL OF THE SESSION IS
REALLY TO HIGHLIGHT THE WORK
THAT'S AIMED AT IDENTIFYING,
VALIDATING, IMPLEMENTING
IMPROVED CLINICAL OUTCOME
ASSESSMENTS AND MEASURES TO
INCREASE THE EFFICIENCY AND
LIKELIHOOD OF SUCCESS IN
CLINICAL TRIALS AND POST
MARKETING DATA COLLECTION.
THE SESSION WILL BEGIN WITH A
PATIENT PERSPECTIVE, SO DONOVAN
DECKER IS A FORMER MEMBER OF
MDCC, LIVING WITH MUSCULAR
DYSTROPHY, LINDA AND MINDY AND
DAMIANO.
NOW I'LL TURN IT BACK TO YOU,
DR. BIANCHI, TO INTRODUCE
MR. DECKER.
>>GREAT JOB SETTING THE STAGE.
THE TOPIC OF IMPROVED OUTCOME
MEASURES WAS RECOMMENDED BY THE
NEXT SPEAKER, A A FORMER MEMBER
OF MDCC.
WE WELCOME YOU TO GIVE YOUR
PERSPECTIVES ON THIS TOPIC.
GOOD TO SEE YOU TODAY.
>>THANK YOU.
I'D LIKE TO THANK THE MUSCULAR
DYSTROPHY COORDINATING
COMMITTEE.
SINCE 1999 WHEN I STARTED GENE
THERAPY IN MUSCULAR DYSTROPHY,
THE OUTCOME MEASUREMENTS HAVE
NOT CHANGED.
ALL MUSCULAR DYSTROPHY GENE
THERAPY OUTCOMES ARE BASED ON
NORTH STAR ASSESSMENT;
SIX-MINUTE WALK, GETTING UP FROM
FLOOR, CLIMBING STAIRS, USED IN
MY JUNE CLINICAL TRIAL, SCORING
A 52.
OUTCOME MEASUREMENTS MIGHT BE
GOOD FOR SOME TYPES OF TRIALS
BUT NOT ALL TYPES OF TRIALS.
IF THERE WERE DIFFERENT OUTCOME
MEASUREMENTS APPROVED, THIS
WOULD INCREASE THE NUMBER OF
PATIENTS AVAILABLE TO BE USED IN
RESEARCH.
MANY PATIENT GROUPS ARE LIMITED
FROM TRIALS, SINCE MANY PATIENTS
ARE IN WHEELCHAIR RARELY MEETING
THE CRITERIA FOR NORTH STAR
ASSESSMENT.
I SEARCHED SEVERAL TRIALS ON
clinicaltrials.gov AND NONE
HAVE RESPIRATORY IMPROVEMENTS AS
AN OUTCOME MEASUREMENT.
SOME HAVE RESPIRATORY IMPAIRMENT
AS AN EXCLUSION FOR CRITERIA.
A COMPANY IN FRANCE HAS STARTED
TO DOSE PATIENTS IN A TRIAL, ONE
MAIN INCLUSIONS IS TO HAVE
MODERATE RESPIRATORY IMPAIRMENT,
BELOW 80%.
OTHER THAN SAFETY TRIALS, ALL
THE TILES USED THE PATIENT'S
BELOW THE AGE OF 18, WHEN I WAS
18 MY RESPIRATORY SYSTEM WAS NOT
AFFECTED.
I DID NOT START TO HAVE ISSUES
UNTIL I WAS 50 YEARS OLD.
SO TESTING CHILDREN BELOW AGE OF
18 MOST LIKELY WON'T SHOW
IMPAIRMENT.
HOWEVER, FOR GENE THERAPY
INCLUDING PATIENTS WHOSE LUNG
CAPACITY IS AFFECTED,
IMPROVEMENT COULD BE SHOWN.
I'VE BEEN TOLD THERE ARE 200
MUSCLES THAT ARE INVOLVED IN
WALKING.
AND 100 ARE CRITICAL FOR
WALKING.
IN CONTRAST, BREATHING INVOLVES
18 MUSCLES, ONE MAJOR IS
DIAPHRAGM.
SEEMS PUTTING EMPHASIS ON
IMPROVING FUNCTION IMPROVES
FEWER MUSCLES COULD BE
WORTHWHILE.
FOR LIMBGERDLE, RESPIRATORY
FAILURE IS CAUSE OF DEATH, MAYBE
RESEARCH SHOULD BE FOCUSED
TOWARD STRENGTHENING RESPIRATORY
MUSCLES IN ADULTS.
BY THE WAY I'VE READ ABOUT
TECHNOLOGY AVAILABLE TODAY THAT
ASSESSES DIAPHRAGM STRENGTH AS
PRESENTED IN 2016 ARTICLE,
VALIDATION OF ULTRASOUND FOR
NON-INVASIVE ASSESSMENT BY DR.
WHITEHEAD AND FRANER AND OTHERS
IN JOURNAL OF PHYSICAL --
PHYSIOLOGY.
IF IT CAN RESULT IN STRONGER
MUSCLES AND DIAPHRAGM CAN BE
STRENGTHED WOULD HAVE A MAJOR
IMPACT ON QUALITY OF LIFE.
NOT ONLY WOULD I BE ABLE TO
BREATHE EASIER, BUT IT WOULD
ALLOW ME TO COMMUNICATE WITH A
STRONGER VOICE AND TALK LONGER
WITHOUT GETTING SO TIRED.
MY WEAKENED LUNG AND DIAPHRAGM
MUSCLES REDUCE LUNG CAPACITY, I
CANNOT LAY FLAT ON A BED ANYMORE
OR FLY ON AN AIRPLANE WITHOUT MY
VENTILATOR.
IF I DRINK TOO MUCH OR EAT A
LITTLE TOO MUCH, IT PUTS
PRESSURE ON MY DIAPHRAGM, HARDER
TO BREATHE.
THEN I NEED TO USE VENTILATOR TO
GIVE MUSCLES A REST.
WITH STRONGER BREATHING MUSCLES
COULD DECREASE OR DISCONTINUE
USING VENTILATOR THROUGH THE
DAY OR NIGHT, REDUCING INSURANCE
BURDEN OF COVERING COST OF
VENTILATOR AND ASSOCIATED MASK
AND FILTERS.
THE SPEAKERS FOLLOWING ME WILL
TALK ABOUT TECHNOLOGY THEY
DEVELOPED FOR ASSISTING OUTCOME
MEASUREMENTS.
BECAUSE OF CHANGING TECHNOLOGY,
I BELIEVE THE FDA SHOULD BE
WORKING TO HELP LIMBGERDLE
PATIENTS BEYOND JUST WALKING AN
BEING ABLE TO WALK IS EXTREMELY
IMPORTANT AND SHOULD BE
MEASURED, BUT HELPING SOMEBODY
BREATHE BETTER SHOULD BE A
TARGET.
TO ME BREATHING IS ACTUALLY MORE
IMPORTANT THAN WALKING FOR OLDER
PATIENTS.
RESEARCH IN THAT DIRECTION MAY
BE EASIER TO DO, IN MY OPINION,
AS YOU'RE NOT TRYING TO
STRENGTHEN SO MANY MUSCLES.
THANK YOU.
I'VE LOST TWO SISTERS TO THE
DISEASE FROM RESPIRATORY
FAILURE.
THANK YOU.
>>THANK YOU VERY MUCH, DONAVAN,
FOR YOUR LIVED AND FAMILY
EXPERIENCE.
ARE THERE QUESTIONS FOR
MR. DECKER?
>>GREAT TALK, DONAVAN.
>>THANK YOU, DAN.
>>IN THE CHAT BOX, EXCELLENT
POINTS.
OKAY.
THANK YOU VERY MUCH.
NEXT THREE MEASURES FOR
MEASURING PHYSICAL FUNCTION.
WE'LL TAKE QUESTIONS AFTER EACH
INDIVIDUAL PRESENTATION.
FIRST PRESENTER IS DR. LINDA
LOWE'S, PRINCIPAL INVESTIGATOR
AT THE WEXNER INSTITUTE, USING
COMPUTER VISION TO QUANTIFY AND
EVALUATE MOVEMENT.
WELCOME, DR. LOWES.
>>THANK YOU VERY MUCH.
THANK YOU FOR THE OPPORTUNITY TO
SHARE OUR WORK THAT'S GOING ON
IN MY LAB.
I THINK WE ALL AGREE THAT
FINDING OPTIMAL OUTCOME MEASURE
TO HAVE DEFINITIVE TRIAL ANSWERS
IS REALLY IMPORTANT.
SO HERE ARE TWO THINGS THAT
WE'RE WORKING ON.
THE FIRST ONE IS A SYSTEM WE
MADE THAT LOOKS AT MOVEMENT
COMPLEXITY, IT LOOKS AT THE
HEALTHINESS OF THE MOVEMENT,
HOPEFULLY THAT WE CAN IDENTIFY
INFANTS EARLY WHO HAVE ATYPICAL
MOVEMENT BUT ALSO THAT WE CAN
QUANTIFY IT AS IT CHANGES AND
BECOMES HEALTHIER.
THE GOAL WOULD BE TO USE IN
NEONATAL STUDIES, AND HOPEFULLY
WILL REDUCE THE TIME, THE
DURATION OF STUDIES BECAUSE WE
WON'T HAVE TO WAIT UNTIL THEY
DEVELOP MOTOR.
WE HAD TWO INFANTS, 26 DAYS OLD,
HEALTHY CONTROL INFANT 21 DAYS
OLD.
THEY HAD A SIMILAR SCORE ON THE
TEST THAT'S TYPICALLY USED IN
THESE KINDS OF TRIALS THAT
CHILDREN'S HOSPITAL PHILADELPHIA
INTEND PERFORMANCE BASED TEST,
THERAPIST ENCOURAGES THE INFANT
OR FACILITATES MOVEMENT AND THEY
SCORE BASED ON WHAT THEY SEE.
LOOKING AT COMPLEXITY, A
DIFFERENCE ABLE TO BE DISCERNED.
YOU'RE LOOKING AT HANDS AND
FEET, TWO DIMENSIONAL TRACING OF
MOVEMENTS.
MOVEMENT OF THE HEALTHY CHILD IS
MORE COMPLEX.
THOSE ARE THE TWO DIMENSIONAL.
WE LOOK AT THE OTHER SIDE,
ANTI-GRAVITY MOVEMENTS, INFANTS
WITH SMA WERE NOT MOVING AS HIGH
OR WERE NOT AS FREQUENTLY OFF
THE GROUND, NOT PICKED UP
BECAUSE BOTH SCORES ARE
RELATIVELY HIGH SCORE.
WE TRIED TO SEE IF WE COULD
ESTIMATE THERE SCORE AND TRIED
TO PREDICT IT USING OUR MOTOR
COMPLEXITY SYSTEM.
THIS FIGURE SHOWS YOU THAT WE
ENDED UP MAKING A MOVEMENT -- A
MOTOR FUNCTION SCORE, AND SO IF
YOU LOOK ON THE Y-AXIS, THAT'S
PROPENSITY CLASSIFIED AS
HEALTHY.
WE USED ARTIFICIAL INTELLIGENCE
TO QUANTIFY MOVEMENT COMPLEXITY.
TWO SETS ON EITHER END WITH
SPINAL MUSCULAR ATROPHY, AND
THEY HAD MOTOR FUNCTION SCORES
BELOW 10.
WHEN YOU LOOK AT THE HEALTHY
INDIVIDUALS WITH BLUE SQUARES,
THEY ALL HAD MOTOR FUNCTION
SCORES, COMPLEXITY WAS WELL
ABOVE 80.
WHAT WE THOUGHT WAS MOST UNIQUE
IS ON THE LAST GROUP, YOU CAN
SEE THAT THE INFANT STARTED OUT
LOW BELOW 10 BUT POST-GENE
THERAPY MOTOR FUNCTION SCORE
IMPROVED, SHOWING THAT MOVEMENT
BECAME MORE LIKE THEIR HEALTHY
PEERS.
WHEN THE GENE WAS APPROVED, WE
STARTED SEEING BABIES THAT WERE
IDENTIFIED AS THROUGH NEWBORN
SCREENING, WE SAW SOMETHING
REALLY INTERESTING THAT WE COULD
DETECT DIFFERENCES BETWEEN THE
HEALTHY BABY AND BABY WITH SMA
TYPE 1, AT ONE WEEK OF AGE.
SO THERE REALLY IS NO SUCH THING
AS SYMPTOMATIC PERIOD.
THE REASON THE BABY SEEMS
ASYMPTOMATIC OR PRESYMPTOMATIC
IS BECAUSE THE DEMANDS OF THE
TEST AREN'T MUCH.
WHEN YOU'RE A BABY ALL YOU HAVE
TO DO IS MOVE AROUND, THERE'S NO
FUNCTIONAL DEMAND.
SO YOU DON'T NOTICE DEFICITS
UNTIL THEY ARE ASKED TO DO
HARDER THINGS LIKE REACHING FOR
SOMETHING OR SITTING UP.
THE GRAPH AT THE BOTTOM SHOWS
THAT WE WERE ABLE TO DETECT
INFANTS WITH SMA EVEN THOSE THAT
HAVE THREE AND FOUR COPIES, AN
INFANT WITH FOUR COPIES MIGHT
NOT BE EXPECTED TO BE DIAGNOSED
WITHOUT NEWBORN SCREENING UNTIL
THEY WERE MUCH LETTER, ABLE TO
WALK, ELEMENTARY SCHOOL OR
LATER.
EVEN IN THIS VERY EARLY THEY DO
NOT HAVE THE SAME MOVEMENT
COMPLEXITY AS HEALTHY PEERS.
WE WENT ON TO SEE IF WE COULD
NOTICE ANY DIFFERENT KINDS OF
MOVEMENT DISORDERS, SO THESE ARE
TWO BABIES WE RECORDED AND THEY
LOOK VERY GOOD BUT WHEN YOU LOOK
AT THE MOVEMENT COMPLEXITY THE
ONE ON THE RIGHT HAS BEEN
DIAGNOSED WITH CEREBRAL PALSY,
LEFT IS A TYPICAL MOVEMENTS.
YOU CAN SEE BY THE TRACINGS ONCE
AGAIN MOVEMENT COMPLEXITY IS
LACKING.
HERE AGAIN ARE TWO BABIES THAT
WE HAVE RECORDED, ABOUT THE SAME
AGE, WE NOTICE ONE INFANT HAS
DUCHENNE MUSCULAR DYSTROPHY, THE
OTHER IS TYPICALLY DEVELOPING
INFANT.
THE DIFFERENCE BETWEEN THE
TRACINGS IS QUITE OBVIOUS THAT
INFANT WITH DUCHENNE MUSCULAR
DYSTROPHY IS NOT MOVING QUITE AS
COMPLEXITY BUT HE LOOKS LIKE A
HAPPY BABY WIGGLING ARMS AND
LEGS.
JUST A COUPLE MORE EXAMPLES OF
INFANTS WITH DMD WE'VE NOTICED.
SO, WE'RE IN THE MIDDLE OF A
RESEARCH STUDY, NOW WE HAVE 1400
RECORDINGS, AND WE'RE CONTINUING
TO LOOK AT DIFFERENT WAYS TO USE
COMPUTER VISION, RIGHT NOW WE'RE
LOOKING AT SKELETAL TRACKING,
CURRENTLY WE LOOK AT HANDS AND
FEET, WE'RE ABLE TO DO QUITE A
FEW MORE DATA POINTS.
WE'RE LOOKING AT DIFFERENT WAYS
TO QUANTIFY THE ARTIFICIAL
INTELLIGENCE.
ONE THING THAT WILL HELP IS
MOVEMENT TO NEWBORN SCREENING
AND ALL OF THESE HAVE BEEN UNDER
THE AGE OF 6 MONTHS BUT WE'RE
WORKING WITH A NEWBORN HOSPITAL
TRYING TO GET THEM WITHIN THE
FIRST COUPLE DAYS OF LIFE TO SEE
HOW EARLY WE COULD POSSIBLY DO
IT.
THEN OF COURSE WE NEED TO LOOK
AT LONGITUDINAL CHANGE OF THE
INFANTS WITH DISABILITIES,
ESPECIALLY PROGRESSIVE ONES LIKE
DUCHENNE OR SPINAL MUSCULAR
ATROPHY.
