Tip:
Highlight text to annotate it
X
MY PRESENTATION IS A
LITTLE BIT DIFFERENT THAN
ANYTHING YOU HAD BEFORE.
I'M NOT A MEDICAL DOCTOR OR
RESEARCHER, I'M A PATIENT.
I HAVE BEEN A PATIENT FOR A LONG
TIME, FOR 37 YEARS HERE.
THEY WORKED ON ME BECAUSE I HAD
MELANOMA, THYROID CANCER, AND
PROSTATE ISSUES THAT THEY STILL
CAN'T FIGURE OUT WHAT'S GOING
ON.
BUT I'M HERE REALLY ON BEHALF OF
MY FELLOW PATIENTS TO SHARE OUR
EXPERIENCES, OBLIGATIONS AND
SUGGESTIONS WITH YOU WHO ARE
INTERESTED IN -- MEDICAL
RESEARCHERS, THE RESEARCH IS AN
ACUMULATION OF EXPERIENCES AND
SUGGESTIONS OF A NUMBER OF MY
FELLOW NIH PATIENTS A HOT OF
THIS MAY BE ORIENTED TO NIH BUT
I THINK IT'S PROBABLY HOLDING
TRUE FOR RESEARCHING OUTSIDE OF
THE CLINICAL CENTER IN THE NIH.
SO WHY DO PATIENTS PARTICIPATE
IN CLINICAL TRIALS?
THEY'RE REALLY BASICALLY TWO
TYPES OF PATIENTS.
THOSE WHO ARE HEALTHY, WHO WANT
TO PARTICIPATE AND HELP OTHERS
BY CONTRIBUTING TO MEDICAL
RESEARCH AND ADVANCING SCIENCE,
AND THOSE WHO ARE SICK, THOSE
WHO ARE ILL WHO MAY HAVE BEEN
REFERRED BY OUTSIDE PRIVATE
PHYSICIANS OR WHO ARE
SELF-REFERRED.
THAT'S MORE AND MORE THE CASE
THESE DAYS.
IN MANYCACIES THEY'VE X HAWSED
ALL OTHER OPTIONS TO TAKE
ADVANTAGE.
THEY'VE COME TO TAKE ADVANTAGE
AND SOMETIMES THE EXPERIMENTAL
AND SOMETIMES POTENTIALLY RISKY
TREATMENTS, THAT ARE OFTEN
INACCESSIBLE IN ANY OTHER WAY.
AND MANY ARE LOOKING FORWARD,
REALLY LOOKING FOR MEDICAL
MIRACLES.
MY THESIS IS THAT IT'S AN
IMPORTANT AND BENEFICIAL FOR YOU
AS RESEARCHERS TO FORM A
PARTNERSHIP WITH YOUR PATIENT
VOLUNTEERS.
A PARTNERSHIP THAT'S BASED ON
TRUST AND UNDERSTANDING, A
PARTNERSHIP OF PALM BEACHES, ONE
THAT -- PIERS, ONE THAT ADVANCES
MEDICINE AND ALSO ULTIMATELY
SAVES LIVES.
TO BE SUCCESSFUL YOUR RESEARCH
BEIN SOME MEASURE BE DEPENDENT
ON THE COOPERATION OFF YOUR
PATIENT VOLUNTEERS, THEIR
CONFIDENCE ENYOU WILL HELP
ESTABLISH A POSITIVE
RELATIONSHIP, ONE THAT CAN BE
EXTREMELY HELPFUL TO YOU AND FOR
THE OUTCOME OF YOUR STUDY.
AT THE HEART OF THIS PARTNERSHIP
FOR PATIENT AND SCIENTISTS ALIKE
IS THE BASIC OPTIMISM AND HOPE
FOR A POSITIVE OUTCOME.
SO I'VE CREATED AN ACRONYM THAT
HOPEFULLY IS APPRECIATE AS WE
DISCUSS THIS.
AND I CALL THE -- THIS CUE.
C IS FOR COMMUNICATION.
U, UNDERSTANDING AND E, EMPATHY.
COMMUNICATION.
VERBAL AND NON VERBAL SKILLS.
YOU ONLY HAVE ONE CHANCE TO MAKE
AN INITIAL IMPRESSION.
IT'S MY POSITION THAT THE
PRINCIPLE INVESTIGATOR SHOULD BE
PRESENT AND TAKE THE TIME FOR
YOU AND THE INVESTIGATOR TO BE
THOROUGH IN A VERY PRIVATE
SETTING.
YOU MUST EXPLAIN THE ROLE OF
FELLOWS OR INVESTIGATORS AS THE
CASE MAY BE, AND THAT YOU NOT
PUSH FOR AN INITIAL DECISION
FROM THE PATIENT TO MAKE A --
THAT DECISION TO CONTINUE TO
PROCEED WITH THE PROJECT.
YOU NEED TO HAVE A FULL
EXPLANATION OF EVERY ASPECT OF
HOW THE PROCESS WILL WORK, AND
UNDERSTAND THAT PATIENTS MAY BE
INTIMIDATED AND OVERWHELMED
ESPECIALLY IN THEIR INITIAL
MEETING, AND DO ENCOURAGE NOTE
TAKING SO THAT THEY CAN HAVE A
PRETTY GOOD RECALL OF WHAT WAS
DISCUSSED AT THE MEETING.
EXPLAIN THE RISK, POSSIBLE LIFE
STYLE EFFECT CHANGES.
WHILE UNDERGOING TREATMENT, WILL
THEY BE ABLE TO WORK, WILL THEY
TAKE CARE OF THEIR FAMILY?
WHAT WILL BE THE DURATION OF THE
TRIAL.
TRANSPORTATION ISSUES AND
POSSIBLE COST IF ANY, AND SHOULD
THEY BRING A CAREGIVER.
MAKE SURE THIS CONVERSATION
DOESN'T TAKE PLACE IN HALLWAYS.
OR IN THE MIDST OF A BUSY
CLINIC.
AND RESPECT BY ALL MEANS,
RESPECT THEIR PRIVACY.
SITTING WHEN YOU'RE TALKING TO
YOUR PATIENT, CONVEYS A SENSE OF
IMPORTANCE AND A CONVERSATION OF
PEERS.
MAKE EYE CONTACT.
IT CONVEYS A SENSE OF DIRECT
ENGAGEMENT AND THAT THEY HAVE
YOUR COMPLETE ATTENTION AND
FOCUS AND LISTEN INTENTLY, NO
WRITING, NO TYPING.
TODAY, IN THIS WORLD, IT SEEMS
THAT SO MANY CLINICIANS, WHEN
THEY'RE MEETING WITH A PATIENT,
ARE ON THEIR DESKTOP TYPING AWAY
OR LAPTOP, TIMING AWAY AND
HARDLY MAKING -- TYPING AWAY AND
HARDLY MAKING EYE CONTACT WITH
THE PATIENT.
I HAVE TO TELL YOU, FROM
PERSONAL EXPERIENCE, THAT IS
EXTREMELY OFF PUTTING.
LISTEN INTENTLY AND TYPE AFTER
THE VISIT.
AND REVIEW YOUR PATIENTS FILE
AND HISTORY BEFORE, NOT DURING
THE MEETING.
THINK THROUGH IN ADVANCE THE
LIKELY QUESTIONS OR THOSE THAT
SHOULD BE ASKED AND COVER THEM,
EVEN IF THE PATIENT DOESN'T ASK.
UNDERSTAND THAT THE EXPERIENCE
CAN BE INTIMIDATING,
OVERWHELMING, AND GIVE THEM TIME
TO OR SO MUCH AND ENCOURAGE NOTE
TAKING.
BE TOTALLY ACCESSIBLE BETWEEN
CLINICAL VISITS.
YOU CAN BE ASSURED THAT
PARTICULARLY IN THE FIRST VISIT,
BUT PERHAPS ON ENSUING ADVICE AS
WELL, THE PATIENT IS NOT GOING
DO REALLY BE ABLE AT A ABSORB
EVERYTHING THAT YOU SAY.
THERE ARE GOING TO BE QUESTIONS
THAT ARISE AFTER SHE OR HE
LEAVES YOU.
BE TOTALLY ACCESSIBLE BETWEEN
CLINICAL VISITS.
RETURN PHONE CALLS AND E-MAILS
IN A TIMELY FASHION.
BEING ABLE TO STAY IN CONTACT
WITH THE RESEARCHER IS EXTREMELY
IMPORTANT.
AND IF YOU RESPOND QUICKLY IT
DOES SHOW A SENSE YOUR REGARD
FOR THIS PERSON AND INTEREST IN
THEIR WELLBEING.
IF THE SITUATION WARRANTS IT,
KEEP OUTSIDE PRIMARY CARE
PHYSICIANS REGULARLY APPRISED OF
DEVELOPMENTS.
UNDERSTANDING.
LISTENING IS MORE THAN AN NINE
LETTER WORD.
YOU NEED TO ASSESS THE PATIENT
VOLUNTEERS UNDERSTANDING.
DO THEY REALLY GET IT?
BE CAREFUL OF THE OVER-USE OF
MEDICAL JARGON.
TRANSLATE TECHNICAL TERMS.
UNDERSTAND THAT MANY RETURNING
PATIENTS HAVE BEEN COMING FOR
YEARS.
THEIR KNOWLEDGE AND
UNDERSTANDING OF THEIR ILLNESS
AND RESEARCH MAY POSSIBLY BE
GREAT IRRELEVANT YOURS AS A NEW
FELLOW OR RESEARCHER.
IT'S AN INDICATION OF RESPECT
FOR YOU TO RECOGNIZE AND
ACKNOWLEDGE THIS.
RESPECT AND ENCOURAGE PATIENT
VOLUNTEERS OWN RESEARCH.
I'M SURE YOU'RE AWARE THAT
EVERYBODY IS ON THE INTERNET
THESE DAYS, MORE THAN LIKELY
THOSE PATIENTS WHO HAVE THAT
DEGREE OF INTEREST AND
AVAILABILITY OF COMPUTERS WILL
BE ON THEIR GOOGLE SITE AND
LOOKING FOR AS MUCH INFORMATION
AS THEY CAN.
SOME OF THIS RESEARCH IS NOT
GOING TO BE ACCURATE BUT
RESPECTFULLY, CORRECT THEIR
MISINFORMATION AND DIRECT THEM
TO RERYABLE SOURCES.
BE HONESTLY OPTIMISTIC.
NO FALSE HOPE.
BUT ACKENIATE THE POSITIVE
WITHOUT ELIMINATING THE GIVE.
UNDERSTAND PATIENTS --
UNDERSTAND PATIENTS PREVIOUSLY
TREATED IN THE PRIVATE SECTOR
MAY FEEL THE CLINICAL RESEARCH
ENVIRONMENT IS INTIMIDATING AND
OFF PUTTING.
BE NEGATIVE SENSITIVE -- BE
SENSITIVE TO THAT.
MAKE SURE PATIENTS UNDERSTAND
THEY CAN DISCONTINUE PATIENTS --
CAN DISCONTINUE THE TRIAL AT ANY
TIME WITHOUT NEGATIVE
CONSEQUENCES OR MISTREATMENT.
PLEASE, NEVER USE THE FACT THAT
PATIENTS ARE RECEIVING FREE
CARE.
THIS CAN BE OFFENSIVE TO
PATIENTS.
SO RATHER ENFORCE THE IDEA THAT
THEY ARE VERY -- A VERY
COMPONENT TO THE OVERALL PROCESS
OF CLINICAL RESEARCH.
THIS PROCESS COULD NOT BE DONE
WITHOUT THEM.
REMEMBER THE SO-CALLED FREE CARE
IS OFTEN EXPERIMENTAL, AND
SOMETIMES COMES WITH POTENTIAL
RISKS FOR THE PATIENT.
EMPATHY.
THE ACT OF SIMPLY COMING TO MOST
LARGE MEDICAL FACILITIES IN THE
ENTIRE INITIAL EXPERIENCE AND
EVEN SUBSEQUENT VISITS CAN BE
INTIMIDATING AND OVERWHELMING.
ILL PATIENTS CAN BE EXERCISED,
EMOTIONAL.
REMEMBER, FOR SOME, YOU WILL
REPRESENT THEIR LAST HOPE.
SOME PATIENTS HAVE COMPLAINED
THAT BEING TREATED LIKE GUINEA
PIGS OR LAB RATS AND FEEL THAT
THEY'RE ONLY VALUE IS TO PROVIDE
DATA AND RESENT BEING MADE 250
FEEL THIS WAY.
SO GO OUT OF YOUR WAY TO MAKE
YOUR PATIENTS UNDERSTAND AND
BELIEVE THAT YOU TRULY CARE
ABOUT THEIR WELFARE.
TIME MANAGEMENT.
DON'T ACT RUSHED.
THE WORST THING THAT CAN -- I
THINK THAT CAN SET A PATIENT OFF
IS FORA CLINICIAN TO COME IN TO
DEEXAMINING ROOM, SAY I ONLY
AFTER FEW MINUTES TO TALK TO
YOU.
LET'S GET ON WITH THIS.
WHAT COULD BE MORE IMPORTANT AT
THAT TECH MOMENT IN TIME THAN TO
GO FACE TO FACE WITH YOUR
PATIENT.
BE ON TIME.
LONG CLINIC WAITS ARE
DISRESPECTFUL.
AND OFF PUTTING.
AND TO SICK AND ANXIOUS PATIENTS
IT'S EXTREMELY OFF PUTTING.
I CAN GIVE TESTIMONY THAT HAVING
SAT IN SOME CLINICS, WAITED FOR
AN EXTRAORDINARY LONG TIME FOR
MY FELLOW DO COME JOIN ME.
SO PLEASE, PUT THAT IN YOUR BOOK
AND DO MAKE IT AN EXTREME
EFFORT.
DIFFICULT CONVERSATION.
DELIVERING BAD NEWS.
EVERY PATIENT IS A VERY REAL
UNIQUE PERSPECTIVE WITH GENUINE
FEARS AND HOPES AND NOT JUST AN
EXPERIMENT IN YOUR LAB.
A NEGATIVE DIAGNOSIS CAN INCLUDE
THE PERCEPTION THAT LIFE HAS ONE
HAS LIVED IT IS GONE FOREVER.
THERE MAY BE LITTLE HOPE FOR THE
FUTURE.
IT MAY REQUIRE A STRETCH BUT I
SUGGEST THAT YOU TRY TO STRETCH
TO PUT YOURSELF IN THE PATIENT'S
SHOES.
IT'S CRITICAL FOR YOU TO BE
UNDERSTANDING AT THIS
POTENTIALLY VERY, VERY SENSITIVE
MOMENT.
PERHAPS THE REASON THAT THE
TRIAL HAS TO BE CANCELED IS
BECAUSE THE TREATMENT WAS NOT
EFFECTIVE OR BECAUSE THE SEVERE
DEBILITATING SIDE EFFECTS WERE
OVERWHELMING.
OR THE TEST THAT THE PATIENT HAS
TAKEN IS -- HE IS NOT OR SHE IS
NOT COMPLYING.
WHATEVER DEREASON, CANCELLATION
OF A TRIAL CAN BE DEVASTATING.
SO FIND A PRIVATE SETTING.
FIND SOMEPLACE REALLY OUT OF THE
WAY, QUIET, WHERE VERY
CONFIDENTIAL AND SENSITIVE
CONVERSATION CAN BE HAD.
MAKE SURE THAT THE PROPER STAFF
IS THERE.
