Research ethics & ethical Research ethics & ethical clearanceclearance

EthicsEthics

a set of principles that a set of principles that determine the determine the

right and acceptable conduct right and acceptable conduct

Hippocratic OathHippocratic Oath

Main principles of the Main principles of the Hippocratic Oath are summarized Hippocratic Oath are summarized as as

do no harmdo no harm not to assist suicide or administer not to assist suicide or administer euthanasiaeuthanasia

not to cause abortionnot to cause abortion to refer patients for specialized to refer patients for specialized treatmenttreatment

not to abuse professional not to abuse professional relationships, especially for sexual relationships, especially for sexual motivesmotives

to maintain patientto maintain patient’’s confidences confidence Do not share patient informationDo not share patient information

Research ethicsResearch ethics

The application of moral rules and The application of moral rules and professionalprofessional

codes of conduct to the collection, codes of conduct to the collection, analysis, analysis,

reporting, and publication of information reporting, and publication of information aboutabout

research subjects, in particular active research subjects, in particular active acceptanceacceptance

of subjects' right to privacy, of subjects' right to privacy, confidentiality, andconfidentiality, and

informed consent.informed consent.

How did research ethics evolve?How did research ethics evolve?

Tuskegee Study ( Alabama)Tuskegee Study ( Alabama)1932 -1972 1932 -1972 399 poor and mostly 399 poor and mostly illiterate illiterate Negro males Negro males suffering from Syphilis suffering from Syphilis were studiedwere studied to observe to observe the natural progression of the natural progression of the disease the disease

The The subjects were not told subjects were not told they had syphilisthey had syphilis and and consequently they went consequently they went into into infecting many of infecting many of their wivestheir wives, which , which resulted in 19 of their resulted in 19 of their children being born with children being born with congenital syphiliscongenital syphilis..

by 1947 penicillin had by 1947 penicillin had become the standard become the standard treatment for syphilis. treatment for syphilis. However, the treatment was However, the treatment was withheldwithheld. .

Eventually the study was leaked to the press and the program was terminated.

Nazi human experimentation Nazi human experimentation early 1940 early 1940’’ss

Experiments carried out on large Experiments carried out on large numbers of prisoners in concentrated numbers of prisoners in concentrated camps by the German Nazi regime camps by the German Nazi regime during World War II during World War II

They were forced into participatingThey were forced into participating

Typically, the experiments resulted Typically, the experiments resulted in death, disfigurement or permanent in death, disfigurement or permanent disability of the subjectsdisability of the subjects

Nazi human experimentationNazi human experimentation

Freezing/hypothermia experiment Freezing/hypothermia experiment

- 1941- 1941 Victims troops; healthy Victims troops; healthy Jews/RussiansJews/Russians

They were usually stripped They were usually stripped naked and prepared for the naked and prepared for the experimentexperiment

A insulated probe was inserted A insulated probe was inserted into the rectum to measured into the rectum to measured the drop in the body the drop in the body temperaturetemperature

The victim The victim put into an air force uniform, was then placed was then placed in the tub of cold water and in the tub of cold water and started to freezestarted to freeze

Results: most victims lost Results: most victims lost consciousness and died (about consciousness and died (about a 100) when the body a 100) when the body temperature dropped to temperature dropped to 77 °F (25 °C).

Nazi human experimentationNazi human experimentation Malaria experiments (1942-1945) – conducted on

over 1200 prisoners to test for immunization and treatment of to test for immunization and treatment of malaria. Prisoners were infected by mosquitoes or by malaria. Prisoners were infected by mosquitoes or by injections of extracts of the mucous glands of female injections of extracts of the mucous glands of female mosquitoes. About a half died of the disease and subsequent mosquitoes. About a half died of the disease and subsequent complications. complications.

Mustard gas experiments Mustard gas experiments (1939-1945) - (1939-1945) - subjects subjects were deliberately exposed to mustard gas which inflicted were deliberately exposed to mustard gas which inflicted severe chemical burns. Then they were tested to find the most severe chemical burns. Then they were tested to find the most effective treatment for the mustard gas burns. effective treatment for the mustard gas burns.

Sulfonamide experiments (1942-1943) - Wounds Wounds inflicted on the subjects were infected with bacteria, such as inflicted on the subjects were infected with bacteria, such as Streptococcus, gas gangrene and tetanus. Streptococcus, gas gangrene and tetanus. Blood circulation to Blood circulation to these wounds was interrupted to create a condition similar to these wounds was interrupted to create a condition similar to that of a battlefield wound. Infection was aggravated by that of a battlefield wound. Infection was aggravated by forcing wood shavings and ground glass into the wounds. The forcing wood shavings and ground glass into the wounds. The infection was treated with sulfonamide and other drugs to infection was treated with sulfonamide and other drugs to determine their effectiveness.determine their effectiveness.

