ใหลกจรยธรรมการวจยในคน และ

ความสาคญ

การอบรมพฒนาศกยภาพนกวจย ดานหลกจรยธรรมการวจยในคน ดานหลกจรยธรรมการวจยในคน

๒๓ เมษายน ๒๕๕๘

นายแพทยศภชย ฤกษงาม นายแพทยศภชย ฤกษงามประธานกรรมการจรยธรรมการวจย กรมควบคมโรค กระทรวงสาธารณสข

หลกจรยธรรมการวจยในคนหลกจรยธรรมการวจยในคน

Codes of Research Ethics:

The Nuremberg Codethe first set of principles outlining professional ethics

Declaration of Helsinkiby World Medical Association for the medical

itcommunity

B l t R tBelmont Reportby the National Commission in 1979

The Nuremberg Code:a voluntary consent is absolutely essentialanimal experimentation should precede humananimal experimentation should precede humanunnecessary physical and mental suffering and injury should be avoidedinjury should be avoidedthe degree of risk to the participants should never exceed the humanitarian importance of the problemexceed the humanitarian importance of the problemrisk should be minimized through proper preparation

ti i t h ld l b t lib t t ithdparticipants should always be at liberty to withdraw

D l ti f H l i kiDeclaration of Helsinki:informed consent is a central requirement

research with incompetent participant physically orresearch with incompetent participant, physically or mentally incapable of giving consent, or a minor should only be conducted when it is necessary to promote the health of the population representedpromote the health of the population represented

assent must be obtained in addition to the consent f h l ll h dof the legally authorized representative

…the benefits, risks, burdens and effectiveness of…the benefits, risks, burdens and effectiveness of new method should be tested against the best current methods ( not exclude placebo)

Belmont Report:Belmont Report:Three principles of research ethics

Respect for personsRespect for personsindividuals be treated as autonomous,

special protection to those diminished autonomyspecial protection to those diminished autonomy Beneficence

minimize possible risks, maximize possible benefitsJustice

equitably distribution of benefits and burdensq y

Respect for persons:Respect for persons: Informed consent

Is a process, not a single actionEmphasis on comprehension and choiceAmount of information should not beAmount of information should not be overwhelming or work against

h icomprehensionNeed explicit action to indicate decisionNeed explicit action to indicate decisionReimbursements should be appropriate to th tti d i tthe setting and circumstances

Beneficence:Beneficence:Assessment of risks vs. benefits

Risks:physical …harm or injurypsychological …uncomfortable feelingsocial …improper disclosure of private information economic …income loss

Benefits:something of positive value related to health or welfare

f fAssessment of risks vs. benefits

Risks and Benefits must be “balanced”the nature probability and magnitude of riskthe nature, probability and magnitude of risk should be distinguished from the validity of the researchresearchthe method of ascertaining risks should be

li itexplicit

…whether it is in fact necessary to use human subjects at all !!

Assessment of risks vs. benefits

Minimizing risks!

precautions safeguards and alternativesprecautions, safeguards, and alternativesresearchers’ competency, dual roles (clinician vs. researcher)research design yielding useful dataresearch design yielding useful data

J tiJustice:Selection of Subjectsj

Individual justicefairness in selection of subjects j

Social justiceSocial justicean order of preference in the selection of

classes of subjectsclasses of subjects

ความสาคญของความสาคญของ

หลกจรยธรรมการวจยในคนหลกจรยธรรมการวจยในคน

N i E i t WWII1940-1945 Nazi Experiments WWII:

23 physicians and administrators…...23 physicians and administrators, leading members of the German medical hierarchy involved in systematic torturehierarchy involved in systematic torture, mutilation, and killing of the prisoners in experimentexperiment

N i E i t WWII1940-1945 Nazi Experiments WWII:

(A) HIGH ALTITUDE EXPERIMENTS(B) FREEZING EXPERIMENTS.(C) MALARIA EXPERIMENTS.(D) LOST (MUSTARD) GAS EXPERIMENTS.(E) SULFANILAMIDE EXPERIMENTS.(F) BONE, MUSCLE, AND NERVE REGENERATION AND BONE TRANSPLANTATION

EXPERIMENTSEXPERIMENTS,(G) SEAWATER EXPERIMENTS.(H) EPIDEMIC JAUNDICE EXPERIMENTS. (I) STERILIZATION EXPERIMENTS….. by means of X-Ray, surgery, and various drugs. (J) SPOTTED FEVER EXPERIMENTS…to investigate the effect of spotted fever and other vaccines. (K) EXPERIMENTS WITH POISON…. secretly administered to experimental subjects in their food (L) INCENDIARY BOMB EXPERIMENTS…. to test the effect of various pharmaceutical preparations

on phosphorus burnson phosphorus burns(M) ….a skeleton collection for the Reich University of Strasbourg, (N) …. Poles were infected with incurable tuberculosis.

(O) "euthanasia“ the mass extermination of Jews(O) euthanasia …. the mass extermination of Jews.

The Nuremberg War Crimes TrialsThe Nuremberg War Crimes TrialsThe defendants at Nuremberg. F t f l ft tFront row, from left to right: Hermann Göring, Rudolf Hess, Joachim von Ribbentrop, Wilh l K it l E tWilhelm Keitel, Ernst Kaltenbrunner, Alfred Rosenberg, Hans Frank, Wilhelm Frick, J li St i hJulius Streicher, Walther Funk, HjalmarSchacht. Back row from left to right: Karl Dönitz, E i h R d B ldErich Raeder, Baldur von Schirach, Fritz Sauckel, Alfred Jodl, Franz von Papen, A th S I tArthur Seyss-Inquart, Albert Speer, Konstantin van Neurath, Hans Fritzsche.