IN ALLOCATIONS IF AT ALL
POSSIBLE, THE PRINCIPLE
INVESTIGATOR SHOULD BE THERE.
ANY ONE THAT YOU MAY FEEL IS
IMPORTANT DO THE PATIENT TO --
TO THE PATIENT TO BE PRESENT AND
PRESENT THE CASE TO HIM OR HER.
ALLOW NECESSARY TIME.
IT'S AWFULLY IMPORTANT AT THIS
MOMENT PARTICULARLY AT THIS
MOMENT THAT YOU GIVE ALL THE
TIME NECESSARY TO GIVE THE
PATIENT WHAT SHE OR HE NEEDS TO
HEAR IN THE MOST POSITIVE, IF
POSSIBLE, FASHION POSSIBLE.
AND WHEN THIS -- WHEN BAD NEWS
HAS TO BE GIVEN DO ADVISE THE
PATIENT IN ADVANCE TO BRING
SOMEBODY WITH THEM.
PERHAPS A CAREGIVER, PERHAPS A
RELATIVE.
BUT TO BE THERE WITH THEM AT
THIS VERY TRAUMATIC MOMENT.
BE CAREFUL WITH YOUR CHOICE OF
LANGUAGE A COMPLAINT THAT SOME
CANCER SURVIVERS HAVE VOICED IS
THE PHRASE THAT SOME PHYSICIAN
AND MANY OTHERS MAY HAVE USED
FROM TIME TO TIME, W YOU FAILED
YOUR CHEMO.
OR ANOTHER TREATMENT.
AND -- BECAUSE BY MOST
REASONABLE AMERICANERS THE
FAILURE -- MEASURES, THE FAILURE
OF THE TREATMENT IS THE
TREATMENT, NOT THE PATIENT IS AT
FAULT.
HEARING THE PHRASE UTTERED CAN
CONTRIBUTE MIGHTILY TO
CONTINUING BAD NEWS EVEN WORSE.
THIS TIME OF PEJORATIVE LANGUAGE
SHOULD NEVER BE USED AN SHOULD
BE FORBIDDEN.
SO PLEASE, UNDERSTAND THAT.
IT'S IMPORTANT ALSO TO HAVE AN
ADVANCE PREPARED WHAT OTHER
POSSIBLE OPTIONS ARE.
IF THERE ARE OTHER STUDIES IN
OTHER FACILITATES AROUND THE
COUNTRY, MAKE SURE THAT THEY
KNOW ABOUT THEM.
IF THIS ARE OTHER DRUGS, ANY
OTHER POSSIBILITIES, THIS IS THE
TIME TO TALK TO THE PATIENT AND
MAKE SURE THAT SHE OR HE
UNDERSTANDS THAT THERE ARE OTHER
OPTIONS.
MAKE THE PATIENT AWARE THAT
THERE IS SUPPORTIVE CARE.
FOR EXAMPLE, PSYCHOLOGIST,
SOCIAL WORKERS, SPIRITUAL
PROFESSIONALS.
ALL THIS NEEDS TO BE ARRANGED IN
ADVANCE SO THAT YOU'RE PREPARED
FOR WHATEVER EVENTUALITY,
WHATEVER REACTION THIS PATIENT
MAY HAVE.
AND WHEN IT'S APPROPRIATE, MAKE
SURE THAT THE PHYSICIAN AT HOME
UNDERSTANDS WHAT THE SITUATION
IS SO THAT SHE OR HE CAN BE
PREPARED TO DEAL WITH A PATIENT
WHEN THEY RETURN TO THEIR HOMES.
BASICALLY, WHAT I'VE SAID HERE
IS THAT WE TAKE MY CUE, AND THAT
MAKE COMMUNICATION UNDERSTANDING
AND EMPATHY CARDINAL ELEMENTS OF
YOUR PARTNERSHIP RELATIONSHIP
WITH YOUR PATIENT VOLUNTEER.
AND NEVER FORGET, NEVER FORGET
THAT IN ADDITION TO BEING YOUR
PATIENT, AN PERHAPS JUST ONE
ELEMENT IS YOUR RESEARCH THAT WE
PATIENTS ARE HUMAN, VERY REAL,
WITH SENSITIVITIES, CONCERNS,
AND FEELINGS.
WHEN WE WERE PRESENTING THIS --
I PRESENT THIS TO THE NEW
FELLOWS HERE EVERY YEAR.
AND WE HAVE PATIENTS WHO GATHER
HERE TWICE A YEAR TO BE PART OF
A GROUP CALLED A PATIENT
ADVISORY GROUP.
DR. GALLIN HAS ASKED WE PATIENTS
COME TOGETHER AND DISCUSS WITH
HIM WHAT ISSUES WE SEE AS WE GO
THROUGH THE CLINICAL TRIALS
HERE.
AND I ASKED AT ONE OF THE
MEETINGS IF ANY OF MY FELLOW
PATIENTS HAD ANY COMMENTS THAT
THEY WANTED ME TO CONVEY TO THE
FELLOWS.
AND I THINK IT'S APPROPRIATE FOR
ME TO READ TO YOU THE LETTER
THAT SHE WROTE TO ME AND ASKED
TO BE PRESENTED TO HER FELLOWS.
IT GOES LIKE THIS.
DEAR FELLOWS.
WE ARE HONORED TO BE UNDER YOUR
CARE.
WE SEE YOU AS INCREDIBLE CURIOUS
PEOPLE, SOME ADVANTAGE TO BE
NAMED A FELLOW AT THE NIH.
WE WANT YOU TO KNOW WE PRESENTER
YOUR INTELLECTUAL FORITUDE AND
LACK OF SELFISHNESS.
BUT WE ALSO WANT YOU TO
UNDERSTAND THAT YOUR NOT OUR
FIRST SHOPPING EXPERIENCE.
WE HAVE BEEN POKED, PRODDED,
TESTED BY OTHERS, YOUR
COLLEAGUES, YOUR ELDERS, YOUR
NURSES, NOW, HOWEVER, ARE NEW TO
US.
WE WANT YOU TO KNOW WE ARE NOT
OUR DISEASE.
YES, WE UNDERSTAND THAT YOU LOVE
INVESTIGATING.
INVESTIGATING THE DISEASE.
AND HAVE AN URGENT SKY FOR
INVESTIGATION.
BUT WE ARE MORE THAN OUR
DISEASE.
WE ARE GRANDMOTHERS, WORRIED
PARENTS, FRIGHTENED CHILDREN, WE
HAVE HOPE, LOVE, AND COMPASSION.
WE SUFFER.
WE WORRY.
WE WORRY A LOT.
WE ALLOW YOU TO BE INTIMATE WITH
OUR INNER WORKERS, AND DO IT
OVER AND OVER AND OVER AGAIN.
FOR THOSE OF US WHO HAVE COME TO
THE NIH TIME AND TIME AGAIN, IF
WE'RE LUCKY, WE GET TO REPEAT
OUR STORY OVER AND OVER AGAIN.
SO WHEN YOU'RE ABLE, MAKE THE
TIME TO READ UP ON US.
BE INFORMED.
WE KNOW YOU LIKE TO BE INFORMED.
YOU TOUCH THE PETE RIDISH OF OUR
LIVES.
WHY NOT READ ABOUT US FIRST?
A PHYSICIAN ONCE WISELY TOLD ME,
KAREN DIAGNOSES IS 90% HISTORY.
I'VE NEVER FORGOTTEN THAT.
WE'RE THE SUM OF OUR PARTS AND
YOUR RECOGNITION OF OUR
WHOLENESS MATCHES IN THE HEALING
PROCESS, AS WELL AS THE SURING
PROCESS.
SO CARRY ON WITH HOPE, LOVE, AND
COMPASSION, BRINGING THOSE
QUALITIES TO THE EXAM ROOM WILL
EPLIGHTEN AND ENRICH YOUR
EXPERIENCE, TOO.
SHE SIGNS THE LETTER KAREN.
SISTER, SHE'S AN RN, BY THE WAY.
MS.
SISTER, MOTHER, GRANDMOTHER,
FRIEND, NURSE, PATIENT,
SURVIVOR.
TO ME IT IS AT THIS THE MOST
MEANINGFUL STATEMENT I COULD
LEAVE YOU WITH TO UNDERSTAND HOW
WE FEEL AND PATIENTS GOING UNDER
YOUR CARE.
AND BE PARTICIPATING WHICH IN
YOUR TRIALS.
SHEATHY VERY MUCH FOR LISTENING.
AND -- THANK YOU VERY MUCH FOR
LISTENING.
I WISH YOU WELL.
AND THANK YOU FOR YOUR INTEREST
IN BECOMING INVESTIGATORS.
ANY QUESTIONS?
THANK YOU AGAIN.
[APPLAUSE]
GOOD EVENING.
I AM KATE STONEY, A PROGRAM
DIRECTOR AT THE NATIONAL HEART
LUNG AND BLOOD INSTITUTE.
AND AT THE NHLBI I OVERSEE A
DIVERSE PORTFOLIO OF CLINICAL
TRIALS THAT REALLY SPAN THE
ENTIRE SPECTRUM OF THE RESEARCH
SPECTRUM, THE TRANSLATIONAL
SPECTRUM.
AND I HAVE BEEN ASKED TO COME
AND TALK TO YOU A LITTLE BIT
TODAY ABOUT WHAT YOU NEED TO
THINK ABOUT WHEN SELECTING
PARTICIPANTS TO ENGAGE IN YOUR
RESEARCH STUDIES.
AND I'M REALLY DELIGHTED TO DO
THAT.
LET ME JUST START BY, I THINK --
JERRY HAS LEFT.
BY I WANTED TO THANK HIM AND
REALLY ENDORSE THE COMMENTS THAT
HE MADE.
I THINK THEY'RE REALLY HEARTFUL
COMMENTS, SOMETHING THAT ALL OF
US AS RESEARCHERS REALLY NEED
250 HEAR.
AND LIVE AS WE GO FORTH WITH OUR
RESEARCH PROGRAMS.
AND IN THAT VAIN, I -- YOU MIGHT
NOTICE IN MY SLIDES I REALLY
DON'T REFER TO PATIENT BUT
RATHER PARTICIPANTS BECAUSE I
REALLY LIKE THIS NOTION THAT THE
PEOPLE THAT PARTICIPATE IN OUR
RESEARCH STUDIES ARE
PARTNERSHIPS.
RIGHT?
THEY'RE PARTNERS WITH US AS
RESEARCHERS, IDENTIFYING THEM AS
PARTICIPANTS UNDERSCORES THAT
PARTNERSHIP.
SOMETIMES I MIGHT -- I MIGHT
SLIP AND CALL THEM PATIENTS BUT
I REALLY MEAN TO CALL THEM
PARTICIPANTS.
THAT IS HOW I SEE THEM.
OKAY.
NOW I'LL FIGURE OUT HOW TO DO
THIS.
OKAY.
SO IT'S AN INTERESTING TOPIC TO
THINK ABOUT.
WHEN YOU ARE UNDERTAKING A
RESEARCH PROGRAM, A STUDY THAT
YOU WANT TO CONDUCT, AND YOU'RE
THINKING BROUGHT RESEARCH
PARTICIPANTS AND WHO YOU WANT TO
SELECT, YOU MIGHT THINK RIGHT
OFF THE BAT, THIS IS NOT A HARD
THING TO DO.
RIGHT?
SO LET'S SAY YOU'RE INTERESTED
IN DIABETES, SO YOUR GOING TO
ENROLL IN YOUR STUDY -- THE
PARTICIPANTS ARE GOING TO BE
THOSE THAT HAVE DIABETES.
THAT SEEMS TO BE OBVIOUS.
BUT I'D LIKE TO KIND OF DEVELOP
DEEPER TO GET TO SOME OF THE
MORE INTRICATE ASPECTS OF
PARTICIPANT SELECTION TO TALK
ABOUT SOME OF THE
CHARACTERISTICS TO REALLY FIGURE
OUT WHAT ARE THE THINGS THAT WE
NEED TO THINK ABOUT CAREFULLY
WHEN WE'RE THINKING ABOUT WHO WE
WANT TO PARTICIPATE IN OUR
STUDIES.
SO SOME OF THE THINGS THAT YOU
MIGHT HAVE QUESTIONS ABOUT, IF
YOU THINK A LITTLE BIT MORE
DEEPLY, IS NOT ONLY HOW YOU
DECIDE WHO TO PARTICIPATE IN
YOUR -- WHO YOU WANT
PARTICIPATING IN YOUR STUDY, BUT
YOU NEED TO ONGOING ABOUT HOW
GENERALIZABLE THE EFFECTS THAT
YOU FIND IN YOUR STUDY, HOW
GENERALIZABLE DO YOU WANT THEM
TO BE TO A BROADER POPULATION?
AND THE ANSWER TO THAT QUESTION
IS NOT A SINGLE AMOUNTS.
IT REALLY DEPENDS ON A LOT OF
FACTORS.
WE'LL TALK ABOUT THOSE BLOOD
PRESSURE HOW DO YOU KNOW THAT
YOUR STUDYING WHO YOU THINK YOU
WANT TO STUDY?
WE'LL TALK ABOUT SOME OF THOSE
ISSUES.
AND REALLY IMPORTANTLY, HOW DO I
MATCH THE CHARACTERISTICS OF THE
PARTICIPANTS THAT YOU ENROLL IN
YOUR STUDIES TO THE OUTCOMES
THAT YOU REALLY WANT TO MEASURE?
THIS IS A CRITICAL FACTOR THAT I
REALLY WANT TO UNDERSCORE AS WE
WALK THROUGH THE STUDY.
AND LET ME JUST SAY NOW THAT
THERE IS AN ADDITIONAL LECT
LECTURE THAT DEALS WITH
PARTICIPANT CHARACTERISTICS IN
TERMS OF INCLUSION OF
UNDER-REPRESENTED MINORITIES IN
WOMEN IN STUDIES.
AND IT'S ARCHIVED ON THE IAPPCR
ARCHIVES.
BY DR. MIRIUM COALTY, I VERY
STRONGLY ENCOURAGE YOU TO LISTEN
TO THAT LECTURE.
IT'S VERY GOOD.
SHE'S AN EXPERT, EXTREMELY WELL
VERSED IN NOT ONLY THE
REGULATIONS BUT THE ETHICAL
ASPECTS.
SO I'M NOT GOING TO TOUCH ON
THOSE, THOUGH ISSUES ARE DEALT
WITH IN HER LECTURE.
BUT I DO WANT TO TOUCH ON THESE
OTHER ISSUES.
SO WE'RE GOING TO START OFF
TALKING ABOUT THE REASONS THAT
YOU WANT TO THINK ABOUT
CHARACTERISTICS OF YOUR
PARTICIPANTS AND HOW TO SELECT
THOSE CHARACTERISTICS.
I WANT TO SPEND A LITTLE BIT OF
TIME TALKING ABOUT THE
TRANSLATIONAL SPECTRUM OF
CLINICAL TRIALS.
AND YOU KNOW SOME OF THIS
ALREADY.
JUST BY VIRTUE OF THE FACT THAT
YOU'RE HERE.
BUT I WANT TO TALK ABOUT THAT
TRANSLATIONAL SPECTRUM
SPECIFICALLY WITH REGARD TO HOW
IT IMPACTS YOUR PARTICIPANTS
SELECTION CRITERIA.
WE'RE GOING TO TOUCH ON
INDENVERSES EXTERNAL VALIDITY.
AND YOU WILL HEAR THIS AGAIN IN
THIS COURSE.