Aftermath of the Aftermath of the experimentationexperimentation

Many of the subjects died, many others were Many of the subjects died, many others were murdered after the tests were completed to murdered after the tests were completed to carryout a post mortem. Those who survived carryout a post mortem. Those who survived were often left mutilated, suffering were often left mutilated, suffering permanent disability, weakened bodies, and permanent disability, weakened bodies, and mental duress.mental duress.

On August 19, 1947, the doctors captured by On August 19, 1947, the doctors captured by Allied forces were put on trial in USAAllied forces were put on trial in USA – – DoctorDoctor’’s trials trial.. At the trial, several of the At the trial, several of the doctors argued in their defense that there doctors argued in their defense that there was no international law regarding medical was no international law regarding medical experimentation. experimentation.

This led to the development of the This led to the development of the Nuremberg Nuremberg Code of medical ethicsCode of medical ethics..

Nuremberg Code - 1949 Nuremberg Code - 1949

The code calls for standards such as,The code calls for standards such as,

voluntary voluntary consentconsent of human subjects of human subjects

to recognize that the to recognize that the expected expected benefits must outweigh the risksbenefits must outweigh the risks, , and that and that unnecessary pain and unnecessary pain and suffering must be avoidedsuffering must be avoided. .

doctors should doctors should avoid actions that avoid actions that injure injure human patients. human patients.

Nuremberg code was updated by WHO as Nuremberg code was updated by WHO as the Declaration of Helsinki (1964)the Declaration of Helsinki (1964)

AftermathAftermath

In 1972 with the termination of the In 1972 with the termination of the Tuskegee Study

The, The, National Commission for the National Commission for the Protection of Human Subjects of Biomedical Protection of Human Subjects of Biomedical and Behavioral Research and the National and Behavioral Research and the National Research Act Research Act were established.were established.

The act required the establishment of The act required the establishment of Institutional Review Boards (IRBs) Institutional Review Boards (IRBs)

Special consideration was given to ethnic Special consideration was given to ethnic minorities and vulnerable groupsminorities and vulnerable groups in the in the design of clinical studies.design of clinical studies.

Codes and GuidelinesCodes and Guidelines

Nuremberg CodeNuremberg Code (1949)(1949)

Declaration Of HelsinkiDeclaration Of Helsinki (1964- 2000)(1964- 2000)

The Belmont ReportThe Belmont Report (1979)(1979)

CIOMS/WHO International Guidelines CIOMS/WHO International Guidelines (1993, 2002)(1993, 2002)

ICH/GCP-International Conference on ICH/GCP-International Conference on Harmonization- Good Clinical Harmonization- Good Clinical PracticePractice (1996)(1996)

Values that commonly apply to Values that commonly apply to medical ethicsmedical ethics AutonomyAutonomy - right to refuse or choose their - right to refuse or choose their treatmenttreatment

BeneficenceBeneficence – the practitioner should act in – the practitioner should act in the best interest of the patientthe best interest of the patient

Non-maleficence Non-maleficence - do no harm- do no harm

JusticeJustice - concerns the distribution of scarce - concerns the distribution of scarce health resources, and the decision of who health resources, and the decision of who gets what treatment (fairness and equality).gets what treatment (fairness and equality).

DignityDignity - the patient (and the person - the patient (and the person treating the patient) have the right to treating the patient) have the right to dignity. dignity.

TruthfulnessTruthfulness and and honestyhonesty - the concept of - the concept of informed consentinformed consent

The 7 principlesThe 7 principles

that makes clinical research that makes clinical research

ethicalethical

1. Social value 1. Social value

Is this research of any value??Is this research of any value??

why do this research?why do this research?

if not done would the information be if not done would the information be missed?missed?

can the results be generalized?can the results be generalized?

Research has no value when,Research has no value when,

results unlikely to be disseminatedresults unlikely to be disseminated interventions could never be practically implementedinterventions could never be practically implemented

2. Is this research scientifically valid?2. Is this research scientifically valid?

for research to be for research to be scientifically valid,scientifically valid, clear scientific objectivesclear scientific objectives design in relation to objectivesdesign in relation to objectives methodology reliable – produce valid methodology reliable – produce valid

datadata practically feasiblepractically feasible principal investigators and the otherprincipal investigators and the other

research personnel should be research personnel should be competent.competent.A socially, clinically, or scientifically useful

research question that will generate useful new knowledge about human health

Research must be conducted in a methodologically rigorous manner.