THERE ARE A NUMBER OF DATA
POINTS WE COULD TRACK INCLUDING
EYE GAZE, HEAD TURNING, SO WE
CAN EXPAND THIS TO BE MORE
COMPLEX IF WE NEED TO.
THE OTHER THING WE'RE USING
COMPUTER VISION FOR TO MEASURE
WORKSPACE VOLUME, THE AREA THAT
YOU CAN INTERACT WITH, WITH YOUR
ARMS AROUND YOURSELF.
AND THIS IS THIS HAS BEEN GOING
ON FOR A WHILE.
THESE ARE ALL OF OUR GAMES,
GAME-BASED SYSTEM.
AS IT PROGRESSES WE'RE DOWN TO
THE AVATAR WITH THE ROCKET BUT
THE BOYS WANT US TO END UP CAN
CALL OF DUTY BUT YOU'RE NOT
ALLOWED TO KILL THINGS IN
CHILDREN'S HOSPITALS SO WE'RE
STUCK WITH THE AVATAR.
EVERY TASK YOU DO HAS A DISCRETE
AMOUNT OF SPACE YOU NEED.
TO PUT A SHIRT ON, LIFT A CUP TO
DRINK, TO USE A COMPUTER.
HERE IS OUR SYSTEM.
THE AVATAR TELLS THE PLAYER
WHERE TO REACH.
IT GIVES ALL OF THE
INSTRUCTIONS, ALL OF THE
ENCOURAGEMENT.
YOU DON'T NEED TO BE A SKILLED
THERAPIST TO ADMINISTER THIS,
YOU TURN THE GAME ON AND THEN
EVERYONE GETS THE SAME
INSTRUCTIONS.
AND WHAT WE GET FROM THAT IS
WORKSPACE VOLUME IN DIFFERENT
AREAS.
YOU CAN CHOOSE RIGHT VERSUS
LEFT, CHOOSE TEN DIFFERENT
QUADRANTS.
IT CAN SPAN AMBULENT AND
NON-AMBULENT.
IF THEY HAVE WEAKNESS IN THE
TRUNK THEY DON'T GET AS HIGH A
SCORE.
WE ALLOW THEM TO REACH AND
COMPENSATE.
IT'S ABLE TO DETECT VERY SUBTLE
CHANGES IN INDIVIDUALS
AMBULATORY AS WELL AS DOWN TO
INDIVIDUALS WHO CAN JUST MOVE
THEIR HANDS.
WE THINK IT WILL ELIMINATE THE
FLOOR AND CEILING EFFECT THAT A
LOT OF ASSESSMENTS HAVE.
WE TRIED IT IN A NUMBER OF
DIAGNOSES, SPINAL MUSCULAR
ATROPHY, LIMBGERDLE, DUCHENNE
AND BECKER.
THUS FAR IT'S WORKING WELL ON
ALL OF THOSE.
WE WANT TO MAKE SURE IT WAS
RELATED TO FUNCTION, WE NOTICE
IT IS CORRELATED TO A NUMBER OF
TYPICAL ASSESSMENTS.
MOST IMPORTANTLY, I THINK, IT'S
ALSO RELATED TO WALKING TESTS
BECAUSE IF YOU THINK ABOUT IT, I
A BUILT TO WALK IS HIGH --
ABILITY TO WALK IS DEPENDENT ON
STABILITY OF TRUNK.
IN LIMBGERDLE OR DUCHENNE THE
TRUNK GOES FIRST.
WE'RE ABLE TO PICK UP DEFICITS
THERE.
THE OTHER THING WE THINK IS
UNIQUE, WE'VE HAD KIDS PLAY AS
YOUNG AS 3 YEARS OLD.
THE AVERAGE 3-YEAR-OLD MY NOT BE
ABLE TO BUT WE'VE HAD SUCCESS
WITH 4 AND UP, AS OLD AS '90s
PLAY.
WE MEASURED CHANGE, AND WE WERE
ABLE TO DEMONSTRATE THAT PEOPLE
WITHOUT TREATMENT WOULD DECLINE
IN THEIR WORKSPACE VOLUME BUT
PEOPLE WHO ARE TREATED WOULD
INCREASE.
IT DOES NOT HAVE THE SAME
CEILING EFFECT.
THE PERFORMANCE OF UPPER LIMB,
SOME PEOPLE ABLE TO GET A
PERFECT SCORE EVEN THOUGH THE
WORKSPACE VOLUME COULD CONTINUE
TO GO UP.
SO HERE'S YOUR PERCENTAGE OF
PUL, ROOM TO IMPROVE ON
WORKSPACE VOLUME BUT THEY HIT
THE CEILING EFFECT.
WE SAW TWO DIFFERENT PROBLEMS
WITH HAMMERSMITH, A NUMBER OF
INDIVIDUALS THAT COULD NOT
PERFORM BECAUSE YOU HAVE TO BE
ABLE TO ROLL AND SIT.
THERE IS A TEST TO SPANS FROM
MINIMAL USE WITH HANDS TO
WALKING.
WE ASKED PEOPLE TO YOUR THE
PROMIS SCALE, IT CORRELATED WELL
WITH THAT.
PEOPLE RATED THEMSELVES HIGHER,
GOT A HIGHER WORKSPACE FOLLOW,
WE TOOK ANSWERS FROM THE PROMIS,
THOSE ABLE TO DO IT AND UNABLE
TO DO AN ACTIVITY.
WE HAVE AN ESTIMATE OF WHAT IS
THE MINIMUM WORKSPACE VOLUME YOU
NEED TO PULL YOUR SHIRT OVER, TO
YOUR HEAD, ZIP UP CLOTHES OR PUT
TOOTHPASTE ON A TOOTHBRUSH.
THAT WE CAN TELL, THE PAYERS AND
REGULATORS, IF YOU DO IMPROVE BY
A SCORE OF 10 IT'S GOING TO MEAN
YOU CAN DO THESE DIFFERENT
ABILITIES.
AND THAT IS ALL I HAD.
I'M HAPPY TO ANSWER ANY
QUESTIONS.
>>THANK YOU VERY MUCH.
QUESTIONS?
>>DAN PEREZ, I HAVE A QUESTION.
>>YES.
>>WITH THESE TECHNOLOGIES,
YOU'RE ABLE TO VISUALIZE THE
DATA VERY WELL, AND I GUESS THE
QUESTION I HAVE IS, HOW DO WE
RELATE THAT TO A FUNCTION OF
CHANGE.
IN TERMS OF REACHING THE
WORKSPACE, AS I LOOK, WHAT DOES
THIS MEAN?
>>I'M NOT SURE YOU'RE FINISHED.
YOU'RE MUTED NOW.
I THINK THE QUESTION IS, WHAT'S
REALLY IMPORTANT, JUST LIKE
PEOPLE DON'T KNOW WHAT ONE POINT
ON THE NORTH STAR MEANS, WHAT
DOES IT MEAN TO IMPROVE IN YOUR
WORKSPACE VOLUME.
A COUPLE THINGS.
WE TRIED TO SET MINIMUM AMOUNTS
OF VOLUME YOU NEED FOR AN
ACTIVITY.
SO, IF YOU COULD GO FROM 14 TO
20 PERHAPS THAT WOULD MEAN THAT
YOU COULD BRUSH YOUR TEETH OR
LIFT YOUR OWN CUP.
THAT'S WHAT WE'RE WORKING ON
NOW, IT DOES CORRELATE WELL TO
PATIENT REPORTS OF CHANGE BUT WE
NEED TO GET A DISTINCT AMOUNT
THAT IS MEANINGFUL.
IT REALLY DEPENDS ON THE
ACTIVITY.
IF YOU NEED CERTAIN AMOUNT OF
WORKSPACE TO USE YOUR COMPUTER,
YOU NEED A DIFFERENT AMOUNT TO
LIFT THE CUP TO DRINK, SO THAT
IS OBVIOUSLY VERY IMPORTANT,
THAT'S WHAT WE'RE WORKING ON.
I THINK ONE THING THAT'S
DIFFERENT ABOUT OUR SYSTEM IS
THAT WE SCALE FOR YOUR HEIGHT,
SO IT DOESN'T MATTER THE CUBIC
CENTIMETERS, THEY DON'T MATTER,
IT'S THE AMOUNT YOU CAN REACH.
IT'S SCALED SO IF YOU CAN JUST
LIFT YOUR ARMS UP OVER YOUR HEAD
YOU GET A 100.
IF YOU CAN LEAN AND REACH,
YOU'LL GET A HIGHER SCORE THAN
100.
SO WE'RE TRYING, AGAIN, TO MAKE
IT SO WE CAN COMPARE DIFFERENT
PEOPLE AND THAT IT'S NOT JUST A
THREE CUBIC CENTIMETERS, IT'S AN
AMOUNT TOWARDS BEING ABLE TO DO
AN ACTIVITY.
DOES THAT ANSWER YOUR QUESTION?
>>YOU'RE SAYING YOU CAN DO IT,
FOR AN INDIVIDUAL, A GROUP OF I?
TWO UPPER QUADRANTS, ONE IN
THREE, NOT TWO AND FOUR, THE
OTHER QUADRANTS, IT CAN BE QUITE
A DIFFERENT PERSON TO PERSON,
AND BASED ON COMPENSATION, THEY
ARE GOING TO FUNCTION
DIFFERENTLY.
THERE MUST BE SOME NATURAL
HISTORY.
>>OH, RIGHT, RIGHT.
SO, I'M NOT SURE IF WE -- WHAT
WE DO IS WE PUT IT BASED ON YOUR
SIZE, DANIEL.
IF YOU'RE A CHILD, THEN YOU
GROW, WE CAN STILL SAY YOU
IMPROVED COMPARED TO YOUR FORMER
SELF.
AND THAT WAY WE DON'T NEED TO
KNOW, IT'S A 10% CHANGE OR 4%
CHANGE, FOR YOU BASED ON YOUR
SIZE, THE SAME AS A 4% CHANGE
BASED ON SOMEONE FROM ANOTHER
SIZE.
SO YOU'RE CORRECT, IT DOES
MATTER HOW MUCH TO GET THE
HURDLE, TYPING TAKES 12% OF
WORKSPACE VOLUME, DRINKING A CUP
IS MORE LIKE 22.
YOU'RE RIGHT, IT DOES MATTER
WHERE IN THAT CHANGE YOU GAIN.
SO THAT YOU KNOW WHAT MEANINGFUL
DIFFERENCE THAT'S GOING TO MAKE.
>>THE OTHER QUESTION I HAVE,
ARE THERE PHONE LINK, UNLIKE
CHANGES IN LENGTH, FOR WHICH
CASE GROWING QUICK ENOUGH
CAUSING QUICK CHANGES IN GROWTH?
>>YES, THAT'S WHY YOU WOULD PUT
IN THE PERSON'S HEIGHT.
THAT'S HOW WE KNOW, WE CAN
ESTIMATE YOUR WING SPAN, THE
LENGTH OF YOUR ARMS.
IF YOU DO GROW, YOU STILL WOULD
SAY PROPORTIONAL, 100 IS THE
LENGTH OF YOUR ARMS.
SO IT WOULD ACCOMMODATE GROWTH.
NO MATTER WHAT SIZE YOU ARE, IF
YOU HAVE FULL RANGE OF MOTION
YOU STAY A 100.
>>THANK YOU.
>>MICHELE HAS A QUESTION AND
THERE'S A QUESTION IN THE Q&A
BOX AND WALTER HAS A QUESTION.
MICHELE CAMPBELL.
>>THANK YOU.
THANK YOU FOR YOUR PRESENTATION.
THIS IS MICHELE CAMPBELL FROM
OFFICE OF NEUROSCIENCE AT FDA,
GREAT TO SEE THE UPDATED WORK.
FOLLOWING THE QUESTION, WE
TALKED ABOUT MINIMAL GAINS.
MINIMAL AND MEANINGFUL AREN'T
ALWAYS ALIGNED, HOW DO YOU
COLLECT INFORMATION TO DETERMINE
THAT, THAT YOU'RE ABLE TO
MONITOR AN COLLECT DATA OVER
TIME WHEN YOU'RE SEEING
PATIENTS, YOU'D BE ABLE TO
DEVELOP WHAT WOULD BE A
MEANINGFUL CHANGE, FOR OUR
INTERPRETATION OF OUR RESULT OF
A TRIAL, WAS THAT CHANGE
MEANINGFUL, I CAN'T REMEMBER,
LINDA, I THOUGHT YOU COLLECTED
CONTROL DATA AND THE ACTIVE
STUDY TO HELP INFORM THAT,
WONDERING HAVE YOU MORE
ADDITIONAL THOUGHTS TO THIS
DISCUSSION?
>>RIGHT.
THAT'S ABSOLUTELY MEANINGFUL AND
STATISTICAL ARE TWO DIFFERENT
THINGS.
WE DID LOOK AT MINIMUM
CLINICALLY IMPORTANT DIFFERENCE
USING THE TEST/ RETEST
RELIABILITY, FOUR SCALE POINTS,
USING ONE-THIRD STANDARD
DEVIATION FOR THE COHORT WITH
SMA IT WAS TEN SCALED POINTS.
BUT WHAT YOU'RE TALKING ABOUT
MORE IS WHETHER THEY FEEL LIKE
THEY ARE HAVING A CHANGE.
LOOKING AT THAT BY COMPARING TO
THE PROMIS, SO IF SOMEONE SAYS
THEY ARE BETTER ON THE PROMIS,
WE SAY THEY ARE BETTER, THAT
WOULD SEEM LIKE IT WOULD BE A
MEANINGFUL DIFFERENCE.
WE HAVE MORE WORK TO DO, BASED
ON PATIENT-REPORTED OUTCOMES TO
PROMIS TO SEE IF WE CAN TELL IF
WE'RE GOING IN THE RIGHT
DIRECTION AND HOW MUCH WE NEED
TO CHANGE SO THEY NOTICE A
DIFFERENCE.
>>THANK YOU.
>>UH-HUH.
>>NEXT QUESTION IS IN THE CHAT
BOX FROM AMY BROWER, HOW DO YOU
ENVISION THIS WORKING WITH
NEWBORN SCREENING?
ALSO WITH THE BIRTHING HOSPITAL
OR PEDIATRICIAN?
>>WE'RE WORKING TOWARDS BOTH.
RIGHT NOW WE'RE DOING INFANTS
THAT COME IN TO NATIONWIDE
EITHER AS PRIMARY CARE OR AS
SPECIALTY CLINIC.
SO WE'RE COLLECTING FROM BIRTH
TO SIX MONTHS OF AGE.
BUT WHAT WE REALLY LOVE TO DO IS
TO BE ABLE TO SCREEN EVERY
SINGLE INFANT, NOT JUST THOSE
THAT WE CAN CATCH IN THE
PEDIATRICIAN, THAT'S WHAT WE'RE
WORKING ON NEXT BUT WE KNOW IN
THE FIRST TWO DAYS OF LIFE YOU
HAVE ANESTHETIC AND YOU HAVE
CHANGES TO THE ENVIRONMENT, SO
WE'RE NOT SURE IF WE CAN DO IT
IN THE FIRST COUPLE DAYS OF
LIFE.
ALL OF OUR DATA NOW HAVE BEEN A
WEEK OLDER OR MORE.
IT'S SOMETHING WE NEED TO MOVE
TOWARDS AND SEE, IT WOULD BE
GREAT IF EVERY BABY COULD BE
SCREENED BEFORE THEY LEFT THE
HOSPITAL, AND THEN ALERTED TO
THOSE THAT SHOULD SEEK FURTHER
CARE OR SHOULD GET MORE
DIAGNOSTIC TESTING.
>>IF YOU COULD COORDINATE WITH
AUDITORY SCREENING, GOING TO THE
SOUNDS THEY ARE HEARING.
>>THAT'S A GREAT IDEA.
THAT'S THE THING.
A HEALTHY BABY CAN LOOK LIKE
SOMEONE WHO HAS GOT MOVEMENT
DISORDERS, IF THEY ARE JUST
BEING LAZY.
BUT AN UNHEALTHY BABY CAN NEVER
LOOK LIKE A HEALTHY BABY.
SOMETIMES WE DO NEED TO JIGGLE
SOMETHING, RANGE A BELL, A GREAT
IDEA TO DO IT WITH THE HEARING.
>>LOGISTICALLY THAT WOULD HELP
TOO THAT YOU'RE NOT LIKE DOING
TWO SEPARATE SETS OF SCREENS.
ANYWAY, VERY INTERESTING
PRESENTATION.
