Ethical considerations

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2. Ethical
Considerations In
Bioequivalence
Studies
Usama Jamshaid
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3. Ethics
Ethics means: Moral principles that govern
a person's behavior or the conducting of an
activity.
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4. Bioavailability
Bioavailability means the rate and extent to which
the active ingredient or active moiety is absorbed
from a drug product and becomes available at the
site of action.
In case of IV administration, bioavailability is
almost 100% but when a drug is administered
orally, bioavailability is decreased.
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5. Bioequivalence
Two products are bioequivalent if
they are pharmaceutically equivalent
the bioavailable concentrations following
administration are same and giving the same
effect
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6. Ethical Guidelines for Research with Humans
One set of guidelines specifically developed to
guide research conducted by educational
researchers is the AERA Guidelines.

The AERA is the largest professional association
in the field of education, and is also known as
the American Educational Research Association.
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7. Basic Ethical Principles
1. Respect for Persons
2. Beneficence
3. Justice
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8. Essential Parameters
1. Informed Consent
2. Assessment of Risks and Benefits
3. Selection of Subjects
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9. Study Design
In order to reduce variability a cross over
design usually is the first choice.
Other designs or methods may be chosen in
specific situations, but should be fully
justified in the protocol and final study report.
The subjects should be allocated to
treatment sequences in a randomized order.
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10. Selection of subjects
Subjects could belong to both sexes; however, the risk to women of
childbearing potential should be considered on an individual basis.
In general, subjects should be between 18 – 55 years old, capable of
giving informed consent and of weight within the normal range or
Body Mass Index (BMI) of 18 - 30.
They should be screened for suitability by means of clinical
laboratory tests, an extensive review of medical history, and a
comprehensive medical examination.
Subjects should preferably be nonsmokers and without a history of
alcohol or drug abuse. If moderate smokers are included (less than
10 cigarettes per day) they should be identified as such and the
consequences for the study results should be discussed.
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11. If the purpose of the bioequivalence
study is to address specific questions such
as investigation of differences in
bioavailability in different subsets of the
population or drug/drug interactions the
selection criteria and the statistical
analysis should be adjusted accordingly.
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12. Inclusion of Volunteers
If the investigated active substance is known to
have adverse effects or risks then it is considered
unacceptable for healthy volunteers, it may be
necessary to use patients instead under suitable
precautions and supervision.
In this case the applicant should justify the
alternative.
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13. Informed Consent
This is the process of providing the research participants
with information enables them to make an informed
decision as to whether they want to participate in the
research study.
State the purpose of the research and describe the procedures to be followed.
Describe any potential risks or discomforts the participant may encounter.
Describe any potential benefits from participation.
Describe extent to which results will be kept confidential.
Give a list of names the participants may contact with any questions they have.

State that participant is voluntary and that they are free to withdraw from the study at
any time.
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14. Informed Consent with Minors as
Research Participants
Consent must be obtained from parents or
guardians.
Assent must also be obtained from minors
who are old enough or have enough
intellectual capacity to say they are willing to
participate.
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15. Deception
Providing false information to the participant
about the nature and/or purpose of the study
It is discouraged by the AERA, but not disallowed in all It is discouraged by the AERA, but not disallowed in all
cases. cases.
Sometimes deception is required in order to conduct a valid Sometimes deception is required in order to conduct a valid
research study. The researcher must justify the use of research study. The researcher must justify the use of
deceptiondeception..
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16. Freedom to Withdraw
Participants must be informed that they
are free to withdraw from the study at any
time without penalty.