3. Fair subject selection3. Fair subject selection

Justice Justice subject selectionsubject selection – – Selection of subjects for Selection of subjects for

reasons of science, related to the purpose of reasons of science, related to the purpose of the study, not because they are readily the study, not because they are readily available, vulnerable, or otherwise easily available, vulnerable, or otherwise easily exploited, or are favored.exploited, or are favored.

- - select subjects to minimize risks and select subjects to minimize risks and maximize benefitsmaximize benefits

- - have clear inclusion/exclusion criteriahave clear inclusion/exclusion criteria

4. Favorable Risk-Benefit Ratio4. Favorable Risk-Benefit Ratio

for research to be ethical, for research to be ethical, any risks mustany risks must

be balanced by the benefits to be balanced by the benefits to subjects subjects

5. Independent Review5. Independent Review

Minimize conflict of interest Minimize conflict of interest

Public AccountabilityPublic Accountability

Independent review of clinical Independent review of clinical research ensures the public research ensures the public that investigator biases have that investigator biases have not distorted the approach, not distorted the approach, that ethical requirements have that ethical requirements have been fulfilled, and that been fulfilled, and that subjects will not be exploited.subjects will not be exploited.

6. Informed consent of 6. Informed consent of subjectsubject

What is informed consent ?What is informed consent ?Respect for Persons Respect for Persons voluntary decision taken by an individual to participate in research based on based on understanding the objectives, risks, understanding the objectives, risks, benefits, and alternatives of the research.benefits, and alternatives of the research.

the principal investigator has the principal investigator has responsibility to obtain voluntary informed responsibility to obtain voluntary informed consent (either consent (either verbal or writtenverbal or written) from all ) from all prospective participants orprospective participants or

in the case of individuals who are not in the case of individuals who are not capable of giving informed consent, the capable of giving informed consent, the permission of their legally authorized permission of their legally authorized guardians (proxy consent). guardians (proxy consent).

Components of informed Components of informed consent consent

information sheetinformation sheet

seek consent only after the participant has seek consent only after the participant has received and adequately understood all received and adequately understood all necessary information and the consequences necessary information and the consequences of participation as given in the information of participation as given in the information sheetsheet

if written, the if written, the consent form consent form has to be in has to be in all three all three languageslanguages

if written, consent should be obtained by if written, consent should be obtained by signing on a consent form signing on a consent form

Informed consent contin..Informed consent contin..

Information sheet should contain Self introduction – from where & who you are;Self introduction – from where & who you are; purpose of the research;purpose of the research; description of benefits from participating;description of benefits from participating; description of risks from participating;description of risks from participating; details of time commitment required;details of time commitment required; details of any remuneration;details of any remuneration; plans to ensure the confidentiality of data;plans to ensure the confidentiality of data; details about the right to withdraw at any time for details about the right to withdraw at any time for

any reason;any reason; information about how to communicate a decision to information about how to communicate a decision to

withdraw from the study;withdraw from the study; name(s) of investigator(s) contact details.name(s) of investigator(s) contact details.The wording should suit the individual’s level of

understanding

7. Respect for enrolled subjects 7. Respect for enrolled subjects

Beneficence and Respect for Persons Beneficence and Respect for Persons

should be concerned about the wellbeing of should be concerned about the wellbeing of the subjects as the study proceedsthe subjects as the study proceeds

assure confidentiality of informationassure confidentiality of information permitting them to change their mind – permitting them to change their mind – withdraw without penaltywithdraw without penalty

informed of new information – new risks informed of new information – new risks /treatment/treatment

share results of subjects share results of subjects ensure privacyensure privacy maintain anonymitymaintain anonymity minimise disruption to workminimise disruption to work

As for research ethics, where do As for research ethics, where do we stand today?we stand today?

Faculty of Medicine, University of Colombo was the first Faculty of Medicine, University of Colombo was the first institution in Sri Lanka to establish an institutional Ethics institution in Sri Lanka to establish an institutional Ethics Review Committee, in 1981. Review Committee, in 1981.

In 1991, NARESA drew up a draft code for scientific In 1991, NARESA drew up a draft code for scientific research, animal experimentation, biomedical research research, animal experimentation, biomedical research on humans and social sciences research. on humans and social sciences research.

Since then several organisations such as, SLMA, SLAAS, Since then several organisations such as, SLMA, SLAAS, Min. of Health, NASTEC, NSF, SLMC have set up their Min. of Health, NASTEC, NSF, SLMC have set up their own institutional Ethics Review Committee. own institutional Ethics Review Committee.

Ethical review is mandatory for the presentation and Ethical review is mandatory for the presentation and publication of research.publication of research.