1. Research ethics & ethicalResearch ethics & ethical
clearanceclearance
Kantha LankatilakeKantha Lankatilake
Senior LecturerSenior Lecturer
Dept. of Community MedicineDept. of Community Medicine
Faculty of Medicine, ColomboFaculty of Medicine, Colombo

2. EthicsEthics
 a set of principles that determine thea set of principles that determine the
right and acceptable conductright and acceptable conduct
Hippocratic OathHippocratic Oath

3. Main principles of the Hippocratic Oath areMain principles of the Hippocratic Oath are
summarised as,summarised as,
 do no harmdo no harm
 not to assist suicide or administernot 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

4. Research ethicsResearch ethics
The application of moral rules and professionalThe application of moral rules and professional
codes of conduct to the collection, analysis,codes of conduct to the collection, analysis,
reporting, and publication of information aboutreporting, and publication of information about
research subjects, in particular active acceptanceresearch subjects, in particular active acceptance
of subjects' right to privacy, confidentiality, andof subjects' right to privacy, confidentiality, and
informed consent.informed consent.

5. How did research ethics evolve?How did research ethics evolve?

6. Tuskegee Study ( Alabama)Tuskegee Study ( Alabama)
1932 -19721932 -1972
 399 poor and mostly illiterate Negro males suffering from399 poor and mostly illiterate Negro males suffering from
Syphilis were studied to observe the natural progression ofSyphilis were studied to observe the natural progression of
the disease.the disease.
 The subjects were not told they had syphilis andThe subjects were not told they had syphilis and
consequently they went into infecting many of their wives,consequently they went into infecting many of their wives,
which resulted in 19 of their children being born withwhich resulted in 19 of their children being born with
congenital syphilis.congenital syphilis.
 by 1947 penicillin had become the standard treatment forby 1947 penicillin had become the standard treatment for
syphilis. However, the treatment was withheld.syphilis. However, the treatment was withheld.
 Plenty of papers were published from this study. EventuallyPlenty of papers were published from this study. Eventually
the study was leaked to the press and the programme wasthe study was leaked to the press and the programme was
terminated.terminated.

7. Nazi human experimentationNazi human experimentation
early 1940’searly 1940’s
 Experiments carried out on large numbers ofExperiments carried out on large numbers of
prisoners in concentrated camps by the Germanprisoners in concentrated camps by the German
Nazi regime during World War IINazi 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 thedisfigurement or permanent disability of the
subjectssubjects

8. Nazi human experimentationNazi human experimentation
Freezing/hypothermia experiment - 1941Freezing/hypothermia experiment - 1941
 Victims troops; healthy Jews/RussiansVictims troops; healthy Jews/Russians
 They were usually stripped naked andThey were usually stripped naked and
prepared for the experimentprepared for the experiment
 A insulated probe was inserted into theA insulated probe was inserted into the
rectum to measured the drop in therectum to measured the drop in the
body temperaturebody temperature
 The victimThe victim put into an air force uniform,
was then placed in the tub of coldwas then placed in the tub of cold
water and started to freezewater and started to freeze
 Results: most victims lostResults: most victims lost
consciousness and died (about a 100)consciousness and died (about a 100)
when the body temperature dropped towhen the body temperature 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”.

9. 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 ofPrisoners were infected by mosquitoes or by injections of extracts of
the mucous glands of female mosquitoes. About a half died of thethe 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 weresubjects were
deliberately exposed to mustard gas which inflicted severe chemicaldeliberately exposed to mustard gas which inflicted severe chemical
burns . Then they were tested to find the most effective treatment forburns . Then they were tested to find the most effective treatment for
the mustard gas burns.the mustard gas burns.
 Sulfonamide experiments (1942-1943) - WoundsWounds
inflicted on the subjects were infected with bacteria, such asinflicted on the subjects were infected with bacteria, such as
Streptococcus, gas gangrene and tetanus.Streptococcus, gas gangrene and tetanus. Blood circulation to theseBlood circulation to these
wounds was interrupted to create a condition similar to that of awounds was interrupted to create a condition similar to that of a
battlefield wound. Infection was aggravated by forcing wood shavingsbattlefield wound. Infection was aggravated by forcing wood shavings
and ground glass into the wounds. The infection was treated withand 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.

