>> GOOD AFTERNOON, THANK YOU ALL FOR JOINING US FOR ETHICS GRAND ROUNDS TODAY. WE'RE VERY EXCITED TO LAUNCH A NEW LECTURESHIP, THE ZEKE EMMANUEL LECTURE IN BIOETHICS. WE IN THE DEPARTMENT OF BIOETHICS DECIDED TO ESTABLISH A LECTURESHIP IN ZEKE'S NAME TO SHOW HIM HOW MUCH HE MEANS TO US AND TO THE NIH COMMUNITY. AS MANY OF YOU KNOW ALREADY, ZEKE WAS THE CHAIR OF THE DEPARTMENT OF BIOETHICS HERE AT THE CLINICAL CENTER FOR MORE THAN A DECADE. HE THEN SPENT TWO YEARS AT THE WHITE HOUSE AS A HEALTH POLICY ADVISOR FOR THE OMB, DIRECTOR OF OMB, EXCUSE ME AND CURRENTLY HE'S THE CHAIR OF THE DEPARTMENT OF MEDICAL ETHICS AND HEALTH POLICY, VICE PROVOST FOR GLOBAL INITIATIVES AND HE IS THE DIANE AND ROBERT LEVEE UNIVERSITY PROFESSOR AT THE UNIVERSITY OF PENNSYLVANIA. >> THEY'RE TRYING TO KEEP HIM BUSY. IF YOU DID NOT KNOW ZEKE WHEN HE WAS HERE AT THE NIH OR DON'T KNOW HIS EXTENSIVE AND IMPRESSIVE SCHOLARSHIP, YOU MAY KNOW HIM THROUGH ONE OF THE RECENT SERIES OF ARTICLES HE'S WRITTEN FOR THE NEW YORK TIMES, VERY ELOQUENT AND ARTICULATE SERIES ON HEALTH CARE OR SEEN HIM ON TV, RECENTLY DEFENDING THE AFFORDABLE CARE ACT OR COMMENTING ON THE SUPREME COURT DECISION OR MIGHT EVEN HAVE READ HIS FOOD BLOG. ZEKE IS A WORLD-RENOWNED BIY ETHICIST, HE HAS AN MD AND A Ph.D. FROM FLITICAL PHILOSOPHY--POLITICAL PHILOSOPHY. HE STARTED HERE AT THE NIH, IN THE LATE 1990S WITH A COUPLE OF PEOPLE AND SOME BOLD IDEAS AND SOME SUPPORT AND ENCOURAGEMENT FROM DR. GOWAN. WITH THAT ZEKE CREATE WHAD A NOW A WORLD CLASS DEPARTMENT OF BIOETHICS KNOWN FOR EXCELLENT SCHOLARSHIP AND SERVICE AND FOR TRAINING TOMORROW'S LEADERS AND BIOETHICS. ZEKE'S OWN RESEARCH SPANS A WIDE RANGE OF TOPICS INCLUDING HEALTH POLICY, ALLOICATION AND RESOURCES HEALTHCARE REFORM, INTERNATIONAL CLINICAL RESEARCH, EXPLOITATION, INFORMED CONSENT AND MANY, MANY, OTHER THINGS. ZEKE IS A CUTTING EDGE SCHOLAR, ENTHUSIASTIC LEADER AND WARM, GENEROUS AND FUN PERSON. THIS LECTURESHIP IS JUST ONE SMALL WAY WE HOPE TO CONTINUE TO HONOR ZEKE HERE AT THE NIH. WE PLAN TO HAVE ANNUAL ZEKE EMMANUEL LECTURESHIP IN CONJUNCTION WITH GRAND ROUNDS ROUNDS AND WE WILL PROVIDE SCHOLARS AND LEADERS FOR THE EMMANUEL LECTURESHIP. FOR THIS ONE WE COULD THINK OF NO OTHER TO DELIVER THE FIRST ANNUAL LECTURE THAN ZEKE HIMSELF AND WE ARE DELIGHTED HE IS HERE WITH US TODAY BUT FIRST I WOULD LIKE TO INTRODUCE JOHN GOWAN, AND THEN TURN IT OVER TO DAVE, WINLER, OUR EMCEE. >> THANK YOU CHRISTINE AND WHEN I THINK ABOUT WHAT'S BEEN SO SPECIAL ABOUT SPENDING MY CAREER HERE AT THE NIH, BY FAR THE NUMBER ONE COMPONENT OF THE NIH ARE THE PEOPLE AND IT'S A FAMILY. AND ZEKE'S A MEMBER OF THAT FAMILY SO HE MAY HAVE MOVED FOR A WHILE UP TO PHILADELPHIA, BUT HE'S STILL PART OF THIS FAMILY. AND FAMILY'S HAVE MILESTONES, ZEKE WAS AT THE NIH 13 YEARS, SO HE'S BEEN BAR MITZVAHED AND NOW THAT HE'S GONE OUT AS AN ADULT HE'S DONE THAT BUT HE'LL CAN KEEP COMING HOME BUT I WANT TO RELATE THAT INFORMATION AND SAY HOW PROUD EVERYBODY IS OF ZEKE AND WHAT HIS CAREER PATH HAS BROUGHT HIM INTO THE WORLD. THANK YOU. [ APPLAUSE ] >> SO I'M DAVE FROM THE DEPARTMENT OF BIOETHICS, A COUPLE THINGS, THIS IS STAND ARD EGHT LICKS GRAPED ROUNDS DESPITE THE WONDERFUL GIFT OF ZEKE'S PRESENCE HERE, THAT MEANS A COUPLE THINGS, ONE THIS IS AN ACTUAL CASE WHERE WE PRESENT THE CASE AND THEN ASK ZEKE TO COMMENT ON IT. THESE ARE ALL ACTUAL CASES AND TYPICALLY THEY'RE CASE IN THE SENSE THAT WE KNOW A LOT OF THE FACTS ABOUT, WE KNOW THE PEOPLE, WE KNOW THEIR NAMES, WE KNOW THEIR HISTORIES, AGES, WE KNOW THEIR FAMILIES AND WHAT I'VE SAID MANY TIMES HERE BEFORE IS THAT FOR CONFIDENTIALITY PURPOSES WE'LL MAP VARIOUS ASPECTS OF THE CASE, WE'LL MASK AGES AND GENDERS THIS, IS A VERY DIFFERENT CASE AS YOU'LL FIND OUT THIS, WAS AN ANON MOUSE PHONE CALL WE GOT AND AS A RESULT WE KNOW VERY LITTLE ABOUT THE CASE SO THIS ISN'T A MASK CASE, YOU'LL HEAR LITTLE OF THE SPECIFIC DETAILS OF THIS CASE, BUT THE SIMPLE FACT THAT WE DON'T KNOW THEM. AND AS A RESULT, I THINK IT'S GOING TO REQUIRE MORE BRAINSTORMING, AS YOU'LL SEE IN A MINUTE ON ZEKE'S PART BUT ALSO ON ALL OF OUR PARTS TO TRY TO ASK OURSELVES, WE DESCROAPT A LOST THE DETAILS OF THIS CASE AND THAT'S GOING TO RAISE THE QUESTION OF, WHICH DETAILS ARE RELEVANT AND WHAT WOULD THEIR RELEVANCE IMPLY WITH THE SPECIFIC QUESTION AND THE SPECIFIC QUESTION, TODAY, I THINK IS AT THE HEART OF DOING ETHICAL CLINICAL RESEARCH AND IT'S BASICALLY THE QUESTION OF WHEN PATIENTS SHOULD BE ABLE TO GET ACCESS TO EXPERIMENTAL MEDICATIONS, THAT'S A QUESTION WE'LL GET TO IN A MINUTE. THE LAST THING TO REMIND PEOPLE WE STREAM THIS ON TO THE WEB SO IF HAVE YOU QUESTIONS, PLEASE IF YOU CAN, GET TO THE MIC'S IN THE AISLES. IF YOU CAN'T DO THAT, LET ONE OF US REPEAT THE QUESTION INTO A MIC BEFORE WE TRY TO ANSWER IT. SO TO GIVE US THE CASE WE HAVE MARRIAN DANIS AN INTERNIST AT THE NIH FOR A LONG TIME. MARY NOT ONLY TOOK THIS CALL BUT MARRIAN IS THE PERSON WHO'S BEEN RUNNING THE ETHICS SERVICE HERE AT THE CLINICAL CENTER AND SHE'S IN CHARGE OF THE SERVICE THAT'S PRESENTING ALL OF THESE CASES SO IT'S NICE TO HAVE HER PRESENT ONE OF THEM. [ APPLAUSE ] >> THANKS, DAVID. IT IS A TREAT TO PRESENT THIS CASE FOR ZEKE TO DISCUSS. HE RECRUITED ME TO BE IN ROLE OF RUNNING OUR CONSULT SERVICE. SO THE CASE AS DAVID MENTIONED IS ONE OF AN ANON MOUSE CASE. LET ME SAY FIRST I HAVE NO CONFLICT OF INTEREST AND WE HAVE SEVERAL OBJECTIVES FOR YOU TO--IN THE COURSE OF THIS HOUR, THINK ABOUT WAWE OWE TO PARTICIPANTS IN CLINICAL TRIALS AND PERHAPS GAIN SOME CAPACITY TO BETTER EXPLAIN TO RESEARCH PARTICIPANTS WHAT THEY CAN AND SHOULD EXPECT REGUARDING BENEFITS FROM THEIR PARTICIPATION. SO THE CALL WAS TAKEN BY A FELLOW WORKING WITH MEOT SERVICE. THE CALL WAS FROM A 50 YEAR-OLD WOMAN WHO WAS PARTICIPATING IN AN NIH STUDY AND SHE WANTED TO DISCUSS WHETHER IT WOULD BE POSSIBLE FOR HER TO GET ACCESS TO AN EXPERIMENTAL TREATMENT THAT SHE WAS--KNEW WAS THE ONE BEING TESTED IN THE TRIAL SHE WAS IN. THE CALLER HAD A PROGRESSIVE NEUROLOGIC CONDITION FOR 10 YEARS. FROM WHAT WE GLEANED