Research ethics, lecture by Prof Mohamed Ali Albar)

1. ‫الرحيم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬
Research Ethics
Dr. Mohamed Albar FRCP.
Medical Ethics Center International
Medical Center
Jeddah, Saudi Arabia

2. HIPPOCRATIC OATH
(Modern)
I swear to fulfill, to the best of my ability and
judgment, this covenant:
I will respect the hard -won scientific gains of
those physicians in whose steps I walk, and
gladly share such knowledge as is mine with
those who are to follow.

3.  BENEFICENCE
 Acting For The Benefit Of The patient
 NON—MALEFICENCE
 Do No Harm
 AUTONOMY
 Informed Consent
 Decision Making Capacity
 JUSTICE
 Benefit Society
PRINCIPLES OF
MEDICAL ETHICS

4.  Performed lumbar punctures on 29
hospitalized infants and children to perfect
the technique.
 All of the procedures were non-therapeutic
and were done solely to elicit painful
responses from the children.
Harvard Medical School
Arthur Wentworth, M.D. (1896)

5.  Targeted 600 poor and illiterate African
American Males (399 with syphilis and 201
without)
 Told they were being treated for “bad blood”
 Followed their progress without providing
penicillin which was a known antidote as of
1943.
Tuskegee Syphilis
Experiment (1932-1972)

6.  Conducted painful lumbar punctures under
the fraudulent precept of “free treatment” to
test the progression without providing any
benefit to the researchees.
 Provided no beneficial treatment and
admittedly shortened the lives of the
researchees.
 29 men died directly from syphilis and 100
others died of illnesses related to syphilis
Tuskegee Syphilis
Experiment (1932-1972)

7.  Hypothermia Experiments--Subfreezing
Water Immersion
 Sun Lamp
 Internal Irrigation
 Oxygen Deprivation--Study of Endurance
 Injection of Lethal Organisms
 Sexual Sterilizations
 Dr. Josef Mengele’s Sadistic
Experimentation of Twins
 Infecting prisoners and patients in
hospitals with Malaria
Occurred in the United States by the Military
World War II Research

8.  Developed in October of 1946 for the
Nuremberg Military Tribunal as
standards by which to judge Nazi based
human experimentation
 Initiated the basic principles of
Research Ethics involving Human
Subjects
ETHICAL CODES
NUREMBERG CODE

9. ETHICAL CODES
NUREMBERG CODE (1946)
“The voluntary consent of the human of
subject is absolutely essential”
Research Subjects “should be so situated
as to be able to exercise free power of
choice”
Research Subjects “should have sufficient
knowledge and comprehension of the
elements of the of subject matter involved as
to make an understanding and enlightened
decision”

10. ETHICAL CODES
NUREMBERG CODE (August 19, 1947)
10 Rules for “Permissible Medical Experiments”
1) voluntary consent without coercion
2) results must benefit society and must only
use human subjects when there is no
alternative
3) should be based upon non-human studies
with justifiable expected results
4) avoidance of all unnecessary physical and
mental suffering
5) no experimentation where death or serious
disability is foreseen unless performed on the
medical provider as a subject

11. 10 Rules for “Permissible Medical
Experiments”
6) degree of risk less than potential benefit
7) proper preparations must be made to
minimize injury
8) experiment should be conducted by only
scientifically qualified person
9) subjects can cease their participation at
any time
10) experimentor must stop if it is believed
it will result in death or serious disability
ETHICAL CODES
NUREMBERG CODE (August 19, 1947)

12.  Mostly African American cancer patients with lower than
average intelligence were exposed to large doses of whole-
body radiation
 None of the patients consented to the experiment or had
any idea of the potential side effects
 They were told they were receiving treatment for their
cancer
 This experiment was sponsored by the United States
Military
 Subjects experienced severe nausea and vomiting,
radiation burns and some died prematurely as a direct result
of the experiment
A lawsuit was finally settled in 1988 with the
United States Government accepting no responsibility
POST-AWARENESS RESEARCH
Cincinnati Radiation Experiment
(1960-1972)

13. POSTPOST-AWARENESS RESEARCH
Jewish Chronic Disease Hospital(New York 1963)
 22 chronically ill and debilitated non-cancer patients
were injected with live human cancer cells
 patients were not told of the cancer injection because
the patients physicians “did not wish to stir up any
unnecessary anxieties in the patients”
 hospital covered up the lack of consent and tried to
hospital fraudulently obtain consent after the fact
2 years after the investigation, the American
Cancer Society appointed the principle
investigator as a Vice President

14. POSTPOST-AWARENESS RESEARCH
Willowbrook State Hospital New York (1964-1971)
 Parents were not allowed to admit their severely
retarded children in this facility after 1964 unless they
“consented” to an injection of the Hepatitis A virus
 The consent form implied the children would receive
an antidote to the Hepatitis virus when they really
received a “subclinical” infection antidote.
 The physicians rationalized that the children had a
70% chance of receiving the Hepatitis virus anyway from
the facility due to the severity of their retardation and the
patients lack of sanitary acumen.