AND YOU'LL HEAR IT SPECIFICALLY
WHEN YOU TALK ABOUT SIGNIFICANCE
TESTING, WHEN YOU TALK ABOUT
ANALYTIC STRATEGIES, AND OTHER
DESIGN ISSUES.
I'M NOT GOING TO TALK ABOUT THE
ANALYTIC PART HERE.
I REALLY WANT TO TALK ABOUT
CONCEPTUALLY WHAT WE MEAN BY
INTERNAL AND EXTERNAL VALIDITY,
AND HOW THAT IMPACTS OUR
DECISIONS REGARDING WHO WE
ENROLL IN OUR STUDIES.
I WANT TO TALK THROUGH SOME OF
THE FACTORS TO THINK ABOUT, THE
CHARACTERISTICS TO THINK ABOUT.
AND HOW TO THINK ABOUT THOSE IN
RELATIONSHIP TO YOUR TRIALS.
I'M GOING TO GIVE YOU AN EXAMPLE
FROM A REALLY INTERESTING STUDY
THAT IS GOING TO ILLUSTRATE MANY
OF THE FACTORS THAT WE'RE
LOOKING AT.
SO LET'S GET STARTED.
SO SOME OF THE REASONS TO THINK
ABOUT PARTICIPANTS SELECTION.
ONE IS THAT IT'S GOING TO -- IF
YOU THINK ABOUT IT CAREFULLY, IT
WILL HELP YOU CLARIFY THE
QUESTION THAT YOU WANT TO ASK.
AND THE STUDY DESIGN THAT'S MOST
APPROPRIATE FOR THAT QUESTION.
AND THE WAY THIS WILL HAPPEN IS
BY UNDERSTANDING WHERE YOUR
SCIENCE, THE QUESTION THAT
YOU'RE ADDRESSING, FITS ON
WHAT'S CALLED THIS RESEARCH
CONTINUUM, OR YOU MIGHT REFER TO
IT AS A TRANSLATIONAL SPECTRUM.
BUT THIS IS THE COURSE OF
SCIENCE.
HOW CLINICAL TRIALS MOVE.
NOT A SINGLE TRIAL BUT THE
SCIENCE BEHIND A SINGLE
QUESTION.
IN TERMS OF THE TRIALS THAT ARE
RUN.
FOR EXAMPLE, WE START IN
TELEPHONING ANY KIND OF TRIALS,
WE START WITH PHASE ONE TRIALS.
AND PHASE ONE TRIALS ARE REALLY
EARLY STAGE RESEARCH THEY'RE
DEALING WITH.
SAFETY ISSUES, DEALING DOSE
RANGING QUESTIONS.
THESE PHASE ONE TRIALS ARE VERY,
VERY SMALL.
BECAUSE THEY'RE DEALING WITH
ISSUES THAT YOU DON'T NEED A LOT
OF PARTICIPANTS TO DEAL WITH.
YOU REALLY WANT TO KNOW WHAT THE
SAFETY CHARACTERISTICS ARE OF
YOUR INTERVENTION.
SO THEY'RE SMALL TRIALS.
AND THEY SOMETIMES, OFTEN TIMES,
ARE HEALTHY INDIVIDUALS.
IF YOU'RE TEARGAS, IF YOU'RE
JUST STARTING TO DEVELOP -- IF
YOU'RE AT THE PHASE AND JUST
STARTING TO DEVELOP AN
INTERVENTION, YOU DON'T KNOW IF
IT'S SAFE, YOU DON'T KNOW THE
DOSE, HOW MUCH OF THE
INTERVENTION YOU NEED DO DELIVER
IN ORDER TO HAVE THE OUTCOME
YOU'RE LOOKING FOR, IF YOU'RE IN
THAT PHASE, THE CHARACTERISTICS
OF YOUR PATIENT POPULATION ARE
GOING TO BE SPECIFIC TO THAT AND
VERY DIFFERENT THAN THEY WOULD
BE IN, SAY, A PHASE 2 TRIAL.
FACE 2 TRYING EFFICACY TRYING.
THESE ARE TRAILS WHERE YOU'RE
REALLY ASK THE QUESTION UNDER
VERY HIGHLY CONTROLLED
CONDITIONS.
DOES MY INTERVENTION THAT I HAVE
DEVELOPED, DOES MY INTERVENTION
DO ANYTHING?
IS THERE A SIGNAL ANYWHERE?
AND LET ME SORT OF SPECIFY WHAT
I MEAN BY HIGHLY CONTROLLED
SITUATIONS.
WHAT I MEAN BY THAT IS THAT YOU
HAVE REAL CLARITY AND -- AS AN
EXPERIMENTER, A RESEARCHER,
YOU'RE IMPOSING A LOT OF CLARITY
AND CONTROL ON THE
CHARACTERISTICS OF YOUR
PATIENT -- OF YOUR PARTICIPANT
POPULATION.
OF THE ENVIRONMENT IN WHICH YOUR
INTERVENTION IS BEING DELIVERED.
THE PEOPLE WHO DELIVER THE
INTERVENTION.
YOU'RE REINING THAT CONTROL IN.
WHAT YOU WANT DO KNOW IS UNDER
THESE VERY TIGHTLY CONTROLLED
SITUATIONS, IS THERE A SIGNAL?
IS THERE SOME INDICATION THAT
YOUR INTERVENTION IS DOING
SOMETHING.
>> IN SHOWS SITUATIONS THE
PATIENT CHARACTERISTICS ARE
GOING TO BE VERY WELL DESCRIBED.
AND YOUR PATIENTS -- AREN'T
GOING TO LOOK -- THERE COULD CAN
BE A LOT OF VARIABILITY.
YOU WANT TO DECREASE THE
VARIABILITY SO YOU CAN TELL
WHETHER THERE IS A SIGNAL.
DOES THROUGH MAKE SENSE?
YES, GO?
OKAY.
AS YOU MOVE FORWARD, LET'S SAY
YOU GOT A SIGNAL.
AND UNDER A PHASE 2 EFFICACY
TRIAL, YOU HAVE SOME INDICATION
THAT YOUR INTERVENTION IS
EFFICACIOUS. YOU, THEN, MIGHT
MOVE GORD TO A PHASE 3 TRIAL
WHICH IS AN EFFECTIVENESS TRIAL.
AND EFFECTIVENESS TRIALS ARE
THOSE WHERE YOU TAKE WHAT WORKS
UNDER HIGHLY CONTROLLED
SITUATIONS AND YOU TEST IT IN A
BROADER CONTEXT.
SO YOU MIGHT, INSTEAD OF TESTING
IT IN YOUR -- IN YOUR ACADEMIC
MEDICAL CENTER, IN THE CRC, YOU
MIGHT GO BEYOND THAT AND TEST IT
IN SOME COMMUNITIES HEALTH
CENTERS.
MAYBE YOU'LL DESIT IN THE -- A
MUNCH OF *** OFFICES.
IT COULD BE IN ANY NUMBER OF
SITUATIONS BUT YOU'RE BROADENING
IT TO SEE IF WHAT WORKS IN
HIGHLY CONTROLLED SETTINGS WORKS
IN MORE REAL WORLD SETTINGS.
OF COURSE THAT'S WHERE WE WANT
TO TAKE OUR INTERVENTIONS.
WE WANT THEM TO WORK IN THE REAL
WORLD.
WHERE WE REALLY DON'T, AS
RESEARCHERS, WE REALLY DON'T
HAVE CONTROL.
WE DON'T KNOW WHO IS GOING TO BE
DELIVERING THE INTERVENTION.
WE DON'T KNOW THE CONDITIONS
UNDER WHICH THOSE INTERVENTIONS
ARE BEING DELIVERED.
AND WE KNOW THAT PATIENTS ARE
GOING TO BE EXTREMELY VARIABLE
IN TERMS OF THE -- THEIR
INDIVIDUAL CHARACTERISTICS.
SO PHASE 3 TRIALS ARE MORE
LIKELY TO MIMIC THOSE REAL WORLD
SITUATIONS.
SO BY NECESSITY IF YOU'RE DOING
A PHASE 3 TRIAL, THEN YOU'RE
GOING TO LOOSEN THE CONTROL THAT
YOU HAVE SO YOU'RE GOING TO
LOOSEN UP THE PATIENT
CHARACTERISTICS.
THAT IS YOU'RE MORE LIKELY TO
TAKE MORE INDIVIDUALS THAT VARY
WITH REGARD TO A WHOLE NUMBER OF
FACTORS.
THEN THERE ARE PHASE 4 STUDIES
AS WELL THAT ARE EVEN BROADER.
THESE ARE COMMUNITY BASED
STUDIES WHERE YOU GO OUT INTO
THE COMMUNITY.
AS A RESEARCHER, YOU HAVE VERY
LITTLE CONTROL.
YOU MAY HEAR THIS -- THESE
PHASES REFERRED TO AS INSTEAD OF
PHASE ONE, PHASE TWO, AS T1, T2
TRANSLATION 1, TRANSLATION 2.
THERE IS SOME SMALL DIFFERENCES
BETWEEN PHASE 1 AND PHASE 2,
TRANSLATION 1, TRANSLATION 2.
BUT THEY REALLY DO PARALLEL EACH
OTHER.
SO IF YOU HEAR TRANSLATION 2,
THAT MEANS SOMETHING SIMILAR TO
AN EFFICACY TRIAL.
OKAY.
SO WHAT I'M HOPING IS THAT IF
UNDERSTANDING THIS SORT OF
RESEARCH CONTINUIAN, YOU GET THE
MESSAGE THAT THE KIND OF
CHARACTERISTICS OF YOUR PATIENT
POPULATION AND HOW CLEARLY YOU
OUTLINE WHAT THOSE
CHARACTERISTICS ARE IS GOING TO
BE DEPENDENT, IN PART, ON WHERE
YOUR PARTICULAR SCIENCE FITS ON
THIS TRANSLATIONAL SPECTRUM.
IN ORDER TO KNOW THAT, YOU HAVE
TO REALLY KNOW THE SCIENCE.
YOU HAVE TO KNOW THE LITERATURE,
YOU HAVE TO UNDERSTAND WHAT'S
BEEN DONE BEFORE YOU.
AND YOU HAVE TO UNDERSTAND WHERE
YOU WANT TO BE GOING.
OTHER REASONS TO THINK ABOUT
PARTICIPANT SELECTION, THE
CHARACTERISTICS OF YOUR STUDY
PARTICIPANTS ARE GOING TO
DETERMINE HOW GENERALIZABLE YOUR
FINDINGS ARE.
WE KIND OF GOT A PEAK OF THAT IN
THE LAST SLIDE WHEN WE TALKED
ABOUT THE CONTINUUM, AND THE
FACT THAT WE'RE MOVING MORE AND
MORE TO A MORE GENERALIZABILITY
AS YOU MOVE THROUGH THE
TRANSLATIONAL SPECTRUM.
LET ME OFFER ANOTHER WAY OF
THINKING ABOUT THIS.
AND THAT WAY IS TO THINK ABOUT
INTERNAL INVESTORS VERSES
EXTERNAL VALIDITY.
I WANT TO THINK ABOUT THIS AND
TALK ABOUT THIS IN VERY
CONCEPTUAL TERMS.
THERE ARE SOME ANALYTIC ANALOGS
TO THIS.
AND YOU'LL TALK ABOUT THOUGH AND
FIGURE OUT WHEN YOU GET TO THAT
POINT IN THE SERIES HERE, YOU'LL
UNDERSTAND MORE HOW YOU MAKE
THAT ANALYTIC BALANCE.
I WANT TO REALLY THINK OF IT AS
A HIGHER LEVEL RIGHT NOW.
AND THINK OF IT IN TERMS OF
CONCEPTUAL UNDERSTANDING.
SO INTERNAL AND EXTERNAL
VALIDITY ARE A BALANCE.
IF YOU HAVE HIGH INTERNAL
VALIDITY, YOU HAVE LOWER
EXTERNAL VALIDITY, AND VICE
VERSA.
SO IT'S A BALANCE.
YOU HAVE TO CHOOSE HOW MUCH OF
EACH YOU'RE WILLING TO LIVE WITH
FOR THE PARTICULAR STUDY THAT
YOU ARE CARING OUT.
OKAY?
ALL RIGHT.
SO HERE IS A LITTLE BIT MORE
WHAT THEY ARE.
SO EXTERNAL VALIDITY REALLY
REFERS TO THE EXTENT TO WHICH
YOU CAN GENERALIZE YOUR
FINDINGS, BEYOND THE SITUATION
THAT YOU -- THE RESEARCH STUDY
THAT YOU JUST CONDUCTED.
SO IF YOU HAVE HIGH EXTERNAL
VALIDITY, THAT MEANS THAT YOU
CAN MORE EASILY GENERALIZE
ACROSS PARTICIPANTS, ACROSS
SITUATIONS, ACROSS PROVIDERS,
ACROSS TIME, A PLACE.
IT'S MORE GENERALIZABLE
GLOBABLY.
YOU MIGHT THINK, THAT SOUNDS G
WHY DON'T WE ALWAYS JUST HAVE
REAL HIGH EXTERNAL VALIDITY?
THAT SOUNDS LIKE WHAT WE'RE
REALLY AIMING FOR IN THE END.
WE WANT TO BE ABLE TO GENERALIZE
ACROSS A LARGE GROUP OF
INDIVIDUALS IN SITUATIONS.
THE PROBLEM WITH THAT IS THAT
THERE IS ALWAYS A RISK.
ALWAYS A RISK FOR EITHER HIGH
EXTERNAL OR HIGH INTERNAL
VALIDITY.
IF YOU HAVE HIGH EXTERNAL
VALIDITY, THE RISK IS THAT
YOU'RE GOING TO MAKE AN ERROR IN
YOUR ANALYSIS.
AND THE ERROR THAT YOU'RE GOING
TO MAKE WITH HIGH EXTERNAL
VALIDITY, IS THAT YOU'RE GOING
TO THINK YOU SEE AN EFFECT
THAT'S NOT REALLY THERE.
YOU'RE GOING TO HAVE A FALSE
POSITIVE.
SO THE HIGHER YOUR EXTERNAL
VALIDITY, THE HIGHER THE
LIKELIHOOD IS THAT YOU'LL MAKE
THAT ERROR.
OKAY?
ANALYTICALLY YOU'LL UNDERSTAND
THIS LATER.
RIGHT NOW, CONCEPTUALLY I WANT
YOU TO UNDERSTAND IT.
SO ON THE OTHER END OF THE STICK
TREMENDOUS, ON THE BALANCE IS
INTERNAL VALIDITY.
WE TALK ABOUT INTERNAL VALIDITY,
BEING ABLE TO MAXIMIZE THE
AMOUNT OF CONTROL THAT YOU HAVE.
THIS IS CONTROL OVER ALL KINDS
OF THINGS.
CONTROL OVER YOUR PARTICIPANTS,
COLE OVER HOW INTERVENTION IS
DELIVERED, CONTROL UNDER THE
SITUATION IN WHICH AN
INTERVENTION IS DELIVERED.
IT ENABLES YOU TO CONTROL MANY
SOURCES OF BIAS, MANY
EXPERIMENTER AND -- AND
MEASUREMENT EFFECTS.
SO THIS IS THAT HIGH CONTROL END
OF THINGS.
WELL, THAT SOUNDS PRETTY GOOD,
TOO.
BUT WHEN YOU HAVE HIGH INTERNAL
VALIDITY, THE RISK IS THAT
YOU'RE GOING TO MAKE THE ERROR
OF A DIFFERENT SORT WITH HIGH
INDENVALIDTY, THE RISK IS YOU'RE
MORE LIKELY TO MAKE A FALSE
NEGATIVE ERROR.