FROM HER DESCRIPTION TO US, IT SOUNDED COMPATIBLE WITH SOMETHING LIKE PRIMARY PROGRESSIVE MULTIPLE SCLEROSIS, ALTHOUGH SHE DID NOT SPECIFICALLY NAME HER ILLNESS. SHE TRIED A NUMBER OF TREATMENTS AND NONE OF THEM HAD HELPED HER BEFORE HER COMING TO THE NIH. SHE HAD--THERE HAD BEEN PRIOR TESTING OF THE EXPERIMENTAL INTERVENTION AND IT WAS FOUND TO BE ACCEPTABLE IN TERMS OF SIDE EASTS AND HAD BEEN APPROVED BY IRB, IN ADDITION, THERE WAS EVIDENCE THAT THE EXPERIMENTAL TREATMENT MIGHT SLOW OR EVEN HALT PROGRESSION OF THE CALLER'S CONDITION. THE EXPERIMENTAL TREATMENT IS CURRENTLY BEING TESTED AS PART OF AN NIH SPONSORED DOUBLE BLIND PLACEBO CONTROL TRIAL AT THE TIME OF THIS CALL. AT THE EPPED OF THE STUDY, ALL PARTICIPANTS GET AN OFFER TO RECEIVE THAT TREATMENT. THE CALLER HAD BEEN ENROLLED IN THIS PROTOCOL FOR ABOUT THREE YEARS AND EXPECTED THAT THE STUDY WOULD GO ON FOR ANOTHER ONE OR TWO YEARS, SO THAT WOULD BE THE LAG TIME BEFORE SHE COULD POSSIBLY GET IT IF SHE WERE ON THE PLACEBO ARM. OVER THE PAST YEAR, THE CALLER'S CONDITION HAS TAKEN A SIGNIFICANT TURN FOR THE WORSE AND SHE BELIEVES SHE'S GETTING PLACEBO. SHE'S EXTREMELY FRIGHTENED WHILE WE WERE TALKING WITH HER AND IS CONCERNED THAT SHE MAY HAVE TO WAIT LONGER AND IF SO, LONGER TO GET THE INTERVENTION IN THE FACTIVE ARM OF THE TRIAL, AND THAT THAT WOULD LEAD TO DIMINISHED CHANCE OF HER BENEFITING. SHE BELIEVES THE TREATMENT REPRESENTS HER LAST CHANCE TO OBTAIN EFFECTIVE TREATMENT TO STOP THE PROGRESSION OF HER DISEASE AND SHE STARTED THAT THE TREATMENT MAY BE A MIRACLE DRUG FOR SOME PATIENTS AND THAT SHE WOULD DO ANYTHING TO TRY AND GET IT. THE CALLER'S HOME NEUROLOGIST AGREED SHE'S LIKELY TO BE ON THE PLACEBO AND ALSO AGREES THAT THE WINDOW FOR TREATING HER CONDITION IS CLOSING. HE RECOMMENDED SHE CALL US TO SEE IF SHE COULD RECEIVE THE TREATMENT NOW. SO THE CONSULTATION TEAM, HE CALLER AND THE FELLOW AND I DISCUSS WHETHER IT WOULD BE APPROPRIATE FOR THE INVESTIGATOR TO GIVE HER THIS TREATMENT. SO THE QUESTIONS WE WOULD LIKE TO BRING TO THE TABLE FOR ZEKE TO CONSIDER ARE: UNDER WHAT CONDITIONS IF ANY, SHOULD PATIENTS HAVE ACCESS TO EXPERIMENTAL TREATMENT? WHO SHOULD PAY SUCH TREATMENT? AND DOES SOMEONE WHO PARTICIPATE INDEED RESEARCH HAVE A GREATER CLAIM TO ACCESS TO EXPERIMENTAL TREATMENTS IN? >> O JUST A REMINDER BEFORE WE ASK ZEKE TO HELP US THINK THROUGH THOSE QUESTIONS QUESTIONS AND ANSWERS TO THEM, WE WANT TO STOP FOR A SECOND, AGAIN IT'S AN ANON MOUSE CASE, WE DON'T HAVE MUCH FACTS BUT THERE ARE ANY SPECIFIC QUESTIONS REGUARDING THE CASE THAT ANYBODY THINK WOULD BE HELPFUL TO KNOW IN THINKING ABOUT THE ETHICS AND THE ANSWERS TO THESE QUESTION SYMPATHETIC NERVOUS SYSTEM--QUESTIONS? >> [INAUDIBLE RESPONSE FROM AUDIENCE ]vhK3 THE QUESTION THAT ZEKE ASKED IS THAT SHOULD HE ASSUME THAT ACCESS TO THE EXPERIMENTAL THERAPY IS GOING TO BE CONTINGENT ON IT BEING POSITIVELY EFFECTIVE, AS FAR AS WE KNOW, WE DON'T KNOW WHAT THE PROTOCOL WAS BUT WE WOULD ASSUME THAT WOULD MAKE LOGICAL SENSE. >> I WAS WONDERING IF THERE WAS GOOD REASON TO BELIEVE THE CALLER ACTUALLY WASN'T ON PLACEBO? HOW GOOD WAS DATA ABOUT EFFICACY AT THAT POINT? >> YOU KNOW WE GOT THIS CALL FROM HER, SHE DID NOT TELL US THE NAME OF THE PROTOCOL. WE DON'T KNOW WHO THE INVESTIGATOR WAS AND WE DON'T HAVE ANY WAY OF FINDING OUT WHAT THE INTERIM RESULTS WERE. >> I WAS GOING TO ADD TO THAT, THAT AT LEAST ACCORDING TO THE CALLER, HER NEUROLOGIST ON WHAT GROUNDS WE DON'T KNOW LEAD TO ALSO THAT SHE WAS ON PLACEBO. >> DO YOU HAVE ANY IDEA IF SHE HAD A CONVERSATION WITH THE INVESTIGATOR? ABOUT THIS? >> WE ENCOURAGED HER TO. >> BUT YOU DON'T KNOW WHETHER OR NOT SHE DID. >> SHE WASENTIOUS SENTIALLY CALLING US TO HELP SORT OUT HOW TO PROCEED. >> SO SHE'S ASKING YOU A HYPOTHETICAL QUESTION? >> NO, WELL, SHE WAS ASKING OUR ADVICE ABOUT HOW TO HANDLE THE SITUATION. >> RIGHT. BUT SOMETIMES, SOMEBODY'S ACTUALLY WORSENING ON THERAPY THERE ARE THINGS THAT ARE BUILT INTO THE TRIAL THAT CAN DEAL WITH THAT. >> YES, WE ASSUME SHE'S BEING MONITORED AND SHE WAS CALLS US-- >> BUT YOU DON'T ACTUALLY NO. >> BUT I THINK THIS CALL WAS BASICALLY PRELIMINARY ON HER PART TO THEN GOING TO TALK TO THE INVESTIGATORS AND SHE WANTED HELP IN SEEKING HOW TO DO THAT? >> ANY SENSE OF THE END POINT OF OF THE TRIAL? RELATED THING TO WHAT SUSAN ASKED? INVESTIGATORS REALLY SHOULDN'T STAND BY AND WATCH SOMEONE GET PROGRESSIVELY, WORSE AND WORSE AND WORSE AND THEN DIE, I THINK. >> WE DON'T KNOW. WE WOULD PRESUME THAT THE PROTOCOL INVOLVES MONITORING AND THAT THERE MAY BE SUPPORTIVE MEASURES PROVIDED FOR THOSE WHO--WE DON'T KNOW THE DETAILS. >> [INAUDIBLE RESPONSE FROM AUDIENCE ] >> WE DON'T KNOW. ONE WOULD ASSUME FROM HER LEVEL OF WORRY AND HER INTEREST IN TREATMENT THAT SHE WAS MOTIVATED TO COMPLY BUT I DON'T KNOW. >> I PRESUME THE ANSWER WOULD BE WE DON'T KNOW BUT WOULD YOU ASSUME THE EXPERIMENT WAS AVAILABLE OFFLABEL OUTSIDE OF THE EXPERIMENT? >> THAT'S A GOOD QUESTION. [LAUGHTER] >> SO HOPEFULLY THIS AND OUR LACK OF KNOWLEDGE ON A LOT OF THIS CASE UNDERSCORES A POINT THEY THINK APPLIES TO ALL OF THESE GRAND ROUND WHICH IS IS BASICALLY THESE AREN'T SUPPOSED TO BE ON THIS PARTICULAR CASE. WE DON'T NECESSARILY WANT TO REFLECT BACK ON WHAT SHOULD HAPPEN IN THIS EXACT CASE, RATHER THE IDEA IS THAT USE THIS CASE AS ESSENTIALLY A LAUNCHING POINT TO LOOK THE GENERAL QUESTION ABOUT ACCESS TO EXPERIMENTAL TREATMENT ON THE PART OF PATIENTS AND I SHOULD SAY, IT'S PARTICULARLY APPROPRIATE TO HAVE ZEKE COME AND GIVE THE FIRST ONE OF THESE FORMATS SEEMS LIKE WE'VE BEEN DOING THIS FOREVER NOW AND IT'S ALWAYS BEEN PART OF WHAT WE DO AT BIOEGHT INCREASE IN BODYS BUT THIS FORMAT WAS INTRODUCED BY ZEKE WHEN HE CAME DOWN HERE FROM DANA-FARBER, AND BEFORE HE CAME UP, KRISTIN AND I WENT UP TO BOSTON TO WATCH HOW IT'S DONE AND AT LEAST HOPING TO GET SOME OF IT RIGHT. I'M GOING TO SAY IT'S A PARTICULAR PLEASURE FOR ME TO HAVE HIM AND HE TAUGHT ME A LOT OF THINGS, I WILL SAY ONE THING IS JUST THAT, ONE OF THE ENDURING LESSONS FOR ZEKE IS YOU CAN DO REALLY GOOD WORK, CAN