Research ethics & ethical Research ethics & ethical clearanceclearance

Kantha LankatilakeKantha LankatilakeSenior LecturerSenior Lecturer

Dept. of Community MedicineDept. of Community MedicineFaculty of Medicine, ColomboFaculty of Medicine, Colombo

EthicsEthics

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

right and acceptable conduct right and acceptable conduct

Hippocratic OathHippocratic Oath

Main principles of the Hippocratic Oath are Main principles of the Hippocratic Oath are summarised as, summarised 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 treatmentto refer patients for specialized treatment not to abuse professional relationships, not to abuse professional relationships,

especially for sexual motivesespecially for sexual motives to maintain patient’s confidenceto maintain patient’s confidence

Research ethicsResearch ethics

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

codes of conduct to the collection, analysis, codes of conduct to the collection, 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, confidentiality, of subjects' right to privacy, confidentiality, andand

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 illiterate Negro males suffering 399 poor and mostly illiterate Negro males suffering from Syphilis were studied to observe the natural from Syphilis were studied to observe the natural progression of the disease. progression of the disease.

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

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

Plenty of papers were published from this study. Plenty of papers were published from this study. Eventually the study was leaked to the press and the Eventually the study was leaked to the press and the programme was terminated. programme was terminated.

Nazi human experimentation Nazi human experimentation early 1940’s early 1940’s

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

They were forced into participatingThey were forced into participating

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

Nazi human experimentationNazi human experimentation

Freezing/hypothermia experiment - 1941Freezing/hypothermia experiment - 1941 Victims troops; healthy Victims troops; healthy

Jews/RussiansJews/Russians

They were usually stripped naked They were usually stripped naked and prepared for the experimentand prepared for the experiment

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

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

Results: most victims lost Results: most victims lost consciousness and died (about a consciousness and died (about a 100) when the body temperature 100) when the body temperature dropped to dropped to 77 °F (25 °C). Results of these experiments were published at the 1942 medical

conference entitled, “medical problems arising from sea and winter”.

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

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

Mustard gas experiments (1939-1945) - Mustard gas experiments (1939-1945) - subjects were subjects were deliberately exposed to mustard gas which inflicted severe chemical deliberately exposed to mustard gas which inflicted severe chemical burns . Then they were tested to find the most effective treatment for burns . Then they were tested to find the most effective treatment for the mustard gas burns. 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 these Blood circulation to these wounds was interrupted to create a condition similar to that of a wounds was interrupted to create a condition similar to that of a battlefield wound. Infection was aggravated by forcing wood shavings battlefield wound. Infection was aggravated by forcing wood shavings and ground glass into the wounds. The infection was treated with and ground glass into the wounds. The infection was treated with sulfonamide and other drugs to determine their effectiveness.sulfonamide and other drugs to determine their effectiveness.

Aftermath of the experimentationAftermath of the experimentation

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

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

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

Nuremberg Code - 1949 Nuremberg Code - 1949

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

voluntary consent of human subjectsvoluntary consent of human subjects

to recognize that the risks must out weigh to recognize that the risks must out weigh the the expected benefit, and that unnecessary expected benefit, and that unnecessary pain and suffering must be avoided. pain and suffering must be avoided.

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

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

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

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

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

Special consideration was given to ethnic Special consideration was given to ethnic minorities and vulnerable groups in the design of minorities and vulnerable groups in the design of clinical studies.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 PracticeHarmonization- Good Clinical Practice (1996)(1996)

Values that commonly apply to medical ethicsValues that commonly apply to medical ethics

Autonomy - right to refuse or choose their Autonomy - right to refuse or choose their treatmenttreatment

Beneficence – the practitioner should act in the Beneficence – the practitioner should act in the best interest of the patientbest interest of the patient

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

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

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

Truthfulness and honesty - the concept of Truthfulness and honesty - the concept of informed consentinformed consent

The 7 principlesThe 7 principles

that makes clinical research ethicalthat makes clinical research ethical

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 missed?if not done would the information be 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 scientifically valid,for research to be scientifically valid,

clear scientific objectivesclear scientific objectives design in relation to objectivesdesign in relation to objectives methodology reliable – produce valid datamethodology reliable – produce valid data practically feasiblepractically feasible principal investigators and the otherprincipal investigators and the other

research personnel should be competent.research personnel should be 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 reasons of Selection of subjects for reasons of science, related to the purpose of the study, not because science, related to the purpose of the study, not because they are readily available, vulnerable, or otherwise easily they are readily available, vulnerable, or otherwise easily exploited, or are favored.exploited, or are favored.