THAT IS NOT SEEING AN EFFECT
THAT REALLY IS THERE.
SO YOU CAN SEE NOW YOU NEED TO
BALANCE HIGH EXTERNAL WITH HIGH
INTERNAL VALIDITY.
AND THAT BALANCE IS GOING TO
LOOK DIFFERENT, DEPENDING ON THE
QUESTION THAT YOU'RE ASKING, AND
WHERE THAT QUESTION SITS ON THAT
TRANSLATIONAL SPECTRUM.
SO YOU MIGHT GUESS THAT EARLY IN
THAT TRANSLATIONAL PHASE, YOU
MIGHT WANT HIGHER INTERNAL
VALIDITY.
THAT'S WHERE YOU WANT A LOT OF
CONTROL.
AND YOU'RE WILLING TO LIVE WITH
FALSE NEGATIVES.
YOU'RE WILLING TO NOT SEE AN
EFFECT THAT'S REALLY THERE.
AS LONG AS YOU HAVE A LOT OF
CONTROL.
AS YOU MOVE ALONG THE
TRANSLATIONAL SPECTRUM, THOUGH,
THE BALANCE TIPS IN THE OTHER
WAY.
AND YOU'RE INCREASINGLY MORE
WILLING TO INCREASE YOUR
EXTERNAL VALIDITY SO THAT YOU
CAN GENERALIZE ACROSS
PARTICIPANTS, ACROSS SITUATIONS
AROUND PROVIDERS, THERE YOU'RE
MORE WILLING TO LIVE WITH THE
FALSE POSITIVE.
SO YOU MAKE THAT DECISION BASED
ON YOUR INDIVIDUAL QUESTION THAT
YOU'RE ASKING.
SO YOU HAVE TO THINK REALLY
CAREFULLY ABOUT WHERE IS MY
QUESTION SITTING?
WHAT DO WE KNOW.
WHAT'S MOST IMPORTANT TO ME?
WHEN YOU MAKE THAT
DETERMINATION, YOU'RE REALLY
TRYING TO STRIKE THE RIGHT
BALANCE FOR YOUR PARTICULAR
QUESTION.
AND I LIKE TO THINK ABOUT THIS
IN TERMS OF WHAT DO I WORRY
ABOUT THE MOST?
DO I WORRY ABOUT FALSE NEGATIVES
OR POSITIVES?
FOR THE QUESTION I'M ASKING, FOR
THE PATIENT, PARTICIPANTS, WHAT
DO I WORRY ABOUT MOST.
THAT GUIDES YOU NOT ONLY WHERE
YOU ARE ON THE TRANSLATIONAL
SPECTRUM BUT WHICH KIND OF
VALIDITY YOU'RE MORE WILLING TO
LIVE WITH.
THE TYPE OF VALIDITY THAT YOU'RE
MORE WILLING TO LIVE WITH IS
GOING TO HELP DETERMINE HOW
TIGHTLY CONTROLLED YOU WANT
TO -- NOT ONLY HAVE ALL ASPECTS
OF YOUR STUDY, BUT HOW TIGHTLY
CONTROLLED YOU WANT YOUR
PARTICIPANT SELECTION FACTORS TO
BE.
OKAY.
FEASIBILITY.
THE PARTICIPANT SELECTION
FACTORS ARE GOING TO IMPACT YOUR
FEASIBILITY.
NOW, YOU WANT TO SELECT
PARTICIPANTS AND MAKE THE
DETERMINATION ABOUT WHAT FACTORS
ARE IMPORTANT BASED ON SCIENCE.
BUT THE REALITY IS THAT YOU HAVE
A BEAUTIFUL SCIENTIFIC AWARD
WINNING QUESTION.
IF IT'S NOT FEASIBILITY, IF YOU
CAN'T IMPLEMENT IT, THEN IT'S
NOT HELPFUL.
SO YOU DO NEED TO THINK ABOUT
FEASIBILITY WHEN YOU THINK ABOUT
THESE KINDS OF ISSUES.
FEASIBILITY REALLY MEANS
DIFFERENT THINGS.
FIRST OF ALL, DO YOU HAVE ACCESS
TO THE PARTICIPANTS WITH THE
KIND OF CRITERIA YOU'RE LOOKING
FOR, WHETHER THEY'RE DEMOGRAPHIC
OR CLINICAL.
DO YOU HAVE ACCESS TO THAT
POPULATION?
IN ADDITION, YOU HAVE TO THINK
ABOUT THE PARTICIPANTS
THEMSELVES.
AND BASED ON THE SELECTION
CRITERIA THAT YOU OF
DETERMINED -- YOU HAVE
DETERMINED, ARE YOU GOING TO BE
ABLE AND ARE THEY GOING TO BE --
ARE THE RESPONSIBILITIES GOING
TO BE ABLE AND WILLING TO
PARTICIPATE IN YOUR STUDY?
ARE THEY GOING TO BE ABLE AND
WILLING TO ADHERE TO YOUR
TREATMENT PROTOCOL?
THOSE QUESTIONS ARE GOING TO BE
DETERMINED IN MANY RESPECTS BY
THE CHARACTERISTICS THAT YOU SET
OUT.
RIGHT?
SO IF YOU WANT TO DO -- IF YOU
WANT TO UNDERTAKE A STUDY THAT
REQUIRES LOTS OF ACTIVE
PARTICIPATION BY YOUR
PARTICIPANTS, THEY HAVE TO COME
TO THE CRC WEEKLY IN ORDER TO
GET SOME KIND OF TESTING DONE,
AND YOU ARE TARGETING
PARTICIPANTS WHO ARE PHYSICALLY
DISABLED, THAT IS GOING TO BE
AIRSTREAM THAT MAY NOT WORK FOR
YOU. -- A STRATEGY THAT MAY NOT
WORK.
IT'S A FEASIBILITY ISSUE.
YOU DO NEED TO THINK ABOUT
ETHICAL QUESTIONS, OF COURSE, IN
ALL OF THESE CASES.
YOU NEED TO THINK ABOUT ETHICAL
QUESTIONS WITH REGARD TO WHETHER
YOU CAN RANDOMIZE IDEAS TO
PLACEBO, WHAT 2 ADVERSE EVENT
RATES.
AND WHAT I WANT TO UNDERSCORE
HERE IS THAT WHEN YOU THINK
ABOUT THESE KINDS OF
CONSIDERATIONS, YOU NEED TO
THINK ABOUT THEM FOR ALL OF THE
ARMS OF YOUR STUDY.
NOT JUST THE ACTIVE
INTERVENTIONAL ARM.
ALL CLINICAL TRIALS HAVE SOME
KIND OF COMPARISON ARM.
YOU'LL AFTER PLACEBO, OR USUAL
CARE, OR MAYBE ANOTHER TYPE OF
INTERVENTION THAT YOU'RE
COMPARING YOUR ACTIVE
INTERVENTION WITH.
AND WHEN YOU THINK ABOUT ETHICAL
ISSUES, YOU NEED TO THINK ABOUT
NOT ONLY IS IT ETHICAL TO
RANDOMIZE THIS -- MY
PARTICIPANTS DO AN ACTIVE
INTERVENTION ARM, BUT IS IT
ETHICAL FOR THE CHARACTERISTICS
OF THAT POPULATION TO RANDOMIZE
THEM TO A CONTROL ARM, TO A MR.
OBAMA ARM, TO A -- PLACEBO ARM,
DO A USUAL CARE ARM.
SOMETIMES WE FORGET ABOUT THAT
AND FOCUS ON THE INTERVENTION
GROUP.
TIMING OF THE INTERVENTION IS
GOING TO BE CRITICAL WHEN YOU
WANT TO CAPTURE THE
PARTICIPANTS.
WHAT I MEAN BY THAT IS THAT IN
SOME CASES WE WANT PARTICIPANTS
WHO HAVE JUST HAD AN EVENT.
THOSE ARE THE PARTICIPANTS WE
WANT 250 STUDY.
AND IT MAY BE VERY DIFFICULT FOR
YOU FEASIBLY DIFFICULT, TO YOU,
ACCESS THE PARTICIPANTS IN THAT
TO EVENT IS VERY SMALL.
IF YOU'RE DOING A STUDY OF
INDIVIDUALS WHO HAVE RECENTLY
COME TO AN EMERGENCY DEPARTMENT
BECAUSE OF AN ELICIT DRUG,
POTENTIAL OVERDOSE, AND YOU WANT
TO ENROLL THEM INTO A STUDY THAT
ASKS THE QUESTION OF WHAT
SATINED OF OUTCOME IS WITHIN 30
MINUTES OF ARRIVING OUGHT AN
EMERGENCY DEPARTMENT, THAT IS
GOING TO BE VERY DIFFICULT. SO
THE TIMING OF YOUR INTERVENTION,
IT MIGHT MAKE PERFECT SCIENTIFIC
SENSE BUT IT MAY NOT BE
FEASIBLE.
WHEN YOU THINK ABOUT WHO YOU
WANT TO BE IN YOUR STUDY, YOU
NEED TO THINK ABOUT THAT IN
RELATIONSHIP TO THE OUTCOMES
THAT YOU WANT TO TARGET FOR
MEASURING.
NOW, OUTCOMES ARE WHAT WE LOVE,
RIGHT?
THAT'S WHAT WE'RE INTERESTED IN.
WHAT THOSE OUTCOMES ARE.
BUT YOU HAVE TO THINK ABOUT
THOSE OUTCOMES IN RELATIONSHIP
TO THE PARTICIPANTS THAT YOU'RE
INCLUDING.
SO OUTCOMES CAN BE LOTS OF
THINGS.
YOU CAN HAVE EVENT OUTCOMES
WHICH WE THINK OF AS HARD
OUTCOMES.
THINGS LIKE MORTALITY, THAT'S A
VERY HARD ENDPOINT.
OR VARIOUS TYPES OF MORBIDITY.
SO FROM THE NATIONAL HEART LUNG
AND BLOOD INSTITUTE, I HAVE A
LOT OF EXAMPLES THAT ARE
CARDIOVASCULAR IN NATURE.
THAT'S WHAT I NEED TO TELL YOU,
BECAUSE THAT'S WHAT I LIVE WITH.
SO A MORTALITY -- MORBIDITY
OUTCOME MIGHT BE SOMETHING LIKE
A HEART ATTACK.
BUT IN A LOT OF STUDIES WE
REALLY DON'T HAVE THE LUXURY OF
MEASURING THESE KINDS OF EVENT
OUTCOMES.
EITHER EVENTS DON'T HAPPEN
FREQUENTLY, OR SAMPLE SIZES ARE
SMALL, OR IT TAKES A LONG TIME
FOR EVENTS TO OCCUR.
SO IF YOU WANT TO STUDY
CHILDREN, YOU DON'T WANT TO HAVE
A MORTALITY ENDPOINT.
IT TAKE ADDS LONG TIME IN MOST
CASES FOR CHILDREN TO REACH THAT
ENDPOINT.
SO WHAT WE DO IS THAT WE
SOMETIMES WILL USE SURROGATE
BIOMARKER OUTCOMES.
YOU PUT A STAR HERE, BECAUSE
THERE IS A DEFINITION OF A
SURROGATE MEASURE.
IT'S A BIOMARKER THAT IS A
SUBSTITUTE, AND IMPERFECT
SUBSTITUTE FOR A CLINICAL
ENDPOINT.
SO EXAMPLES OF SURROGATE
MEASURES ARE SOMETHING LIKE,
AGAIN, FROM THE NHHBI, SOMETHING
LIKE REVASCULARIZATION FOR
SOMEONE WHO HAS HEART DISEASE,
IF THEY HAVE A CORONARY BYPASS.
THAT'S A SURROGATE MEASURE FOR
UNDERLYING CARDIOVASCULAR
DISEASE.
CHOLESTEROL IS A VERY COMMON
SURROGATE MEASURE FOR UPDATE
LYING CARDIOVASCULAR DISEASE.
THERE ARE MANY OTHERS, DEPENDING
ON WHAT YOUR PARTICULAR AREA IS.
AND THESE ARE VERY COMMON
OUTCOMES BECAUSE THEY'RE
ACCESSIBLE, AND THEY'RE MORE
READILY AVAILABLE TO US RATHER
THAN EVENT RELATED OUTCOMES.
THEY'RE ALSO PATIENT SPECIFIC
OUTCOMES.
AND THESE ARE REFERRED TO AS
PROs, AND THESE PATIENT
SPECIFIC OUTCOMES ARE REALLY
IMPORTANT.
FOR SOME TRIALS, THEY REALLY
WILL BE THE PRIMARY ENDPOINT,
THE PRIMARY OUTCOME THAT YOU'RE
INTERESTED IN.
THESE ARE THINGS THAT ONLY THE
PARTICIPANT, IN THIS CASE, THE
PATIENTS CAN REPORT ON.
THINGS LIKE PAIN, OTHER KINDS OF
SYMPTOMS.
THEY'RE QUALITY OF LIFE.
REALLY GOOD WAYS OF MEASURING
THESE OUTCOMES.
THE NIH PUT A LOT OF EFFORT INTO
ESTABLISHING VALID AND RELIABLE
MEASURES OF PROs.
IF YOU HAVE QUESTIONS I'D BE
HAPPY TO ANSWER THEM FOR YOU.
BUT WHEN YOU HAVE THESE PATIENTS
SPECIFICALLY OUTCOMES, YOU WANT
TO THINK VERY CAREFULLY ABOUT
THE MEANING OF THOSE OUTCOMES IN
RELATIONSHIP TO THE PATIENT
CHARACTERISTICS YOU'RE LOOKING
AT.
THEM THERE ARE COMPOSITE
OUTCOMES, THAT DOESN'T HAVE MUCH
RELEVANCE TO THIS CONVERSATION.
THOSE ARE THE TYPES OF OUTCOMES
THAT WE'RE INTERESTED IN.
WHAT DOES THIS HAVE TO DO WITH
PATIENT FACTORS?
ARE THE OUTCOMES THAT YOU WANT
TO INCLUDE, MAYBE YOUR PRIMARY
OR SECONDARY OUTCOME IN YOUR
TRIAL, A FEASIBLE TO MEASURE,
GIVEN THE CHARACTERISTICS OF THE
PARTICIPANTS THAT YOU ARE
TARGETING?
WHAT I MEAN BY THAT, WHAT YOU
REALLY WANT FOR AN OUTCOME IS A
HARD CARDIOVASCULAR EVENT, LIKE
MYOCARDIAL INFARCTION, HEART
ATTACK.
THAT'S THE MEASURE YOU'RE
LOOKING FOR.
IF YOU CHOOSE TO ENROLL IN THIS
EXAMPLE 50 YEAR OLD ESSENTIALLY
HEALTHY WOMEN, YOU'RE NOT GOING
TO SEE TOO MANY OF THOSE
OUTCOMES IN YOUR 5 YEAR TRIAL
FEEL IT'S NOT GOING TO HAPPEN.
IF THEY'RE ESSENTIALLY HEALTHY
WOMEN, MIDDLE-AGED WOMEN.
SO YOU NEED TO MATCH THE
CHARACTERISTICS OF YOUR
PARTICIPANTS THAT YOU NEED TO
LOOK AT.
IN THIS SITUATION YOU HAVE TO
CHANGE THE CHARACTERISTICS OR
CHANGE YOUR OUTCOME.