15. ETHICAL CODES
WORLD MEDICAL ASSOCIATIONDECLARATION OF
HELSINKI (1964-Present)
1) Physicians responsibility to protect the life, health,
privacy and dignity of the human subject
2) Research must follow accepted scientific
guidelines
3) The welfare of the environment and animals must
be respected
4)A protocol must be submitted to an ethical review
committee
ethical considerations must be explained
prediction of risks, burdens and benefits should
be enunciated

16. 5) Conducted only by scientifically qualified persons
6) Each potential subject must be informed, understand
and consent after being told of all material facts
7) Consent must be given without coercion
Legal guardians must provide consent for those that
cannot
Minors must assent to the research
8)Researchers must utilize scientific integrity in reporting
ETHICAL CODES
WORLD MEDICAL ASSOCIATION
DECLARATION OF HELSINKI
(1964-Present)

17. National Commission for the Protection
of Human Subjects of Biomedical and
Behavioral Research (1974)
ETHICAL CODES
Instituted by the 1974 Instituted National
Research Act
Required INSTITUTIONAL REVIEW
BOARDS (IRBs)
45 CFR 46
Title 45 of the Code of Federal
Regulations:
Chapter 46

18.  Respect for Persons (Autonomy)
 Informed Consent
 Beneficence/Non-Maleficence
 Assessment of Potential Risks and
Benefits
 Justice
 Fair Selection of Participants
ETHICAL CODES
THE BELMONT REPORT
Department of Health, Education and Welfare
(April 18, 1978)

19. Pfizer Company Deceived Nigerians
Pfizer agreed to pay 75 million dollars as
compensation for the death of 11 Nigerian
children, used as guinea pigs in none
consensual unlicensed trial in 1996.
The company deceived them and distributed a
new drug “Trovan” as a proven useful drug for
meningitis.

20. USA Today September 2, 2009
Pfizer was ordered to pay 2.3 billion dollars to resolve
criminal and civil allegations that the company illegally
promoted 4 drugs: Pain Killer Bextra, antipsychotic
Geodon, antibiotic Zyvox and antiepleptic Lyrica, which
were promoted in off label uses.
Pfizer to pay $ 2.3 billion fine

21. National Committee of BioEthics
(NCBE)
Implementing Regulations of the
Law of Ethics of Research
on Living Creatures
Second Edition 2016

22. • Research: A systematic experimental
investigation aiming at improvement of
biosciences or enrichment or development of
general knowledge by using a living creature
or parts thereof.

23. • Informed Consent: A person giving his
consent with his free will, without
exploitation or coercion and upon full
understanding of what is required from him
and of the research objectives and potential
risks as well as of rights and obligations arising
out of his participation therein.

24. • Minor: A person under eighteen years of age.
• Fetus: Outcome of pregnancy from the
beginning of nidation in the uterus to the
time of its delivery or removal.
• Guardian: A person having the right of legal
authority over another person.

25. • Human Subject (Participant): A person who
consents or whose guardian consents to
conduct clinical, non-clinical or therapeutic
research or experiments on him.

26. • Clinical Research: Any research related to
collecting and analyzing data for volunteers or
patients for the purpose of obtaining general
knowledge that can be applied to other
individuals with regard to mechanism of
disease, its incidence, prevalence,
transmission or treatment of a disease.
• Clinical Trial: Experiments conducted on
human volunteers to examine safety and
effectiveness of a new medication or medical
device.

27. • Confidentiality: Non-disclosure or passing of
any data, information or results related to the
research or the human subject, to any third
party not connected with the research.
• Privacy: Observing common values, including
traditions, thoughts and norms.

28. • Sharia dictates and professional ethics
enforced in official bodies in the Kingdom as
well as rules and procedures set by the
National Committee shall be observed in
implementing the provisions of the Law and
its Regulations.

29. • Article (10.17) The research does not
violate Sharia rules or laws or regulations
observed in the Kingdom;
• Potential risk for the human subject is
reduced to the minimum level.
• Evaluating benefits and risks that might
ensue from the research;

30. • Ensuring that research subjects have been
selected based on their understanding of
research objectives, place, time and method of
conducting research, with special additional
attention in the cases in which the participation
of persons requiring additional protection is
requested, such as (vulnerable groups)
• Ensuring that sufficient measures are taken to
protect privacy of the human subject and
maintain confidentiality of data.