THANK YOU SO MUCH.
>>REAL QUICK QUESTION.
CAN YOU MEASURE MOVEMENT OF THE
DIAPHRAGM?
>>GLAD YOU ASKED.
WE STARTED DOING THAT IN INFANTS
WITH SMA.
THAT DOESN'T -- WE HAVEN'T
GOTTEN FAR WITH DATA BUT WHAT WE
LOOKED AT WAS DIAPHRAGMATIC
BREATHING, PUTTING COLORED
MARKERS ON THE STERNUM,
BELLYBUTTON, HALFWAY IN BETWEEN.
SO, I'M NOT -- WE'RE A LONG WAY
FROM TRYING IT IN GROWNUPS, BUT
WE WERE LOOKING TO SEE IF WE
COULD QUANTIFY BREATHING, IN THE
INFANTS WITH SMA THEY GO INTO
SEVERE BREATHING PATTERN.
>>THANK YOU.
>>NEXT MEANTER IS MINDY
LEFFLER, PRESIDENT OF CASIMIR,
TO IMPROVE THE QUALITY OF DATA
IN CLINICAL TRIALS BY FOCUSING
ON THE PATIENT EXPERIENCE, ALSO
THE MOTHER OF A YOUNG MAN WHO
LIVES WITH DUCHENNE MUSCULAR
DYSTROPHY.
THE TITLE IS QUANTITATIVE
NEUROMUSCULAR ASSESSMENT IN
NEUROMUSCULAR CONDITIONS.
WE NEED YOUR SLIDES IN
PRESENTATION MODE.
>>AWESOME.
THANK YOU.
THANK YOU FOR THE OPPORTUNITY TO
PRESENT.
I APPRECIATE IT.
I APPRECIATE THE OPPORTUNITY TO
FIELD QUESTIONS AND HOPEFULLY
GET FEEDBACK FROM THIS GROUP.
I'M THE MOTHER OF A NOW
19-YEAR-OLD WITH DUCHENNE
MUSCULAR DYSTROPHY.
HE PARTICIPATED IN HIS FIRST
STUDY WHEN HE WAS 8 YEARS OLD,
OUTCOME MEASURE WAS 6-MINUTE
WALK.
AT THE TIME, HE ASKED ME, WHY DO
THEY THINK THAT I CARE SO MUCH
ABOUT SPEED WALKING?
WHICH IS A GREAT QUESTION FOR AN
8-YEAR-OLD TO ASK, AND REALLY
ILLUSTRATES THE FACT THERE WAS A
SIGNIFICANT DISCONNECT BETWEEN
CONCEPT OF INTEREST BEING
MEASURED, OUTCOME TO MEASURE
EXERCISE INTOLERANCE, AND WHAT
WAS MEANINGFUL TO HIM,
FUNCTIONAL WALKING.
THAT REALLY WAS THE BEGINNING OF
OUR CLINICAL TRIAL JOURNEY.
AND IT'S BEEN FOR A DECADE OF
SUBMERGES IN CLINICAL TRIAL
LANDSCAPE.
THIS IS A LIST OF CLINICAL
TRIALS THAT FAILED TO REACH
STATISTICAL SIGNIFICANCE.
EACH REPRESENTS A GROUP OF
FAMILIES LIKE MY OWN WHO HAVE
GIVEN UP BLOOD, SWEAT, LITERAL
FLESH.
WE DON'T TRULY KNOW IF IT WAS
OUTCOME MEASURE THAT WAS THE
ISSUE OR WHETHER IT WAS THE
STUDY DESIGN THAT WAS THE ISSUE
AND OUTCOME MEASURE IN USE.
THAT'S DRIVING US TO TRY TO
ADDRESS THAT ISSUE WHICH IS
POTENTIAL FOR FAMILIES TO COME
AWAY WITH TRIAL PARTS
PARTICIPATION WITHOUT
DEFINITIVE ANSWERS.
WE ASKED WHAT IS MORE MEANINGFUL
CONCEPT OF INTEREST.
IT BECOMES MORE DIFFICULT TO
MOVE UNTIL PATIENTS ARE UNABLE
TO MOVE.
WE THOUGHT THE MOST MEANINGFUL
OF INTEREST IS EASE OF MOVEMENT.
WE THOUGHT ABOUT WAYS TO DO
THAT.
TALKED TO PARENTS.
WE NOTICED WHAT PARENTS
ARTICULATE IS THAT THEY TRACK
WHETHER THE CHILDREN ARE GETTING
WORSE, BETTER, STAYING STABLE BY
LOOKING AT COMPENSATORY MOVEMENT
PATTERNS THE BOYS ADOPT TO WORK
AROUND PROGRESSIVE WEAKNESS.
WE TOOK A LOOK HOW PATIENTS WERE
FUNCTIONING AS THEY WITHDREW
FROM TREATMENT IN A STUDY PUT ON
CLINICAL HOLD AND SAW
ACQUISITION OF COMPENSATIONS
SIMILAR TO THE WAY PARENTS TALK
ABOUT IT.
THE FIRST TIME POINT RIGHT
BEFORE, AND BY THE SECOND,
ALTERNATING LEGS TO A PATTERN
WHERE HE CLEARS THE STAIRS,
USING ONE ARM ON THE RAIL, ONE
ARM OFF THE THIGH, PICKING UP
COMPENSATIONS, THE FIRST CLUE
THIS COULD BE A RIGOROUS AND
VALID WAY TO QUANTIFY WHAT WE
TALK ABOUT AS PARENTS WITH
DUCHENNE, CHILDREN WITH
DUCHENNE.
WHEN MY SON EATS HIS MEAL LIKE
THIS, AND I START SEEING HIM DO
THIS, SUPPORTING ONE ARM WITH
THE OTHER ARM AT THE WRIST, I
KNOW WHAT THAT MEANS AS A
PARENT.
IT MEANS THE EATING IS GETTING
HARD FOR HIM.
IT WAS THAT FUNDAMENTAL SENSE OF
DISEASE PROGRESSION WE WERE
HOPING TO QUANTIFY IN A VALID
RELIABLE AND RIGOROUS FASHION.
SO, THE WAY IT WORKS, WE HAVE
VALIDATED APP, THAT PARENTS
DOWNLOAD FROM GOOGLE PLAY OR APP
STORE, AND THEY REGISTER FOR THE
APP, WATCH TRAINING VIDEOS, CAN
TAKE THEIR OWN VIDEOS.
WE HAVE SCORE CARDS TO TRAIN AND
CERTIFY CENTRAL READERS TO USE,
WHAT THAT MEANS TO QUANTIFY, WE
CAN BLIND RATERS TO TIME POINT
TO ELIMINATE TIME POINT BIAS.
IT'S DONE AT HOME WHICH WE FELT
WAS NOT ONLY IMPORTANT DUE TO
REDUCTION OF BURDEN ON FAMILIES
BUT ALSO I THINK THAT
REMOTE-BASED CAPTURE IS A MATTER
OF DATA INTEGRITY JUST BECAUSE
WE ALL KNOW HOW MUCH TRAVEL
FATIGUE CAN INFLUENCE DATA
COLLECTION AND DUCHENNE AND
OTHER NEUROMUSCULAR DISEASES.
ONE MAIN THING TO QUANTIFY IS
THE FACT THAT LOSS OF FUNCTION
IS AN EXTRAORDINARILY MEANINGFUL
STEP IN DISEASE PROGRESSION, FOR
PATIENTS WITH NEUROMUSCULAR
DISEASE, SO WE WANTED TO
QUANTIFY INCREMENTAL STEPS
TOWARDS THAT LOSS OF FUNCTION,
SUCH THAT WHEN THEY FINALLY DO
LOSE FUNCTION, IT ISN'T -- IT'S
WEIGHTED APPROPRIATELY.
BY THE TIME BOYS ACQUIRED EVERY
MOVEMENT, IT'S SO COMPENSATED
THE LAST STEP OF LOSS OF
FUNCTION IS WEIGHTED MORE
EQUALLY WITH EACH ACQUISITION OF
A COMPENSATION SO HERE IS A
COUPLE VIDEOS TO DEMONSTRATE.
THIS IS A PATIENT GETTING OFF
THE FLOOR AT ONE TIME POINT.
YOU CAN SEE HE'S HIGHLY, HIGHLY
COMPENSATED, LEGS ARE FAR APART,
WALKING WITH HANDS ALONG SIDES,
PUSHING OFF.
THAT MEANS GETTING OFF THE
GROUND IS SUCH A HIGHLY
COMPENSATED AND DIFFICULT
ACTIVITY THAT BY THE TIME THAT
LOSS OF FUNCTION HAPPENED,
SHORTLY AFTERWARDS, THERE'S NOT
A LOT OF CHANGE IN THAT MOVEMENT
PATTERN.
IT'S JUST BALANCED MORE EQUALLY.
WHEN WE WERE TAKING A LOOK THE A
DESIGNING SCORE CARDS, THERE ARE
TWO WAYS, LOTS OF ACTIVITY ON
THE A.I. FRONT AND THERE'S TWO
WAYS TO COME AT THAT PROCESS OF
AUTOMATION.
ONE ON THE RIGHT IS TO FEED DATA
INTO THE BLACK BOX, IDENTIFY
CONCEPT OF INTEREST AND PATTERNS
THAT EMERGE.
AND TO ANCHOR THAT CHANGE, BASED
ON AN ANCHORING INSTRUMENT TO
DETERMINE HOW MUCH CHANGE IS
MEANINGFUL.
WE WENT A DIFFERENT ROUTE, TO
TALK TO PATIENTS AND FAMILIES,
DETERMINE AMOUNT OF CLINICALLY
MEANINGFUL CHANGE THROUGH
PATIENTS OR CLINICIAN REPORT,
CHOSE TO USE CLINICIANS BECAUSE
IT WAS REALLY AN N OF 100
SITUATION RATHER THAN N-of-1,
TO LIFT MOVEMENT PATTERNS
UTILIZED ACROSS THE POPULATION
RATHER THAN MAYBE SOMETHING
UNIQUE TO A PARTICULAR PATIENT
AND OUR HOPE IS TO AUTOMATE BY
TRAINING ALGORITHM TO RECOGNIZE
THOSE MOVEMENT PATTERNS.
DIFFERENT WAYS TO APPROACH THAT,
ONE OF THE MAIN REASONS IS THAT
THIRD STEP ON THE RIGHT, EVERY
TIME WE TRIED TO DIG IN, WHAT
ANCHORING INSTRUMENTS COULD WE
USE THAT MIGHT BE APPROPRIATE TO
DUCHENNE, WE RAN AGAINST
PROBLEMS OF PERHAPS ANCHORING
INSTRUMENT MIGHT NOT BE
SUFFICIENTLY SENSITIVE TO DETECT
CHANGE, MIGHT STILL BE
MEANINGFUL TO PATIENTS AND
FAMILIES.
AND THEN I THINK IT'S WORTH
NOTING THAT THE USE OF PROs IN
THIS POPULATION CAN BE
PROBLEMATIC.
SOME PATIENTS KNOW MORE ABOUT
THEIR PROGNOSIS AND PROGRESSION
THAN OTHERS.
AND SO THEY ARE GOING TO ANSWER
DIFFERENTLY ON INSTRUMENTS WHEN
THEY KNOW MORE ABOUT WHAT'S
GOING TO HAPPEN TO THEM THAN IF
THEY DON'T KNOW THE
MEANINGFULNESS OF WHAT'S
HAPPENING.
THAT'S SOMETHING WE NEED TO TAKE
INTO ACCOUNT WHEN WE LOOK AT
ANCHORING WITH PRO INSTRUMENTS.
THE OTHER PIECE I SEE IN MY OWN
SON, HE USES DENIAL AS A COPING
MECHANISM.
IT'S NOT UP TO ME TO SAY THAT'S
NOT APPROPRIATE BUT IT DOES
PRESENT ISSUES UTILIZING PATIENT
REPORTED OUTCOMES OF ANCHORS,
THE DENIAL INTRODUCES
COMPLEXITY.
JUST TO TALK ABOUT THE PROCESS
TO DEVELOP THIS OUTCOME, THE
FIRST THING WE DID WAS IDENTIFY
THE TASK LIST OF THINGS THAT WE
WERE GOING TO PUT ON VIDEO, TO
MAKE SURE WE WEREN'T USING
STANDIN TASKS, BUT TASKS THAT
INDICATED INDEPENDENCE LIKE
GETTING OFF THE FLOOR, A CELL
PHONE, FROM VERY YOUNGER MORE
FUNCTIONAL AGES UP TO
NON-AMBULATORY PATIENTS WITH
LESS FUNCTION.
WE DESIGNED CAPTURE PROCEDURES
AND VALIDATED CAPTURE
PROCEDURES, PUBLISHED IN THE
MANUSCRIPT, DETAILED ON THE
SLIDE.
NEXT STEP IS THAT WE GOT TO
UTILIZE THE SERVICES OF THESE
WONDERFUL LADIES, AND THIS WHOLE
GROUP AT THE NATIONWIDE
CHILDREN'S HOSPITAL, BUILDING A
LIST OF COMPENSATIONS WE SHOULD
CONSIDER QUANTIFYING.
THIS IS A GROUP OF PEOPLE THAT
SEE HUNDREDS OF PATIENTS IN THE
CONTEXT OF CLINIC ASSESSMENT AND
CLINICAL TRIAL ASSESSMENT.
WE FELT IT WAS THE PERFECT
GROUP, EXTRAORDINARILY GENEROUS
WITH TIME.
WE BUILT A LIST OF
COMPENSATIONS, WHEN WE BUILT
SCORE CARDS NEEDED TO MAKE SURE
IF ONE LEVEL TRANSITIONED INTO A
COMPENSATION THAT WAS MORE
SEVERE, IT WAS QUANTIFIED THAT
WAY, AND SO FOR EXAMPLE WHEN
KIDS GO UP THE STAIRS THEY USE A
WIDE BASE OF SUPPORT, THEY
COLLAPSE THAT WIDE BASE AND IN
TURN SIDE STEP UP THE STAIRS.
WE WANTED TO MAKE SURE THE
DISAPPEARANCE DIDN'T LOOK LIKE
IMPROVEMENT, SO SOME CRITERIA
ARE NESTED, SOME CRITERIA ARE
LISTED INDEPENDENTLY FOR THAT
REASON.
NEXT THING WE DID, LIKE I
MENTIONED BEFORE, TO ESTABLISH
EACH COMPENSATORY ACQUISITION ON
OUR SCORE CARDS AS CLINICALLY
MEANINGFUL IN THE OPINION OF A
GROUP OF EXPERTS IN DUCHENNE
MUSCULAR DYSTROPHY.
THESE ARE P.T.s THAT ASSESS
PATIENTS.
WE REACHED AGREEMENT ON THE
SCORE CARDS AS THEY MOVE
FORWARD, REMOVED COMPENSATIONS
THAT THIS GROUP OF EXPERTS FELT
REPRESENTED LESS THAN CLINICALLY
MEANINGFUL AMOUNT OF CHANGE.
THAT WAS PUBLISHED RECENTLY IN
THE MANUSCRIPT INDICATED ON THE
SLIDE.
NEXT WAS ESTABLISH PSYCHOMETRIC
PROPERTIES ON THE SCORE CARD,
GREAT RELIABILITY AND STRONG
CONCEPT VALIDITY, LET US KNOW
THIS COULD BE DONE RELIABLY,
MEASURING WHAT WE INTENDED TO
MEASURE.
THE LAST STAGE, PUTTING THIS
TOGETHER, LIKE I MENTIONED OUR
APPROACH TO IDENTIFYING AMOUNT
OF CHANGE THAT WOULD CONSTITUTE
MEANINGFUL CHANGE WAS ESTABLISH
EACH PATTERN AS A CLINICALLY
MEANINGFUL AMOUNT OF DISEASE
PROGRESSION, MOUNTING OUR LAST
STUDY IN THE DUCHENNE
POPULATION, 150-PATIENT STUDY,
SPANS FROM YOUNG BOYS TO ADULT
PATIENTS WITH DUCHENNE, ANYONE
CAN PARTICIPATE.