YOU ALSO WANT TO THINK ABOUT
WHETHER YOUR OUTCOMES CAN CHANGE
WITHIN THE PARAMETERS OF YOUR
TRIAL, THE LENGTH OF YOUR TRIAL.
AND THE FOLLOW-UP PERIOD THAT
YOU HAVE DESIGNED FOR YOUR
TRIAL.
GIVEN THE PATIENT
CHARACTERISTICS.
SO, FOR EXAMPLE, AGAIN, IF YOU
HAVE -- LET'S SAY YOU'RE DOING A
TRIAL OF -- LET'S SAY YOU WANT
TO LOOK AT CORODED IMT, BLOCKING
IN THE CORODED ARTERY OVER THE
COURSE OF YOUR TRIAL AND
FOLLOW-UP PERIOD OF 6 MONTHS AND
YOU'RE LOOKING AT ESSENTIALLY
HEALTHY PEOPLE.
THAT'S NOT GOING TO HAPPEN.
YOU HAVE TO CHANGE YOUR OUTCOME
OR YOUR PARTICIPANT
CHARACTERISTICS.
IF YOUR FOCUS OF YOUR OUTCOME IS
GOING TO BE ON PATIENT REPORTED
OUTCOMES, PROs, THEN YOU NEED
TO THINK ABOUT THE
CHARACTERISTICS OF YOUR
PARTICIPANTS, WHETHER THEY WILL
BE ABLE TO GIVE YOU THOSE KINDS
OF OUTCOMES.
SO, FOR EXAMPLE, THE EXAMPLE I
HAVE HERE IS IF YOU ARE HOOKING
AT PAIN IN CHIRP, IF YOU'RE
ENROLLING 2-YEAR OLD CHIRP TO
REPORT ON THEIR PAIN SYMPTOMS,
YOU WILL GET AN OUTCOME BUT IT
MAY NOT BE VERY RELIABLE.
NOW, I WILL PREFACE THIS BY
SAYING THAT WE CAN GET GOOD
RELIABLE PATIENT REPORTED
OUTCOMES FROM CHILDREN IF YOU
USE THE RIGHT MEASURES.
BUT YOU HAVE TO THINK ABOUT
THAT.
IN THE CONTEXT OF YOUR TRIAL.
THE BOTTOM LINE WITH ALL THESE
THINGS IS THAT DECISIONS THAT
YOU MAKE REGARDING THE
CHARACTERISTICS OF THE
PARTICIPANTS THAT YOU STUDY ARE
GOING TO INFLUENCE THE CAUSAL
INFERENCES THAT YOU CAN MAKE.
AND THE BOTTOM LINE WITH ALL OUR
TRIALS, WHAT WE WANT TO DO IS
MAKE CAUSAL INFLUENCE --
INFERENCES.
YOU WANT TO BE ABLE TO SAY THE
REASON I FOUND THIS OUTCOME IS
BECAUSE I EMPLOYED THIS
INTERVENTION.
THAT'S A CAUSAL INFERENCE. YOU
WANT TO BE ABLE TO DO THAT.
YOU WANT THAT INFERENCE TO BE
HIGH.
SO YOU WANT TO MAKE THESE
DECISIONS VERY CAREFULLY.
SO I WANT TO MOVE NOW -- ANY
QUESTIONS?
OKAY.
I WANT TO MOVE NOW TO TALKING
ABOUT SOME OF THE THINGS TO
THINK ABOUT IN OUTLINING YOUR
PARTICIPANT CHARACTERISTICS.
WE'LL TALK ABOUT ENTRY CRITERIA,
CONTEXTUAL FACTORS, ACCESS,
ADHERENCE, AND RECRUITMENT
RETENTION.
LET'S START OFF WITH ENTRY
CRITERIA.
WHEN YOU ARE STARTING A STUDY --
BEFORE YOU START A STUDY YOU
WANT TO ESTABLISH WHAT YOUR
CRITERIA ARE FOR ENTRY.
YOU'RE GOING TO ESTABLISH BOTH
YOUR INCLUSIONARY CRITERIA AS
WELL AS YOUR EXCLUSIONARY
CRITERIA.
AND BY THE WAY, YOU ALSO -- AND
I HAVE NOTE HERE THAT YOU WANT
TO IDENTIFY WHAT THE TARGET OF
THE INTERVENTION IS.
MOST OF THE TIME IT'S GOING TO
BE AN INDIVIDUAL PATIENT OR
PARTICIPANT IN YOUR STUDY.
BUT SOMETIMES IT COULD BE A
DIAD, A FAMILY, SOMETIMES IT CAN
BE A PROVIDER OR HEALTHCARE
DELIVERY SYSTEM.
IT'S IMPORTANT TO IDENTIFY THAT
STRAIGHT UP.
SO LET'S TALK ABOUT ENTRY
CRITERIA.
INTERESTINGLY, DEMAIN PURPOSE OF
INCLUSIONARY CRITERIA IS
DIFFERENT THAN THE MAIN PURPOSE
OF EXCLUSIONARY CRITERIA.
OKAY?
SO WITH INCLUSIONARY CRITERIA,
THE MAIN PURPOSE IS TRYING TO
IDENTIFY THE PARTICIPANTS WHO
ARE GOING TO BE MOST RELEVANT TO
THE OUTCOMES OF YOUR STUDY.
THAT'S THE MAIN PURPOSE.
YOU ALSO NEED TO ENROLL -- TO
THINK ABOUT INCLUSIONARY
CRITERIA, BECAUSE YOU NEED TO
REPORT ON IT.
YOU NEED TO REPORT IN YOUR
CONSORT STATEMENT WHAT YOUR
INCLUSIONARY AND EXCLUSIONARY --
BOTH CRITERIA, AND NEED TO BE
ABLE TO IDENTIFY INDIVIDUALS
THAT YOU'VE IDENTIFIED THAT ARE
FITTING YOUR INCLUSIONARY
CRITERIA.
AND THEN YOU NEED TO BALANCE
BETWEEN PARTICIPANT VARIABILITY.
SO WHAT DO I MEAN BY BALANCING
BETWEEN PARTICIPANT VARIANCE?
SO YOUR PARTICIPANTS ARE GOING
TO BE -- HAVE LOTS OF DIFFERENT
CHARACTERISTICS.
AND WHEN YOU INCLUDE
PARTICIPANTS, WHEN YOU SET OUT
WHAT YOUR INCLUSIONARY CRITERIA
ARE, YOU HAVE TO BE HOW LOOSE
YOU WANT THEM TO BE.
SO IF YOU SAY YOU'RE
INCLUSIONARY CRITERIA ARE ANYONE
BETWEEN THE AGES OF 18 AND 70,
THAT'S A WIDE, WIDE OPEN
CRITERIA.
AND THAT'S FINE.
BUT IT'S GOING TO HAVE LOTS OF
VARIABILITY IN IT.
FOR SOME STUDIES THAT'S GOING TO
BE APPROPRIATE BUT FOR MANY IT
WON'T BE.
THE VARIANCE WILL BE TOO WIDE.
WHAT ARE THE EXAMPLES -- ONE OF
THE EXAMPLES I GIVE, LET'S SAY
YOU'RE DOING A STUDY OF
MIGRAINE, YOU HAVE A NEW
TREATMENT FOR MIGRAINE.
SO YOU HAVE TO SET OUT
INCLUSIONARY CRITERIA.
MAYBE YOU'LL SAY I'M GOING TO
IDENTIFY THE TYPE OF MIGRAINES,
IDENTIFY THE DURATION THAT THE
MIGRAINES IN ANY INDIVIDUAL
PARTICIPANT OCAN YOU FOR.
AND THE FREQUENCY OF THOSE
ATTACKS.
AND I'M GOING TO SPECIFY WHAT
OTHER MEDICATIONS PARTICIPANTS
CAN USE WHEN THEY'RE ENROLLED IN
THE STUDY.
THOSE ARE INCLUSIONARY CRITERIA.
THOSE YOU REPORT OUT ON.
THOSE ARE GOING TO TARGET FORTH
THIS QUESTION SPECIFIC
CHARACTERISTICS THAT ARE
RELEVANT.
NOW, CONTRAST THAT WITH
EXCLUSIONARY CRITERIA.
THE MAIN PURPOSE OF EXCLUESRY
CRITERIA IS FOR FEASIBILITY.
HEN YOU SET OUT THE CRITERIA BY
WHICH YOU'RE NOT GOING TO ALLOW
SOMEONE TO PARTICIPATE IN THE
STUDY, THE MOST IMPORTANT REASON
TO NOT ALLOW SOMEONE TO BE IN
YOUR STUDY IS FOR SAFETY
REASONS.
IF THE STUDY IS GOING TO BE TOO
HIGH RISK FOR THAT TECH
CHARACTERISTIC OF A PARTICIPANT,
YOU DON'T WANT THEM IN YOUR
STUDY.
IT'S GOING TO BE TOO RISKY.
IF YOU'RE NOT SURE ABOUT THE
SAFETY ISSUE, YOU MAY USE -- YOU
MAY USE SOME OF THE CRITERIA AS
EXCLUSIONARY CRITERIA.
THERE MAY BE THINGS THAT
PARTICIPANTS CHARACTERISTICS
BRING WITH THEN THAT MIGHT
CONFOUND YOUR FINDINGS.
LET'S SAY YOU ARE TRYING TO TEST
A NEW DRUG.
AND YOU WANT TO MAKE SURE THAT
THE AFFECTS OF THAT DRUG ARE
CLEAR.
YOU MAY NOT WANT TO ALLOW OTHER
MEDICATIONS TO BE USED.
THEY WOULD CONFOUND THE EFFECTS
THAT YOU'RE LOOKING AT FOR YOUR
INTERVENTION.
AND THEN FEASIBILITY WHICH WE'VE
TALKED ABOUT BEFORE.
SO THE EXAMPLE I GIVE HERE,
LET'S STAKE YOU'RE TESTING A DO
MEDICATION FOR HIGH BLOOD
PRESSURE.
YOU MAY WANT TO EXCLUDE PEOPLE
WITH HEART FAILURE FOR SAFETY
REASONS.
PEOPLE WITH HEART FAILURE ARE
COMPLEX AND DIFFICULT TO TREAT
AND SO WE MAY NOT WANT TO
INCLUDE THEM IN A TRIAL OF A NEW
MEDICATION.
YOU MAY ESCLUDE PEOPLE WITH
DIABETES.
BUT THERE MAY BE CONFOUNDING
FACTORICS.
SO YOU MAY DECIDE TO EXCLUDE
THOSE PARTICIPANTS.
AND FEASIBILITY ISSUES, IF YOU
HAVE TO DO LOTS OF TESTING, YOU
MAY NOT WANT TO INCLUDE
INDIVIDUALS WHO ARE BEDRIDDEN,
FOR EXAMPLE, BECAUSE IT WOULDN'T
BE FEASIBLE FOR THEM TO COME TO
THE CLINIC FREQUENTLY FOR
TESTING.
SO THE REASON FOR EXCLUDING
PARTICIPANTS IS VERY DIFFERENT
THAN THE REASON FOR INCLUDING
PARTICIPANTS.
NOW, ONE OF THE QUESTIONS I GET
ALL THE TIME IS WHEN DO I
ESTABLISH INCLUSIONARY AND
EXCLUSIONARY CRITERIA ARE?
THE ANSWER IS VERY, VERY EARLY.
WE WANT TO ESTABLISH THIS BEFORE
YOU START YOUR STUDY OBVIOUSLY,
NEED TO ESTABLISH IT BEFORE YOU
GO TO YOUR IRB FOR APPROVAL.
YOU NEED TO ESTABLISH IT BEFORE
YOU GET FUNDING BECAUSE IT'S
GOING TO BE SO CRITICAL TO THE
SUCCESS OF YOUR STUDY.
SO YOU DO IT VERY, VERY EARLY
ON.
THE REASON THESE CRITERIA ARE SO
IMPORTANT IS BECAUSE THIS IS A
EASY WAY FOR UNINTENTIONAL BIAS
TO CREEP INTO YOUR STUDY DESIGN.
IF YOU'RE NOT CLEAR AND I MEAN
CRYSTAL CLEAR WHAT YOUR
INCLUSIONARY AND EXCLUSIONARY
CRITERIA ARE, NOT ONLY FOR YOU,
AS A PI, BUT ALSO FOR ANY STAFF
THAT YOU HAVE WHO ARE GOING TO
BE RECRUITING PARTICIPANTS.
IF YOU DON'T HAVE CRYSTAL CLEAR
CRITERIA, IT'S POSSIBLE THAT YOU
MAY END UP WITH A BIAS SAMPLE.
YOU MAY -- YOUR OWN BIAS IN
WANTING TO ENROLL PARTICULAR
PARTICIPANT INTO YOUR STUDY MAY
CREEP IN, UNLESS YOU HAVE REALLY
CLEAR REASONS TO INCLUDE THEM OR
EXCLUDE THEM.
SO I ENCOURAGE YOU TO DO THIS
EARLY, TO BE VERY, VERY
SPECIFIC.
TO WRITE IT ALL DOWN.
AND TO MAKE SURE THAT EVERY ONE
ON YOUR STAFF UNDERSTANDS WHAT
THESE CRITERIA ARE.
SO THE NEXT QUESTION THAT I GET
IS WELL, CAN I CHANGE THEM?
NOW, WHY DO PEOPLE WANT TO
CHANGE THEIR ENTRY CRITERIA?
THE MOST DIFFICULT PART OF DOING
A CLINICAL TRIAL IS WHAT?
RECRUITMENT! EVERY ONE KNOWS
THAT.
SO IF YOU START A TRIAL, YOU
HAVE ENTRY CRITERIA THAT'S
CLEARLY LAID OUT.
YOU CAN'T ENROLL ADEQUATELY.
YOU'RE NOT MEETING YOUR MILE
ZONES.
ONE OF THE THINGS THAT PEOPLE
WANT TO DO IS CHANGE THEIR ENTRY
CRITERIA.
YOU CAN DO THAT.
BUT YOU PAY A PRICE.
SO THE PRICE YOU PAY IS THE
PRICE THAT YOU MAY ACTUALLY
ALLOW SOME OF THAT BIAS TO CREEP
IN.
SO IF YOU'RE GOING TO GO -- IF
YOU'RE GOING DOWN THIS ROAD AND
CHANGE YOUR ENTRY CRITERIA, YOU
WANT TO MAKE SURE THAT YOU DO IT
AS UNBIASED A WAY AS POSSIBLE.
YOU DON'T CHANGE YOUR ENTRY
CRITERIA WHEN YOU'RE ACROSS FROM
SOMEONE THAT YOU REALLY WANT TO
ENROLL IN YOUR STUDY, THEY'RE
REALLY PERFECT. THERE IS ONE
LITTLE INCLUSIONARY CRITERIA
THEY DON'T QUITE MEET.
BUT THEY'RE CLOSE.
AND YOU NEED TO MEET YOUR
MILESTONE THIS MONTH.
THAT'S NOT THE TIME AND WAY YOU
CHANGE YOUR ENTRY CRITERIA.
IF YOU IMMEDIATE TO CHANGE IT
YOU GO TO YOUR DSMB, YOUR IRB,
DO IT IN AN IN BIASED WAY AS
POSSIBLE AND EXTREMELY
INFREQUENTLY.
SO IF YOU'RE GOING TO DO IT
BECAUSE OF RECRUITMENT ISSUES,
DO IT ONCE.
DON'T KEEP COMING BACK TIGHT.
YOU DO NOT WANT TO BIAS YOUR
SAMPLE.