31. Article (10.18)
• The local committee may approve certain research
by using the expedited review procedure in the
following cases:
• If the risk that the human subject may be exposed to
does not exceed the minimal risk level;
• If the research does not reveal the identity of the
human subject, audiometry devices, (MRI) or
ultrasonography imaging devices; (ECG & EEG),
echocardiography
• Search for information, records or samples that were
previously collected or will be collected in the future
for non-research purposes;

32. • Article (10.32) Research involving study of
information and data previously collected,
provided one of the two following terms is
fulfilled:
• a. If the information is generally and publicly
available;
• b. If the information is recorded in a manner
that does not reveal the
• identity of the source person.

33. • Research including educational tests, surveys,
interviews or public behavior monitoring,
except in the two following cases:
• If the information is recorded in a manner that
reveals the identity of the source person.
• If participation in the research should bring a
person outside the scope of research to be
subject to criminal or civil liability or
jeopardize his financial position or career.

34. Informed Consent
• Article 11 No investigator may conduct research
on any human subject prior to obtaining an
informed consent from him or from his guardian
in accordance with procedures specified by the
Regulations.
• The researcher shall provide all research-related
information to the human subject. Such
information shall include research objective,
potential risk and expected benefit, if any.

35. • Article (11.2) The “Informed Consent” form shall
include the following: (Name of principal
investigator) Research title, name of institution,
research objectives.
• expected benefit and expected risk or harm
alternative treatments available outside the scope
of the research, if any;
• Duration of the research project and requirements
to be fulfilled by the human subject;
• Use of samples taken from the human subject and
commitment to dispose with excess or leftover
samples through recognized scientific methods;

36. • Participation in the research is voluntary. Refusal to
participate shall not entail penalty or loss of
benefits to which the human subject would
otherwise be entitled. He / She may withdraw from
the research at any phase without loss of benefits.
• The participant shall be notified of all information
that may emerge during the research period,
especially harms or complications not stated in the
“Informed Consent.
• The participant should be provided with telephone
numbers to contact for any needed information.

37. • Article (12.1) The investigator shall, explain in a
clear and simple language, the information stated in
the “Informed Consent” form to the participant (or
his guardian if the subject is incompetent).
• He shall answer any question raised by the human
subject (or guardian if the subject is incompetent);
and should ensure that participant has understood
all the information provided to him prior to signing
the “Informed Consent” form;

38. • Article (12.2) The “Informed Consent” form or the
explanation presented by the investigator to obtain
the consent may not include any statement
absolving the investigator (or the institution) from
liability against any unexpected error or harm that
may occur during the research.
• Article 13 The informed consent shall be
documented in accordance with conditions and
procedures specified by the Regulations.

39. • Article (13.4) The principal investigator or his
duly appointed designee shall issue the
“Informed Consent” form in three copies, one for
the principal investigator, one for the human
subject of the research to be conducted, and the
third for the local committee or in the patient’s
file in the case of a clinical research.
• If the human subject of the research is a patient,
the researcher must document obtaining the
“Informed Consent” in the patient’s medical file.

40. • Article 14 The local committee may approve
conducting the research without obtaining the
informed consent if it is not possible to relate the
information obtained by the researcher from the
records or pathological samples to the source
person or if the results related to individuals are
available to the public.

41. Research on human zygotes, gametes
or fetuses
• Article 21 No research may be
conducted on human zygotes,
gametes or fetuses except under
controls specified by the
Regulations.

42. • Article (21.3) No research may be conducted on
human fetuses except for one of the following
purposes:
• 1. Find a treatment for reproductive problems, in
which case the research shall be conducted in an
institution approved for treatment of such
problems;
• 2. Conduct a new experiment expected to benefit
human fetuses; 3. Acquire new knowledge about
the condition of fetuses if it is not expected to
achieve a direct benefit.

43. • Article (21.4) The research proposal on human
fetuses shall include the indication that the
expected benefit from the research would not
be realized without using such fetuses, and
that a similar benefit has been previously
obtained through conducting research on
animals, and that the research is justified in
terms of its contribution to improvement of
treatment techniques or knowledge of human
diseases.

44. • Article (21.5) The investigator shall use the
minimum number of fetuses to achieve research
purposes.
• Article (21.7) The investigator shall prepare and
keep records of the source of each fetus and the
results of using said fetus in the research, and shall
submit periodic reports on the research to the local
committee.
• Article 22 No research may be conducted for the
purpose of human cloning.