10. Aftermath of the experimentationAftermath of the experimentation
 Many of the subjects died, many others were murdered afterMany of the subjects died, many others were murdered after
the tests were completed to carryout a post mortem. Thosethe tests were completed to carryout a post mortem. Those
who survived were often left mutilated, suffering permanentwho survived were often left mutilated, suffering permanent
disability, weakened bodies, and mental duress.disability, weakened bodies, and mental duress.
 On August 19, 1947, the doctors captured by Allied forcesOn August 19, 1947, the doctors captured by Allied forces
were put on trial in USAwere put on trial in USA –– Doctor’s trialDoctor’s trial.. At the trial, severalAt the trial, several
of the doctors argued in their defense that there was noof the doctors argued in their defense that there was no
international law regarding medical experimentation.international law regarding medical experimentation.
 This led to the development of theThis led to the development of the Nuremberg Code ofNuremberg Code of
medical ethics.medical ethics.

11. Nuremberg Code - 1949Nuremberg 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 theto recognize that the risks must out weigh the
expected benefit, and that unnecessary pain andexpected benefit, and that unnecessary pain and
suffering must be avoided.suffering must be avoided.
 doctors should avoid actions that injuredoctors should avoid actions that injure
human patients.human patients.
Nuremberg code was updated by WHO as theNuremberg code was updated by WHO as the
Declaration of Helsinki (1964)Declaration of Helsinki (1964)

12. In 1972 with the termination of theIn 1972 with the termination of the Tuskegee Study
 The,The, National Commission for the Protection of HumanNational Commission for the Protection of Human
Subjects of Biomedical and Behavioral ResearchSubjects of Biomedical and Behavioral Research and theand the
National Research ActNational Research Act were established.were established.
The act required the establishment ofThe act required the establishment of Institutional ReviewInstitutional Review
Boards (IRBs)Boards (IRBs)
 Special consideration was given to ethnic minorities andSpecial consideration was given to ethnic minorities and
vulnerable groups in the design of clinical studies.vulnerable groups in the design of clinical studies.

13. 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 GuidelinesCIOMS/WHO International Guidelines (1993, 2002)(1993, 2002)
 ICH/GCP-International Conference onICH/GCP-International Conference on
Harmonization- Good Clinical PracticeHarmonization- Good Clinical Practice (1996)(1996)

14. Values that commonly apply to medical ethicsValues that commonly apply to medical ethics
 Autonomy - right to refuse or choose their treatmentAutonomy - right to refuse or choose their treatment
 Beneficence – the practitioner should act in the bestBeneficence – the practitioner should act in the best
interest of the patientinterest of the patient
 Non-maleficence - do no harmNon-maleficence - do no harm
 Justice - concerns the distribution of scarce healthJustice - concerns the distribution of scarce health
resources, and the decision of who gets whatresources, and the decision of who gets what
treatment (fairness and equality).treatment (fairness and equality).
 Dignity - the patient (and the person treating theDignity - 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 informedTruthfulness and honesty - the concept of informed
consentconsent

15. The 7 principlesThe 7 principles
that makes clinical research ethicalthat makes clinical research ethical

16. 1. Social value1. 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

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

18. 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.

19. 3. Fair subject selection3. Fair subject selection
 JusticeJustice
 subject selectionsubject selection –– Selection of subjects for reasons ofSelection of subjects for reasons of
science, related to the purpose of the study, not becausescience, related to the purpose of the study, not because
they are readily available, vulnerable, or otherwise easilythey 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

20. 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 subjectsbe balanced by the benefits to subjects

21. 5. Independent Review5. Independent Review
Minimize conflict of interestMinimize conflict of interest
Public AccountabilityPublic Accountability
 Independent review of clinical researchIndependent review of clinical research
ensures the public that investigator biasesensures the public that investigator biases
have not distorted the approach, thathave not distorted the approach, that
ethical requirements have been fulfilled,ethical requirements have been fulfilled,
and that subjects will not be exploited.and that subjects will not be exploited.

22. 6. Informed consent of subject6. Informed consent of subject

23. What is informed consent ?What is informed consent ?
Respect for PersonsRespect for Persons
 voluntary decision taken by an individual to
participate in research based on understanding thebased on understanding the
objectives, risks, benefits, and alternatives of theobjectives, risks, benefits, and alternatives of the
research.research.
 the principal investigator has responsibility to obtainthe principal investigator has responsibility to obtain
voluntary informed consent (eithervoluntary informed consent (either verbal orverbal or
writtenwritten) from all prospective participants or) from all prospective participants or
 in the case of individuals who are not capable ofin the case of individuals who are not capable of
giving informed consent, the permission of theirgiving informed consent, the permission of their
legally authorized guardians (proxy consent).legally authorized guardians (proxy consent).