WE'RE GOING TO DO A TEST-RETEST
AT BASELINE TO ALLOW US TO
ESTABLISH INHERENT INSTRUMENT
VARIABILITY, OUR APPROACH TO
DEFINING CHANGE IS TO TAKE A
LOOK AT AMOUNT OF CHANGE IN
EXCESS OF THAT INSTRUMENT
VARIABILITY AND WE'RE GOING TO
TAKE A LOOK HOW THIS MEASURE
MOVES ALONGSIDE GOLD STANDARDS
CURRENTLY IN USE IN DUCHENNE
MUSCULAR DYSTROPHY, SO IN THE
INTEREST OF FAMILIES WITH
DUCHENNE THAT MIGHT BE WILLING
TO PARTICIPATE, I'LL LEAVE THIS
UP.
WE'RE GOING TO RECRUIT THIS
WEEK.
WE HAVE A LOT OF AMBITION IN
TERMS OF NUMBER OF PATIENTS
WE'RE TRYING TO REACH, HOPEFULLY
WE GET SOME INTEREST FROM THAT.
WE'RE ALSO LOOKING TO ADAPT THIS
APPROACH TO OTHER NEUROMUSCULAR
DISEASES, SO CRITERIA FOR THAT
IS THAT THAT OTHER NEUROMUSCULAR
DISEASE ALSO HAS AN UNMET NEED,
THE LAST THING WE WANT TO DO IS
WASTE TIME, EFFORT, MONEY.
WE'RE LOOKING AT OTHER DISEASE
AREAS THAT WOULD BE WELL SERVED
WITH SAME SHARED CONCEPT OF
INTEREST.
IN THOSE EVENTS WE EVALUATE
DEGREE OF TASK OVERLAP, SHOULD
WE PUT THE SAME THINGS ON VIDEO,
IF THERE ARE ADDITIONAL TASKS
SPECIFIC TO THE NEW DISEASE AREA
WE HAVE TO IDENTIFY CAPTURE
PROCEDURES, COLLECTED SOURCE
MATERIAL.
THEN WE LOOK AT ADAPTING SCORE
CARDS.
ARE THERE MOVEMENT PATTERNS THAT
WERE NOT REFLECTING IN OUR
EXISTING SCORE CARDS?
ARE THERE COMPENSATIONS IN THE
EXISTING SCORE CARDS NOT
MANIFESTING IN THIS NEW DISEASE
AREA?
SO WE'LL ADAPT THOSE SCORE CARDS
TO THIS DISEASE AREA IN A WAY
THAT'S SPECIFIC AND AVOIDS SOME
PITFALLS OF BORROWING MEASURES
FROM ONE DISEASE TO THE NEXT
WITHOUT THAT VALIDATION EFFORT.
WE'LL REESTABLISH THE
PSYCHOMETRIC PROPERTIES OF THOSE
NEW SCORE CARDS TO MAKE SURE
THEY ARE PERFORMING THE WAY WE
HOPE THEY WILL.
WE'RE COLLECTING DATA THAT WILL
GET US TO THE LAST STEP, THE
DEFINITION OF WITHIN PATIENT
MEANINGFUL CHANGE WITHIN TWO
ARMS, THROUGH OUR STUDY WE'RE
RECRUITING THIS WEEK AND A
NUMBER OF OTHER DISEASES WE'RE
COLLECTING THIS MATERIAL TO LOOK
AT ADAPTATION OF SCORE CARDS
INCLUDING PMM, VWP, AND
LIMB-GIRDLE.
AND ALWAYS INTERESTED IN
ADAPTING THIS APPROACH TO OTHER
DISEASES IN WHICH IT MIGHT SERVE
THAT POPULATION.
AND JUST LAST TO MENTION WE'RE
TAKING A LOOK AT THIS APPROACH,
VARIOUS NEURODEVELOPMENTAL
DISEASES.
THIS SLIDE IS IN REFERENCE TO
THAT.
AND OBVIOUSLY ACTIVITIES LOOKING
BEYOND JUST EASE OF MOVEMENT IN
OTHER CONCEPTS OF INTEREST SUCH
AS COMMUNICATION.
LASTLY, I WANT TO ACKNOWLEDGE
THAT WE'VE HAD AN EXTRAORDINARY
AMOUNT OF HELP TO GET US TO THIS
POINT, ARE GRATEFUL FOR ALL OF
IT.
HAPPY TO ANSWER ANY QUESTIONS.
>>THANK YOU.
THIS IS GREAT AND SHOWS INTEREST
AND COMMITMENT.
WE'RE HAPPY TO TAKE QUESTIONS.
THERE MIGHT BE ONE IN THE Q&A
BOX.
DOUGLAS ALBRECHT ASKING HOW MANY
OF THE ASSESSMENTS ARE FOR
NON-AMBULENT PARTICIPANTS?
>>THE HOPE WE'RE EVENTUALLY
ABLE TO BUILD A COMPOSITE TO
SPAN PROGRESSION OF DUCHENNE.
IN TERMS OF TASKS, ABOUT HALF
FOR NON-AM BLAH AMBULATORY
PATIENTS.
WE NEED TO LOOK AT ARISE DATA,
WHETHER WE CAN COUNTER THE
FLOOR-CEILING EFFECTS BY
DETERMINING WHICH SCORE CARDS --
WHICH INABILITIES CORRESPOND TO
100% SEVERITY ON ONE END AND
WHICH ABILITY IN DUCHENNE
CORRESPOND TO ZERO PERCENT ON
THE OTHER END TO MINIMIZE BURDEN
ON PATIENTS.
IF WE'RE SUCCESSFUL AT THAT, AND
THAT HAPPENS TO BE RELIABLE DATA
IN OUR ARISE STUDY, THE HOPE IS
WE CAN BUILD A COMPOSITE ACROSS
THE ENTIRE SPECTRUM OF DUCHENNE
PROGRESSION.
IF NOT WE HAVE BRANCHED
COMPOSITES FOR AMBULATORY VERSUS
NON-AMBULATORY, HALF THE TASKS
ARE TARGETED TO NON-AMBULATORY.
WE GOT QUITE A BIT OF INPUT
ABOUT WHAT TASKS TO PUT ON VIDEO
THAT MADE SENSE FOR THEM,
CORRESPONDING TO A DEGREE OF
INDEPENDENCE THAT THEY WERE
HOPING TO MAINTAIN.
FOR EXAMPLE, GETTING THE ARM
BACK UP ON THE WHEELCHAIR ARM
REST WHICH SEEMS SIMPLE TO US
BUT FOR THOSE YOUNG MEN WITH
DUCHENNE THE AMOUNT OF
COMPENSATION TO GET THAT ARM
BACK ON IF IT COMES OFF WAS
REALLY IMPACTFUL BECAUSE THAT
ARM REST GIVES THEM LEVERAGE TO
GET THAT ARM HIGHER, LINKED TO
EATING, GETTING YOUR CLASSES ON
AND OFF, MAKING SURE THE HAIR
LOOKS NICE, ALL THESE THINGS THE
YOUNG MEN CARE ABOUT,
CORRESPONDING TO A CERTAIN
DEGREE OF INDEPENDENCE.
THANKS FOR THE QUESTION.
>>I SEE ONE FROM MICHELE
CAMPBELL.
WOULD YOU LIKE TO ASK YOUR
QUESTION?
AND THEN WALTER.
>>YES.
THANK YOU.
MINDY, THANK YOU FOR A GREAT
PRESENTATION AND GLAD TO SEE
PROGRESSION ON THIS EFFORT.
TWO QUESTIONS.
ONE IS SIMPLE, IF YOU CAN REMIND
ME TWO YOUR CENTRAL RATERS ARE
FOR THE VIDEO, AND SECOND MY
THEME FOR TODAY, MEANINGFUL
CHANGE.
IT'S CONVERSATION THAT COMES UP
ALL THE TIME IN RARE DISEASES,
SOMETHING WE WANT TO FULLY
UNDERSTAND WHEN HAVING TO MAKE
AND INFORM A REGULATORY
DECISION.
YOU SAID SOMETHING, HOW THE BOYS
WITH DUCHENNE HELPED IN
SELECTING ITEMS WHICH SOUNDS
LIKE THEY THOUGHT THEY WERE
MEANINGFUL TO THEY WILL, TO HAVE
THOSE ABILITIES.
CAN YOU CONTINUED WITH
QUALITATIVE WORK ON CLINICALLY
MEANINGFUL FOR THEM?
I UNDERSTAND YOUR CLINICIANS ARE
PROBABLY UNDERSTANDING WHAT THAT
LOOKS LIKE BUT HAVE YOU
CONSIDERED SOME TYPE OF
ASSESSMENT ASKING ABOUT FUNCTION
AND WHAT NOT, TO HELP CONTINUE I
GUESS WHAT I LOOK AT THIS, THIS
IS A STORY WHERE MORE
INFORMATION IS ACTUALLY BETTER,
A BETTER STORY, A BETTER LIVED
EXPERIENCE.
JUST WONDERING HOW THIS
PROGRESSED OVER TIME SINCE
INITIAL WORK, REALLY TRYING TO
PUT THIS CONCEPT TOGETHER.
>>YEAH, ABSOLUTELY.
YOU'LL NOT BE SURPRISED I HAVE
STRONG OPINIONS.
FIRST THE CENTRAL RATERS, IN OUR
PHASE 1 ESTABLISHING THE
PSYCHOMETRIC PROPERTIES OF THE
SCORE CARDS WHETHER RELIABILITY
IS HIGHER IN OUR PHYSICAL
THERAPISTS WITH SPECIFIC
DUCHENNE EXPERTISE VERSUS
GENERALISTS, WE DID NOT SEE A
DIFFERENCE BETWEEN THE GROUP
WITH DUCHENNE SPECIFIC EXPERTISE
AND GENERALISTS.
WE'RE UTILIZING RATERS THAT PASS
OUR CERTIFICATION REQUIREMENTS,
AN EXTENSIVE TRAINING PROGRAM
AND CERTIFICATION REQUIREMENTS
TO SERVE AS CENTRAL RATER,
MINIMUM AMOUNT OF EXPERIENCE
REQUIRED THAT'S BEEN
ESTABLISHED, DOES NOT INCLUDE
DUCHENNE EXPERTISE WHICH WE'RE
EXCITED ABOUT BECAUSE IT ALLOWS
US TO EXPAND THE POOL BEYOND A
GROUP OF P.T.s THAT ARE VERY
MUCH IN DEMAND, GIVEN THE NUMBER
OF CLINICAL TRIALS THAT ARE
PROGRESSING IN DUCHENNE.
WE ALSO HAVE RECENTLY HIRED A
RATER MANAGER WHO IS SOLELY
RESPONSIBLE FOR TRAINING AND
CERTIFYING THAT GROUP OF PEOPLE,
SOLE RESPONSIBILITY IS ENSURING
THAT ACCURACY OF THOSE RATERS.
WE'RE STILL -- ICCs WERE QUITE
HIGH, WE'RE STILL UTILIZING A
PLAN OF HAVING SCORE BY THREE
ADJUDICATING DIFFERENCES AT THE
CRITERIA LEVEL SO DISCREPANCIES
BUILDING AN OVERALL SEVERITY
PERCENTAGE.
YOU CAN LET ME KNOW IF THAT
DIDN'T FULLY ANSWER YOUR
QUESTION ON RATERS.
IN TERMS OF MEANINGFUL CHANGE,
SO, IN TERMS OF MEANINGFUL
CHANGE, WE UTILIZED PATIENT
FEEDBACK TO SELECT THE TASKS AND
THE WAY THE CAPTURE PROCEDURES
WERE DEVELOPED BECAUSE WE WANTED
TO MAKE SURE THAT THE TASKS WE
INCLUDED REPRESENTED A
MEANINGFUL AMOUNT OF
INDEPENDENCE, SO LET ME GIVE
EXAMPLES.
THE BOYS WITH DUCHENNE
ARTICULATE THEY NEED TO REACH
ACROSS THE TABLE TO PULL CELL
PHONES TOWARD THEM, THEY WANT TO
STORE THE CELL PHONE SCREEN DOWN
BECAUSE THEY DIDN'T WANT ANYBODY
IN THEIR BUSINESS.
IT'S MEANINGFUL TO THEM, PULLING
IT TOWARDS THEM AND FLIPPING IT
WHICH REQUIRES A CERTAIN --
LARGER AMOUNT OF MUSCLE FUNCTION
THAN JUST PULLING IT TOWARDS
THEM.
ANOTHER EXAMPLE OF THAT WAS
GETTING OFF OF THE FLOOR, IN
DUCHENNE WE UTILIZE THE
INABILITY TO GET OFF THE FLOOR
WITHOUT THE ASSISTANCE OF
FURNITURE AS A DEFINITION OF
INABILITY IN THIS TASK BECAUSE
BOYS WITH DUCHENNE ARE
SUSCEPTIBLE TO FALLS, WHEN
THERE'S NO FURNITURE AROUND.
THE MEANINGFULNESS OF THE TASK
IS ONCE THEY LOSE ABILITY TO DO
THAT WITHOUT ASSISTANCE OF
FURNITURE.
NOW THAT WE'RE WORKING IN PMM,
THOSE PATIENTS DON'T TAKE THE
TYPES OF FALLS KIDS WITH
DUCHENNE DO AND THEY WON'T DO
THAT UNLESS THERE'S FURNITURE
AROUND, WE'RE CONSIDERING
ALLOWED FURNITURE TO GET OFF THE
FLOOR, SO EVEN SOME LITTLE
NUANCES, IT'S IMPORTANT TO HAVE
THEM REFLECTIVE OF REALITY OF
THAT PARTICULAR DISEASE AREA.
SO IN TERMS OF THE COMPENSATORY
PATTERNS, THAT IS A PIECE IN
WHICH WE ARE NOT ASKING PATIENTS
ABOUT THE MEANINGFULNESS OF
THOSE COMPENSATORY ACQUISITIONS,
AND THE REASON FOR THAT IS
MULTI-FOLD.
ONE IS THAT WE ARE QUANTIFYING
THESE COMPENSATORY MOVEMENT
PATTERNS BECAUSE THEY ARE TO A
CERTAIN EXTENT SUBCONSCIOUSLY
ACQUIRED.
WE WANTED TO QUANTIFY SOMETHING,
BOYS WITH DUCHENNE AREN'T ALWAYS
AWARE THEY ARE ACQUIRING
COMPENSATIONS, THEY ARE DOING
WHAT THEY NEED TO DO TO MAINTAIN
INDEPENDENCE THROUGHOUT THEIR
DAY.
THAT'S WHAT MADE IT AN
ATTRACTIVE TARGET TO QUANTIFY,
OBSERVERS SEE THE BOYS MOVING
AROUND THAT ARE VERY AWARE OF
COMPENSATORY ACQUISITIONS.
THE BOYS DON'T NOTICE THEM
BECAUSE IT'S A COPING MECHANISM.
THEY DON'T WANT TO THINK ABOUT
THE ACQUISITION OF THESE
COMPENSATIONS BECAUSE IT PUTS IT
UP IN THEIR FACE, THE DEGREE OF
PROGRESSION THAT THEY ARE GOING
THROUGH.
LIKE I MENTIONED BEFORE, IT'S
TEMPTING TO THINK IF WE SPEAK TO
PATIENTS, WE'VE CHECKED THAT
BOX, WE'VE SPOKEN TO THE
PATIENT, BUT YOU'RE NOT GOING TO
GET, LIKE I MENTIONED, THE SAME
INFORMATION FROM A BOY WHO KNOWS
WHAT'S GOING TO HAPPEN TO HIM AS
YOU ARE FROM A BOY WHO DOESN'T
KNOW WHAT'S GOING TO HAPPEN TO
HIM.
AND SO EVEN THAT LEVEL OF
AWARENESS ABOUT THEIR
PROGRESSION AND PROGNOSIS IS A
HUGE CONFOUNDER, WHEN YOU'RE
TRYING TO QUANTIFY
MEANINGFULNESS FROM THE
PATIENT'S PERSPECTIVE.
AND SO THAT WAS ONE OF THE
ISSUES WE WERE TRYING TO --
WELL, THERE WERE LARGER REASONS
WE CHOSE P.T.s AS OUR
REPORTERS OF COMPENSATORY
ACQUISITION BUT THOSE ARE A FEW.
IN THE INTEREST OF TIME I'LL END
WITH THAT.
>>MINDY, YOU'VE GOT A COUPLE
MORE QUESTIONS.
NOW THREE MORE.
WALTER, JACKIE, DAN.
WE'LL MOVE TO THE NEXT SPEAKER.
>>A GENERAL COMMENT AND
QUESTION.