YOU BE CREATIVE AND YOU CAN BE PRODUCT OF AND YOU CAN ENJOY YOUR JOB AND HAVE FUN. I THINK THE LESSON FROM HIM S&P THOSE CHARACTERISTICS OF A PLACE TO WORK MAKE PEOPLE MORE PRODUCTIVE AND CREATIVE SO THEY'VE GOT AN ENDURING LEG AS THAT'S I THANK ZEKE FOR. [ APPLAUSE ] >> WELL, IT'S A TREMENDOUS PLEASURE TO BE BACK HERE AND TO STAND HERE AND GIVE A PRESENTATION INcf GRAPED ROUPEDS I DID SPEND 13 YEARS HERE AND I DID GROW UP HERE AND ALWAYS VIEW THE NIHs THE MOST CONDUCIVE PLACE WITH GREAT RESEARCH AND CERTAINLY THE MOST AND IT'S GREAT HERE IN THE COUNTRY AND I WAS PRIVILEGED TO HAVE JOHN AS OUR BOSS AND HAVE THE DEPARTMENT AROUND--THAT JUST DID MAKE IT A HUGELY WONDERFUL PLACE TO DO WORK. I WOULD SAY, THIS IS AN INCREDIBLY FRUSTRATING CASE AND IF I WERE THE HEAD OF CONSULT SERVICE, I WOULD NOT HAVE TAKEN IT. I DON'T THINK THERE'S ENOUGH. I SAY THAT IRONICALLY BECAUSE MANY OF YOU KNOW, I AM ANTICASES. I DON'T ACTUALLY LIKE ONE OF THE REASONS I HAVE NEVER DONE CONSULTS IN MY ENTIRE LIFE IS BECAUSE I'M NOT VERY GOOD ABOUT PARTICULAR CASES, YOU'LL SEE WHY IN A SECOND. BECAUSE I'LL BE CHARACTERISTIC ABOUT HOW I THINK ABOUT THIS CASE. THIS IS A VERY, VERY, IMPORTANT QUESTION, NOT EXACTLY THE WAY MARION POSED IT BUT THE QUESTION OF WHAT THAT ENTITLEMENT EXTENDS TO BEYOND EXPERIMENTAL THERAPIES, MAY BE ONE OF THE MOST IMPORTANT QUESTIONS IN BIY ETHICS TODAY. I DON'T HAVE THE ANSWER TODAY, BUT I'VE BEEN THINKING ABOUT IT OVER THE LAST FEW YEARS, I'M GOING TO POINT TO SOME FOR MOTION TO SOME DIRECTIONS, I CERTAINLY KNOW WHAT IS WRONG IN THAT DIRECTION, SO THIS MAY BE A LITTLE DIFFERENT THAN WHAT MOST PEOPLE EXPECT WHERE I LIKE TO GIVE DEFINITIVE ANSWERS, SO I'VE BEEN GOING AROUND FOR MANY YEARS, HAVING TO GIVE A DISCLAIMER AND WHEN THEY ASK ME TO COME AND TALK HERE AGAIN, I HAVE TO GIVE ANOTHER DISCLAIMER. THESE ARE MY VIEWS, THEY'RE NOT THESE PEOPLE'S VIEWS, THEY NEVER WERE THESE PEOPLE'S VIEWS AND NOW IT'S OFFICIAL. YOU KNOW IT'S BEEN OFFICIAL FOR ABOUT SEVEN MONTHS THAT THEY'RE NOT THE GOVERNMENT'S VIEWS AND IT'S A TOTAL JOY TO EXPRESS MY OWN OPINION AND BY THE WAY, NOT TO GET ANYONE'S PERMISSION TO EXPRESS MY OWN PERMISSION. ALL RIGHT, SO YOU'VE GOT SOME OF THE OBJECTIVES, SO I WANT BEGIN WITH THE PLACE THAT THAT I THINK THIS CASE AND THE REASON IT'S--ONE REASON IT'S SALIENT IS THAT IT DOES CALL UPON OUR SYMPATHY, COMPASSION, CALL IT WHAT YOU WILL, AS DOCTORS AND JUST PLAIN OLD HUMAN BEINGS, YOU HEAR THAT CASE ASK WE WANT TO HELP THIS PERSON. WE'RE ESPECIALLY SYMPATHETIC OBVIOUSLY TO TERMINALLY ILL AND SERIOUSLY ILL PATIENTS LIKE THIS PATIENT AND THOSE WHO HAVE TRIED EVERYTHING AND HAVE NO TREATMENT OPTIONS LEFT. JUST ASSUMING THAT ON THE FACE OF IT, WHAT YOU TOLD MARY IT IS, IT'S TRUE THAT SHE HAS A SERIOUS CONDITION, MAYBE LIFE THREATENING, CERTAINLY, COMPROMISING AND SHE'S EXHAUSTED ALL THE OTHER TREATMENTS. THIS PULLS AT OUR HEART STRINGS AND IT SHOULD, HOWEVER, AND THIS IS WHY I'M NEVER GOOD AT CASES, SYMPATHY FOR A PATIENT DOESN'T RENDER AN ENTITLEMENT TO HEALTHCARE SERVICES OR MEDICAL SERVICES. IT'S CLEARLY AN EMOTIONAL REACTION, EVOLUTIONARY CALLED FOR, BUT IT'S NOT WHAT WE SHOULD BE DOING HERE AND THAT WHAT'S REALLY AT ISSUE HERE IS THE QUESTION OF ENTITLEMENT. IS THIS PATIENT ENTITLED TO THIS TREATMENT AS A MATTER OF JUDGE, I ASSUME THAT'S THE REASON, SHE CALLED US AND THE BIOETHICS PEOPLE BEFORE SHE WENT TO THE PI OF THE STUDY IS SHE WANTED TO KNOW WHETHER SHE HAD A MORAL ARGUMENT TO MAKE ON THE BASIS OF YOU KNOW JUSTICE REQUIRES THAT YOU GIVE ME THE STUFF OFF PROTOCOL AND I THINK WE CAN ONLY UNDERSTAND THAT, IF WE HAVE A THEORY ABOUT WHAT PEOPLE ARE ENTITLED TO AS A MATTER OF JUSTICE IN THE REALM OF HEALTHCARE. I ALSO THINK IT'S WORTH OUR THINKING ABOUT, NO ONE IS OWED SYMPATHY. YOU CAN'T SAY, YOU OWE IT TO ME. RIGHT? ON THE OTHER HAND IT IS IRONIC WE CAN SAY AS A MATTER OF ENTITLEMENT, YOU OWE ME, THIS. BECAUSE OF JUSTICE. SO I DO THINK THERE'S A CERTAIN COUNTER INTUITIVENESS TO THIS ON THE SYMPATHETIC BASIS, WE REALLY WANT TO HELP BUT WE'RE NOT OBLIGED TO HELP HER. SO, THE QUESTION OF ENTITLEMENT IS DO PEOPLE HAVE AN ENTITLEMENT TO OBTAIN ANY DRUG THEY WANT? SO AS A MATTER OF JUSTICE, TERMINALLY AND SERIOUSLY ILL PEOPLE ENTITLED TO OBTAIN ANY DRUG THEY WANT OR THINK, WILL BE BENEFICIAL FOR THEM AND EVEN MORE IF IT'S AN EXPERIMENTAL THERAPY. HOW DOES THAT COLOR THE QUESTION OF THE ENTITLEMENT? I THINK THIS, AS I SAID, SERIOUS, DEEP, MAY BE THE MOST PRESSING ISSUE IN BIOETHICS TODAY. NOW WHEN WE DECIDE IF A PERSON IS ENTITLED TO A SPECIFIC TREATMENT, WE'RE MAKING JUDGMENTS ABOUT WHAT SOCIETY SHOULD GUARANTEE THAT PERSON AS A MATTER OF JUSTICE. SO IT'S SOMEHOW SEPARATE FROM WHO'S PAYING FOR IT HERE, IF IT'S AN ENTITLEMENT SHE CAN GO TO THIS PI, THE QUESTION IS SOCIETY GUARANTEEING HER SOME KIND OF ACCESS AND WE WOULD HAVE TO PRESUMABLY APPEAL TO SOME THEORY OF JUSTICE FOR THAT. I HAVE SPENT THE LAST I DON'T KNOW FOUR OR FIVE YEARS MAKING THIS POINT, WHICH IS THAT EVEN IN A RICH COUNTRY LIKE OURS THAT SPENDS A GAZILLION DOLLARS OR 2.6 TRILLION ON HEALTHCARE, GIVING ONE PERSON OR ONE GROUP SOME GOOD ENTAILS A TRADE OFF. THERE IS ALWAYS, ALWAYS A TRADE OFF. TYPICALLY IT'S HID EXTEN TYPICALLY WE WANT TO SAY IT'S MINOR BUT WE SHOULDN'T IGNORE THE FACT THAT WE ARE GOING TO BE MAKE SOMETHING TRADE OFFS AND TAKE SOMETHING RESOURCE AWAY FROM SOME OTHER PERSON. AND THAT'S IMPORTANT BECAUSE IT DOES BRING US BACK TO THE WHOLE ISSUE OF JUSTICE. WE ONLY ARE CONCERNED ABOUT JUSTICE. AS JOHN ROLES SAID SOMETHINGOT FIRST BASE OF A THEORY OF JUSTICE, BECAUSE THERE ARE SOME SCARCITY IN SOCIETY. IF THERE WERE ENOUGH RESOURCES TO SATISFY EVERYONE'S NEED, WE WOULD NEVER NEED A THEORY OF JUSTICE, WE ONLY HAVE THE THEORY OF JUSTICE, OR THE NEED TO APPEAL TO JUSTICE BECAUSE WE'RE SHORT RESOURCES. NOW, MANY THINGS ARE NECESSARY FOR US TO LEAD RICH AND FLOURISHING LIVES, WE NEED FOOD, CLOTHING, EDUCATION, ELGT CARE, WE NEED A LOT OF THINGS, INCLUDING SPARE MONEY TO DO WHATEVER THE HELL WE WANT AND PART OF THE ROLL OF JUSTICE IS TO FIGURE