45. • Article 23 Research may be conducted on tissues,
living cells and separated parts, including stem cells
extracted from the umbilical cord or adult stem
cells, upon obtaining the info rmed consent.

46. • Article 25 Research may not be conducted on
minors, incompetent or disabled persons
unless the interest of these categories so
requires. The Regulations shall specify ethical
controls for conducting research on said
categories

47. • Article (25.1) Research may not be conducted
on minors, incompetent or mentally disabled
persons without obtaining the “Informed
Consent” from either parent, or the legal
guardians. The minors or incompetent person
should also assent.
• If the child reaches adulthood or the
incompetent becomes competent his / her
informed consent should be obtained.

48. • Article (25.2) The local committee shall grant its
approval for research on incompetent persons
subject to the following :
• It is not possible to conduct the research on a
competent person;
• The interest of the incompetent requires subjecting
him to the research, provided he / she is not
exposed to more than the minimal potential risk;

49. • Article (25.4) If the local committee finds that
the research does not directly benefit the
incompetent person but does not expose him
to more than the minimal potential risk, it
may approve the research : If there are
sufficient reasons that make it possible to
obtain significant information understanding
the case under study.

50. • Article (25.6) The physically, but not mentally,
disabled person shall be treated as a normal
person

51. • Article 26 Pregnant women, fetuses and the
product of pregnancy may not be used in
research except after confirming the safety of
methods and means of research.
• The research shall not lead to a change in
pregnancy termination.
• Provide health requirements for the pregnant
woman and her fetus.
• Obtain the “Informed Consent” from both the
pregnant woman and her husband.

52. • Article (26.2) No research on fetuses may be
initiated unless the following conditions are
satisfied: The research shall not harm or
endanger the life of the fetus, provide health
requirements for the fetus and acquire
information that cannot otherwise be obtained.
No research may be conducted on a living fetus
unless it is certain that its life is threatened.

53. • Article 27 Cells, tissues and derivatives of
human sperms, gametes and zygotes may not
be transported or exploited for the purpose of
research except in accordance with conditions
and restrictions laid down by the National
Committee.

54. • Article 28 Fetuses may not be cloned for the
purpose of obtaining embryonic stem cells,
nor may male or female gametes taken from
sperms or eggs be donated to produce
fertilized eggs that can grow into a fetus for
the purpose of generating stem cells there
from and conducting research thereon.

55. • Article 29 Banks for preserving reproductive
male or female cells with the intent of
conducting research thereon may not be
established.

56. • Article 30 Organs and tissues of fetuses
aborted before reaching one hundred twenty
days may be used in research and experiments
in accordance with controls and conditions set
forth in the Regulations.

57. • Article 36 Research with negative impacts on
society may not be conducted, especially
research reinforcing racial discrimination.

58. Ethical Codes
• Nuremberg Code 1947
• 10 Rules for “Permissible Medical Experiments”
• (1) Voluntary consent without coercion.
• (2) Results must benefit society and must only use
human subjects when there is no alternative.
• (3) Should be based upon non-human studies with
justifiable expected results.
• (4) Avoidance of all unnecessary physical and
mental suffering.

59. • (5) No experimentation where death or serious
disability is foreseen unless
• performed on the medical provider as a subject.
• (6) Degree of risk less than potential benefit.
• (7) Proper preparations must be made to minimize
injury.
• (8) Experiment should be conducted by only
scientifically qualified person.
• (9) Subjects can cease their participation at any
time.
• (10) Experimentor must stop if it is believed it will
result in death or serious disability.

60. • This was followed by many codes, which regulated
Bioethical Research. These codes stressed not only
consent but informed consent and made many
requirements for accepting or allowing biomedical
research e.g. the research should be approved by
Institution Review Board (IRB). The National
Commission for the protection of
• Human Subjects of Biomedical and Behavioral
Research instituted the National
• Research Act in 1974 in USA. It required the
formation of institution Review as follows:

61. • Boards (IRB) in order to evaluate any research
proposal.
• This was followed by Belmont Report 1978
and World Medical Association:
• Declaration of Helsinki, which was amended
several times since it was declared in 1964.
• The prominent features of these two codes
are given here.
• The main issues in Medical Research are

62. • The Belmont Report—Department of Health,
Education and Welfare, April
• 18, 1978
• The Belmont Report summarizes ethical principles
and guidelines for research
• involving human subjects. Three core principles are
identified: respect for persons,
• beneficence, and justice. Three primary areas of
application are also stated. They are informed
consent, assessment of risks and benefits, and
selection of subjects.