COP TEXT.
THERE ARE LOTS OF CONTEXTUAL
FACTORS.
AND I'M NOT GOING TO GO THROUGH
ALL THE FACTORS THAT ARE
POTENTIALLY FACTORS TO THINK
ABOUT WHEN YOU'RE THINKING ABOUT
WHO TO INCLUDE IN YOUR STUDIES.
BUT CONTEXT IS REALLY IMPORTANT.
AND JUST HIKE JERRY WAS SAYING
EARLIER, WHEN YOU'RE A
RESEARCHER, AND YOU ARE ENGAGING
WITH A PARTICIPANT IN YOUR
STUDY, YOU HAVE A
RELATIONSHIP -- THAT IS A
RELATIONSHIP.
AND THAT RELATIONSHIP HAS
CONTEXT.
AND NOW ONLY THAT,
PARTICIPATANTS WHO COME INTO
YOUR STUDY HAVE A WHOLE WORLD OF
CONTEXT.
ALMOST NONE OF WHICH YOU'RE
AWARE OF.
SOME OF WHICH YOU MAYBE.
BUT ALMOST NONE OF WHAT YOU'RE
AWARE.
BY CONTEXT WHAT I MEAN ARE
THINGS LIKE PERSONAL
EXPERIENCES.
BACKGROUND MOVE CULTURE.
SOCIAL ENVIRONMENT.
HOW A PARTICIPANT FEEL ON THAT
PARTICULAR DAY.
THE RELATIONSHIP THAT YOU AS AN
EXPERIMENTER OR RESEARCHER.
ALL OF THESE ARE CONTEXTUAL
FACTORS AND THEY MAKE A
DIFFERENCE.
I'M GOING TO PROVE TO YOU THAT
THEY MAKE A DIFFERENCE.
I HAVE A COUPLE STUDIES TO SHOW
YOU.
SO THESE ARE THE FINDINGS FROM A
STUDY CALLED SWAN WHICH IS A
STUDY -- A LONGITUDINAL STUDY.
NOT A TRIAL.
A LONGITUDINAL STUDY FOR
MIDDLE-AGED WOMEN.
AND THE PURPOSE OF SWAN WAS TO
LOOK AT WOMEN LONGITUDINALLY AS
THEY GO THROUGH -- AS THEY AGE.
AND TO LOOK AT A VARIETY OF
HEALTH OUTCOMES.
ONE OF THE OUTCOMES THAT THEY'RE
PARTICULARLY INTERESTED IN WAS
METABOLIC SYNDROME.
BUT THEY TOOK A LOT OF MEASURES.
AS OFTEN WE ALL DO AS
RESEARCHERS.
WE TAKE A LOT OF MEASURES.
ONE OF THE MEASURES THAT THEY
HAPPEN TO TAKE WERE MEASURES ON
EARLY CHILDHOOD TRAUMA.
AND THE INVESTIGATORS HAD SOME
MEASURES OF MET BOTIC SYNDROME
AT TWO DIFFERENT TIME POINTS.
WHEN THEY HOOKED TO SEE HOW
METABOLIC SYNDROME WAS
PROGRESSING IN THIS LARGE COHORT
OF WOMEN, SOMEBODY HAD THE VERY
CLEVER IDEA TO LOOK AT THE
PROGRESSION OF METABOLIC
SYNDROME IN RELATIONSHIP TO
EARLY CHILDHOOD PHYSICAL ABUSE.
THERE IS A LITERATURE THAT
SUGGESTIONS THAT MIGHT BE
SOMETHING INTERESTING TO LOOK
AT.
WHAT THEY FOUND WAS THAT THE
PERCENTAGE OF WOMEN WHO ACTUALLY
WERE MORE LIKELY TO DEVELOP
METABOLIC SYNDROME WAS MUCH,
MUCH HIGHER, TWICE AS HIGH IN
WOMEN WHO HAD EXPERIENCED EARLY
CHILDHOOD PHYSICAL ABUSE.
THE EXPERIENCE OF HAVING EARLY
CHILDHOOD TRAUMA IS A CONTEXTUAL
FACTOR.
AND I'M NOT SUGGESTING THAT YOU
GO OUT NO MATTER WHAT YOUR
QUESTION IS AND ASK EVERY ONE
ABOUT EARLY CHILDHOOD TRAUMA BUT
I AM SUGGESTING THAT YOU LOOK AT
THE LITERATURE CAREFULLY IN
TERMS OF THESE CONTEXTUAL
FACTORS, AND THINK CAREFULLY
ABOUT WHO MEASURES YOU NEED TO
BE TAKING IN ADDITION TO YOUR
PRIMARY OUTCOMES.
BECAUSE CONTEXT IS IMPORTANT
HAVE AND I HAVE ANOTHER EXAMPLE
IN CASE THIS INCIDENT SWAY YOU.
THIS IS A FINDING THAT PEOPLE
KNOW ABOUT.
IT'S VERY FAMILIAR.
BUT IT'S INTERESTING TO POINT
OUT.
THIS IS A STUDY LOOKING AT
AMBULATORY BLACKBERRY.
HOOKING AT CARDIAC EVENTS.
I'M FROM THE NATIONAL HEART LUNG
BLOOD INSTITUTES.
THAT'S WHAT I TALK ABOUT.
THEY FOLLOWED UP INDIVIDUALS WHO
WERE HYPERTENSIONIVE AND TAKING
HYPERTENSIONIVE MEDICATION, AND
FOLLOWED UP TO FIND OUT WHAT THE -- WHAT T HE SURVIVAL WAS.
AND -- IN THESE PATIENTS.
WHAT THEY FOUND WAS THAT -- I
DIDN'T SHOW YOU THE FIRST CURVE,
WHICH WAS SOMETHING LIKE A CURVE
IN BETWEEN HERE.
WHAT THEY FOUND, THOUGH, WAS
THAT IF YOU SEPARATED OUT
PATIENTS THAT TOOK AT LEAST ONE
OF THEIR BLOOD PRESSURE BED
MEDICATIONS BEFORE BED FROM
THOSE THAT TOOK THEM ALL IN THE
MORNING, YOU FIND VERY DIFFERENT
SURVIVAL CURVES.
AND AS I SAY, IT'S BETTER TO
TAKE IT -- BETTER TO TAKE IT
BEFORE YOU GO TO BED, BY THE
WAY.
AS I SAY THIS IS A FAMILIAR
FINDING TO US NOW.
WE KNOW THAT THE TIMING OF
MEDICATION IS IMPORTANT.
FOR BLOOD PRESSURE MEDICATION
IT'S IMPORTANT TO TAKE AT LEAST
ONE OF YOUR MEDICATIONS AT
NIGHT.
BUT WHAT I'D SUGGEST TO YOU IS
THAT THE TIME AT WHICH OUR
PARTICIPANT TAKES MEDICATION IS
A CONTEXTUAL FACTOR.
SO AGAIN YOU WOULDN'T KNOW THAT
UNLESS YOU READ THE LITERATURE,
AND IT IS A BIG LITERATURE NOW.
INCREASING LITERATURE.
BUT IT'S CONFEDEXIAL.
SO CONTEXT IS IMPORTANT.
THAT DOESN'T MEAN THAT YOU NEED
TO MEASURE EVERYTHING BECAUSE
YOU CAN'T.
BUT YOU NEED TO THINK ABOUT
CONTEXT WHEN YOU ARE THINKING
ABOUT YOUR PARTICIPANT
CHARACTERISTICS.
AND YOUR OUTCOMES SO ACCESS
ANOTHER FEASIBILITY ISSUE.
CAN YOU ACCESS THE PARTICULAR
PARTICIPANTS WITH A PARTICULAR
CHARACTERISTICS THAT YOU'RE
HOOKING FOR.
YOU NEED TO THINK ABOUT THIS
EARLY.
YOU CAN HAVE A FANTASTIC STUDY,
CAN BE THE BEST SCIENCE IN THE
WORLD.
IF YOU CAN'T GET PARTICIPANTS
INTO YOUR STUDY BECAUSE THEY
DON'T LIVE IN YOUR GEOGRAPHIC
AREA OR DON'T COME TO YOUR
CLINIC, OR YOU -- IN ANY OTHER
WAY DON'T HAVE ACCESS, YOU CAN'T
CARRY OUT THE STUDY.
AND ONE WAY OF INCREASING ACCESS
TO THE PARTICIPANTS THAT YOU
WOULD LIKE TO STUDY, IS TO BUILD
AN INTERDISCIPLINARY TEAM.
THIS ARE LOTS OF GOOD REASONS TO
BUILD A INTERDISCIPLINARY TEAM.
ONE, IT HELPS ENHANCE ACCESS TO
PARTICIPANTS THAT YOU MIGHT NOT
HAVE ACCESS TO BUT SOMEONE ON
YOUR TEAM MIGHT.
AND AS YOU BUILD THIS
INTERDISCIPLINARY TEAM AND AS
YOU HAVE, YOU KNOW, ACCESS
ISSUES YOU MAY NEED TO HAVE MANY
SITES IN YOUR TRIAL.
THAT'S OKAY.
IT HAS ITS, YOU KNOW, DOWN SIDES
BUT THAT'S OKAY.
BUT, AGAIN, THINKING ABOUT THESE
IN THE CONTEXT OF THE PATIENT
CHARACTERISTICS THAT YOU ARE
IDENTIFYING. I'D LIKE TO MAKE A
PLEA TO NOT INCLUDE YOUR OWN
PATIENTS OR PRACTICE IN YOUR
RESEARCH.
SEPARATION HELPS YOU MAINTAIN
ECHO POISE, AND DELIVER GOOD
CLINICAL CARE.
WE'LL TALK A LITTLE BIT ABOUT
RECRUITMENT AND RETENTION,
BECAUSE IT'S SUCH A CRITICAL
ISSUE YOU THINK E IN RUNNING A
TRIAL.
AND I ACTUALLY DO A WHOLE COUPLE
OF LECTURES ON RECRUITMENT
INTENTION.
BECAUSE IT IS SO IMPORTANT AND
BECAUSE IT'S COMPLEX.
IT DOESN'T SEEM THAT WAY.
WE ALL START OUR TRIALS SAYING
OKAY WE'RE GOING TO RECRUIT
PEOPLE AND THEY'RE GOING TO STAY
BECAUSE THEY LOVE US BUT IT'S
HARD, REALLY HARD WORK.
IT'S GOOD TO THINK ABOUT IN ALL
PHASES OF YOUR TRIAL.
MOST OF THE TRIALS THAT DON'T
COMPLETE, FAILED TRIALS IS A
TRIAL THAT DECENT COMPLETE.
MOST FAILED TRIALS DON'T
COMPLETE BECAUSE OF RECRUITMENT
ISSUES, SOMETIMES RETENTION BUT
MOSTLY RECRUITMENT.
WHAT DO YOU NEED TO THINK ABOUT
IN TERMS OF BOTH RECRUITMENT AND
RETENTION?
PROBABLY THE NUMBER ONE THING IS
THE BURDEN THAT YOU IN YOUR
PROTOCOL ARE PUTTING ON THE
PARTICIPANTS, THE PARTICIPANTS
THAT YOU'RE SELECTING.
TO BE IN YOUR STUDY.
AND THAT BURDEN IS PART OF
YOUR -- THE ASSESSMENTS THAT YOU
DO, THE MEASUREMENTS THAT YOU
DO.
AS WELL AS THE COMPLEXITY AND
THE DURATION OF THE TREATMENTS,
IF YOU'RE PLANNING A FIVE YEAR
TRIAL THAT REQUIRES FOUR YEARS
OF FOLLOW-UP FROM YOUR
PARTICIPANTS, THAT'S A HEAVY
BURDEN.
IF YOU'RE REQUIRING
PARTICIPATANTS TO COME INTO YOUR
CLINIC EVERY DAY FOR A COUPLE OF
WEEKS THAT'S A HEAVY BURDEN.
AND THE HIGHER THAT BURDEN, THE
MOTHER DIFFICULT IT WILL BE TO
GET PARTICIPATANTS INTO YOUR
STUDY, FO MATTER WHO THEY ARE
AND TO RETAIN THEM.
IT WILL BE MORE IMPORTANT
DEPENDING ON THE CHARACTERISTICS
OF YOUR PARTICIPANTS, THINGS
LIKE HOW HEALTHY YOUR
PARTICIPANTS ARE, HOW SICK, WHAT
ARE THEIR NEEDS.
AND REMEMBER, THOSE NEEDS EXTEND
BEYOND THEIR OWN PERSONAL NEEDS.
TO THEIR FAMILY NEEDS AS WELL.
SO IF YOU WANT TO TO A STUDY OF
CHILD BEARING WOMEN, FOR
EXAMPLE, IT'S GREAT TO IDENTIFY
THAT POPULATION FOR STUDY.
BY THEY MAY HAVE CHILD BEARING
ISSUES.
YOU MAY NEED TO PROVIDE
CHILDCARE FOR THEM.
OTHER PARTICIPANTS MAY HAVE --
OTHER KINDS OFF LOGISTICS
ISSUES, LIKE TRANSPORTATION
ISSUES.
EVERY ONE HAS PARKING ISSUES
BECAUSE IT'S DIFFICULT TO PARK,
SO THOSE KINDS OF THINGS ARE
THINGS THAT YOU WANT TO THINK
ABOUT AND TRY TO DO SOMETHING
ABOUT.
TO REDUCE THE BURDEN.
I HAVE HERE THIS NOTION THAT
INTENTION TO TREAT IS THE
ANALYSIS THAT YOU WILL DO AND
INTENT 250 TREAT ANALYSIS MEANS
THAT YOU WILL THAT WOULD EVERY
ONE THAT YOU'RE RANDOMIZED INTO
YOUR TRIAL.
YOU WILL ALL DO INTENT TO TREAT
ANALYSIS.
THAT MEANS AS SOON AS YOU
RANDOMIZE SOMEONE INTO YOUR
TRIAL THEY'RE YOURS.
THEY ARE YOURS.
THAT MEANS THAT YOU WILL CARRY
THEM THROUGHOUT THE DURATION OF
THE TRIAL.
THEY MAY NOT GIVE YOU ANYMORE
DATA BEYOND THE FIRST VISIT, BUT
YOU MUST INCLUDE THEM.
INYOUR ANALYSIS.
IN YOUR PRIMARY ANALYSIS.
WHAT THAT MEANS -- YOU'LL TALK
ABOUT IN THIS THE ANALYTIC
SECTION.
THAT MEANS THAT YOU WANT TO BE
REALLY CAREFUL ABOUT WHO YOU
RANDOMIZE INTO YOUR STUDY.
SO I KNOW THAT A LOT OF YOU HAVE
HAD EXPERIENCE IN TRYING TO
ENHANCE RECRUITMENT AND YOU DO A
LOT OF THINGS.
WE'LL TALK WITHOUT WHAT SOME OF
THOSE THINGS MIGHT BE.
AND WHAT YOU WANT IS TO
ENCOURAGE PEOPLE TO SIGN UP FOR
YOUR TRIAL.
THAT'S WHAT YOU TRY TO DO WHEN
YOU MAKE THESE ACTIVE AND REALLY
INTENSE RECRUITMENT EFFORTS.
THAT'S A GOOD IDEA.
BUT I WOULD SUGGEST TO YOU THAT
WHEN YOU ARE DOING YOUR
RECRUITMENT EFFORTS, WHAT YOU
ACTUALLY DO IS MAKE IT HARD.
MAKE IT HARD FOR PARTICIPANTS TO
SIGN UP FOR YOUR STUDY.