GENERAL COMMENT THAT GOOD NEWS
IN OUR AREAS THERE'S MORE AND
MORE TARGETS COMING TO THE
FOREFRONT WHICH PUTS PREMIUM
BEING ABLE TO DETECT WHETHER A
THERAPY AIMED AT CERTAIN TARGET
IS ACTUALLY HAVING AN EFFECT IN
THE KIDS.
SO THE BIOMARKER IN THAT
SITUATION, THE KEY FEATURE IS
KNOWING HOW SOON DOES YOUR
MEASURE GET YOU A STATISTICALLY
SIGNIFICANT INDICATOR OF
WORSENING OR WHAT TIME FRAME TO
PREDICT A SLOPE, TO PREDICT IF
THEY DON'T INTERVENE, ANY
LONGITUDINAL INFO?
>>YEAH, WE DO HAVE A SET OF
STUDY RESULTS FROM INITIAL
SOURCE MATERIAL STUDY, 30 WEEKS
APART, SIGNIFICANT COMPENSATORY
ACQUISITION OVER THE 30 WEEKS.
AND SO THIS NEXT STUDY THAT
WE'RE ABOUT TO GET STARTED WITH
IS A 2-YEAR STUDY, IT WILL
CAPTURE DUCHENNE VIDEO
ASSESSMENT EVERY SIX MONTHS, AND
WE'LL DO STANDARD -- GOLD
STANDARD ASSESSMENT AT BASELINE,
12 AND 24 MONTHS, WE'LL BE ABLE
TO SEE HOW THE DBA MOVES
ALONGSIDE GOLD STANDARD
ASSESSMENTS TO GET INFORMATION
ABOUT ABILITY TO DETECT
LONGITUDINAL CHANGE ACROSS A
LARGER PATIENT POPULATION, THE
ORIGINAL SOURCE MATERIAL STUDY
WAS IN 60 PATIENTS BUT WE DID
SEE SIGNIFICANT COMPENSATORY
ACQUISITION DEPENDING ON AGE
GROUP, SOME ARE MORE STABLE THAN
OTHERS BUT WE SAW COMPENSATORY
ACQUISITION WITHIN THAT 30 WEEKS
FOR A LARGE AMOUNT OF THOSE
PATIENTS.
>>THANK YOU.
>>JACKIE, YOU'RE NEXT.
>>THANK YOU, MINDY, FOR A GREAT
PRESENTATION.
YOU SHOULD BE COMMENDED ON YOUR
ITERATIVE RIGOROUS PROCESS.
MY QUESTION IS FORWARD LOOKING,
IN ADDITION TO COMPENSATION AS
PART OF PROGRESSION, ASPECT OF
EFFORT OR FATIGUE, FATIGABILITY,
DO YOU ENVISION A WAY THAT
YOU'LL BE ABLE TO CAPTURE THAT
QUALITATIVELY, QUANTITATIVELY,
AS A COMPONENT OF THE PRESENCE
OF COMPENSATIONS.
>>THAT'S A REALLY INTERESTING
QUESTION.
IN DUCHENNE, WE'RE TRYING TO
KEEP IT AS MUCH OF A REFLECTION
OF EVERYDAY LIFE AS POSSIBLE.
AND SO IN DUCHENNE YOU WOULDN'T
GET OFF THE FLOOR THREE TIMES IN
SUCCESSION.
AS PARENTS I THINK WHAT WE'VE
NOTICED IS THAT THE BOYS DON'T
ADOPT NEW COMPENSATORY PATTERNS
UNTIL THEY NEED TO, IF THAT
MAKES SENSE.
YOU DON'T SEE A LOT OF INFLUENCE
BUT THAT'S ANECDOTAL.
WE DO HAVE A TEST-RETEST AS LACE
-- BASELINE.
THAT'S OUTSIDE.
WE'RE LOOKING AT DIFFICULTY,
EASE OF MOVEMENT, AS PATIENTS
MOVE ABOUT THEIR DAILY LIVES.
SO, FATIGUE ISN'T AS MUCH A
COMPONENT OF WHAT WE'RE TRYING
TO MEASURE.
HOW HARD IS IT FOR THEM TO DO
THOSE ACTIVITIES, THAT THEY ARE
REQUIRED TO DO THROUGHOUT THEIR
DAILY LIVES.
IT'S A GREAT QUESTION THOUGH AND
SOMETHING WE THOUGHT ABOUT A LOT
WITH CARDIOMYOPATHY, BASED ON
TALKING TO THOSE PATIENTS
THERE'S MUCH MORE OF AN
INFLUENCE ON FATIGABILITY AND
MYOPATHY IN TERMS OF THE NATURE
OF COMPENSATORY PATTERNS.
DOING A THREE-PEAT TO LOOK AT
THAT SPECIFICALLY.
IT WASN'T SOMETHING ARTICULATED
BY FAMILIES TOO MUCH INITIALLY
IN DUCHENNE.
>>I WAS THINKING TOO OF THE
MORE TIME IT TAKES TO EVEN DO
ONE ACTIVITY.
>>INTERESTING.
YEAH, THAT'S AN INTERESTING
THING TO TAKE A LOOK AT WITH
ARISE DATA.
WITH VIDEO RECORDING WE CAN
PRETTY ACCURATELY PINPOINT TIME
OF THOSE ASSESSMENTS, THAT'S A
GREAT ONE.
>>BRIEF QUESTION OR COMMENT,
DAN PEREZ.
>>JUST A COMMENT.
CONCEPTUALIZING THIS CLINICAL
TRIAL, COMPENSATORY MECHANISM,
SOMETHING VERY INTERESTING,
DIFFERENT PROBLEMS THROUGHOUT
THE LIFETIME, I WONDERED WHETHER
OR NOT THIS IS A TOOL THAT COULD
BE USED, PERCEPTION OF DISEASE
PROGRESSION, SOMEBODY SAYS I
HAVE A LOT OF DECLINE ALL OF A
SUDDEN, THE STEPS TO NO LONGER
COMPENSATE, A GUIDE WITH NATURAL
HISTORY STUDIES IN TERMS OF
DYNAMIC TOOL IN THE CLINICAL
TRIALS PROCESS, CLINICIAN AND
RESEARCHER TO A PARTICULAR
ACTION AS OPPOSED TO TRYING TO
QUANTIFY THE CHANGE IN A DRUG.
MRI-GUIDED BIOPSIES, SIGNAL WITH
DUX4, A TOOL TO GUIDE TO
UNDERSTANDING DISEASE
PROGRESSION.
>>YEAH, I APPRECIATE THAT.
I'M BREAKING WHAT YOU SAID INTO
A NUMBER OF DIFFERENT POINTS.
FIRST OF ALL, UTILIZING THIS IN
A CLINICAL TRIAL SETTING, IT IS
LIVE IN SEVERAL CLINICAL TRIALS
AS A SECONDARY AND EXPLORATORY
MEASURE, SO WHAT WE'RE TAKING A
LOOK AT IS WE'RE LOOKING AT THE
TRAJECTORY OF INDIVIDUAL
PATIENTS BY COMPARING CHANGE IN
ONE PATIENT OVER TIME, YOU KNOW,
COMPOSITE ACROSS THE GROUP TO A
TREATED ARM.
WE'RE NOT LOOKING AT A
CROSS-SECTIONAL COMPARISON
BETWEEN TREATED AND PLACEBO AND
THEN ANOTHER CROSS-SECTIONAL
COMPARISON.
WE'RE LOOKING AT CHANGE WITHIN
AN ARM OVER TIME BECAUSE WE WANT
TO SEE IF RATE OF CHANGE IN THIS
PROCESS IS SIGNIFICANTLY
DIFFERENT BETWEEN THE TREATED
ARM AND PLACEBO ARM.
SO THAT IS IN USE IN CLINICAL
TRIALS ALREADY BUT I THINK WHAT
YOU'RE TALKING ABOUT IS
POTENTIALLY ABILITY TO VALIDATE
THE RELIABILITY OF
PATIENT-REPORTED DISEASE
PROGRESSION AGAINST WHAT'S SEEN
ON VIDEO, IF I'M INTERPRETING
YOUR ANSWER CORRECTLY, WHICH
WOULD BE AN INTERESTING PROJECT
AND ADDRESSES CONCERNS I
ARTICULATED ABOUT RELIABILITY
OF PATIENT-REPORTED OUTCOMES.
A REALLY GREAT IDEA.
I APPRECIATE THAT VERY MUCH.
>>THANK YOU, EVERYONE, FOR YOUR
TREMENDOUS ENGAGEMENT FOLLOWING
THIS PRESENTATION.
FINAL PRESENTER, DR. DAMIANO
ZONOTTO, ASSOCIATE PROFESSOR IN
THE DEPARTMENT OF MECHANICAL
ENGINEERING, STEVENS INSTITUTE
OF TECHNOLOGY IN HOBOKEN, NEW
JERSEY, HAS BEEN COLLABORATING
WITH DR. JACKIE MONTES,
ASSOCIATE PROFESSOR AT COLUMBIA,
WEARABLE TECHNOLOGY FOR GAIT
ANALYSIS, A.I. ENABLED SHOE
INSOLES TO ASSESS WALKING
FUNCTION IN SMA AND DMD.
OVER TO YOU, DR. ZANOTTO AND
MONTES.
>>I'M GOING TO SUMMARIZE SOME
OF THE RECENT STUDIES THAT WE
CONDUCTED IN COLLABORATION WITH
JACKIE MONTES AND HER GROUP AT
COLUMBIA, HOW TO USE SMART
INSOLES TO ASSESS WALKING
FUNCTION IN SMA AND DMD IN
CONTROLLED ENVIRONMENTS AND IN
REAL LIFE.
DISEASE-MODIFYING TREATMENTS FOR
SEVERAL MONTHS, CLINICIANS, AND
OTHERS, OTHER TREATMENTS
CURRENTLY UNDER DEVELOPMENT,
THERE IS A GROWING NEED TO
INTRODUCE NEW WAYS, NEW TOOLS TO
ASSESS SAFETY AND EFFECTIVENESS
IN A MORE SUFFICIENT, SCALABLE,
AFFORDABLE WAY, MEASURING GAIT
AND BALANCE, CAPTURING CAPACITY,
IN CONTROLLED ENVIRONMENTS,
PROVIDE SNAPSHOT, MIGHT NOT BE
REPRESENTATIVE OF REAL LIFE.
ONE HAS POTENTIAL TO CAPTURE
DMOs, MATRIX THAT RELATE TO
REAL LIFE PERFORMANCE.
AS WAS MENTIONED AT THE
BEGINNING, THOSE WEARABLES CAN
ALSO REDUCE COST OF FUTURE
CLINICAL TRIALS, FOR EXAMPLE BY
REDUCING NUMBER OF IN-PERSON
VISITS REQUIRED BY STUDY
PARTICIPANT, POTENTIALLY
REDUCING TARGET ENROLLMENT AND
DURATION OF FUTURE TRIALS
THROUGH INTRODUCTION OF MORE
SENSITIVE AND STABLE OUTCOME
METRICS.
CONSUMER GRADE WEARABLES ARE
INCREASINGLY BEING USED IN
CLINICAL TRIALS, BUT THOSE
DEVICES IN TERMS OF MOBILITY
METRICS CAN PROVIDE A VERY SMALL
SET OF VOLUME METRICS, DISTANCE
WALKED PER DAY, STEP COUNT,
QUITE INACCURATE EVEN WHEN THEY
ARE USED WITH HEALTHY
INDIVIDUALS.
AND WE KNOW THAT ACCURACY IS A
MAJOR ISSUE FOR CLINICAL
RESEARCH, DOESN'T ALLOW US TO
MEASURE CLINICALLY MEANINGFUL
CHANGES IN MOTOR OUTCOME THAT
CAN REFLECT RESPONSIVENESS TO
TREATMENT.
THE RESEARCH-GRADE ACTIVITY
TRACKERS ARE MORE ACCURATE THAN
CONSUMER-GRADE.
ON THE OTHER HAND, MULTI-SENSOR
DEVICES CAN PROVIDE A LARGE
NUMBER OF PARAMETERS, THEY ARE
CUMBERSOME AND EXPENSIVE, NOT
REALLY DEPLOYABLE AND SCALABLE
AS A SOLUTION TO MEASURE REAL
LIFE GAIT.
THEY CAN NOT MEASURE PARAMETERS,
FOOT PRESSURE TRAJECTORY FOR
EXAMPLE, PARAMETERS ARE
IMPORTANT IN ASSESSING THE
NON-BALANCE.
WE BELIEVE AMONG TECHNOLOGIES
WELL POSITIONED TO MEASURE GAIT
IN REAL LIFE BECAUSE THEY SHOW
THE SAME ADVANTAGES OF FOOT AND
ANKLE MONITORS, IN ADDITION TO
MEASURE INTERLIMB PARAMETERS AND
KINETIC PARAMETERS.
IF WE LOOK AT ALGORITHMS THAT
ARE IMPLEMENTED IN MOST OF THE
COMMERCIALLY AVAILABLE
INSTRUMENT INSOLES ON THE
MARKET, THEY ONLY ALLOW FOR
MODERATE ACCURACY.
OUR WORK IN THE LAST FEW YEARS
HAS FOCUSED ALLOWED US TO HAVE
MORE ACCURATE METRICS.
THIS IS HOW OUR CURRENT DEVICE
LOOKS LIKE, A PAIR OF INSOLES
INSTRUMENTED WITH SENSORS,
SIMILAR TO REGULAR PAIR OF
INSOLES, LIGHT WEIGHT AND CAN
COLLECT DATA CONTINUOUSLY UP TO
FIVE HOURS.
APPROACH LIES IN MACHINE
LEARNING MODELS, TO LEVERAGE
WHAT WAS PREVIOUSLY COLLECTED,
ALLOWS US TO OBTAIN RELIABLE
SPATIAL, TEMPORAL METRICS,
VOLUME DMOs.
THIS IS THE PARAMETERS WITH
INSOLES, BOTH STRIDE BY STRIDE
DMOs THAT PERTAINS TO
DIFFERENT DOMAINS, AND ALSO MORE
STANDARD VOLUME DMOs, NUMBER
OF STEPS PER DAY, DISTANCE
COVERED PER HOUR, PER DAY, SO
FORTH.
WE'RE USING THIS TECHNOLOGY IN
COLLABORATIVE STUDIES WITH
SEVERAL RESEARCH HOSPITALS IN
THE NATION.
SO, I'M GOING TO TALK ABOUT SOME
RECENT STUDIES WE CARRY OUT TO
ASSESS VALIDITY OF MACHINE
LEARNING METHODS.
THIS WAS ONE OF THE AREAS STUDY,
WE RAN ON A GROUP OF HEALTHY
INDIVIDUALS, ASKED THEM TO WALK
AND RUN AT DIFFERENT SPEEDS ON
TREADMILL WHEEL THE GAIT --
WHILE THE GAIT WAS MONITORED BY
A REFERENCE CAMERA SYSTEM TO
EXTRACT MEASUREMENT AND BY OUR
INSOLES.
WE WANTED TO VALIDATE TWO
MODELS, GENETIC MODEL
ONE-SIZE-FITS-ALL MODEL THAT
DOES NOT REQUIRE REFERENCE DATA
FROM THE INDIVIDUALS, AND STUDY
SPECIFIC MODEL THAT IS
ESSENTIALLY SPECIFICALLY FOR AN
INDIVIDUAL, USING REFERENCE DATA
COLLECTED WITH MOTION SYSTEM FOR
THAT PARTICULAR INDIVIDUAL.
IN ORDER TO ASSESS THE ACCURACY
OF OUR MODELS WE LOOK AT THREE
TARGET GAIT PARAMETERS, ASSESS,
MEASURE MEAN ABSOLUTE ERROR.
SUBJECT SPECIFIC MODELS WERE
MOST ACCURATE.
THE GENETIC MODELS WERE LIKELY
LESS ACCURACY, AROUND 2% FOR
WALKING, 5% FOR RUNNING.
BOTH MODELS PROVIDED EXCELLENT
TEST RELIABILITY.
THE TAKEHOME MESSAGE, WE KNOW IN
PRACTICE IT MIGHT BE HARD OR
IMPRACTICAL TO COLLECT REFERENCE
DATA FROM EACH STUDY PARTICIPANT
BECAUSE OF BUDGET OR TIME
CONSTRAINTS.
SO NEXT QUESTION WAS CAN WE
DETERMINE, DERIVE PERSONALIZED
MODELS WOULD THE -- WITHOUT NEED
FOR HAVING THE SUBJECT TEST IN A
GAIT LAB.