63. • World Medical Association—Declaration of Helsinki
1964–Present
• (1) Physician’s responsibility to protect the life,
health, privacy and dignity of the human subject.
• (2) Research must follow accepted scientific
guidelines.
• (3) The welfare of the environment and animals must
be respected.
• (4) A protocol must be submitted to an ethical review
committee
• • Ethical considerations must be explained
• • Prediction of risks, burdens and benefits should be
enunciated

64. • (5) Conducted only by scientifically qualified
persons
• (6) Each potential subject must be informed,
understand and consent after being
• told of all the material facts
• (7) Consent must be given without coercion
• • Legal guardians must provide consent for
those that cannot give consent
• • Minors must assent to the research
• (8) Researchers must utilize scientific integrity
in reporting.

65. Consent
• Consent should be informed. The research
should be fully explained to the participants in
simple language, which he could fully
comprehend. Any questions should be
answered. A written document in simple
language should be given to the participant.
He should be given enough time to review it,
ask questions and have free choice to accept
or refuse participation; alternatives (in case of
refusal) should be explained.

66. • Refusal of Participation
• Refusal of participation will not in anyway
affect his/her right to full treatment
• and management.

67. Participant Withdrawal
• The participant can withdraw at any time frame.
The researched person even then, will not affect
his right to full treatment and management.
• Risks to Participants
• 1. The foreseeable risks, discomforats, and
hazards should be explained, indicating the
probability, magnitude, and duration.
• 2. The risks should include the physical,
psychological, social, legal, and economic risks.

68. • 3. If any hazard occurs during research, the
research should be stopped immediately and
the participants should be informed, treated
of any injury, and compensated duly.
• 4. All the consent documents in Saudi Arabia
declare that no compensation will be paid in
case of injury or even death. (This should be
changed, and some IRB’s do not accept the
research until the sponsors agree to treatment
and compensation).

69. Consent of Minors
• Children should not be exposed to nontherapeutic
clinical research. The coansent of the minor is
invalid and hence it is obligatory to obtain the
consent of the guardian.
• Children under seven cannot comprehend the
intricacies of medical research.
• However, children who can comprehend and
understand should be informed in 94 5 Regulation
of Medical Profession and Medical Research simple
language and their consent obtained. If they refuse,
no research should be done on them, despite the
consent of the guardian.

70. Consent of Incompetent Adults
• Incompetent adults should not be exposed to
any nonthaerapeutic research. The consent of
the guardian is imperative. The research
should be useful to the person (patient) or his
group. There should be no other alternative to
obtain that information.

71. Consent of Prisoners
• Prisoners and incarcerated persons should not
be exposed to research unless it is
• going to help the person or group. The
consent of the prisoner is legally invalid,
• however it should be obtained without
duress.

72. Research on Pregnant and Lactating Ladies
• 1. Ladies should be scrutinized for pregnancy prior
to any research. If there is any harm expected to the
mother or fetus no research should be carried on.
The lady should avoid pregnancy, if the research
period is prolonged and contraception should be
used.
• 2. The informed consent of the lady should be
obtained. The consent of the husband or any other
member of the family is not enough.
• 3. The consent of the husband may be essential in
research involving reproduction.

73. Benefit of Research
• 1. The research should benefit the pregnant
lady, her fetus, or the group.
• 2. The clinical research should in no way
expose the pregnant lady, nursing
• mother, her fetus, or baby to any harm.

74. Monitoring Research
• 1. Provision to monitor data for the safety of the
participants should be available.
• 2. Potential benefits to the participants, his group
or community should be explained to the
participant.
• 3. Protection of privacy and confidentiality of the
participant /patient should be assured.

75. • 4. Medical care and compensation for injury. If
the research involves more than minimal risk
of the participant (discomfort during medical
exam) provisions for medical care and
compensation should be explained to the
participant prior to carrying the research.
Pharma companies in developing countries
declare that they will not compensate for any
harm caused by the experiment.

76. Holding No Responsibility
• 1. The researcher should not obtain from the
researched subject, any agreement that makes him
irresponsible for any injury that can accrue from the
research. Even if he gets a written consent, it is
considered invalid legally. The subject has the right
for proper compensation for any injury.
• 2. Costs and payments to the researched subjects
should be explained prior to starting the research.
The amount should be appropriate to compensate
the subjects for their lost time.

77. Research on Embryos and Fetuses
• 1. Research on embryos and fetuses is not allowed
unless the research is going to benefit the embryos
or fetus.
• 2. Left over pre-embryos (fertilized ova) in IVF
projects could be used in stem cell research after
obtaining the consent of the parents.
• The Fatwa of the Islamic Jurisprudence Council of
the Islamic World in Makkah Al-Mukarama in its
17th session (19-23-10-1424H 13-17 December
2003G)