OUT WHICH OF THESE SHOULD BE SATISFY WIDE WE CAN'T SATISFY THEM ALL. AND IT'S ALSO IMPORTANT TO PREVENT ONE NEED FROM TRUMPING ALL THE OTHER NEEDS AND CROWDING OUT FULFILLING THE OTHER THINGS WE DO. SO I THINK TELL BE--IT WOULD BE EASY TO TAKE THIS CASE AND THIS DEMAND IN ISOLATION AND NOT THINK ABOUT THE OTHER LARGER CONSEQUENCES. I MAKE THIS POINT ALMOST EVERY TIME I TALK ABOUT ELGT CARE, WE ARE IN THE EDUCATION WHERE THEY'RE COSTS ARE FORCING US TO THINK ABOUT TRADE OFFS WITH ALL OTHER AREAS OF SOCIETY, INCLUDING PRIMARY AND SECONDARY EDUCATION WHICH I SINGLE IMPORTANT SO WE ALWAYS NEED TO THINK ABOUT WHETHER HEALTHCARE WITH AN OLDER PERSON OR LIFE THREATENING ILLNESS, IS MORE IMPORTANT THAN EDUCATION BECAUSE IF PARENTS ARE ENTITLED TO EVERY AVAILABLE SERVICE LIKE THIS, WE WOULD BE ROBBING PETER TO PAY PAUL BECAUSE WE'RE GOING TO TAKE AWAY SOMETHING FROM SOMEONE ELSE. ALL RIGHT. AND THIS IS WHY I'M NO GOOD AT INDIVIDUAL CASES. PROVIDING LESS THAN EVERY AVAILABLE MEDICAL SERVICE TO AN INDIVIDUAL IS BOTH NECESSARY BECAUSE WE CAN'T AFFORD TO DO IT BUT IT'S ALSO A MATTER OF JUSTICE. AND I KNOW THAT IS A VERY COUNTER INTUITIVE THING BUT JUST--IT'S JUST BECAUSE--JUSTICE IS ABOUT MAKING DECISIONWHAT GOODS ARE SCARCE AND HOW TO ALLOCATE THOSE SCARCE GOODS. IN ESSENCE JUSTICE DOES REQUIRE US TO SAY NO. IF WE WERE ALWAYS SAYING YES, AS I SAID BEFORE, IT WOULD BE ABOUT JUSTICE, OKAY. SO THIS IS WHY I'M NOT A VERY GOOD CASE PERSON. I BELIEVE IF WE JUST SAID, YES, TO EVERYTHING, WE WOULD BE UNJUSTICE AND IRRESPONSIBLE. SO, WHICH IS WHAT MAKE THIS IS CASE REALLY HARD, THIS SLIDE. HOW MUCH HEALTHCARE AS A MATTER OF JUSTICE, DO WE HAVE TO PROVIDE TO PEOPLE THERE IS NO GENERAL THEORY THAT IS OPERATIVE TODAY. WE HAVE COMPETING THEORIES, AWE THOSE ARE FLAWED, NONE OF THEM ARE ACCEPTABLE. I'M NOT GOING TO GO THROUGH THROUGH ALL OF THEM, I WILL MENTION A FEW OF THEM AND A COUPLE OF PROBLEMS, JUST TO POINT OUT. I DON'T I THINK WE HAVE A SPECIFIC THEORY TO HANDLE THIS CASE AND THAT MAKES IT EXTREMELY FRUSTRATING TO DEAL WITH IT. I DO THINK THIS IS A TOP PRIORITY, SO TAKE A REIGNING CASE, COST EFFECTIVENESS. WE WILL DECIDEo r WHAT IS COST EFFECTIVENESS AND DRAW A LINE. MANY OF YOU REMEMBER THAT OREGON DID SOMETHING LIKE THAT. HAD ALL SORTS OF FLIES, ONLY APPLIED TO MEDICAID, THE DATA WHICH IT WAS RELIANT WAS COUNTER PRODUCTIVE, CERTAIN THEY THINKS WERE RATED LOWER THAT APPENDECTOMY WERE RATED LOWER THAN TEETH CAPPING. ALL SORTS OF ISSUES, DISTRIBUTION, WHO GETS BENEFITS SHOULD IS IT FAIR THEY ACCRUE TO ONE SEGMENT AND MAYBE NOT OTHERS. THERE'S A PROBLEM WITH DISCRIMINATION, AGAINST PEOPLE WHO ARE DISABLE, OR PEOPLE HAVE SERIOUS ILLNESS AND ARE NOT LIKELY TO GET A BIG BOOST. THAT'S NOT TO SAY WE DON'T USE IT BUT IT IS TO SAY THAT PEOPLE GENERALLY RECOGNIZE IT'S GOT FLAWS. ONE OF OUR COLLEAGUE WHAT WHO WAS BRIEFLY A VISITING SCHOLLOR IN OUR DEPARTMENT IS A FEAR OF EQUALITY ABOUT OUR DEPARTMENT. DISTRIBUTING RESOURCES TO INSURE PEOPLE CAN REALIZE THE FAIR RANGE OF LIGHT PLANS. WIDELY WRITTEN UP IN THE EARLY TO MID80S. TWO BIG POLICY DECISIONS NOT HELPFUL FOR MAKING TRADE OFFS, SPECIALLY WHEN YOU AGGREGATE PEOPLE. SO AGAIN, JUST TO MAKE THE POINT WE HAVE SEVERAL THEORIES OUT THERE. I DON'T THINK SWREE A GENTLEMEN THEOR THAT'S HELPS US IN THESE PARTICULAR CASES. BUT I DO THINK WE HAVE THAT IS IN PART BECAUSE THIS IS A MATTER OF EXPERIMENTAL THERAPY. I THINK CLEARLY ARE NOT ENTITLED TO EVERY MEDICAL SERIOUS, EVEN EVERY MEDICAL SERVICE THEY SINGLE BENEFICIAL. ENTITLED TO MEDICAL SERVICES THAT PROVIDE A REASONABLE RANGE OF OF LIFE PLANS WITHIN THEIR SOCIETY, COMPATIBLE WITH ALLOWING OTHER MEMBERS OF SOCIETY TO HAVE SIMILAR REASONABLE RANGE OF LIGHT PLANS. AND OW INTUITION IS MEANT TO IMPROVE QUALITY OF LIFE SO PEOPLE CAN HAVE A COMPLETE LIFE AND PURSUE WHAT THEY WANT TO DO. TYPICALLY ENTITLEMENT IS ACCESS MEDICAL SERVICES THAT ARE PROVEN, IMPROVE SURVIVAL OR IMPROVE QUALITY OF LIFE. NOW, HOW DOES THAT EXTEND OR NOT EXTEND TO EXPERIMENTAL THERAPIES. IT SEEMS TO ME, YOU CANNOT EXTEND THAT TO AN ENTITLEMENT FOR AN EXPERIMENTAL THERAPY. THEY'RE NOT PROVEN TREATMENTS, THEY'RE NOT LIKELY TO GENERATE ANY BENEFITS FOR THE RESOURCES WE INVEST. AND, GUARANTEE PEOPLE AS LIKELY TO BE A WASTE OF THE SCARCE RESOURCES THAT WE HAVE. SO I THINK THE IDEA THAT SOMEONE MIGHT HAVE AN ENTITLEMENT TO AN EXPERIMENTAL THERAPY IS PROBABLY A PRETTY WEAK ARGUMENT. TO THE EXTENT THAT SOCIETY MIGHT PROVIDE EXPERIMENT TREATMENTS PAID FOR BY SOCIETY, THERE'S A REASONABLE REQUIREMENT SO IF YOU WANT TO GO DOWN THAT LINE, IT WOULD SEEM TO ADD CERTAIN REQUIREMENTS, RIGHT THAT WE WOULD ACTUALLY GAIN FROM THE EXPERIMENTAL THERAPY AND ACTIVITIES AND PROJECTS THAT'S WOULD BE SOCIAL VALUE, FROM HAVING THAT PERSON RECEIVE THE EXPERIMENTAL THERAPY. IT IS ONE OF THE REASONS THAT WHEN OUR DEPARTMENT WROTE A PAPER ABOUT WHAT MAKES CLINICAL RESEARCH ETHICAL AND WE INCLUDE RIGHT AT THE TOP, THERE HAS TO BE SOCIAL VALUE FROM THE RESEARCH AND IT SEEMS TO BE HARD TO JUSTICIFY THAT IF YOU ALLOW PEOPLE OR SOCIETY WILL PAY FOR PEOPLE TO GET EXPERIMENTAL THERAPIES, THAT WE WOULDN'T REQUIRE THAT WHEN THEY GET IT. WE GAIN SOCIAL KNOWLEDGE OUT OF THAT, SO IT'S HARD TO IMAGINE, IT SEEMS TO ME FROM THOSE VERY SIMPLE PROVISIONS HOW SOCIETY CLAIMS TO OWE THEM. AND MORE DIFFICULT TO SAY SOMEONE IS OWED THAT TREATMENT WITHOUT CONTRIBUTING TO SOCIAL KNOWLEDGE. SO AS TRAGIC AS IT IS THAT THERE'S NO CURE OR EFFECTIVE TREATMENT. SHORT OF A CURE FOR PEOPLE WITH A GIVEN DISEASE LIKE MS, DOESN'T MEAN PEOPLE ARE OWED AS A MATTER OF JUSTICE, ACCESS TO EXPERIMENTAL TREATMENT, ESPECIALLY OFFPROTOCOL WHEN THEY WILL NOT PROVIDE ANY BENEFITS, TO OTHERS THROUGH THEIR RECEIVING OF THAT TREATMENT. SO IN GENERAL, I THINK, ACCESS TO EXPIMENTAL THERAPY SHOULD RECEIVE A LESSER PRIMATES'RE PRIORITY TO PROVEN HEALTH THERAPIES AND THAT THERE'S NO ENTITLEMENT. SO, IT SEEMS TO ME THAT CAN ANYTIME WE CONSIDER IT, IT'S BET TORE ASSURE PEOPLE, IMPROVE QUALITY OF LIFE THAN TO PROVIDE EXPERIMENTAL THERAPIES THAT ARE NOT GUARANTEED TO