AND THE REASON FOR THAT -- I
DON'T MEAN MAKE IT HARD IN THE
FEASIBLE SENSE.
BUT I THINK YOU WANT TO BE
REALLY, REALLY BRUTALLY HONEST
WITH PARTICIPANTS IN TERMS OF
WHAT IT WILL TAKE TO BE IN YOUR
TRIAL.
WHAT THEY WILL HAVE TO DO.
I RECOMMEND THAT IF YOU HAVE A
GROUP RECRUITMENT EFFORT, THAT
IS, YOU HIRE A ROOM -- YOU HAVE
A ROOM LIKE THIS AND HAVE A
BUNCH OF PEOPLE COME TO LISTEN
TO YOUR PITCH ABOUT BEING IN THE
STUDY, YOU HAVE DISCUSSIONS
ABOUT WHAT THE DOWN SIDES OF
BEING IN YOUR STUDY IS.
HAVE THE DISCUSSIONS OUT RIGHT.
I CAN GUARANTY YOU THAT
PARTICIPANTS ARE GOING THROUGH
THOSE THINGS IN THEIR HEADS SO
YOU MIGHT AS WELL GET IT ON
TABLE.
YOU MAY GET A FEW FEWER PEOPLE
TO RECRUIT -- TO ACTUALLY ENROLL
IN YOUR STUDY OR SAY THAT
THEY'RE INTERESTED IN ENROLLING
IN YOUR STUDY BUT YOU WILL GET
PEOPLE WHO ARE MORE LIKELY TO BE
REORDAINED IN YOUR STUDY.
LIKELY TO BE RETAINED.
IT IS MORE IMPORTANT TO GET
PEOPLE TO BE RETAINED IN THE
STUDY THAN 250 GET -- A LOT OF
PEOPLE ENROLLED, THEN DROP OUT.
THAT HURTS YOUR POWER, HURTS
YOUR ABILITY, MAKES CAUSAL
INFERENCES.
MUCH MORE IMPORTANT TO RETAIN
PARTICIPANTS.
AS YOU'RE DOING RECRUITMENT
EFFORTS WITH ALL THE CRITERIA
THAT YOU HAVE LAID OUT IN TERMS
OF WHO YOU WANT TO ENROLL AND
WHO YOU NEED TO EXCLUDE, BE
REALLY CRITICALLY HONEST BOW
WHAT IT WILL TAKE FOR
PARTICIPANTS TO BE IN YOUR
TRIAL.
SO OFTEN TIMES PEOPLE WANT TO
KNOW -- I'VE TRIED EVERYTHING.
WHAT MORE CAN I DO?
SO I WANT TO WALK THROUGH A FEW
THINGS.
WE'RE A LITTLE BIT -- IT'S
RELATED TO WHAT WE'RE TALKING
ABOUT BUT IT'S IMPORTANT, I
THINK.
SO WHAT ARE SOME OF THE THINGS
THAT YOU CAN DO TO ENHANCE
RECRUITMENT?
AND ONE OF THE THEM IS TO USE
THIS LAYERED APPROACH.
WHICH IS ANOTHER WAY OF SAYING
MULTIPRONGED APPROACH.
DO NOT REPLY ON ONE APPROACH.
IT'S PROBABLY NOT GOING TO DO IT
FOR YOU.
SO IF YOUR IRB WILL ALLOW IT,
USE SOCIAL MEDIA.
IT'S VERY EFFECTIVE.
YOU NEED TO GO TO YOUR IRB TO
MAKE SURE IT'S ALLOWABLE.
IF IT'S NOT YOU CAN USE
COMMUNITY BASED KINDS OF
STRATEGIES AND EVEN THOUGH YOU
WOULDN'T GO THROUGH SOCIAL
MARKETING STRATEGIES YOU MAY
HAVE COMMUNITY BASED OUTREACH
PROGRAMS THAT YOU CAN PIGGYBACK
ON TO.
THE OLD FASHION WAY IS TO DO
TARGETED DISTRIBUTIONS OF
MAILINGS.
IT'S OLD FASHIONED BUT IT WORKS.
YOU GET ABOUT 1%.
AND THAT'S OKAY.
BECAUSE THIS IS PRETTY CHEAP.
BUT IT IS AN EFFECTIVE STRATEGY
BUT YOU HAVE TO HAVE A LOT OF
PEOPLE AVAILABLE TO SEND OUT
YOUR MAILINGS TO IN ORDER FOR IT
TO WORK FOR YOUR PARTICULAR
STUDY.
A LOT OF PEOPLE DO PRESENTATIONS
AT HEALTH FAIRS OR COMMUNITY
SETTINGS.
THAT'S A GREAT IDEA.
ENCOURAGE YOU TO DO IT.
NONE OF THESE WILL GIVE YOU HALF
OF YOUR SAMPLE.
THEY'RE ALL GOING TO BE THIS
LAYERED APPROACH THAT YOU TAKE.
ONE THING THAT I DON'T SEE AS
FREQUENTLY BUT RECOMMEND IT TO
YOU IS TO PAIR UP WITH ONE OR
TWO OTHERS WHO WERE DOING
RESEARCH IN A DIFFERENT AREA.
BUT MAYBE HAVE SORT OF SIMILAR
CRITERIA, ENTRY CRITERIA, THAT
YOU DO BUT DIFFERENT
EXCLUSIONARY CRITERIA.
BECAUSE WHAT MIGHT HAPPEN --
I'VE SEEN THIS DONE VERY
SUCCESSFULLY, WHAT CAN HAPPEN IS
THAT SOMEBODY WHO IS NOT
ELIGIBLE FOR YOUR STUDY MAY BE
ELIGIBLE FOR THE STUDY NEXT DOOR
AND VICE VERSA.
AND IF YOU CAN PURPOSE WITH
OTHER RESEARCHERS -- PARTNER
WITH OTHER RESEARCHERS, AND YOU
MUST DO THIS WITH THE PERMISSION
OF POTENTIAL RESPONSIBILITIES.
IT CAN BE VERY EFFECTIVE.
YOU HAVE SOMEBODY ALREADINISTED
IN RESEARCH.
THEY ALREADY WANT TO CONTRIBUTE.
AND SO ONCE YOU HAVE THAT
PERSON, EVEN IF THEY'RE NOT
ELIGIBLE FOR YOUR STUDY, THEY
MAY BE ELIGIBLE FOR ANOTHER
STUDY.
SO THINK ABOUT THAT EARLY --
REFERRAL PROCESS.
SET YOUR MILESTONE GOALS
REASONABLY.
YOUR RECRUITMENT MILE STOPS.
MAKE SURE THAT YOU ARE --
STONES.
MAKE SURE YOU'RE BEING
REALISTIC.
IN SOME CASES YOU CAN EMPLOY A
RUN-IN STRATEGY.
THIS IS NOT UNIVERSE SIMPLY
APPLICABLE FOR ALL STUDIES.
YOU HAVE TO THINK ABOUT WHETHER
IT IS APPROPRIATE FOR YOUR
STUDY. THIS IS WHEN YOU HAVE
POTENTIAL PARTICIPANTS BEFORE
YOU RANDOMIZE THEM.
CONSENT THEM BUT BEFORE YOU
RANDOMIZE THEM, YOU HAVE THEM DO
SOMETHING.
YOU HAVE THEM DO SOMETHING
SIMILAR TO WHAT THEY WOULD DO IN
THE STUDY BUT IT'S SOMETHING
THAT BOTH ARMS WOULD DO, OR ALL
THREE ARMS.
HOWEVER, MANY YOU HAVE.
IF YOU HAVE PEOPLE THAT YOU WANT
TO RECORD IN A DIARY, SEND THEM
HOME FOR TWO WEEKS.
ASK THEM TO RECORD WHATEVER YOU
WANT THEM TO RECORD IN A DIARY.
AND THAT RUN-IN PERIOD CAN HELP
YOU IDENTIFY WHO WILL BE
ADHERING AND WHO WILL NOT BE
ADHERENT.
IT'S A MUCH MORE SELF-SELECTED
POPULATION THAT YOU END UP WITH,
IF YOU GO THROUGH THIS STRATEGY.
SO IF YOU'RE LOOKING TO DO
SOMETHING ON THE EFFECTIVENESS
END OF THE TECHRAM, IT MAY NOT
BE THE RIGHT STRATEGY.
IF YOU'RE LOOKING TO DO
SOMETHING ON THE EFFICACY END OF
THE SPECTRUM, IT MAY WORK FOR
YOU.
AND, OF COURSE, YOU ALWAYS WANT
TO EMPLOY STRATEGIES TO MAKE
SURE YOU HAVE A REPRESENTATIVE
SAMPLE.
RETENTION IS AS IMPORTANT, MAYBE
MORE IMPORTANT THAN RECRUITMENT.
IF YOU CAN GET PEOPLE INTO YOUR
STUDY BUT YOU CAN'T KEEP THEM
THERE, THAT'S A PROBLEM.
SO HOW DO YOU IMPROVE RETENTION?
AND THERE ARE LOTS OF THINGS YOU
CAN DO.
PROBABLY THE MOST IMPORTANT IS
TO THINK ABOUT BURDEN AND THINK
ABOUT HOW YOU CAN REDUCE BURDEN.
THE OTHER THING TO THINK ABOUT
IS -- AND BY REDUCING BURDEN
WHAT I MEAN IS SHORTEN YOUR
STUDY DURATION, SHORTEN THE
AMOUNT OF QUESTIONNAIRES PEOPLE
HAVE TO FILL OUT.
SHORTEN THE NUMBER OF VISITS
THEY HAVE TO DO.
OR MAKE IT EASIER FOR THEM TO DO
THOSE THINGS.
PROVIDE VOUCHERS, GO TO THEIR
HOMES SOMETIMES.
GO TO A MORE CENTRAL LOCATION.
THIS ARE LOTS OF THINGS THAT YOU
CAN DO DEPENDING ON YOUR
PARTICULAR STUDY.
BUT MAKE YOUR INTERVENTION AS
SIMPLE AS YOU CAN.
COMPLEX INTERVENTIONS ARE A
REASON THAT PARTICIPANTS DO NOT
ADHERE AND EVENTUALLY WHY THEY
DROP OUT.
IF YOU CAN OPTIMIZE THE VISITS,
I KNOW THEY'RE COMING TO THE CRC
FOR A MEDICAL VISIT, MAKE SURE
THAT'S ALWAYS A STUDY VISIT AS
WELL.
THAT HELPS.
REDUCING BARRIERS, WE'VE TALKED
ABOUT THAT.
PROVIDING INCENTIVES.
INCENTIVES DON'T HAVE TO BE
COSTLY BUT THEY HAVE TO BE
MEANINGFUL A REFRIGERATOR MAG IN
THE, PENCIL, MAYBE NOT.
BUT SOMETHING THAT REALLY MEANS
SOMETHING.
TO PARENTS.
IF YOU'RE GETTING PARTICIPANTS A
MEDICATION THAT, FOR EXAMPLE,
REALLY INCREASES DRY MOUTH,
THAT'S A BURDEN FOR
PARTICIPANTS.
NOBODY LIKES THAT.
SO MAYBE YOU GIVE THEM A WATER
BOT THAT WILL HAS YOUR LOGO ON
IT.
THAT'S MEANINGFUL BECAUSE IT
TELLS PARTICIPANTS THAT YOU
UNDERSTAND WHAT SOME OF THESE
SIDE EFFECTS ARE AND YOU'RE
TRYING TO HELP THEM OUT.
MAKE YOUR VISITS -- SET UP YOUR
VISITS EARLY IN THE PROCESS.
IF YOU SET EACH VISIT AT A TIME
WHEN YOU HAVE A CURRENT VISIT,
THEN YOU -- WHAT AM I TRYING TO
SAY?
SET UP THE FOLLOW-UP VISITS
EARLY ON.
SET THEM ALL UP AT THE SAME
TIME.
SODA PARTICIPANTS WHAT THEY'RE
GETTING INTO AND KNOW WHEN
THEY'RE GOING TO COME BACK.
IF YOU DO THAT THEY'RE MORE
LIKELY TO BE ABLE TO MAKE THOSE
VISITS.
SO ADHERENCE.
THE ONLY THING I REALLY HAVE TO
SAY IS ADHERENCE, YOU NEED TO
MEASURE IT.
AND IT'S A HARD THING TO
MEASURE.
YOU NEED TO AS MUCH AS YOU CAN,
ENHANCE IT.
AND BE ADHERENCE, I MEAN
PARTICIPANT ADHERENCE,
OBVIOUSLY.
BUT ALSO PROVIDER ADHERENCE.
WHOEVER IS DELIVERING YOUR
INTERVENTION, YOU WANT TO --
THAT PERSON TO BE AS ADHERENT AS
POSSIBLE AS WELL.
AND WE TALKED ABOUT USING A
RUN-IN PHASE IN ORDER TO
INCREASE ADHERENCE.
THIS IS AN EXAMPLE THAT MANY
PEOPLE ACTUALLY USE.
IF YOU'RE DOING A STUDY OF
OBSTRUCTIVE SLEEP APNEA, THEN
THE TREATMENT OF CHOICE FOR MOST
PATIENTS WITH OBSTRUCTIVE SLEEP
APNEA IS TO USE CPAP, USE
CONTINUOUS POSITIVE AIR PRESSURE
FOR THEM.
BUT IT'S VERY, VERY BURDENSOME,
BECAUSE IT'S THE MASKS THAT
PEOPLE HAVE TO WEAR, AT NIGHT.
NOBODY LIKES IT.
EVEN IF YOU'RE NOT RUNNING A
STUDY PATIENTS WHO USE IT DON'T
LIKE IT.
BUT SOME PEOPLE WILL DO IT AND
SOME PEOPLE ABSOLUTELY WON'T.
SO HOW DO YOU KNOW WHO THOSE
PEOPLE ARE BEFOREHAND?
BECAUSE NOBODY IS GOING TO WEAR
THE CPAP, THEN YOU'RE NOT GOING
TO BE ABLE TO FIND OUT THE
ANSWER TO YOUR QUESTION.
THAT'S PART OF THE INTERVENTION.
IN THAT CASE WHAT YOU MIGHT WANT
TO DO IS HAVE A [INDISCERNIBLE]
WITH YOU HAVE PEOPLE WEAR A
CPAP.
YOU DON'T DELIVER ANYTHING.
NO POSITIVE -- BUT THEY WEAR THE
MASK.
PEOPLE THAT CAN'T ADHERE TO THAT
LIKELY WON'T ADHERE TO THE
INTERVENTION.
SO THAT'S AN IDEA OF HOW YOU CAN
DO THESE.
THERE ARE WAYS TO OPTIMIZE
ADHERENCE.
I RECOMMEND YOU FET SOMEONE ON
YOUR TEAM WHO KNOWS HOW TO DO
THIS.
THERE IS A SCIENCE TO ADHERENCE.
ONE OF THE STRATEGIES THAT CAN
BE USED IS CALLED MOTIVATIONAL
INTERVIEWING.
CAN BE USED WITH PARTICIPANTS
AND WITH BROADERS.
IT IS A WAY TO INCREASE
ENGAGEMENT OF YOUR PARTICIPANTS
IN YOUR STUDY.
AND PROVIDERS.
BUT YOU CAN'T LEARN HOW TO DO IT
THERE A BOOK.
YOU NEED TO BE TRAINED IN IT.