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

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

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

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

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

5. Independent Review5. Independent Review

Minimize conflict of interest Minimize conflict of interest

Public AccountabilityPublic Accountability

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

6. Informed consent of subject6. Informed consent of subject

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 understanding the based on understanding the objectives, risks, benefits, and alternatives of the objectives, risks, benefits, and alternatives of the research.research.

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

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

Components of informed consent Components of informed 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 sheetof participation as given in the information sheet

if written, the if written, the consent form consent form has to be in all three has to be in 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 any reason;details about the right to withdraw at any time for any reason; information about how to communicate a decision to withdraw information about how to communicate a decision to withdraw

from the study;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 the should be concerned about the wellbeing of the subjects as the study proceedssubjects as the study proceeds

assure confidentiality of informationassure confidentiality of information permitting them to change their mind – withdraw permitting them to change their mind – withdraw

without penaltywithout 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 we stand As for research ethics, where do we stand today?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.

Ethics Review Committee, Faculty of Medicine received Ethics Review Committee, Faculty of Medicine received renewal of SIDCER/FERCAP Recognition Award for renewal of SIDCER/FERCAP Recognition Award for

2012-2016 on 212012-2016 on 21stst November 2012 November 2012

"The Strategic Initiative for Developing Capacity in Ethical Review” (SIDCER) is a network of

independently established regional fora for ethical review committees

Process for ethical clearanceProcess for ethical clearanceEthics Review Committee Ethics Review Committee

Faculty of MedicineFaculty of MedicineUniversity of ColomboUniversity of Colombo

Submission of application to the ERC/FM-ColomboSubmission of application to the ERC/FM-Colombo

Standard Operating Procedures (SOP) Ethics Review Standard Operating Procedures (SOP) Ethics Review Committee, Faculty of Medicine, University of Colombo, Committee, Faculty of Medicine, University of Colombo, version 3 June 2012version 3 June 2012

Purpose: To describe the overall function and scope of responsibilities of the ERC

OVERALL FUNCTION of the ERC, FM-ColomboOVERALL FUNCTION of the ERC, FM-Colombo

1. is to protect the mental and physical welfare, rights, dignity 1. is to protect the mental and physical welfare, rights, dignity and safety of human participants and animals used in and safety of human participants and animals used in research, to facilitate ethical research through efficient and research, to facilitate ethical research through efficient and effective review and monitoring processes, to promote ethical effective review and monitoring processes, to promote ethical standards of human and animal research and to review standards of human and animal research and to review research in accordance with the research in accordance with the Guidelines of the Forum of Guidelines of the Forum of Ethics Review Committees in Sri Lanka (FERCSL Guidelines) Ethics Review Committees in Sri Lanka (FERCSL Guidelines) and relevant national and international guidelines. and relevant national and international guidelines.

SCOPE OF RESPONSIBILITIES SCOPE OF RESPONSIBILITIES

i. To provide independent, competent and timely review and i. To provide independent, competent and timely review and monitoring ofmonitoring of

human research projects in respect of their ethical acceptability. human research projects in respect of their ethical acceptability.

ii. To provide ethical oversight, monitoring and advice for human ii. To provide ethical oversight, monitoring and advice for human and animal research projects. and animal research projects.

iii. To prescribe the principles and procedures to govern human iii. To prescribe the principles and procedures to govern human research projects including those involving human tissue and/or research projects including those involving human tissue and/or personal records. personal records.

Applications received by ERC

Preliminary review Comments / Requests for

Revision

Allocation of the proposals Revised/ Ammended proposal

Regular review Exempt from Review Expedited Review

Executive Committee Send to Reviewers

Decision

Request for Revisions Approval Approval with conditions

Rejection

Ethical Clearance

Resubmission

Ethics Review ProcessEthics Review Committee, Faculty of Medicine, University of Colombo

Agreement for the conditions

ReferencesReferences

bioethics.nih.gov/slides/10-29-03-Emmanuel.pdfbioethics.nih.gov/slides/10-29-03-Emmanuel.pdf

http://www.pgis.lk/download/forms/uniform_guidelines.pdf http://www.pgis.lk/download/forms/uniform_guidelines.pdf 

Emanuel E, Wendler D, Grady C. What makes clinical research Emanuel E, Wendler D, Grady C. What makes clinical research ethical? ethical? Journal of the American Medical Association Journal of the American Medical Association 2000; 2000; 283(20):2701-11283(20):2701-11

http://fercsl.net/Colombo%20ERC%20SOP%20version%202.2.pdfhttp://fercsl.net/Colombo%20ERC%20SOP%20version%202.2.pdf