IMPROVE QUALITY OF LIFE. A GUARANTEED BENEFIT, TWO PEOPLE IS MUCH MORE VALUABLE TO SOCIETY AS A MUCH HIGHER PRIORITY FOR BEING GUARANTEED BY SOCIETY THAN A VERY LOW PROBABILITY BENEFIT TO ANY PERSON IN ANY SINGLE EXPERIMENTAL THERAPY HAS THAT A PRIORI HAVE A LOW BENEFIT. NOW YOU MIGHT ARGUE, WELL, THERE'S SOME COMPLEX FORMULA TO COMPARE THE MAGNITUDE OF BENEFITS INCLUDING ADD SOCIAL VALUE OF KNOWLEDGE, PROVEN THERAPIES TO EXPERIMENTAL THERAPY, THAT I CAN THERE IS THAT FORMULA, WE DON'T KNOW IT. AND WITHOUT IT, SWREE TO ERROT SIDE OF EXPERIMENTAL THERAPY. FURTHER MORE ENTITLEMENT OF EXPERIMENTAL THERAPY OFFPROTOCOL AS THIS PERSON WANTS WOULD HAVE SERIOUS HARMS THAT WOULD BE A FURTHER REASON NOT TO PROVIDE THIS AND NOT TO BREAK THE PROTOCOL. THEY INCLUDE HAVE YOU THIS AS A GENTLEMEN RULE, DELAYED TRIAL AND DELAYED CREATION OF KNOWLEDGE, FORCE, THAT'S POTENTIAL SOCIETY, AND WHILE THE ASSESSMENT MAY BE THAT THE RISK BENEFIT RATIO OF THIS DRUG, THIS EXPERIMENTAL THERAPY IS SUFFICIENTLY POSITIVE TO GO INTO A TRIAL THAT DOESN'T MEAN THAT THE PERSON ISN'T GOING TO BE HARMED. AND WE'VE SEEN PLENTY OF CASES OF OF WHERE WE RUN THE TRIALS INCLUDING PHASE ONE, PHASE TWO AND PHASE THREE TRIALS AND THE BIG IMPORTANT HARMS DON'T GET NOTICED UNTIL WE RELEASE THE DRUG TO A BROADER RANGE OF PEOPLE. SO WE SHOULDN'T RULE OUT THE FACT THAT THIS PERSON COULD BE HARMED FROM GETTING THIS DRUG. LET ME JUST REMIND PEOPLE THAT THERE ARE IN MY MIND TWO BIG CASES OF WHERE WE ALLOW THINGS OFFPROTOCOL THAT HAVE UNDERMINED OUR ABILITY TO GAIN THE SOCIAL VALUE. ONE IS BONE MARROW TRANSPLANTS FOR METASTATIC BREAST CANCER. IT'S ESTIMATE THAD BETWEEN 24 AND 40,000 WOMEN RECEIVE AN OFF-TRIAL. BETWEEN 1989 AND 2002, WHILE JUST A THOUSAND WOMEN RECEIVED IT ON TRIAL ASK THIS WAS THE CASE OF WHERE THE DELAY PUT 10S OF THOUSANDS OF WOMEN AT RISK FOR A HARM, EVEN PREMATURE DEATH BEFORE THIS WAS COMPLETELY INEFFECTUAL TREATMENT. SO THERE'S A VERY HIGH BURDEN TO GO OF TRYING SOMETHING OFFPROTOCOL, TRYING EXPERIMENTAL THERAPY OFFPROTOCOL AND AGAIN, UNLIKELY, CERTAINLY NOT A GOODBYIZED POLICY. DDI IS ANOTHER ONE. RIGHT? WE HAD PLENTY OF USE PEOPLE OUTSIDE CLINICAL TRIAL BEFORE WE COULD COMPLETE ENROLLMENT IN THE TRIAL. AND ACCESS TO THE DRUG OFFPROTOCOL WAS A MAJOR REASON FOR NOT GETTING THE RESULTS. IT SEEMS TO ME THAT PROVIDING THIS PATIENT ACCESS TO EXPERIMENTAL THERAPY WOULD SEEM TO UNDERMINE THE STUDY. YOU WOULD TAKE HER OUT OF THE STUDY, YOU WOULDN'T KNOW THE LONG-TERM EFFECTS HERE. IT WOULD REMOVE SOMEONE FROM THE STUDY. AND UNDERMINE THE SOCIAL VALUE OF THAT STUDY. MAYBE NOT CATASTROPHICALLY IN THIS INDIVIDUAL CASE BUT CERTAINLY THE GENERAL POLICY IT WOULD BE TERRIBLE. LET ME CONCLUDE BY REMINDING YOU OF A SIMILAR KIND OF CASE, AND THE ISSUE THERE WAS MORE LEGAL THAN ETHICAL, BUT ABIGAIL BURROS WAS A COLLEGE STUDENT DIAGNOSE WIDE HEAD AND NECK CANCER, SO VERY YOUNG, HER FATHER FORMED THE ABIGAIL ALLIANCE FOR DEVELOPMENTAL DRUGS AND SUED FDA PER HERBACTUX FOR HEAD AND NECK CANCER AND THERE WAS PRELIMINARY DATA IT COULD BE AFFECTED AT THE TIME IT WAS AVAILABLE ONLY FOR PATIENTS PARTICIPATE NOTHING COLON CANCER CLINICAL TRIALS. IN MAY 2006, THE D. C. CIRCUIT OF APPEALS RULE INDEED FAVOR OF THE ABIGAIL ALLIANCE AND FOUND THAT THE U.S. CONSTITUTION PROTECTS THE RIGHTS OF TERMINALLY ILL PATIENTS TO ACCESS TREATMENTS THAT ARE NOT APPROVED BY THE FDA. AND SO BY TWO TO ONE, THE COURT SAID, YES, HAVE YOU A CONSTITUTIONAL RIGHT TO ACCESS THE DRUG. THE FDA ACTUALLY ASKED THE COURT TO REHEAR IT IN WHAT'S CALLED OMBAC, ALL THE JUSTICE COME BECAUSE THE TWO TO ONE RULING DID NOT SEEM RIGHT AND WHEN ALL THE JUSTICE'S MET IN AUGUST OF 07, THEY ACTUALLY REVERSED THE RULING WITH ALL THE JUSTICE'S, BUT THE TWO ORIGINAL ONES RULING THAT THERE WAS NO CONSTITUTIONAL RIGHT. IN 2008, THE SUPREME COURT DECLINED TO REVIEW THE CASE SO THAT APPELLATE COURT RULE TAG THERE'S NO CONSTITUTIONAL RIGHT HOLDS, DETAILS CISION STOOD THAT TERMINALLY--DECISION STOOD THAT TERMINAL ILL PATIENTS HAVE NO RIGHT TOY DID MANDATORY A TOXIC DRUG WITH NO PROVEN THERAPEUTIC BENEFIT. SO AT LEAST ON THE EASY, IS THERE A LEGAL ISSUES RIGHT TO HAVE EXPERIMENTAL RIGHT TO THIS DRUG, NO, THIS IS BASED ON UPON THE ABIGAIL ALLIANCE CASE. THE MUCH MORE DIFFICULT QUESTION OF WHAT WE'RE ENTITLED TO IS AS MART OF HEALTHCARE. WE DON'T HAVE A GENERAL ANSWER TO BUT I THINK EVEN WITHOUT A GENERAL ANSWER TSEEMS VERY HARD TO SAY HAVE YOU AN ENTITLEMENT TO AN EXPERIMENTAL THERAPY UNPROVEN EFFECTIVENESS WITH YOUR ACCESS TO IT WOULD CREATE A PRINCIPLE THAT WOULD UNDERMINE THE SOCIAL VALUE, THE INDIVIDUAL RESEARCH, BUT I THINK ALSO OF THE LONG-TERM PROSPECTS OF GETTING PEOPLE TO PARTICIPATE IN RESEARCH. THANK YOU VERY MUCH. [ APPLAUSE ] I'M SUPPOSED TO WE'RE SUPPOSED TO--TOLD WE'RE SUPPOSED TO TAKE QUESTIONS. >> SO THE ONE THING I THINK ABOUT IN THIS CASE, I AGREE WITH THE IDEA THAT A PERSON DOESN'T HAVE AN ENTITLEMENT TO AN EXPERIMENTAL THERAPY BUT THIS PERSON WAS ALREADY ENROLL INDEED THE STUDY SO THE QUESTION IS, ARE THERE ANY RELEVANCE TO THAT IN TERMS OF EITHER RECIPROCITY FOR WHAT THESE CONTRIBUTED OR MAYBE A PROMISE THAT WAS MADE THAT SLEY WOULD AT SOME POINT GET THE EXPERIMENTAL THERAPY. DOES THAT CHANGE THE ARGUMENT IN HER FAVOR? >> IT DOESN'T CHANGE THE ARGUMENT NOW, ONE TO TWO YEARS BEFORE THE END OF THE TRIAL, IT SEEMS TO ME BECAUSE HER PARTICIPATION IN TAKING HER OFF THE TRIAL WOULD GET RID OF DATA. RIGHT? EMPLOY SO IT WOULD BE WORSE, SHE CAN'T CLAIM BECAUSE I'M ENROLLED, I AM ACTUALLY GOING TO MAKE IT WORSE DATA BY GETTING AGAIN, WE DON'T KNOW IF SHE'S ON PLACEBO IN THIS CASE, YOU HAVE TO SAY, HER INTUITION OR NEUROLOGIST INTUITION OR PLACEBO, WORTHLESS. SO, I THINK THAT IT DOESN'T. AFTER THE FACT THEY'VE ALREADY BUILT IN. IT SEEMS TO ME A GUARANTEE, SOME KIND OF GUARANTEE THAT THE DRUG IS EFFECTIVE THAT SHOO HAS ACCESS TO IT, AND SLEEP APNEA AND OBESITY SEEMS TO ME, THAT SEEMS A PRETTY GOOD GUARANTEE. IS THAT NECESSARY? I DON'T THINK TAKEN--THEY'S EVEN NECESSARY. IT SEEMS TO ME IT'S HARD TO ARGUE UNTIL IT'S APPROVED