SO IF YOU WANT TO EMPLOY THIS
STRATEGY, IF YOU HAVE A LARGE
TRIAL, AND WANT TO --
BURDENSOME, WANT DO EMPLOY THIS
IT'S A GOOD IDEA TO THINK ABOUT
FINDING SOMEBODY THAT CAN DO IT.
THIS ORIENTATION SESSION IS
SOMETHING THAT I WAS ALLUDING TO
BEFORE.
WHEN YOU HAVE A GROUP OF PEOPLE
AND YOU'RE TELLING THEM ABOUT
THE STUDY TO SEE IF THEY WANT TO
PARTICIPATE.
THIS IS BEFORE YOU ACTUALLY
ENROLL ANYONE, BEFORE YOU
RANDOMIZE ANYONE.
YOU'RE LAYING OUT YOUR CASE FOR
WHY THEY MAY WANT TO
PARTICIPATE.
THIS IS A GREAT OPPORTUNITY FOR
YOU TO PROVIDE INFORMATION.
AND TO DEVELOP THIS RELATIONSHIP
WITH POTENTIAL PARTICIPANTS.
I REALLY LIKE -- IT'S NOT
APPROPRIATE FOR YOU'LL STUDIES
BUT IF I SAID APPROPRIATE FOR
YOUR STUDY I REALLY THINK THIS
IS A FANTASTIC STRATEGY.
IT EASTBOUND ABLEST YOU TO
ANSWER QUESTIONS, ENABLES YOU TO
GET FAIRLY ADHERENT PEOPLE.
THEY'VE ALREADY COME TO AN
ORIENTATION SESSION.
PEOPLE INTERESTED IN THE STUDY.
AND ENABLES YOU TO GIVE THEM THE
CASE WHY THEY SHOULDN'T ENROLL.
ALL THE REASONS THEY SHOULDN'T.
YOU'RE ALSO GOING TO TALK ABOUT
WHY THEY SHOULD ENROLL IN THE
STUDY.
BUT IT REALLY GIVES YOU
ABOPPORTUNITY TO GET PEOPLE INTO
YOUR STUDY WHO MAY BE -- YOU MAY
BE ABLE TO RETAIN INTO THE
STUDY.
CONTACT BACKUPS.
THESE ARE FAMILY MEMBERS, IF YOU
CAN GET THOSE.
THAT'S A GOOD IDEA IF YOU'RE
DOING A LONGITUDE TECHNOLOGY
STUDY.
PEOPLE MOVE AND SOMETIMES THEY
FORGET TO TELL YOU.
SO IT'S A GOOD IDEA TO HAVE A
BACKUP.
AND AGAIN YOU GET THAT FROM THE
PARTICIPANTS WITH THEIR CONSENT
ON THE CONSENT FORM.
IF YOU CAN MAINTAIN CONTACT
AGAIN WITH TRIALS THAT ARE
LONGITUDINAL, MAINTAIN CONTACT
WITH PARTICIPANTS, ONE WAY TO DO
IS IT TO PHONE THEM.
IF THAT'S PART OF YOUR
INTERVENTION.
BUT IT'S NICE TO SEND BIRTH AT
THAT CARDS.
DOESN'T COST HAVE.
PEOPLE REALLY APPRECIATE IT.
AGAIN I RECOLLECT PART OF THIS
RELATIONSHIP -- AGAINST IT'S
PART OF THIS RELATIONSHIP THAT
YOU'RE BUILDING.
NEWS LETTERS ARE ALSO VERY
EFFECTIVE.
THEY TAKE TIME BUT VER VERY
EFFECTIVE.
SO I WANT TO END WITH AN EXAMPLE
OF A STUDY THAT KIND OF
HIGHLIGHTS SOME OF THE POINTS
THAT I'VE TRIED TO LAY OUT FOR
YOU.
AND THIS IS A STUDY CALLED
ENRICHED, DONE A COUPLE YEARS
AGO.
IT'S OVER NOW, CALLED ENHANCING
RORY IN CORONARY HEART DISEASE
PATIENTS.
THE BASIC PREMISE COMES FROM
DATA LIKE THESE.
THIS IS NOT THE ENRICH DATA.
THESE ARE FROM AN EARLIER STUDY.
AND IT'S A PHENOMENON THAT WE
KNOW VERY WELL.
AND THE PHENOMENON IS THIS.
THAT AFTER SOMEBODY HAS A HEART
ATTACK, IF THEY'RE DEPRESSED
THEY'RE MUCH MORE LIKELY TO DIE
THAN IF THEY'RE NOT DEPRESSED.
SO WHAT YOU CAN SEE, THIS IS A
MONTH POST MI, POST HEART
ATTACK.
AND WITHIN TWO MONTHS POST MI,
AS YOU CAN SEE HERE, WE SEE A
DIVIRGINS, PARTICIPANTS WHO
BECOME DEPRESSED VERSES THOSE
THAT DO NOT.
THE MORE TALLDY RATES JUST GO
UP.
A PHENOMENON THAT -- IT'S VERY
REAL.
SO THE EVAN RICHED TRIAL SAID WE
NEED TO DO SOMETHING ABOUT THIS.
LET'S SEE WHAT HAPPENS IF WE
TREAT THE DEPRESSION.
LET'S TRY THAT.
SO THAT'S WHAT THE ENRICHED
TRIAL WAS.
AND THEY ALSO KNEW THAT
DEPRESSION WAS VERY STRONGLY
LINKED TO SOCIAL SUPPORT.
SO THEY ACTUALLY HAD AN
INTERVENTION, A DUAL
INTERVENTION TO TARGET LOW
SOCIAL SUPPORT AND HIGH
DEPRESSION.
AND SO THE HYPOTHESIS WAS THAT
THEY
THEY WANTED TO TEST WHETHER
TREATING DEPRESSION AND LOW
SOCIAL SUPPORT RIGHT AFTER A
HEART ATTACK WAS GOING TO REDUCE
DEATH RATES, AND NON FATAL
RECURRENT HEART ATTACKS.
SIMPLE STUDY, RIGHT?
IT WAS NOT SIMPLE.
SO ULTIMATELY, THEY ENROLLED
ALMOST 2500 POST HEART ATTACK
PARTICIPANTS THAT EITHER
PRESENTED WITH DEPRESSION OR LOW
SOCIAL SUPPORT OR BOTH.
COMMONLY BOTH.
AND THEY RANDOMIZED INTO A GROUP
THAT GOT USUAL CARE.
VERSUS ONE THAT GOT A PSYCHO
SOCIAL INTERVENTION TO TREAT THE -- TO TRE AT THE SOCIAL
SUPPORT AND DEPRESSION.
AND THEIR ENDPOINTS WERE CARDIAC
MORTALITY, AND RECURRENT HEART
ATTACK.
AND THEY FOLLOWED THEM FOR
ALMOST 3-YEARS -- 3 AND A HALF
YEARS, DETERMINE TOTALLY
MOVINGED.
SO HERE IS WHAT I WANT YOU --
THIS IS NOT WHAT -- THEIR
INCLUSIONARY CRITERIA WERE THAT
THEY WERE GOING TO ENROLL PEOPLE
WIN 28 DAYS OF HAVING A HEART
ATTACK.
NOW, THEY WANTED TO ENROLL THEM
QUICKER.
THEY WANTED TO GET THEM MORE
QUICKLY THAN THAT.
BECAUSE YOU SAW IN THAT GRAPH
THE DIVIRGINS HAPPENED AT TWO
MONTHS.
THEY NEW IT WOULD NOT BE
FEASIBLE TO ENROLL THEM MORE
QUICKLY THAN THIS.
WHY IS THAT?
WELL, YOU HAVE A PATIENT, JUST
HAD A HEART ATTACK, IN THE
HOSPITAL.
THEIR FAMILY IS INVOLVED.
THEY HAVE OTHER THINGS DO THINK
ABOUT BESIDES YOUR STUDY.
SO THEY SETTLED ON RECRUITING
THEM WITHIN ABOUT A MONTH AFTER
A HEART ATTACK.
AND THEY HAD A BUNCH OF CRITERIA -- THEY H AD -- THEY HAD
INCLUSIONARY CRITERIA THAT COULD
SUNSTONIATE THE FACT THAT THEY
HAD A HEART ATTACK.
THEY HOOKED AT ENZYMATIC
INCREASES, THEN IDENTIFIED
WHETHER THEY WERE DEPRESSED OR
HAD LOW SOCIAL SUPPORT AND THERE
WERE GOOD MEASURES TO DO THAT.
THIS IS WHAT I WANT TO SHOW YOU.
THIS IS THE CONCERT DIAGRAM.
THEY SCREENED HEADLINE 34,000 --
ALMOST 34,000 PEOPLE.
34,000 PEOPLE.
TO GET 2,481.
SO THEY SCREENED THIS NUMBER,
SOME DIDN'T MEET CRITERIA FOR
HAVING HAD A HEART ATTACK.
RIGHT?
BUT NOT THAT MANY.
THEN SOME OF THEM, FAIR NUMBER,
7,000 ALMOST, WEREN'T DEPRESSED
OR HAD LOW SOCIAL SUPPORT.
LOOK AT THIS.
23,000 DIDN'T MEET THEIR MEDICAL
ELIGIBILITY.
GIVEN WHAT WE'VE JUST TALKED
ABOUT WHAT DOES THAT MEAN?
TH THEY TOOK SOMETHING WRONGTH
EXCLUSIONARY CRITERIA?
THESE ARE THE BEST RESEARCHERS
AROUND.
IT'S NOT WRONG BUT WHEN YOU STEP
BACK AND LOOK AT IT, THIS IS
WHERE THEY HAD THE PROBLEM.
THIS IS WHERE IT HAPPENED.
IT WASN'T THAT IT WAS WRONG BUT
THEY HAD DO SCREEN SO MANY
PEOPLE IN ORDER TO GET 2500
PEOPLE BECAUSE OF THESE
ELIGIBILITY CRITERIA.
SCIENTIFICALLY, IT WAS THE RIGHT
THING TO DO BUT IT MADE FOR A
VERY DIFFICULT STUDY.
TO OPERATIONALIZE THIS MORE
CLEARLY FOR YOU, WHAT THIS MEANS
IS THAT FOR EVERY 100
PARTICIPANTS THAT THEY SCREENED,
THESE WEREN'T PEOPLE THAT CALLED
UP AND SAID I WANT TO SPATE.
THESE ARE 100 PARTICIPANTS THAT
THEY SCREENED.
ONLY 7 WERE ACTUALLY ENROLLED
AND RANDOMIZED INTO THE TRIAL.
THAT'S A LOT OF WORK.
ANOTHER WAY OF THINKING ABOUT
IT, IN ORDER TO GET 1 THEY HAD
TO SCREEN 14.
AND, OF COURSE, THEY HAD A LOT
OF FIGHTS.
AND NONE OF THE SITES WERE ABLE
TO ADEQUATELY ENROLL
PARTICIPANTS.
WHEN YOU HAVE A MULTISITE TRIAL
YOU WILL FIND THAT SITES RECRUIT
AT DIFFERENT RATES.
THERE MAY BE REASONS TO KEEP
SITES THAT HAVE LOW RECRUITMENT,
BECAUSE THEY'RE RECRUITING
PARTICULAR CHARACTERISTICS OF
THE PATIENT POPULATION THAT
YOU'RE INTERESTED IN.
BUT IT IS A PHENOMENON THAT
OCCURS FAIRLY FREQUENTLY.
THERE HAS BEEN A LOT OF TALK
AMONG THE INVESTIGATORS WHY
THERE ARE DIFFERENCES --
PROBLEMS WITH RECRUITMENT AND
RETENTION.
AND SOME OF THEM HAD TO DO WITH
AXIS.
SOME OF -- ACCESS.
SOME HAD TO DO WITH THE EXACT
THEY WERE RECRUITING AT VERY
RESEARCH HEAVY SITES.
SO THERE WAS A LOT OF RESEARCH
GOING ON.
AND YOU HAVE TO THINK ABOUT
THAT.
IS THERE A LOT OF STUFF GOING ON
IN THIS AREA?
WHERE YOU'RE GOING TO BE
RECRUITING.
THEY DIDN'T HAVE ADEQUATE
COLLABORATIVE TEAMS.
AND SO THAT REDUCED THEIR
ABILITY TO RECRUIT.
THEIR BURDEN WAS HIGH.
SO THESE PARTICIPANTS HAD TO
COME IN AND PARTICIPATE IN A
PSYCHO SOCIAL INTERVENTION,
WHICH ALWAYS IS A LITTLE BIT
MORE BURDENSOME THAN TAKING
PHARMACOLOGIC PILL.
AND THEY HAD A LOT OF
ASSESSMENTS.
THIS STUDY WENT ON FOR 3 AND A
HALF YEARS.
SO THIS WAS A VERY BURDENSOME
STUDY.
THEY -- BUT THE REAL KEY IS HERE
THEY HAD REALLY RESTRICTIVE
ELIGIBILITY CRITERIA.
AS YOU CAN SEE FROM THE
EXCLUSION.
THE HIGH NUMBER OF PATIENTS THAT
WERE EXCLUDED.
SO LET ME WALK THROUGH A COUPLE
OF OVERALL CONCLUSIONS.
KNOW YOUR LITERATURE.
KNOW THE HISTORY OF YOUR
LITERATURE.
KNOW WHERE THINGS FIT.
BE ABLE TO IDENTIFY CONTEXTUAL
FACTORS.
KNOW WHERE YOUR QUESTION LIES.
ON THAT RESEARCH CONTINUUM.
THAT'S REALLY CRITICAL.
MAKE SURE YOU'RE DESIGNING THE
RIGHT STUDY FOR THE RIGHT TIME.
FOR THAT LITERATURE.
MAKE SURE YOU HAVE CLARITY ON
YOUR QUESTION.
THIS SOUNDS KIND OF SILLY, OF
COURSE I HAVE CLARITY.
I WANT TO KNOW IF THIS DOES
THIS.
UNDERSTANDING THE COMPLEXITY OF
YOUR QUESTION REALLY MEANS THAT
YOU HAVE TO DIVE DEEP INTO SOME
OF THE ISSUES THAT WE'RE TALKING
ABOUT AND MORE AS WELL.
TO UNDERSTAND WHAT YOUR -- ALL
OF THE COMPLEXITIES OF YOUR
QUESTION.
HAVE A REALLY GOOD, VERY
SPECIFIC TARGETED UNDERSTANDING
OF THE PATIENT CHARACTERISTICS
THAT YOU WANT DO TARGET.
MAKE SURE THE PARTICIPANTS MATCH
THE OUTCOMES.
YOUR PRIMARY OUTCOMES.
MAKE SURE IT'S A GOOD MATCH,
FEASIBLE MATCH.
AND MAKE SURE THAT YOU'RE ASKING
THE RIGHT QUESTIONS AT THE RIGHT
DIME.
GOING BACK TO INTERNAL VERSES
EXTERNAL VALIDITY, FIGURE OUT IN
THE CONTEXT OF YOUR QUESTION
WHAT'S MOST IMPORTANT OR, IN
OTHER WORDS, THINKING ABOUT WHAT
WE WORRY ABOUT THE MOST.
FALSE NEGATIVES OR FALSE
POSITIVES.
AND THAT'S ALL I HAVE.
ARE THERE ANY QUESTIONS?
IF AS YOU'RE READING THROUGH
YOUR MATERIAL, IF YOU HAVE
QUESTIONS FEEL FREE TO SUBMIT
THEM TO ME.
I'D BE HAPPY TO ANSWER THEM FOR
YOU.
THANK YOU.