WE ASKED A GROUP OF 95 OLDER
ADULTS IN FIVE SENIOR CENTERS
AROUND THE NEW YORK CITY AREA TO
COMPLETE SIX-MINUTE WALK TEST
USING OUR WEARABLE SYSTEM.
WE SEE THE MEAN.
THOSE ARE ERRORS, THE LARGER THE
BARS, THE WORSE, SMALLER THE
BETTER.
INDIVIDUALS REQUIRE WALKING AID
TO PERFORM 6-MINUTE TEST VERSUS
THOSE THAT DID NOT REQUIRE ANY.
RED BOXES INDICATE THE
MEASUREMENT ERROR WE OBTAINED
WHEN APPLYING CONVENTIONAL
METHOD.
IT IS OFTEN IMPLEMENTED IN MANY
SMART INSULTS, FOOT TO ANKLE
TOUCH DEVICES IN THE MARKET.
THE ERRORS ARE QUITE
SUBSTANTIAL.
THE ERROR SUBSTANTIALLY REDUCED,
THIS METHOD IS NOT PRACTICAL.
WHAT WE INTRODUCED WAS TYPE OF
MODEL THAT IS BASED ON THE
TRANSDUCTIVE FRAMEWORK
EXTRACTING FROM A DATABASE, MOST
SIMILAR TO THE SUBJECT WE WANT
TO TRY TO TRAIN A NEW MODEL FOR.
WE'RE ABLE TO REDUCE MEASUREMENT
ERRORS BY 42% COMPARED TO
CONVENTIONAL, REDUCE ERRORS IN
SLEEP TIME BY 34%.
RESULTS WERE ENCOURAGING, BUT
OBTAINED FOR SIMPLE STRAIGHT
LINE WALKING TASK, DO NOT
NECESSARILY RESEMBLE REAL LIFE.
SO, TO EVALUATE THE VALIDITY OF
OUR METHODS IN TASKS THAT ARE
MORE CLOSE TO REAL LIFE WALKING,
WE'RE ASKED A GROUP OF
INDIVIDUALS TO PERFORM A SET OF
ACTIVITIES THAT ARE LISTED HERE.
FIRST, IN STRUCTURE CONDITION,
MEANING EACH ACTIVITY WAS
CARRIED OUT FOR SPECIFIC TIME
SLOT, SPECIFIC SEQUENCE.
AND AFTERWARDS THE SAME
ACTIVITIES BUT IN STRUCTURE
CONDITION MEANING WE LET THEM
NAVIGATE IN AN INDOOR
ENVIRONMENT WITH OBSTACLES,
CHAIRS, STAIRCASE, SO FORTH, AND
WE LET THEM PERFORM ALL THOSE
TASKS IN THE ORDER THEY WANT,
FOR THE TIME DURATION THEY WANT.
THIS DOES SHOW THE MEASUREMENT
ERRORS THAT WE FOUND, THE BLUE
BARS INDICATE COMMERCIAL
METHODS, THOSE THAT ARE
IMPLEMENTED IN MOST OFF THE
SHELF DEVICES VERSUS OUR MACHINE
LEARNING METHODS BASED ON
SUPPORT VECTOR ADRESS IN LIGHT
BLUE HERE AND FOUND THAT MACHINE
LEARNING METHOD REDUCED
MEASUREMENT ERRORS BOTH IN
STRUCTURE AROUND STRUCTURE
CONDITION REGARDLESS OF TYPE OF
WALKING TASKS.
WE LOOKED AT ACCURACY OF OUR
SYSTEM IN CLASSIFYING
ACTIVITIES, WE FOUND THE AVERAGE
ACCURACY FOR THE UNSTRUCTURED
CONDITION WAS 97%, AVERAGE
ACCURACY WE OBTAINED ASKING OUR
INDIVIDUALS TO USE THE DEVICE
FOR FOUR HOURS DOING THEIR
ACTIVITIES, IN THIS CASE
ACCURACY WAS 95%.
STILL PRETTY HIGH.
WE ALSO LOOKED AT HOW THE
LOCATION OF THE WEARABLE SENSOR
IN THE USER BODY MIGHT AFFECTS
ACCURACY OF THOSE ACTIVITY
CLASSIFICATION MODELS, AND SO TO
DO THAT WE TESTED THREE TYPES OF
SENSORS, WRIST WORN, SMARTPHONE
LOCATED IN THE SUBJECT'S
POCKETS, AND INSOLES.
THIS RESULTED IN SEVEN
INDEPENDENT ACTIVITY
CLASSIFIERS.
HERE YOU SEE THE AVERAGE
ACCURACY THAT WE OBTAINED FOR
THE UNSTRUCTURED CONDITION.
ALL THE CLASSIFIERS RESULTED IN
ACCURACY THAT WAS ABOVE 95%,
WHEREAS THE CLASSIFIER THAT
RELIED ON THE WRIST SENSOR ALONE
WAS CONSISTENTLY THE WORST
PERFORMING ONE IN THOSE
CONDITIONS, AND THIS IS
CONSISTENT WITH RESULTING IN THE
LITERATURE.
THIS IS ONGOING VALIDATION STUDY
IN A GROUP OF PATIENTS WITH SMA
AND DMD, AND ALTHOUGH THE
ENROLLMENT IS STILL ACTIVE WE
ARE ALMOST CLOSE TO COMPLETION.
WE'LL SHOW YOU THE PARTIAL
RESULT WE'VE OBTAINED SO FAR.
THIS STUDY IS CARRIED OUT
CLINICAL SITES, AND WE ASKED OUR
PARTICIPANTS TO COMPLETE THREE
ASSESSMENTS.
AFTER THAT WE ASKED THEM TO
COMPLETE A SET OF AD HOC WALKING
TASKS DESIGNED TO SIMULATE REAL
LIFE WALKING.
AS IN PREVIOUS STUDY I DESCRIBED
WE USE INSTRUMENTED WALKWAY TO
PROCEED REFERENCE SYSTEM TO
EXTRACT MEASUREMENT ERRORS.
SO THIS IS THE RESULT FROM 22
SUBJECTS, 13 CONTROLS WE'RE
SCREENING TO DATE.
TOP TABLE HERE SHOWS MEAN
OPPOSITE ERROR ON FIVE
REPRESENTING PARAMETERS, AND
CONTROLS AND PATIENT.
SO, WE FOUND WHEN INCLUDING ALL
DATA FROM WALKING TASKS,
STRAIGHT LINE WALKING AND CURBS
AND SO FORTH, THE ERROR FOR THE
CONTROLS WAS BELOW 5%, BOTTOM
SHOWS MEASUREMENT ERROR, FOR THE
CONTROLS AND PATIENT.
WE FOUND THAT WHEN COMBINING
DIRECTIONS COMBINED ERROR WAS
BELOW 3% FOR THE CONTROLS AND
BELOW 4% FOR THE PATIENT.
HERE YOU CAN SEE SOME
REPRESENTATIVE DATA IN TERMS OF
RIGHT FOOT THAT WE OBTAINED FROM
PARTICIPANT WITH DMD AND HEALTHY
CONTROL DURING THE 6-MINUTE WALK
TEST.
IN ORDER TO FURTHER VALIDATE OR
QUANTIFY, NOW WE'RE RUNNING
PILOT TESTS IN SMALL SAMPLE OF
PATIENTS WITH SMA AND DMD, FIVE
DAYS IN A ROW, FOUR HOURS PER
DAY.
I'M GOING TO SO YOU PRELIMINARY
DATA.
WE HAVE NOT COMPLETED DATA
COLLECTION BUT THIS IS DATA WE
COLLECTED FROM 16-YEAR-OLD BOY
WITH TYPE 3 SMA, TOP SHOWS
DISTRIBUTION OF DATA, 5 DAYS.
WE SPLIT DISTRIBUTION TO 3
COLORS, INDICATING DIFFERENT
DURATION.
WE SEPARATED.
THE PLOT SHOWS CORRESPONDING
RESULT OBTAINED FROM HEALTHY
CONTROLS.
PATIENTS TENDED TO WALK SLOWER
BY TAKING SHORTER STRIDES
COMPARED TO CONTROL, AND ALSO
OBVIOUSLY THE VOLUME OF THE
STRIDES WE RECORDED OVER FIVE
DAYS WAS MUCH SMALLER FOR THE
PATIENTS COMPARED TO CONTROL.
ANOTHER OBSERVATION HERE IS THAT
DISTRIBUTION IS MUCH MORE
OVERLAPPING, FOR THE SMA THAN
FOR THE HEALTHY INDIVIDUAL.
WE BELIEVE THIS MIGHT BE RELATED
TO VERSATILITY IN THE RANGE OF
REAL LIFE WALKING SPEED, THOSE
PATIENTS SHOW IN THEIR
DAY-TO-DAY LIFE, THIS MIGHT BE
RELATED TO MUSCLE WEAKNESS OR
MAYBE FEAR OF FALLING.
WE NEED TO COLLECT MORE DATA TO
CONFIRM WHETHER OR NOT THESE ARE
PLANS THAT WE'RE OBSERVING IN
OTHER PARTICIPANTS AS WELL.
TO CONCLUDE ONCE WE HAVE
FINISHED THIS PILOT TEST THE
NEXT IS TO EXTEND THE DURATION
OF THESE REAL LIFE GAIT MONITORS
TO FOLLOW THE MONITOR, MONITOR
STUDY PARTICIPANTS FOR 180 HOURS
OVER 30 DAYS, THIS HAS BEEN
REPORTED TO BE A GOOD TRADEOFF
BETWEEN NECESSITY OF REALLY
PROVIDING TRUTHFUL PICTURE OF
DAILY FUNCTION IN THOSE
INDIVIDUALS AND AT THE SAME TIME
PROVIDING OR GUARANTEEING GOOD
LEVEL OF PATIENT COMPLIANCE.
WE WANTED TO ADMINISTER IN
CLINICAL ASSESSMENT, TIME
POINTS, BASELINE, SIX MONTHS,
TWELVE MONTHS, AFTER EACH THE
IDEA IS TO FOLLOW, TO MONITOR
THE STUDY PARTICIPANT GAIT FOR
30 DAYS AND WE WILL USE THIS
DATA TO IDENTIFY THE SUBSET OF
DMOs THAT BEST DISCRIMINATE
ACROSS DIFFERENT TYPES OF
NEUROMUSCULAR CONDITIONS, AND
ALSO TO IDENTIFY THOSE DMOs
THAT BEST STRATIFY PATIENTS THAT
WITHIN THE SAME CONDITIONS IN
TERMS OF SEVERITY OF THEIR
FUNCTIONAL DEFICIT, USE
LONGITUDINAL DATA FOR EACH DMO
TO FIND THE MINIMAL DETECTABLE
CHANGE, AND SENSITIVITY TO
LONGITUDINAL CHANGES AT SIX
MONTHS AND TWELVE MONTHS.
WITH THAT I'D LIKE TO THANK YOU
FOR YOUR ATTENTION AND I'LL TAKE
ANY QUESTIONS.
>>THANK YOU VERY MUCH.
WE CAN TAKE QUESTIONS FROM BOTH
DR. ZONOTTO AND DR. MONTES.
THERE WAS ONE IN THE QUESTION
AND ANSWER BOX FROM DOUGLAS
ALBRECHT.
HAVE YOU ASSESSED YOUR SENSORS
MULTITUDEALLY AS COMPENSATIONS
CHANGE OVER TIME, RESULTS IN
EACH PERSON MAY CHANGE BUT NOT
NECESSARILY THE SAME WAY IN EACH
PERSON, THIS MAY COMPLICATE HOW
THESE MEASURES ARE USED TO
ASSESS TREATMENT EFFECT BECAUSE
IT COULD BE HARD TO DETERMINE
WHAT BENEFITS WILL LOOK LIKE.
>>AS OF NOW WE FOCUSED ON
FUNCTIONAL VALIDATION AND
ECOLOGICAL VALIDATION OF
TECHNOLOGY, LOOKING AT HOW WE
CAN REALLY LEVERAGE TECHNOLOGY
FOR THE DETECTING LONGITUDINAL
CHANGES, THE NEXT GOAL FOR US.
>>I THINK TO THE SECOND POINT,
A VERY GOOD SECOND QUESTION,
VERY GOOD POINT.
WHAT ABOUT THE INTERINDIVIDUAL
CHANGES OVER TIME AND HOW WOULD
THEY BE DIFFERENT, I MEAN, I
THINK IN DEVELOPING THESE
DMOs, COMPOSITE SIGNATURES, I
THINK BETTER ABLE TO UNDERSTAND
THE SORT OF INDIVIDUAL CHANGES
BUT IT'S DEFINITELY SOMETHING,
IT MIGHT BE DIFFERENT FOR EACH
CONDITION, SO I THINK NOT JUST
RELYING ON STRIDE LENGTH AND
USING COMPOSITE OF DMOs MIGHT
HELP UNDERSTAND THAT OR AT LEAST
BRING TO THE FRONT THOSE
NUANCES.
>>DAN HAS A QUESTION.
>>TWO QUESTIONS.
EXCELLENT TALK.
THE FIRST QUESTION HAS TO DO
WITH TECHNOLOGY WITH ANKLE
ORTHOTICS, AND THE SECOND
QUESTION, IN THE CLINICAL TRIALS
DO YOU THINK ABOUT INCLUSION
CRITERIA AND SO THE QUESTION IS
ONLY AMBULATING, NOT USING
ORTHOTICS OR USING ORTHOTICS, IN
A WHEELCHAIR OR NOT, AND THEN
ALSO WAS THE RESEARCH PEDIATRIC
VERSUS ADULT?
OR GERIATRIC SETTING, OR ADULTS
WITH MUSCULAR DYSTROPHY, THOSE
ARE THE TWO CONSIDERATIONS.
>>THANK YOU.
I APPRECIATE BOTH QUESTIONS.
I CAN TAKE THE ONE THAT MORE
RELATES TO TECHNOLOGY .
WE DID TEST THE TECHNOLOGY FOR
INDIVIDUALS THAT ALSO USE
ORTHOTICS, IN TERMS OF
SPATIOTEMPORAL PARAMETERS THERE
ARE NO PROBLEMS.
THE OTHER TECHNOLOGY QUESTION
WAS HOW THE -- WOULD TECHNOLOGY
WORK ACROSS DIFFERENT AGE
RANGES, THE ANSWER IS YES.
THE CURRENT PROTOTYPE WORKS, WE
HAVE VALIDATED THE CURRENT
TECHNOLOGY WITH OVER 500
INDIVIDUALS, AGE RANGE FROM 21
MONTHS TO 100 YEARS.
SO EIGHT DIFFERENT SIZES, OUR
MACHINE LEARNING MODELS WITH
CHANGES IN INSOLE SIZE.
>>I'LL ADD JUST WITH REGARDS TO
ORTHOTICS, THE INSOLES ARE SO
THIN THAT IT'S -- YOU KNOW, WE
CONSIDER THAT THEY ARE
DEFINITELY SOMETHING THAT YOU
COULD WEAR WITHIN A TYPICAL AFO
OR SMO, IN TERMS OUR NEXT -- WE
HAVEN'T STUDIED WITH ORTHOTICS
AT THE MOMENT BUT WE KNOW THAT
WE'RE SORT OF STRUGGLING WITH
UNDERSTANDING SORT OF THE
NATURAL HISTORY TRAJECTORY OF
GAIT IN THESE DISORDERS OVER
TIME, VERSUS HAVING IT ADAPTED,
BUT IT'S DEFINITELY SOMETHING
THAT IS FEASIBLE AND WILL
INCLUDE IF NOT SOONER RATHER
THAN LATER, AND IN TERMS OF SMA
AND DMD STUDIES THAT ARE ONGOING
AND PREDICT THAT THAT WE PREDICT
WHERE THE YOUNGEST CHILDREN
INCLUDING 4 OR 5 YEARS OLD, IT'S
BECAUSE WE'VE INCLUDED THE
SIX-MINUTE WALK TEST AS
REFERENCE CLINICAL ASSESSMENT
AND NEED SOME COOPERATION TO GET
THAT VALIDATED.
>>THANK YOU BOTH.
WE'LL TAKE QUESTIONS FROM GLEN
AND EMILY AND WE'LL MOVE ON.
>>YES, THANKS FOR A GREAT TALK.