AND GONE THROUGH THE PROCESS THAT WOULD ONE GSHT THEM. AGAIN FOR REASONS OF COMPASSION ANDICISM ACTY, HAVE YOU IT IN THERE AND MAYBE EVEN A CLAIM THAT THESE PEOPLE PARTICIPATED IN THERE'S AN INKLING IT'S POSITIVE AND THEY OUGHT TO GET IT, BUT I DON'T THINK THAT NECESSARILY CREATES A SOCIAL OBLIGATION THAT WE HAVE TO. IT'S A GOOD CONSIDERATION BUT I DON'T KNOW IT'S AN OBLIGATION. >> SO I'M CURIOUS HOW MUCH OF YOUR ANSWER RESTS ON THE COSTS PROVIDING THE EXPERIMENTS OF MEDICATION. HOW MUCH RESTS ONOT RISKS OF THE SUBJECT AND HOW MUCH RESTSOT SOCIAL RESEARCH. TWO FACTS, ONE SUPPOSE THE CALLER SAYS, BY THE WAY I'M A MULTIMILL WHEREON AIR AND I'M HAPPY TO PAY THE COST OF THE MANUFACTURE OF THE DRUG AND SECOND, MY PROGNOSE SIS VERY BAD, IF I--I'M ON PLACEBO WHERE I'M NOT GETTING MEDICATION, I REALIZE THIS DRUG MAY HARM ME BUT I'M ENTIRELY WILLING TO TAKE ON THAT HARM. WOULD YOUR ANSWER BE THE SAME? IT OUGHT NOT TO ACOULD YOU WANT FOR ANYTHING HERE, THE PRINCIPLE, THE PRINCIPLE IS MULTIMILLIONAIRES TO BUY EXPERIMENTAL DRUGS AND NOT THE REST OF US, IF THEY SHOULD HAVE ACCESS TO IT, IT DOES SEEM TO ME IF YOU THINK THERE'S LEGITIMATE ACCESS TO IT, THEN THE QUESTION IS WHY SHOULDN'T SOCIETY GET IT TO EVERYONE? I WHACK WE HAVE SAY PROCESS BY SAYING WE'RE GOING TOg+2 PEOPLE ACCESS TO EXPERIMENTAL THERAPIES, QUID PRO QUO IS THAT WE HAVE THE STRUCTURED ARRANGEMENT FOR THAT DATA ACCESS AND WE PROTECT YOU EVEN WHEN YOU MIGHT WANT SOMETHING IN THE SYSTEM TO MAKE SURE HARM'S MINIMIZED AND OTHER CONSIDERATIONS ARE TAKEN INTO ACCOUNT. >> KRAMER NCI, VERY NICE DISCUSSION. SINCE THEY REALLY DON'T KNOW ANYTHING ABOUT THE PROTOCOL, IT'S CLEAR MOST PROTOCOLS HEREq1ed DON'T COMPARE A DRUG TO A PLACEBO BUT THEY USE THE BEST STANDARD OF CARE TO BEGIN WITH, SO THE PATIENT IS GETTING GOOD CARE OR SOMETHING ELSE. AND THEN THEY HAVE THE STATUS SAFETY MONITOR AND COMMITTEE WHO IS VIEWING THE DATA AS IT COMES IN. NOW THIS PATIENT AND THE DR. SEEM TO THINK FOR SOME REASON THAT THE PATIENT IS GETTING THE INFERIOR TREATMENT, FOR WHATEVER REASON, THE DATA SAFETY MONITOR COMMITTEE HAS ALL ACCESS TO THE PATIENT, AND GET IT TO THE DOCTOR AND IF THAT'S TRUE, THEY HAVE THE ABILITY TO STOP THE STUDY EARLIER AND THEN GIVE THE PEOPLE THE ACTUAL TREATMENT. WHEREAS IF THIS PATIENT, BROKE--NOBODY CAN FORCE THIS PATIENT TO STAY IN THE PROTOCOL AT ALL. THEY CAN GO SOMEWHERE ELSE, IF IT'S OFFERED ELSEWHERE. >> WELL, FIRST OF ALL I THINK THERE ARE A NUMBER OF OF PACES WHERE WE DO RUN DRUGS AGAINST PLACEBO IN SITUATIONS WHERE, LIKE IN THIS CASE, SHE PROBABLY IS GOING--PROBABLY IN THAT CRITERIA I WOULD SAY IN THIS PROTOCOL, YOU EXHAUSTED ALL THE OTHER OPTIONS AND THEREFORE RUNNING IT AGAINST PLACEBO IS A REASONABLE CHOICE, WE COULD DO THAT ONCOLOGY A LOT OF TIMES. USED UP ALL THE OPTIONS AND NOW WE'RE GOING TO RUN IT AGAINST PLACEBO IS A PERSPECTLY LEGITIMATE ALTERNATIVE, ESPECIAL FECIAL SLEY IF IT'S REASONABLE FOR THAT PERSON TO SAY, I WANT NO TREATMENT. AND I IN THIS CASE, PRESUMABLY, THE DATA SAFETY MONITORING BOARD IS MONITORING AND IF THERE IS A SUFFICIENT INDICATION OF SEPARATION OF THE TWO ARMS, THEY WOULD STOP THE TRIAL. BUT JUST FOR AN INDIVIDUAL PATIENT, YOU WOULDN'T. >> COMMENT IS SORT OF RELEVANT TO THAT ONE WHICH HAS TO DO WITH THE INTEGRITY OF STUDY DESIGN, I THEN IS AN IMPORTANT TOPIC, I'M NOT SURE IT'S THE RIGHT QUESTION TO COME OUT OF THIS CASE WHICH IS HOW YOU DESIGN STUDIES TO INSURE THAT YOU HAVE THE APPROPRIATE SORT OF INTEGRITY AND THAT THEY'RE BUILT TO AVOID SITUATIONS LIKE THIS, BECAUSE SHE'S GOT A SLOWLY PROGRESSIVE DISEASE, SHE'S PROGRESSING, YOU HAVE NO IDEA AND SHE HAS NO IDEA, WASHE PROGRESSING AT THE RATE FOR OTHERWISE,. >> MAYBE SHE'S PROGRESSING BECAUSE OF THE DRUG. >> WELL, IVS GOING TO MAKE THAT POINT. --I WAS GOING TO MAKE THAT POINT. THE KEY ISSUE HERE ISN'T STUDY DESIGN TO HAVE THE INTEGRITY, TO MAKE THIS KIND OF CHOICE UNNECESSARY IN THIS INDIVIDUAL SITUATION AND SHE CERTAINLY CAN COME OFF, BUT THE WHOLE, THE WHOLE IDEA OF ENCOURAGING THE MAGICAL THINKING THAT IS COMLITELY NORMAL FOR PEOPLE IN SITUATIONS LIKE THIS, IS PROFOUNDLY UNETHICAL FOR US TO DO THAT SO I REALLY JUST SORT OF UNDERLINE THIS LINE BECAUSE IT HAPPENS ALL THE TIME. AND IT'S UNDERSTANDABLE WHY PEOPLE DO THIS BUT ENCOURAGING THAT KIND OF ACCESS IS ACTUALLY BAD FOR MULTIPLE REASONS INCLUDING THE PEOPLE WHO ARE INVOLVED, INSPITE OF THE FACT THAT SOME OF THEM THINK THEY WANT IT. >> AGAIN, PRESUMABLY A COLLEAGUE OF OURS RAN THE STUDY, AND IT WENT THROUGH ONE OF OUR IRBs. I ASSUME THEREFORE, THERE WERE A LOT OF MECHANISMS FOR MONITORING THE WELFARE OF THIS PATIENT INCLUDE TAG MAYBE THEY'RE GETTING THE DRUG AND THE REASON THR PROGRESSING IS THAT THE DRUG IS AGGRAVATING THE UNDER LYING CONDITION MPLET IF THEY'RE ON PLACEBO AND PROGRESSING, THERE MAY BE--THIS N THIS CASE THERE MAY NOT BE ALTERNATIVES SO THERE MAY NOT BE AN INTERVENTION AND I DO THINK, THE WILLINGNESS TO GIVE PEOPLE ACCESS TO THE EXPERIMENTAL THERAPY, AFTER THE FACT, AFTER THEY GET SUFFICIENT DATA IS ANOTHER INDICATION IS THAT IF IT'S POSITIVE, THEY WANT TO GIVE PEOPLE PRIORITY AND ACCESS MAY BE IN BETWEEN COMPLETING THE TRIAL AND GETTING APPROVAL. >> ZEKE, YOUR DISTINCTION BETWEEN SYMPATH SCHEJUSTICE AND MEN AND WOMEN YOU OWE OR DO NOT OWE THE PATIENT, THE PRINCIPLES OF THAT WERE VERY CONVINCING AND I AGREE WITH IT COMPLETELY BUT WHEN YOU'RE REFERRINGNfyk TO THE EXAMPLE, FOR EXAMPLE OF AIDS DRUGS, WHICH AS YOU KNOW, WE HAD SOME REALLY SERIOUS DISCUSSIONS BACK THEN, I WAS THINKING AS YOU WERE TALKING FROM THE INDIVIDUAL STANDPOINT, IT'S LESS WHAT YOU OWE A PATIENT THEN WHAT'S THE RIGHT THING TO DO FOR THE PATIENT. SO PUTTING ETHICAL PRINCIPLES ASIDE, AS LONG AS YOU DON'T DO ANYTHING THAT'S UNETHICAL, I WAS STRUCK BY THE ISSUE OF OWING VERSES WHAT'S THE RIGHT THING TO DO BECAUSE WON--ONE OF THE EXAMPLES YOU GAVE WITH DDI IS WHEN WE INSTITUTED THE PARALLEL TRACK, THERE WAS A DRUG THAT WAS ALREADY FULLY ACCRUED SO YOU WEREN'T DELAYING THE ONSETS OF THE CLIPICAL TRIAL, THE CLINICAL TRIAL IS A RESTRICTED CLINICAL