.Courtesy of the National Archives

ขอสรปจากคาตดสนคด Nuremberg:

การขอความยนยอมเปนสงสาคญ

การวจยในคน ควรมผลจากการวจยในสตวทดลองกอน

ความเสยงควรมเหตผลอนสมควรเมอเทยบกบประโยชนทคาดหวงความเสยงควรมเหตผลอนสมควรเมอเทยบกบประโยชนทคาดหวง

แพทยทมคณสมบตเหมาะสมเทานน ทจะเปนผดาเนนการวจยได

ตองหลกเลยงความทกขทรมานทงทางรางกายและจตใจ

ไ ไ ไมควรดาเนนการวจยทคาดไดวาจะมการตายหรอความพการเกดขน

N i E i t WWII1940-1945 Nazi Experiments WWII:

the Nuremburg Military Tribunals condemned the experiments as ‘crimes against humanity’

12 defendants sentenced to death by hanging

1944 Human Radiation Experiments:1944 Human Radiation Experiments:involved radioactive tracers administered in amounts not likely to have caused physical harm

1 Injecting radioactive iodine into pregnant women seeking1. Injecting radioactive iodine into pregnant women seeking abortion, in order to track the mass transfer between placenta and carriers bloodstream. Another experiment administered radioactive iodine to newborns

2. Irradiating the heads of children3. Feeding radioactive material to mentally disabled childreng y4. Exposing U.S. soldiers and prisoners to high levels of radiation5. Irradiating the testicles of prisoners, which caused severe birth

defectsdefects6. Exhuming bodies from graveyards to test them for radiation

(without the consent of the families of the deceased)

1944 Human Radiation Experiments:1944 Human Radiation Experiments:

little attention given to issues of fairness in the selection of participantsselection of participants

Participants did not a are of the research norParticipants did not aware of the research nor consent

Participants were not likely to derive direct benefit

1962 Jewish Chronic Disease Hosp. Study:

22 elderly patients at the Jewish Chronic Disease Hospital in Brooklyn, New York were injected with live cancer cells

to understand whether the body’s inability to reject cancer cells was due to cancer or debilitation

Consent given orally, did not include a discussion on the i j ti f llinjection of cancer cells

A consent was not documented

1963-1966 Willowbrook Study:

a series of studies at the Willowbrook State School, a New York institution for ‘mentally defective’ childrenNew York institution for mentally defective children

to gain an understanding of the natural history of infectious hepatitis under controlled circumstances

…..newly-admitted children were deliberately infected with the hepatitis virus

1963-1966 Willowbrook Study:

…the Relevant Ethical Considerations !

Respect for persons and fairness were violated. The study provided an undue inducement students wereThe study provided an undue inducement …students were given a coveted spot in Willowbrook in a newer part of the facility

Parents and their children were not truly informed about ythe risks of the study. Also, the study could have been done with adults in the facility instead of children.

R t f P

1963-1966 Willowbrook Study:Respect for Persons:

Children in a mental health facility can’t fully understand the risks of a study they are participating in. The methods by which children were recruited are also questionable. Parents were unduly induced to give their consent…. parents had little choice over whether or not to participate in the researchparents had little choice over whether or not to participate in the research.

It is not appropriate to use a vulnerable, institutionalized population for experiments.population for experiments. Feeding live hepatitis virus to mentally disabled children in order to deliberately infect them does not respect them y pas persons.

U f i A t ( ):1963-1966 Willowbrook Study:Unfair Aspects (fairness):

There is no compelling reason to study viral hepatitis inThere is no compelling reason to study viral hepatitis in children before studying it in adults

Hepatitis was present at high levels because of overcrowding and unsanitary conditions, which theovercrowding and unsanitary conditions, which the healthcare professionals had a duty to improve. Instead, they took advantage of the situation to conduct an experiment.

1932 1972 T k S h li St d1932-1972 Tuskegee Syphylis Study:used disadvantaged rural black men to studyused disadvantaged, rural black men to study the untreated course of a disease that was by no means confined to themno means confined to them

free examinations and medical care were offered but theyfree examinations and medical care were offered, but they were not informed of their diseases, that they were participating in research orthat they were participating in research, or that the research would not benefit them

They were deprived of available effective treatment just in order not to interrupt the projectp p j

Tuskegee Syphylis Study:

Taking a blood sampleTaking a blood sample

Subjects talking with study coordinator, Nurse Eunice Rivers

สรปประเดนดานจรยธรรมการวจย:1. ขาดการใหความยนยอม

2 ใชประชากรทเปราะบางและออนแอในการวจย2. ใชประชากรทเปราะบางและออนแอในการวจย

3. มการบงคบหรอกดดนอยางไมเหมาะสมตออาสาสมคร

( ใ ป )(หรอตอพอแมเพอใหลกเปนอาสาสมคร)

3. แสวงหาประโยชนจากประชากรทเปราะบางและออนแอ

4. มการปดบงขอมล

5. จงใจไมใหการบาบดรกษาทมอย

6. ไมใหขอมลเกยวกบความเสยง

7 ทาใหอาสาสมครตกอยในความเสยง7. ทาใหอาสาสมครตกอยในความเสยง

8. ความเสยงตออาสาสมครมมากกวาผลประโยชน

9. มการหลอกลวง

10. มการละเมดสทธของผถกวจย

Codes of Research Ethics:

t th t ti f th i ht…to ensure the protection of the rights, safety, and well being of human subjects

ผวจย ตองดาเนนการวจย โดยคานงถง ผวจย ตองดาเนนการวจย โดยคานงถง

สทธ สวสดภาพ และความปลอดภยสทธ สวสดภาพ และความปลอดภย

ของผถกวจย