WONDERING IF YOU'RE COLLECTING
DATA THAT WOULD LET YOU MONITOR
ANY FALLS THAT OCCUR IN
PATIENTS, SO THAT PERHAPS YOU
COULD USE THE DATA TO PREDICT
THE LIKELIHOOD OF FALLS AND
ACTUALLY TO HELP TRY AND PREVENT
FALLS IN INDIVIDUALS.
>>THAT'S A GREAT COMMENT.
WE HAVEN'T DONE IT YET BUT WE
ENVISION THAT THAT CAN BE A
POSSIBLE USE OF THIS TECHNOLOGY,
CERTAINLY COLLECT THE DATA,
THERE IS EVIDENCE THAT
COLLECTING DATA CAN BE USED TO
BUILD THOSE PREDICTION MODELS OF
FALLS OR DETECTION OF FALLS,
PREDICTION OF FALLS.
>>THANK YOU.
AND LAST IS EMILY.
>>HI.
THANKS.
THAT WAS A GREAT PRESENTATION.
DR. CAMPBELL HAD TO STEP AWAY, I
FEEL OBLIGATED TO KIND OF TIE IN
TO HER PRIOR QUESTIONS ABOUT
CLINICAL MEANINGFULNESS, JUST
WONDERING WITH ALL THIS KIND OF
FINE GRANULAR DATA THAT YOU'RE
ABLE TO COLLECT, HAVE YOU
THOUGHT ABOUT, LIKE GLEN SAID,
FALLS, WHAT CLINICAL MEANINGFUL
ENDPOINT DO YOU THINK WE COULD
LEVERAGE FROM A REGULATORY
PERSPECTIVE?
>>RIGHT.
SO AS I SAID, FOR NOW WE'RE
PRIMARILY FOCUSED APPROACH,
LOOKING AT LEVEL OF NOISE, THAT
IS IMPORTANT, RIGHT, BUT WE WANT
TO ASSESS WHAT IS MEANINGFUL FOR
THOSE PARTICIPANTS SO WE WANT TO
USE SURVEYS, QUESTIONNAIRES,
LIKERT SCALES AND TYPE OF DATA
TO REALLY LIKE FIGURE OUT WHAT
IS IMPORTANT, WHAT IS THE LEVEL
OF CLINICAL MEANINGFULNESS.
THOSE METRICS.
>>THANK YOU.
I THANK OUR PRESENTERS WHO
PRESENTED SOME REALLY AMAZING
TECHNOLOGY, INNOVATIVE OUTCOME
MEASURES.
WE LOOK FORWARD TO CONTINUED
PROGRESS ON THESE PROJECTS AND
FOR IMPLEMENTATION OF NOVEL
TECHNOLOGIES AND CLINICAL TRIALS
TO DELIVER HIGH QUALITY DATA AND
REDUCE BURDEN TO OUR STUDY
PARTICIPANTS.
NOW WE'RE GOING TO HAVE A COUPLE
BRIEF UPDATES FROM OUR NIH
STAFF, YOU'LL REALLY LAST JUNE
AT THE MDCC MEETING, JUNE LAST
YEAR, FOCUSED ON RESPIRATORY AND
SLEEP COMPLICATIONS.
WE ORGANIZED THAT WITH
COLLEAGUES FROM NHLBI AND DR.
NATARAJAN IS THE PROGRAM
DIRECTOR FOR PEDIATRIC AND
NEONATAL LUNG DISEASE AND
CRITICAL CARE AT NHLBI.
SHE'S HERE TO TELL US ABOUT THE
SPECIAL FUNDING OPPORTUNITY THAT
RESULTED FROM THAT MEETING.
SO, IN A WAY, THIS IS GETTING
BACK TO WHAT DAN ASKED ABOUT,
YOU KNOW, HOW DO WE MONITOR
OURSELVES TO SEE THAT WE DELIVER
ON THINGS THAT WE PROMISE.
SO, WELCOME, DR. NATARAJAN.
>>THANK YOU, DR. BIANCHI.
GOOD AFTERNOON.
THANK YOU FOR THIS OPPORTUNITY
TO PRESENT AN UPDATE ON A NOTICE
OF SPECIAL INTEREST, NOSI, TO
SPECIFICALLY ADDRESS RESPIRATORY
COMPLICATIONS OF MUSCULAR
DYSTROPHIES.
I THANK MY DIVISION DIRECTOR AND
OUR COLLEAGUES IN NINDS, NICHD,
AND NIAMS, HIGHLIGHTING RESEARCH
WE NEED IN THE MUSCULAR
DYSTROPHIES, RECOGNIZING MOST
PATIENTS OF NEUROMUSCULAR OR
CHEST WALL DISORDERS HAVE SOME
FORM OF RESPIRATORY
INSUFFICIENCY.
THE BURDEN ON PATIENTS AND
FAMILIES AS YOU'VE HEARD FROM
DR. DECKER AND OTHERS IS
SIGNIFICANT, CLINICIANS AND
FAMILIES SEEKING BETTER WAYS TO
BRING COMFORT TO THESE
INDIVIDUALS.
IT BRIEFLY RECAP WHAT LED US TO
THE NOTICE OF SPECIAL INTEREST,
AS YOU KNOW, RESPIRATORY
COMPLICATION LEADS TO MORTALITY
AND MORBIDITY, SIGNIFICANT
IMPACT ON HEALTH-RELATED QUALITY
OF LIFE.
SOME OF THESE DISEASES ARE
MENTIONED ON THE SLIDE, AS YOU
CAN SEE, BUT BY NO MEANS
EXHAUSTIVE, THERE ARE MANY
OTHERS.
WE FOUND ASSOCIATED PATHO
BIOLOGY INCLUDES DISORDERS THAT
AFFECT MUSCULOSKELETAL STRUCTURE
OF THE THORAX LEADING TO
PREDISPOSITION FOR RESTRICTIVE
LUNG DISEASE AND COLLAPSE.
THIS GRAPH ON THE LEFT OF YOUR
SLIDES SHOWS THE COMPLICATIONS
ACCOUNT FOR SIGNIFICANT
PERCENTAGE OF THE CAUSES OF
DEATH IN A VARIETY OF
CONDITIONS, AND THIS APPLIES TO
MANY MORE.
THIS LEADS TO SIGNIFICANT STRESS
AND BURDEN ON PATIENTS GIVEN A
PATIENT WITH ARDS WOULD BE AWARE
FOR MANY YEARS PRIOR TO THAT
EVENT OF THE DIFFICULTY IN
BREATHING AND LIMITATION OF
THEIR BREATHING AS MR. DECKER
ELOQUENTLY DESCRIBED EARLIER IN
THE SESSION.
THIS IS BROUGHT HOME BY
INTERVENTIONS THAT ESCALATE FROM
NON-INVASIVE VENTILATION TO
MECHANICAL VENTILATION, AND THE
USE OF COUGH ASSIST DEVICES AS
INDIVIDUALS GET WEAKER WITH
WORSE ABILITY TO CLEAR
SECRETIONS.
THIS IS RELATED TO UPPER AIRWAY,
REMAINING IN MOST OF THESE
CONDITIONS, ALSO AFFECT SLEEP.
AND COULD CONTRIBUTE
SIGNIFICANTLY TO OBSTRUCTIVE
SLEEP APNEA.
THE OTHER RESEARCH QUESTIONS
THAT WE WONDERED ABOUT WERE
DIFFERENCES IN TRAJECTORIES OF
DIFFERENT CONDITIONS AS WELL AS
DIFFERENCES IN THE TRAJECTORY OF
PROGRESSION OF DISEASE IN THE
SAME CONDITION, THIS SLIDE
DEMONSTRATES HOW ONE PATIENT IS
DIFFERENT WITH ANOTHER WITH THE
SAME DIAGNOSIS OF DUCHENNE
MESHED.
SEVERAL PRESSING KNOWLEDGE GAPS
WERE IDENTIFIED, AND I'LL ONLY
HIGHLIGHT A FEW, WHICH INCLUDED
IMPACT OF GENE THERAPY ON
RESPIRATORY FUNCTION ON ANIMAL
MODELS AND IN VITRO MODELS,
UPPER AIRWAYS OBSTRUCTION AND
IMPORTANCE OF SLEEP APNEA IN
DYSTROPHIES, OPTIMAL PRIMARY
FUNCTION TESTING IN SETTING OF
WEAKNESS, AND THERAPIES,
INCLUDING ASSESSMENT OF OUTCOMES
WHICH HAS ALSO BEEN DISCUSSED IN
THE SESSION TODAY, AND LASTLY
THE STUDY OF LONGITUDINAL
COHORTS TO UNDERSTAND THE
REASONS FOR AND VARIATIONS IN
THE TRAJECTORY OF PULMONARY
DECLINE.
SO, FOLKS AT THE NIH TOOK ALL
THE RECOMMENDATIONS OF THE
COMMITTEE VERY SERIOUSLY AND WE
PUT THEM TOGETHER TO BRING OUT A
NOTICE OF SPECIAL INTEREST,
ISSUED ON JULY 18, 2022, ON
RESPIRATORY COMPLICATIONS,
ISSUED BY THE NHLBI, EUNICE
KENNEDY SHRIVER INSTITUTE,
NATIONAL INSTITUTE OF NEUROLOGIC
DISEASE AND STROKE.
AND HERE IS THE LINK THAT I CAN
ALSO PROVIDE TO THE ORGANIZERS
TO SHARE WITH YOU.
THE FIRST AVAILABLE DUE DATE FOR
APPLICATION IS SEPTEMBER 25,
2022, AND NOSI WILL GO ON UNTIL
JANUARY 8, 2025, GIVING
INVESTIGATORS ABOUT A LITTLE
LESS THAN 3 YEARS TO BE ABLE TO
SUBMIT APPLICATIONS TO THIS
NOTICE.
THE MECHANISM UNDER WHICH
INVESTIGATORS CAN APPLY IS THE
CLASSIC NIH RESEARCH PROJECT
GRANT, PARENT R01, CLINICAL
TRIALS ARE NOT ALLOWED UNDER
THIS NOTICE OF SPECIAL INTEREST,
HOWEVER HUMAN SUBJECT RESEARCH
THAT IS LIMITED TO OBSERVATIONAL
STUDIES AND ALSO TO ANSWER
MECHANISTIC QUESTIONS IN HUMANS
ARE PERMITTED.
SOME RESEARCH EXAMPLES ARE SHOWN
ON THE SLIDE, AND MANY ISSUES
ARE ALREADY TALKED ABOUT.
BUT TO SORT OF SUMMARIZE THE
THEME OF THESE, THEY ARE REALLY
TO DRAW ATTENTION OF SCIENTISTS
AND FUNDED CENTERS, UNIVERSITY
CENTERS, TO INCREASE PRIMARY
RESEARCH EXPERTISE, TO INCREASE
COLLABORATION FOR HOLISTIC
ANIMAL MODEL RESEARCH BY THOSE
INVOLVED IN TESTING THERAPIES,
TO INCLUDE IMPACT ON RESPIRATORY
FUNCTION ON MUSCLES SUCH AS
DIAPHRAGM THAT HAS ALREADY BEEN
ALLUDED TO BEFORE, AS ONE OF THE
LARGEST SKELETAL MUSCLES, MOST
IMPORTANT EFFECT ON BREATHING
MITIGATION INTERVENTIONS IN
THESE POPULATIONS, SUCH THAT
WHEN THERE ARE NEW THERAPIES
AVAILABLES THE LUNGS ARE IN
THEIR BEST POSSIBLE CONDITION TO
BE ABLE TO BENEFIT FROM THEM.
IT IS OUR HOPE THIS WILL MAKE A
TANGIBLE DIFFERENCE TO THE LIVES
OF THOSE AFFECTED WITH THESE
CHALLENGING CONDITIONS.
OUR HOPE FOR THIS NOSI SPEAKING
MORE PRACTICALLY AND FOR THE
FIELD IS WE HOPE THIS WILL
ENCOURAGE SCIENTISTS IN THE
SPACE OF THE MUSCULAR
DYSTROPHIES TO INVESTIGATE
RESPIRATORY BREATHING, AND
SCIENTISTS ATTRACTED TO
INVESTIGATE NEUROMUSCULAR
DISEASES.
WE BELIEVE THE
CROSS-COLLABORATION BETWEEN
DISCIPLINES WILL BRING SYNERGY,
WHERE THE WHOLE IS GREATER THAN
THE SUM OF THE PARTS PROVIDING
GREATER BENEFIT TO OUR PATIENTS.
IT IS OUR HOPE THIS RESEARCH
THAT HELPS PATIENTS REMAIN
OPTIMAL PRIMARY HEALTH,
ULTIMATELY INCREASING POTENTIAL
FOR THEM TO BENEFIT FROM FUTURE
INNOVATIVE THERAPIES WHEN THEY
ARISE.
WITH THAT I'D BE HAPPY TO TAKE
QUESTIONS.
THANK YOU.
>>THANK YOU, ARUNA.
QUESTIONS?
I BELIEVE THAT GLEN PUT THE NOSI
LINK IN THE CHAT BOX.
>>I'VE GOT A QUESTION.
>>GO AHEAD, DAN.
>>LET ME TRY TO MOVE IT, IT
SEEMS TO BE STUCK.
>>IN TERMS OF CARDIAC,
(INDISCERNIBLE).
>>THIS PARTICULAR CHART, THE
NUMBER THEY STUDIED, WHICH WAS
21, AND 164 DUCHENNE PATIENTS, I
THINK IN THE NUMBER THAT THEY
STUDIED.
>>OKAY.
THAT SEEMS LIKE A LOT FOR
DUCHENNE, A LOT OF CANCER, WHICH
IS INTERESTING.
THIS IS IN ORDER OF -- OKAY.
I'M TRYING TO UNDERSTAND.
>>SURE.
>>OKAY.
THANK YOU AGAIN.
NEXT UP IS DR. EMILY CARIFI,
PROGRAM DIRECTOR FOR MUSCLE
DISORDERS AND THERAPIES AT
NIAMS.
SHE'S HERE TO GIVE A BRIEF
UPDATE ON THE NIH CENTERS OF
EXCELLENCE PROGRAM IN MUSCULAR
DYSTROPHIES, THE WELLSTONE
CENTERS.
WELCOME.
>>I DO KNOW I STAND BETWEEN YOU
AND THE END OF THE MEETING SO
I'LL GO QUICKLY.
I WANTED TO GIVE A BRIEF UPDATE
ON THE SPECIALIZED RESEARCH
CENTERS.
THIS IS PARTICULARLY TIMELY
BECAUSE TODAY IS THE DUE DATE
FOR THE MOST RECENT RFA, I
SUPPOSE IF YOU HAVEN'T WRITTEN
YOUR APPLICATION YOU'RE A BIT
LATE.
SO, PRETTY MUCH EVERYONE IN THE
ROOM, THE ZOOM HERE, KNOWS THE
HISTORY OF THE WELLSTONE
CENTERS, CREATED BY THE NIH IN
RESPONSE TO THE M.D. CARE ACT OF
2001, IN 2003, THEY REACHED A
STEADY STATE OF SIX CENTERS IN
2005, FUNDED BY NIAMS, NINDS,
NICHD, CO-FOUNDED BY NHLBI.
THE SIX CENTERS ARE STUDYING ALL
OF THE DISEASES LISTED AND HAVE
A SPREAD FROM BASIC PRE-CLINICAL
AND CLINICAL RESEARCH, BECAUSE
MANY OF THE PILLARS OF THE MDCC
IN 2005 AND 2015 ACTION PLANS,
DISEASE MECHANISM, BIOMARKERS,
ALL THE WAY TO THE CLINIC.
THIS PROGRAM WAS EVALUATED IN
2018 AND THE RESULTS OF THAT
EVALUATION WERE PRESENTED TO
THIS COMMITTEE IN 2019, IT WAS
AN OVERWHELMINGLY POSITIVE
EVALUATION, AND SUPPORTIVE OF
THE CENTERS PROGRAM AND
DIRECTION OF THE INVESTIGATORS.
THE CURRENT SIX CENTERS AS I
MENTIONED, ALL THE DISEASE AREAS
FROM REALLY BASIC ASPECTS OF
DISEASE MECHANISM TO THE CLINIC,
CAMPBELL, EMERSON, CHAMBERLAIN,
SWEENEY, WE REALLY DO HAVE A
WIDE RANGE GEOGRAPHICALLY AND
ALSO THE ENTIRE DISEASE, THEY
ARE VERY HAPPY WITH THE PROGRAM.