TRIAL. EVERYBODY WAS ACCRUED AND PEOPLE WERE COMING TO US SAYING, THERE'S NO OTHER DRUGS, MY CD4 COUNT WAS 300, IT'S 200, IT WAS 200 NOW IT'S 50. IS THERE ANY POSSIBILITY WE COULD GET THAT DRUG ON A PARALLEL TRACK OFF THE CLINICAL TRIAL AND TO ME IT WAS A NO BRAINER TNOTHING TO DO WITH WHAT WE OWED THEM, IT WAS ABOUT WHAT WAS THE RIGHT THING TO DO. YOU MAY DISAGREE WITH ME, I THINK YOU DID YEARS AGO WHEN WE DID THAT, BUT SO I'D LIKE TO HEAR YOUR COMMENT NOW. >> FIRST OF ALL, TONE TOW THE EBBS TENT THAT YOUR VIEW OR THE WAY YOU ARRANGE IT IS THAT YOU FULLY ACCRUE TO THE TRIAL BEFORE YOU OPEN UP A PARALLEL TRACK IS COMLITELY DIFFERENT THAN THE EXPERIMENT IN OTHER CASES, ESPECIALLY THE BONE MARROW TRANSPLANT CASE WHERE MANY WOMEN WERE FRUSTRATE WIDE THE FACT THAT EXPERIMENTAL THERAPY, GOT STATE LEGISLATORS AND JUDGES TO SAY, YES, YOU HAVE TO PAY FOR THIS IN THE ABSENCE OF SUFFICIENTLY IN MY OPINION, SUFLY CONVINCING DATA. SO ONCE HAVE YOU A TRIAL GOING AND YOU WANT TO--YOU SINGLE GOING TO BE A DEFINITIVE TRIAL, OPENING UP A PARALLEL TRACK HAS BETTER JUSTIFICATION I STILL WORRY ABOUT JUSTIFICATION BECAUSE WE'RE USING A LOT OF RESOURCES AND THEY ARE NOT--THEY'RE--COMING FROM SOMETHING ELSE, YOU'RE USING RESOURCES IN A TRIVIAL AMOUNT, ISN'T SEEM TO BE AN ACCEPTABLE JUSTIFICATION BECAUSE THE MOMENT HAVE YOU A PRINCIPLE LIKE, IT HAS TO BE APPLIED BROADLY AND THE MOMENT IT'S APPLIED BROADLY, HAVE YOU A LOT OF RESOURCES AT STAKE. SO THAT'S WHAT MAKES ME HAVE FUN. WHICH IS WHY, YES FREQUENCY AN INDIVIDUAL STANDPOINT YOU UNDERSTAND WHY THEY WANT IT AND OUR HEARTS GO OUT TO THEM, THAT'S A DIFFERENT ISSUE THAN A POLICY, THAT HAS TO WAY, NOT JUST THIS CASE, BUT OTHER CASES AND IT'S GENERALIZED IMPACT. WE DON'T LIKE DOING THAT, NOT GIVING AN INDIVIDUAL WHAT THEY NEED IS BECAUSE WE HAVE A POLICY IMPLICATION, WE HAVE TO DO IT AND GET COMFORTABLE DOING IT. >> SO I'M SYMPATHETIC TO YOUR FEELING ABOUT SYMPATHY. BUT I AM SYMPATHETIC TO THE PATIENT AND I'M GETTING BACK TO THE QUESTION OF EXPERIMENTAL DESIGN. I'VE ALWAYS BEEN IMPRESS THAD PARTICULARLY IN RARE DISEASES WHICH I GUESS THIS PATIENT FALLS INTO THAT CATEGORY, THE USE OF THE DOUBLE BLIND COSOVER TRIAL ALLOWS EACH PATIENT TO GET BOTH THE PLACEBO AND THE CONTROL AND THEM YOU CAN ACTUALLY GAIN INFORMATION ABOUT EACH PATIENT IN TERMS OF BENEFITS MAYBE SOMETHING THAT SHOULD BE ENTERTAINED MORE PROPERLY. >> I'M SURE IF THERE WAS A GOOD STATUSITION AND SOMEONE WHO KNEW SOMETHING ABOUT THE DISEASE, THERE PLAY BE A REASON YOU DON'T DO A CROSS OVER BECAUSE OF THE PROGRESSIVE NATURE AND A VERY DIFFICULT ABILITY TO HAVE THE RIGHT CONTROLS I DON'T KNOW BUT IT IS TRUE IN SOME CONDITION WHICH ARE PROBABLY MUCH MORE ACUTE TRANSFORMATIONS, I SUSPECT THAT IS THE REASON BUT WHAT DO I KNOW. I'M JUST A POOR BIY ETHICIST. >> WE ALL LEARN THE IMPORTANCE OF CLINICAL [INDISCERNIBLE], DESIGN WIDE THE DOUBLE LINE STUDY, HOWEVER THAT'S APPROPRIATE TO QUESTION IN TERMS OF THE TYPE OF ILLNESS AND TERMINAL AND SERIOUSLY PROGRESSED ILLNESSES WHETHER THE SAME DESTINATION OR PLACEBO DOUBLE WIDE CONTROL OPPOSE WITH OPEN STUDY WHETHER JUSTICE BECOMES PART OF A-- >> ALL RIGHT, LOOK BEING, LOOK. >> I DIDN'T SHOW THIS SLIDE BUT IT'S IMPORTANT TO REMIND OURSELVES, PUT THE SLIDE AT THE END, I TOOK IT OUT, I SAID FORGET IT. LET'S REMIND OURSELVES, OKAY WHAT WE'RE DEALING WITH HERE. THIS IS ONCOLOGY. BECAUSE IT'S MY FIELD. IT'S CERTAINLY TRUE OF NEUROLOGY AND MAYBE WORSE OF NEUROLOGY SO WHEN WE START OUT IN THE HUMAN CELLULAR ANIMAL, BLAH, BLAH, BLAH, WE GET THE DRUGS HAVE ENTERING THE ONCOLOGY FIELD IN PHASE ONE TRIAL. JUST LOOKING AT SAFETY OKAY WE THROW OUT MORE THAN 40% OF THEM. ALL RIGHT? WE THEN DROP COIN WE GO DOWN TO ABOUT 15%, THREE FOLD, MOST OF WHAT WE BRING TO RESEARCH IS CRAP, WORTHLESS. IT EITHER HURTS PEOPLE OR HAS NO POSITIVE EFFECT. RIGHT, WE ENTER 15 ON THE TRIAL, SUCCESSFUL TRIALS BUYER FOUR AND FDA APPROVES THREE OF THEM, OKAY? SO WE START OUT WITH A HUNDRED DRUGS AND AT THE END END OF THE PIPELINE YOU HAVE THREE OR FOUR OR FIVE EFFECTIVE DRUGS. THIS NEUROLOGY, I'M BET, I DON'T HAVE THE DATA, WORSE. OKAY? SO SO EVERYONE TALKING ABOUT WE SHOULD HAVE SYMPATHY FOR PEOPLE, LAW, BLAH, BLAH, SO MOST OF WHAT WE'RE GIVING PEOPLE HAS NO EFFECT. LET'S JUMP IN, LET'S GET YOU OFF THE PLACEBO ON TO SOMETHING. I HAVEN'T PUT INTO THIS ISSUES RIGHT? , THE FACT THAT SOME OF THESE DRUGS DO GENUINE HARM END UP, KILL PEOPLE, UNFORTUNATELY OR PUT THEM IN THE HOSPITAL OR INTENSIVE CARE UNIT. SO I ALWAYS THINK IT'S IMPORTANT FOR US WE TEND FOR EVOLUTIONARY REASONS TO FOCUS ON SUCCESSES, RIGHT? WE'RE FOCUSED ON THE FAILURES, [LAUGHTER] MOST WHAT HAVE WE DO IS A FAILURE. IT'S AMAZING WE SUCCEED BEFORE. >> IS SUCCESS BASED ON THE FACT THAT WE DID IT AS A DOUBLE BLIND CONTROL? >> ABSOLUTELY. ABSOLUTELY. JUST GO THROUGH THE DOUBLE BONE MARROW TRANSPLANT ESPECIALLY IN THE SLOWLY PROGRESSIVE DISEASE LIKE THIS. I THINK THERE'S--YOU MAKING ME MUCH MORE ENTRENCHED. >> I'M ASKING WHETHER IT ALWAYS HAS TO BE--DOESN'T ALWAYS--WHETHER THE PATIENT STATUS AND WHETHER THEY'RE--DISEASE STATE SHOULD BE CONSIDERED IN MAKING THAT DECISION. >> NO, NO. I THINK THE ANSWER TO THAT QUESTION, SHOULD THE DISEASE STATE BE CONSIDERED IN HOW YOU DESIGN THE TRIAL, THE ANSWER TO THAT IS NO. ON OTHER HAND, DO YOU THINK THAT YOU OUGHT TO HAVE OPT OUTS OR IF YOU CAN'T HAVE A CROSS OVER TRIAL BECAUSE THE DISEASE LENDS ITSELF TO THE PERSON BEING THEIR OWN CONTROL, ALL OF THOSE OUGHT TO BE CONSIDERED, NOT FOR AN INDIVIDUAL CASE, BUT IN THE CASE OF A DESIGN OF A TRIAL FOR A DISEASE CONDITION. ABSOLUTELY. THIS SEEMEDDED TO SUGGEST THAT THEY HAVE THOUGHT ABOUT IN THERAPIST AND QUITE SYMPATHETIC TO THE CASE. FA AGAIN IF WHAT WE HAVE A PROGRESSIVE MULTIPLE SCLEROSIS SITUATION, THERE'S A REASON WE HAVEN'T DONE THE CROSS OVER STUDY, THEY KEEP IT BLINDS THE MULTIPLE CLEAROSEIS PATIENT--MULTIPLE SCLEROSIS PATIENTS ACCOUNTED BE EBBS SEEDING SO. >> I NEVER THOUGHT OF MYSELF, BUT JOINING THE CLUB. YOU BRING THE ISSUE OF SYMPATHY AND WE OPERATE IN THAT MANNER, BUT BUT WE HAVE