24. Components of informed consentComponents of informed consent
 information sheetinformation sheet
 seek consent only after the participant hasseek consent only after the participant has
received and adequately understood allreceived and adequately understood all
necessary information and the consequencesnecessary information and the consequences
of participation as given in the information sheetof participation as given in the information sheet
 if written, theif written, the consent formconsent form has to be in all threehas to be in all three
languageslanguages
 if written, consent should be obtained byif written, consent should be obtained by
signing on a consent formsigning on a consent form

25. 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 from theinformation about how to communicate a decision to withdraw from the
study;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

26. 7. Respect for enrolled subjects7. Respect for enrolled subjects
Beneficence and Respect for PersonsBeneficence and Respect for Persons
 should be concerned about the wellbeing of the subjectsshould be concerned about the wellbeing of the subjects
as the study proceedsas the study proceeds
 assure confidentiality of informationassure confidentiality of information
 permitting them to change their mind – withdraw withoutpermitting them to change their mind – withdraw without
penaltypenalty
 informed of new information – new risks /treatmentinformed of new information – new risks /treatment
 share results of subjectsshare results of subjects
 ensure privacyensure privacy
 maintain anonymitymaintain anonymity
 minimise disruption to workminimise disruption to work

27. As for research ethics, where do we standAs for research ethics, where do we stand
today?today?
 Faculty of Medicine, University of Colombo was the firstFaculty of Medicine, University of Colombo was the first
institution in Sri Lanka to establish an institutional Ethicsinstitution 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 scientificIn 1991, NARESA drew up a draft code for scientific
research, animal experimentation, biomedical researchresearch, 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 theirMin. 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 andEthical review is mandatory for the presentation and
publication of research.publication of research.

28. Ethics Review Committee, Faculty of MedicineEthics Review Committee, Faculty of Medicine
received renewal of SIDCER/FERCAP Recognitionreceived renewal of SIDCER/FERCAP Recognition
Award for 2012-2016 on 21Award for 2012-2016 on 21stst
November 2012November 2012
"The Strategic Initiative for Developing Capacity in
Ethical Review” (SIDCER) is a network of independently
established regional fora for ethical review committees

29. Process for ethical clearanceProcess for ethical clearance
Ethics Review CommitteeEthics Review Committee
Faculty of MedicineFaculty of Medicine
University of ColomboUniversity of Colombo

30. Submission of application to the ERC/FM-ColomboSubmission of application to the ERC/FM-Colombo
 Standard Operating Procedures (SOP) Ethics Review Committee,Standard Operating Procedures (SOP) Ethics Review Committee,
Faculty of Medicine, University of Colombo, version 3 June 2012Faculty of Medicine, University of Colombo, version 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 and1. is to protect the mental and physical welfare, rights, dignity and
safety of human participants and animals used in research, to facilitatesafety of human participants and animals used in research, to facilitate
ethical research through efficient and effective review and monitoringethical research through efficient and effective review and monitoring
processes, to promote ethical standards of human and animalprocesses, to promote ethical standards of human and animal
research and to review research in accordance with theresearch and to review research in accordance with the Guidelines ofGuidelines of
the Forum of Ethics Review Committees in Sri Lanka (FERCSLthe Forum of Ethics Review Committees in Sri Lanka (FERCSL
Guidelines) and relevant national and international guidelines.Guidelines) and relevant national and international guidelines.

31. SCOPE OF RESPONSIBILITIESSCOPE OF RESPONSIBILITIES
i. To provide independent, competent and timely review and monitoring ofi. To provide independent, competent and timely review and monitoring 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 andii. To provide ethical oversight, monitoring and advice for human and
animal research projects.animal research projects.
iii. To prescribe the principles and procedures to govern human researchiii. To prescribe the principles and procedures to govern human research
projects including those involving human tissue and/or personal records.projects including those involving human tissue and/or personal records.

32. Applications received by ERC
Preliminary review
Comments / Requests for
Revision
Allocation of the proposalsRevised/ Ammended
proposal
Regular review
Exempt from ReviewExpedited Review
Executive Committee Send to Reviewers
Decision
Request for Revisions
Approval Approval with conditions
Rejection
Ethical Clearance
Resubmission
Ethics Review Process
Ethics Review Committee, Faculty of Medicine, University of Colombo
Agreement for the
conditions

33. 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 researchEmanuel E, Wendler D, Grady C. What makes clinical research
ethical?ethical? Journal of the American Medical AssociationJournal 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