If you have a power relationship with the
participants you must be extra careful to
make sure that they really do feel free to
withdraw.
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17. Protection from Mental and Physical Harm
This is the most fundamental ethical issue
confronting the researcher.
Educational research generally poses minimal
risk to participants.
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18. Elements of a Bioavailability/Bioequivalence Study
Protocol
I. Title
  A. Principal investigator (study director)
  B. Project/protocol number and date
II. Study objective
III. Study design
  A. Design
  B. Drug products
    1. Test product(s)
    2. Reference product
  C. Dosage regimen
  D. Sample collection schedule
  E. Housing/confinement
  F. Fasting/meals schedule
  G. Analytical methods
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19. Elements of a Bioavailability Study Protocol
IV. Study population
  A. Subjects
  B. Subject selection
    1. Medical history
    2. Physical examination
    3. Laboratory tests
  C. Inclusion/exclusion criteria
    1. Inclusion criteria
    2. Exclusion criteria
  D. Restrictions/prohibitions
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20. Elements of a Bioavailability Study Protocol
V. Clinical procedures
A. Dosage and drug administration
B. Biological sampling schedule and handling procedures
C. Activity of subjects
VI. Ethical considerations
A. Basic principles
B. Institutional review board
C. Informed consent
D. Indications for subject withdrawal
E. Adverse reactions and emergency procedures
VII. Facilities
VIII. Data analysis
A. Analytical validation procedure
B. Statistical treatment of data
IX. Drug accountability
X. Appendix
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21. Institutional Review Board
This is a board consisting of professionals and lay people who review
research proposals to insure that the researcher will adhere to ethical
standards in the conduct of the research.
Researchers must submit a Research Protocol to the IRB for review
Three of the most important categories of review are exempt studies,
expedited review, and full board review
Much educational research falls in the exempt category because the study
involves no or minimal risk
Studies with children, prisoners, and fetal participants are never exempt
Even if your study ultimately falls in the exempt category, it is still essential
that you follow the ethical guidelines
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22. There are three ways, and three ways only, to
encourage participation ethically (Senese
1997):
Anonymity:
Keep promises anonymous.
After identifying your sample try to forget taking
names or other identification.
Reassure people not to go to media.
Confidentiality:
Use confidentiality if you cannot guarantee
anonymity.
It requires that you guarantee that no one will be
individually identified in any way by you.
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23. oInformed Consent:
Be honest and fair with your subjects.
Tell them every thing about your research.
Subjects should not have any pressure to
participate in your research.
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24. Ethical Principles
1. It is the duty of the health care professionals to promote and
safeguard the health of the people.
2. The Declaration of Geneva of the World Medical Association binds
the health care professionals with the words, "The health of my patient
will be my first consideration," and the International Code of Medical
Ethics declares that, "A health care professional shall act only in the
patient's interest when providing medical care which might have the
effect of weakening the physical and mental condition of the patient."
3. Medical progress is based on research which ultimately must rest in
part on experimentation involving human subjects.
4. In medical research on human subjects, considerations related to the
well-being of the human subject should take precedence over the
interests of science and society.
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25. 5. The primary purpose of medical research involving human subjects is to
improve prophylactic, diagnostic and therapeutic procedures and the
understanding of the etiology and pathogenesis of disease. Even the best
proven prophylactic, diagnostic, and therapeutic methods must continuously
be challenged through research for their effectiveness, efficiency,
accessibility and quality.
6. In current medical practice and in medical research, most prophylactic,
diagnostic and therapeutic procedures involve risks and burdens.

7. Medical research is subject to ethical standards that promote respect for
all human beings and protect their health and rights. Special attention is also
required for those who cannot give or refuse consent for themselves, for
those who may be subject to giving consent under duress.
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26. 8. Medical research is only justified if there is a reasonable
likelihood that the populations in which the research is
carried out stand to benefit from the results of the research.

9. The subjects must be volunteers and informed
participants in the research project.
10. When obtaining informed consent for the research
project the health care professional should be particularly
cautious if the subject is in a dependent relationship with
the investigator or may consent under duress.
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27. 11. For a research subject who is legally incompetent, physically or
mentally incapable of giving consent or is a legally incompetent
minor, the investigator must obtain informed consent from the
legally authorized representative in accordance with applicable law.
12. When a subject is able to give assent to decisions about
participation in research, the investigator must obtain that assent in
addition to the consent of the legally authorized representative.
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28. References
Applied Biopharmaceutics & Pharmacokinetics, 5th Edition, Leon
Shargel, Susanna Wu-Pong, Andrew B.C. Yu
Concepts In Clinical Pharmacokinetics - 4th Ed. (2005) ,Joseph T.
DiPiro Pharm.D., William J. Spruill Pharm.D., FASHP, William E.
Wade Pharm.D., FASHP, Robert A. Blouin Pharm.D.
Abernethy DR, Azarnoff DL: Pharmacokinetic investigations in elderly
patients. Clinical and ethical considerations. Clin Pharmacokinet 19:89–
93, 1990 [PMID: 2379383] .
Malaysian guidelines for the conduct of bioavailability and
bioequivalence studies, September 2000, Ministry of Health, Malaysia.
The Code of Ethics of the American Educational Research Association
(AERA) , February 2011.
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29. THANK YOU
THANK YOU
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