IN ADDITION TO THIS IN LOOKING AT THIS GRAPH AND ACCEPTING THAT MANY OF THE THINGS AND FAILURE WHO IS ARE GOING TO FAIL, THEREFORE I THINK THAT EXPERIMENTAL TREATMENT INCREASINGLY ASK AN OPEN QUESTION: WILL IT WORK OR IT WILL NOT WORK. AND THE FACT THAT SOMEBODY IS TAWSING BEFORE KNOWING IT'S WORKING YOU ARE BREAKING THE [INDISCERNIBLE] SOMEHOW AND THIS CASE AFFECTS MOVE OF THE STUFF WE DO, IT'S IMPORTANT WHAT WE DO RESEARCH TO MAKE SURE THAT THIS IS CORRECT, BUT ALSO KEEP IN MIND THAT IT MAY NOT BE AND WHEN YOU MOVE A PATIENT FROM A STUDY TO AN OPEN LABEL AND AND I-- >> I WOULDN'T PUT IT WE HAVE TO HAVE EQUESTIONNAIRES POISE AND MANY OF US HAVE TO HAVE STRONG BELIEFS IT MAY E A WHILE, AND GET UP, RUNNING AND LAUNCH, IT WOULD BE HART TO MOTIVATE PEOPLE UNLESS THEY HAVE SOMETHING THAT'S GOING TO NUMBER THAT--IN GROUP ON THE OTHER HAND, THOSE OF US WHO ARE STANDING OUTSIDE, CAN WITH A LITTLE MORE SOPHISTICATED BRIE ETICSY SAY, YOU KNOW, THE OVERWHELMING ODDS ARE, THIS IS ANOTHER FAILURE AND WE'RE JUST GOING TO PROCEED BACKGROUNDS, I MEAN ONE OF THE THINGS INTERESTINGLY, THIS PATIENT HAS NO IDEA OF I PRESUME IS ONE OF THE OTHER PATIENTS ON THE TRIAL, WHAT IS THEIR EXPERIENCE, RIGHT? THERE MAY--YOU KNOW, THEY COULD BE HAVING THE SAME EXACT EXPERIENCE SHE'S HAVING AND THE ODDS ARE YES, WHETHER THEY'RE GETTING THE ACTIVE AGENT ACTIVE OR WHETHER THEY'RE GETTING PATHWAY GIVES PLACEBO SEEK O. YOU TOUCH OFFICE OF DIVERSITY A POINT, EARLIER HAVING TO DO WITH RISK. AND IT SEEMS TO ME, THAT THIS LADY HAS BEEN TRAPPED BY A IDEA THAT THE DRUG WAS A WINNER IN THE TRIAL, AND YOU BROUGHT UP STUFF, THERE'S CAST TRIAL WHICH WAS HOST MI WITH BBCs, AND THE DRUG WERE TESTED ON AND THEY VANISHED BUT LONG-TERM FOLLOW UP, I PERSONALLY HAVE KILLED SOMEONE WITH QUINADINE AND IN THE INFORMED CONSENT PROCESS THIS BUSINESS OF EQUESTIONNAIRES POISE NEEDS TO BE EMPHASIZED AND I THINK WE ATTEMPT TO HIDE GOOD TREATMENTS. >> LFIRST OF ALL I THINK IT'S A REALLY IMPORTANT QUESTION WHETHER IT'S A INCOMMED CONSENSUS OR NOT TMAY BE THAT THIS WOMAN, AND I SAILED THIS COME CAME IN WANTING THIS THING BECAUSE SHE RUN OUT OF OTHER OPTIONS AND HAD HER BELIEF, NOT NECESSARILY FROM THE INVESTIGATORS BUT FROM OUR LARGER CULTURE, THIS IS HER LAST HOPE, IT'S LIKELY THIS IS--YOU KNOW IT'S A NEW DRUG, NEW EXPERIMENTAL THERAPY, LIKELY TO WORK AND I THINK THAT'S PROBABLY MORE INFORMATIVE. THE ONCOLOGY SETTING, OVERWHELMINGLY PATIENTS ARE BROUGHT IN ALREADY BOUGHT INTO THE DRUG AND WE'RE NOT GOING TO DISSUADE THEM NO MATTER WHAT LIST OF HORRIBLES WE HAVE. OF COURSE IT LEADS TO REASONS AND ONE REASON TO BE FIRMER HERE, AGAIN FOCUS ON THE TO BE OVERWHELMED BY OUR EMOTIONS BUT IN THE CASE OF WHETHER WE SHOULD BE DOING IT. >> WE SHOULD BE TREATING PATIENTS THAT ARE ENTITLED TO TREATMENTS THAT ARE PROVEN BUT ARE EFFECTIVE FOR SOME INDIVIDUALS BUT NOT OTHERS AND WHEN THEY'RE EFFECTIVE THE EFFECT MAY BE SO SMALL AS TO BE COMLITELY RELEVANT BY PROJECTS OF PARTICULAR INDIVIDUALS SO THE PROVEN UNPROVEN INDIVIDUALS SEEPS LIKE A PLACE TO DRAW A LINE FOR DETERMINE WHAT IS SOMEONE IS ENTITLED TO WHEN IT MEANS A GIVEN INDIVIDUAL IS ENTITLED TO A TREATMENT THAT MAY OR MAY NOT BENEFIT THEM AND EVEN IF IT DOES WILL ALMOST CERTAINLY NOT EFFECT THE PROJECT, THAT MAY OR MAY NOT BENEFIT THEM BUT IF DOES HAVE AN EFFECT IT COULD BE MORE RELEVANT, THE Y IS PROVEN VERSES RELEVANT. >> WELL IT DOES HAVE A-RELEVANT WHICH IS YOU CAN'T GET ACCESS TO ONE READ ILLEGALS SCHEYOU CAN'T GET ACCESS TO THE OTHER ONE READILY IN ALL SORTS OF WAYS AND IN ALL CASES, RIGHT, IT IS GOING TO BE PRETTY MUCH A DISTRIBUTION AS TO WHO GETS BENEFIT AND DOESN'T GET BENEFIT, WHERE THERE WOULD BE A SEGMENT OF PEOPLE WHO GET BENEFIT AND PEOPLE WHO WON'T AND PROVEN MEANS YOU SEPARATED OUT THE MEANS OF THOSE TWO THINGS OF SUFFICIENTLY THAT WE CAN DETECT IT, BUT I TAKE YOUR POINT AND I THINK I WAS HINTING AT THE FACT THERE THERE'S PROBABLY THE CASE OF WHAT ARE THE ODDS OF YOUR IMPACT, WHAT IS THE MAGNITUDE OF THE IMPACT HAVING A WAY OF MEASURING IT AND CAN WE COMPARE THE TWO, WE'RE PROVEN AND UNPROVEN WOULDN'T NECESSARILY COME IN EXCEPT AT THE ODDS OF IMPACT WOULD BE HIRE FOR THE PROVEN ONE. RARELY ARE THEY 1.0. SO THERE PROBABLY IS, A WAY INv &C @&C WHICH PROVEN AND UNPROVEN IS DOING WORK THAT WE COULD DO BY THE ODDS OF SUCK SUSES MEASURED BY THE MAGNITUDE OF SUCCESS, WE DON'T HAVE THAT GENERAL FORMULA, WE DON'T HAVE ANY IDEA WHAT THE ODDS OF IMPROVEMENT ARE AND WHAT THOSE MEASURE OF BENEFIT ARE UNTIL WE DO THE STUDY, RIGHT? I'M JUST CURIOUS IF YOUR THOUGHTS ON ENTITLEMENT CHANGE BECAUSE SHE WAS TOLD AT THE END ALL PATIENTS EVER GOING TO GET THE OPPORTUNITY TO RECEIVE THIS DRUG O IN THIS WAYS IT'S JUST A MATTER OF TIME AND HER TIME IS RUNNING OUT. >> NOT ME. NO. I MEAN, YOU KNOW I--I--IT WOULDN'T CHANGE MY VIEW BECAUSE AGAIN HER GOING IN THE TRIAL AND COMING OUT OF THE TRIAL PICKS THE DAY OF THE TRIAL AND IT IS WHAT YOU WANT BUT HER IDEA, HER SUSPICION, A LOT OF THIS IS BASED ON THE BELIEF THAT SHE HAS PLACEBO AND THERE'S ABSOLUTELY NO GRANT SAID FOR THAT VIEW. THE GROUND SYSTEM I'M GETTING WORSE, I'M GETTING DRUG AND I'M GETTING WORSE, WHY THAT LEADS YOU TO THE IDEA THAT WHAT SHE'S GET SUGGEST PLACEBO OPPOSE TO INEFFECTIVE THERAPY. THEE HAD THE IDEA THAT THIS GRAPH DOESN'T WORK. YOU KNOW ON THE BASIS OF THIS GRAPH, YOU WOULD SAY THAT'S AIN'T SURPRISING, YOU KNOW THE CHANCE OF YOU GETTING EXPERIMENTAL THERAPY VERSES PLACEBO, YOU KNOW? BASICALLY THE SAME. THE ONCOLOGY GRAPH WHICH IS WHY I BECAME AN ONCALIFORNIAST OOH POSE TO NEUROLOGIST, YOU KNOW? THEN IT'S OVERWHELMING THAT SHE PROBABLY. SHE HAS NO IDEA SHE'S JUST MAKING A GUESS AND WE SHOULD NOT COUNT AGAINST THAT GUESS WITH ANY PRIVILEGE POSITION FOR THAT TYPE. >> SO THIS IS THE LAST ETHICS GRAND ROUNDS OF THE YEAR. [ APPLAUSE ] I WANT TO TELL EVERYBODY, SO THANKS FOR COMING, I'LL START AGAIN IN THE FALL. I HOPE CAN YOU JOIN US AND I WANT TO ESPECIALLY THANK ZEKE FOR EXEMPLIFYING THE LEGACY HE LEFT US WITH YOU CAN DO GOOD WORK AND HAVE FUN WHILE YOU'RE DOING IT, THANKS, ZEKE.