THIS TOOK ME A LONG TIME, IT
KEPT GETTING TOO BIG, I GOT IT
ON ONE SLIDE.
SOME OF THESE ALREADY MENTIONED
TODAY.
RESEARCH COMING OUT OF THESE
GROUPS IS JUST ENTIRELY TOP
NOTCH, BREAKING THE GROUND FOR
THERAPEUTICS, FOR UNDERSTANDING
DISEASE, FOR OUTCOME MEASURES,
BIOMARKERS, ANYTHING TO MOVE THE
FIELD FORWARD TO FUTURE
THERAPEUTIC PATIENT CARE.
THE OTHER ASPECTS OF THE
WELLSTONE CENTERS, IT'S THE FACT
THAT THEY HAVE RESEARCHERS THAT
THEY HAVE A MANDATE TO SHARE
WITH THE COMMUNITY AND WITH
THEIR OWN INVESTIGATORS.
AND THESE RESOURCES, AS I
MENTIONED, ARE AVAILABLE TO THE
ENTIRE MUSCULAR DYSTROPHY
COMMUNITY, SHARED VERY WELL BY
THE CENTERS.
SO, A LOT OF THESE THINGS MIGHT
BE HARDER FOR ANY ONE
INVESTIGATOR TO BE ABLE TO HAVE
OR TO FIND, AND ANIMAL MODELS
AND THE EXPERTISE TO DO EDITING,
TO DO TESTING ON EXISTING MODELS
TO CREATE NEW MODELS SO, AGAIN,
THE IDEA HERE IS TO CREATE A
WELL CURATED AND EXCELLENT
REPOSITORY FOR THE COMMUNITY AND
LEVEL OF EXPERTISE FOR THE
ENTIRE COMMUNITY.
THEY ALSO HAVE A MANDATE TO
CLEAN UP THE NEXT GENERATION OF
MUSCULAR DYSTROPHY RESEARCHERS,
SO THEY DO THIS IN TWO MAJOR
WAYS, ONE IN THE SPREADING OF
KNOWLEDGE, SO A LOT OF TIMES
THIS HAPPENS IN THE SEMINARS AND
INTERACTIVE COURSES, THEY DO A
LOT OF CROSS TRAINING, HAVING
PhDs IN THE CLINIC, M.D.s
IN THE LAB, LEADSSHIP TRAINING,
DEDICATED FUNDS FOR TRAINEES AND
MANY OF THESE TRAINEES HAVE GONE
ON TO SUCCESSFUL CAREERS,
SEVERAL OF THEM AGAIN I CUT OUT
THE SLIDES, I WAS GIVEN TEN
MINUTES, I HAVE PAGES OF NAMES,
THOSE WHO MOVED TO FACULTY, WHO
HAVE R01s, IT'S BEEN A GOOD
PIPELINE INTO THE DYSTROPHY
COMMUNITY.
THE FUTURE DIRECTIONS FOR THE
CENTER AS I MENTIONED THIS IS A
CENTER THAT'S BEEN AROUND 20
YEARS NOW.
WELL RESPECTED PROGRAM.
LIKE I SAID, THE EVALUATION IN
2018 WAS SUPPORTIVE BUT WE HAVE
IN PARTICULAR IN THE MOST RECENT
RFA STARTED TO MAKE SOME MINOR
CHANGES TO THE PROGRAM, JUST TO
HIGHLIGHT SOME PRIORITIES OF THE
NIH AND BASED ON THE COMMENTS IN
THE EVALUATION.
SO, IN THE RFA THERE IS AN
ENCOURAGEMENT OF SOME NIH
PRIORITIES INCLUDING RESEARCH
AREAS, INCLUDING PULMONARY
ASPECTS.
WE'RE ALSO TRYING TO CONTINUE TO
GROW THESE LEADERS OF THE
MUSCULAR DYSTROPHY COMMUNITY
HERE SO WE'RE ENCOURAGING THAT
NEW INVESTIGATORS LEAD
SCIENTIFIC PROJECTS AND GET
THEIR SKILLS TO THEIR OWN LABS
IN THE FUTURE.
THE GOAL HERE LIKE I SAID IS TO
REALLY INCREASE THE NUMBER OF
LEADERS THAT WE HAVE, AND ALSO
THE NIH COMMITMENT TO INCLUSION,
DIVERSITY, EQUITY.
BUT OUR GOAL HERE IS TO FOCUS ON
THE PATIENT COMMUNITY, MAKING
SURE THAT THESE CENTERS ARE
ABLE, USING RESOURCES WE'RE
GIVEN THEM TO REALLY REACH OUT
TO THOSE WHO ARE HISTORICALLY
UNDERREPRESENTED IN BIOMEDICAL.
THERE HAS TO BE STRONG AND
INCLUSIVE PLANS FOR ALL CLINICAL
PARTICIPANTS, AND ALSO AS I
MENTIONED TRAINEES, WHILE WE
DON'T -- THIS PROGRAM ISN'T --
THE GOAL IS TO ENHANCE
RECRUITMENT OF TRAINEES SO
PEOPLE WHO STUDY PATIENTS LOOK
LIKE THE PATIENTS.
SO, AGAIN, I MENTIONED THE RFA
WAS DONE TODAY, THE PROGRAM IS
MOVING FORWARD, HOPEFULLY IN A
WONDERFUL DIRECTION.
THANK YOU.
I CAN TAKE ANY QUESTIONS IF
NEEDED.
>>DAN PEREZ AGAIN.
>>GO AHEAD, DAN.
>>THE QUESTION I HAVE, THE
CENTERS HAVE BEEN FUNDED,
WELLSTONE CENTERS, SINCE 2003,
FUNDING STATE CONSISTENT, I
REALIZE NOW REQUIRING TWO
SUBJECTS INSTEAD OF THREE, THERE
ARE SOME CHANGES IN TERMS OF NOT
HAVING THE FUNDS FOR THE
POSTDOCTORAL TRAIN, IS THERE A
WAY TO LOOK AT INCREASING THE
AMOUNT OF FUNDING PER CENTER?
BECAUSE THEY ARE LOSING -- WE'RE
LOSING AGAINST INFLATION, AND A
PROJECT WAS PUT TOGETHER, ALL
THE REQUIREMENTS, IS THERE ANY
FLEXIBILITY THERE, IS THERE
ANY -- DO YOU CHOOSE ANOTHER
MECHANISM, DO YOU CREATE ANOTHER
CLASS OF USES?
THE QUESTION IS HOW CAN WE
INCREASE THAT.
>>YEAH, SO, DAN, THANK YOU FOR
POSING THAT QUESTION.
YEAH, THERE'S A LOT WRAPPED IN
THERE.
I'M NOT SURE I FOLLOWED
EVERYTHING, BUT PART OF -- ONE
OF THE POINTS YOU RAISE IS
SOMETHING THAT WE'RE CHALLENGED
WITH GENERALLY, WHICH IS THAT
THE COST OF DOING RESEARCH IS
INCREASING FASTER THAN THE
SUPPORT THAT WE RECEIVED TO DO
RESEARCH, THAT'S A GENERAL
CHALLENGE, INVESTIGATORS FACE
THAT CHALLENGE, INSTITUTES AND
CENTERS FACE THAT CHALLENGE.
YOU KNOW, ONE OF THE WAYS WE
LOOK TO, YOU KNOW, ENSURE THAT
THE DOLLARS GO FURTHER IS BY
TRYING TO LEVERAGE OTHER
RESOURCES FUNDING IN-KIND
RESOURCES, SO I THINK SOMETIMES
THAT'S WHERE CENTERS CAN BE MORE
EFFICIENT IF THERE ARE
INSTITUTIONAL OR OTHER LEVERAGES
THAT CAN BE LEVERAGED, TO
SUPPORT THE RESEARCH, AND OF
COURSE ONE OF THE BENEFITS OF
FOCUSING ON TRAINING AND
EARLY-STAGE INVESTIGATORS IS SO
THAT THEY WILL DEVELOP INTEREST
AND COMMITMENT IN THESE AREAS
AND PROPOSE THEIR OWN STUDIES
THROUGH THE R01 OR OTHER
MECHANISMS.
IN TERMS OF RECEIVING MORE MONEY
FROM -- IN THE NIH BUDGETS FOR
THE WELLSTONE CENTER OR MUSCULAR
DYSTROPHY I DON'T KNOW THAT
THAT'S A QUESTION WE CAN TACKLE
IN THIS MEETING BUT I THINK OF
COURSE THE ADVOCACY THAT YOU AND
EVERYBODY ELSE PARTICIPATING IN
THIS MEETING PROVIDES IS ONE OF
THE MOST EFFECTIVE WAYS TO TRY
TO ENSURE THERE'S ONGOING
ATTENTION TO THESE CHALLENGES,
YOU KNOW, THE GAPS AS WELL AS
THE OPPORTUNITIES.
LET ME JUST PAUSE THERE AND SEE
IF OTHER -- IF DIANA OR WALTER
WANT TO ADD TO WHAT I HAD TO SAY
FROM THEIR PERSPECTIVES.
WALTER CAME OFF MUTE.
>>WELL, DAN, THE ANSWER IS
ALWAYS YES.
THEY COULD USE MORE MONEY.
THE ISSUE IS, AS LINDSEY PUT IT,
THIS APPLIES TO ALMOST EVERY
GRANT MECHANISM WE HAVE.
FOR INSTANCE, THE MODULAR R01,
HAS BEEN $250,000 FOR 20 YEARS,
IT HASN'T CHANGED, IT'S A BAD
THING TO KEEP UP WITH INFLATION,
BUT THE ONLY THING WE CAN DO,
WE'RE BALANCING ADDING MONEY TO,
YOU KNOW, X AND THAT MEANS WE
FUND FEWER GRANTS.
THE GENERAL CENSUS, IT'S
PROBABLY HEALTHY TO KEEP MORE
PEOPLE IN THE GAME, THE WORST
THING IS TO LOSE SMART PEOPLE,
BUT THIS IS SOMETHING WE
STRUGGLE WITH ALL THE TIME.
AND THE ONLY THING WE CAN --
UNLESS WE GET MORE FUNDS, WE RUN
INTO THIS PROBLEM.
OUR PERCENTILE NOW FOR GETTING A
GRANT IS 14 PERCENTILE, 86% OF
PEOPLE DON'T GET THEIR GRANTS
FUNDED.
>>I'M TALKING ABOUT THE
WELLSTONE CENTERS, PREMIER
CENTERS OF NIH.
TOP DOCTORS IN THE FIELD.
WE'RE IN THE GOING TO GO IN
BECAUSE BY THE TIME WE END UP
NINE DIFFERENT WAYS, WE CAN'T
GET ANYTHING DONE.
ARE YOU NO LONGER INTERESTED
BECAUSE IT'S JUST NOT WORTH YOUR
WHILE?
>>THAT'S A GOOD POINT.
>>IT'S NOT A GOOD PLACE TO BE.
>>I'D LIKE TO ALSO THROW A
PUBLIC/PRIVATE PARTNERSHIP INTO
THE MIX, SOME SITUATIONS THE
ONLY, YOU KNOW, I MEAN IT'S A
ZERO SUM GAIN FOR EVERY
INSTITUTE AND WE'RE TRYING TO DO
AS BEST AS WE CAN TO BALANCE
MULTIPLE PRIORITIES.
SO THAT'S WHERE ORGANIZATIONS
LIKE THE FOUNDATION FOR NIH COME
IN, WHO CAN ARC STRAIGHT THESE
PUBLIC/PRIVATE PARTNERSHIPS.
AND THINK THAT THE NIH FUNDING,
IT'S SO PRESTIGIOUS AND IT'S
GONE THROUGH MULTIPLE LAYERS OF
REVIEW, THAT THAT CAN SOMETIMES
HELP TO ATTRACT ADDITIONAL
PRIVATE FUNDING.
IT'S NOT OPTIMAL BUT AT LEAST
IT'S SOMETHING.
YOU NOTICE THAT IN MANY
PRESENTATIONS WE SAW THAT GROUPS
ARE BEING FUNDED INCREASINGLY BY
COALITIONS OF FOUNDATION,
INDUSTRY, AND NIH FUNDING.
>>I WOULD ADD A GREAT EXAMPLE
ALONG THOSE LINES IS THE SUCCESS
OF THE ACCELERATING MEDICINES
PARTNERSHIP PROGRAMS.
I DON'T RECALL OFFHAND THE
PROPORTION OF FUNDING THAT COMES
FROM NIH INSTITUTES VERSUS
INDUSTRY AND NON-PROFIT
ORGANIZATIONS, BUT THE NIH
DOLLARS GO A VERY LONG WAY IN
THAT ENVIRONMENT, WHERE, YOU
KNOW, THERE ARE PARTNERSHIPS AND
IN THAT, THAT'S ANOTHER EXAMPLE
WHERE FRO SERVES A CRITICAL
LIAISING FUNCTION.
>>THANK YOU, LINDSEY.
SO WITH THAT, I THINK WE ARE
GOING TO MOVE TOWARDS CLOSING.
IT'S ALMOST 5:00.
I WOULD LIKE TO THANK OUR
SPEAKERS WHO ARE REALLY
OUTSTANDING TODAY.
I WAS REALLY IMPRESSED WITH SOME
OF THE NOVEL TECHNOLOGIES THAT
HAVE BEEN DEVELOPED, AS A
NEONATOLOGIST I REALLY WAS
IMPRESSED.
I WAS IMPRESSED BY ALL OF THEM
BUT DR. LOWES PRESENTATION WAS
NEWBORNS, AS A CLINICIAN I WAS
TRYING TO GUESS WHICH WAS THE
AFFECTED INFANT, I REALLY
COULDN'T.
BUT IT WAS PRETTY OBVIOUS WITH
THE PATTERNS THAT WERE GENERATED
BY THE NEW TECHNOLOGY.
SO THAT'S ONE OF MANY OF THE
EXCITING THINGS WE HEARD ABOUT
TODAY.
I'D LIKE TO THANK DR. NUCKOLLS
AND HIS STAFF FOR HELPING US TO
PUT TOGETHER THIS PROGRAM, WE'RE
WORKING ON BOTH THE TIMING AND
THE AGENDA FOR THE SPRING
MEETING.
I THINK WE'RE GOING TO OFFER A
HYBRID MEETING BUT STAY TUNED ON
THIS.
COULD YOU HAVE THE OPTION BE
BEING IN PERSON OR BEING ON
VIDEO.
PROBABLY MORE OR LESS THE SAME
TIMING, FOUR-HOUR MEETING ON A
SPRING AFTERNOON LIKELY.
GLEN, DID YOU HAVE ANYTHING ELSE
YOU WANTED TO ADD?
>>I'D LIKE TO ALSO SAY THANKS
TO ALL THE PRESENTERS WE HAD
TODAY.
GREAT PRESENTATIONS.
THANKS TO COMMITTEE MEMBERS AND
THANKS TO YOU, DR. BIANCHI, FOR
KEEPING US ON TIME AND A GREAT
MEETING.
WE'RE LOOKING FOR MARCH, APRIL,
OR MAY FOR FOUR-HOUR AFTERNOON
MEETING, I'LL BE CONTACTING
COMMITTEE MEMBERS TO IDENTIFY
THAT SPECIFIC DATE.
>>YEAH.
I THANK IT'S COMMITTEE MEMBERS.
ONE MORE POP QUIZ BEFORE WE SIGN
OFF, TOTAL NUMBER OF NOBEL
PRIZES, WHAT PERCENT HAVE BEEN
GIVEN TO WOMEN?
THESE ARE THE ONES IN SCIENCE.
ANYBODY WANT TO TAKE A GUESS?
TOO BAD WE DON'T HAVE POLLS.
>>FIVE.
>>SEVEN PERCENT.
>>CLOSE.
IT'S ACTUALLY UP TO 10% NOW, SO
IT'S A LITTLE BETTER, BUT WE
COULD DO BETTER IN THE FUTURE..
ON THAT NOTE I SEE FLOATING
APPLAUSE HERE.
THANK YOU ALL.
HAVE A GREAT HOLIDAY SEASON.
THE END OF THE SUMMER, GOES BY
SO FAST, SUDDENLY THANKSGIVING.
HAPPY HOLIDAYS.
STAY SAFE.
GET YOUR BOOSTERS IF YOU HAVEN'T
GOTTEN THEM ALREADY, FLU SHOT,
WE'LL SEE YOU IN THE SPRING.