• The goal of clinical research is to generate useful knowledge about human health and illness, and ways to prevent, diagnose and treat diseases. • The goal is not benefit to the individuals who participate (although there is sometimes benefit). • People are the means to developing useful knowledge; and are thus at risk of exploitation.

1. Researching a Bioethical
Question
Mohamed Abdulmongy
MBBCh Candidate
Egypt

6. • Are these studies ethical?
• How do we know?

7. Ethics of clinical research
• The goal of clinical research is to generate useful
knowledge about human health and illness, and
ways to prevent, diagnose and treat diseases.
• The goal is not benefit to the individuals who
participate (although there is sometimes benefit).
• People are the means to developing useful
knowledge; and are thus at risk of exploitation.

9. Ethics of clinical research
• Promote benefits to
society and future
Patients.
• Protect and respect
rights and welfare of
Participants.

10. • Types of Bioethical Issues.
• Types of Bioethical Research Methodologies.
• Special Considerations in Bioethical Research.
• Examples of Important Bioethical Research:
Historical Research Methodology
Conceptual Analysis
Cross-Cultural Analysis
Empirical Research
Policy Analysis

11. • During the past 35 years,
there has been a significant
increase in interest in
bioethical questions.
• Common questions include
the following:
Is it ethical to pay children up to $1,400 to
participate in clinical research on a new antiasthma
drug?
Does payment for participation in clinical research
lead to having more socio-economically vulnerable
subjects?
Does payment for participation in clinical research
lead to worse informed consent?
Is it appropriate to conduct research on a stored
biological sample without the patient’s informed
consent?
Should international clinical research studies offer
all participants the best therapy available
anywhere in the world? Or is it sufficient to
provide subjects in an international clinical
research study only the local standard of care?

12. TYPES OF BIOETHICAL ISSUES

13. TYPES OF BIOETHICAL RESEARCH
METHODOLOGIES
• Historical Research Methodology
• Conceptual Analysis
• Cross-Cultural Analysis
• Empirical Research
• Policy Analysis

14. 1) Historical Research Methodology
• One of the most interesting uses of
historical research on bioethical
questions is related to informed
consent.
 that the first reported legal case in the
English language involving informed
consent was Slater vs. Baker &
Stapleton in 1767.
 A patient sued two surgeons for
rebreaking a partially healed leg
fracture in an effort to improve its
alignment.
 Relying on the statement of physicians,
the court ruled that it is “the usage and
law of surgeons” to obtain the patient’s
consent before performing an
operation.
 The court held that the two
practitioners had violated the well
known and accepted rules of consent.

15. • In the late 19th century, significant efforts were made to identify the
etiology of yellow fever.
• Example, In 1897, the Italian researcher Guiseppe Sanarelli claimed he
identified the yellow fever bacillus and, using this bacillus, had produced
yellow fever in several patients.
• William Osier condemned these experiments, saying “to deliberately
inject a poison of known high degree of virulency into human beings,
unless you obtain that man’s concent, is not ridiculous, it is criminal.”
• When Walter Reed conducted his experiments on the etiology of yellow
fever, he developed a written “contract” with the subjects that outlined
“the risks of participation in the study as well as the benefits.

16. • Meticulous historical research using the traditional
methods of historians- examining published articles
and government documents, reading correspondence,
journals, and notebooks, etc.- reveals that the
informed consent for clinical care and research is not a
recent, post-WorldWar II phenomenon.
• So, historical research into informed consent has made
several important contributions.

17. • Another interesting example of the value of historical research for
bioethical questions relates to the debate over euthanasia and
physician-assisted suicide.
• The standard view is that advances in technology create interest in
desire for euthanasia and physician-assisted suicide.
• Start the debate by ancient Greece then in the United States and
Britain in the latter third of the 19th century.
• The situations changes ?

18. • So, the historical research can help answer
some important bioethical questions,
including:
- What bioethical concerns are caused by advances in medical
technology and what are inherent in medicine?
- How have these bioethical issues been addressed and resolved
previously?

19. 2) Conceptual Analysis
• conceptual analysis has been essential to advancing bioethics and clinical
research.
• The first example, is the development of the justification for randomized
controlled trials (RCTs).
 RCTs are deemed justifiable when physicians have no reason to believe
that one therapy is better than a second therapy and that there is no
other therapy better than both. This was termed equipoise.
 “If a clinician knows, or has good reason to believe, that a new therapy (A)
is better than another therapy (B) he cannot participate in comparative
trials of therapy A versus therapy B. Ethically, the clinician is obligated to
give therapy A”

20. • A second example of the importance of
conceptual analysis may be found in the issue of
coercion, undue inducement, and exploitation.
These are critical concepts for research ethics.
• Coerced consent is involuntary and therefore not
valid. Consent rendered in response to undue
inducements also is thought to be invalid.

23. • A third example of helpful conceptual analysis
is a clarification about the physician-patient
relationship.

24. 3) Cross-Cultural Analysis
• One of the more important cross-cultural studies in bioethics related to how
different cultures in the United States approach explicit discussions of death.
• many years, there has been pressure for physicians to be more frank in disclosing a
patient’s terminal status;
• data showed that the vast majority of Americans wanted to be told when they
were dying. However, there was growing experience that at least some people
from other cultures did not desire such frankness about death and dying.
• But surveyed Mexican Americans and Korean Americans about their preferences
regarding end-of-life decision making.
• They found significant differences between these groups and the dominant white
population in the United States :
o only 47% of Korean Americans
o and 65% of Mexican Americans
o 87% of Anglo-Americans

25. 4) Empirical Research
• Beginning in the mid- to late-1980s, there was increasing
understanding that many bioethical questions required rigorous
empirical research.
• This research is important for many reasons. Many ethical norms
invoke a “reasonable person” standard; for example,
 what information would a reasonable person want for informed
consent?
 Do research participants really want to know whether their
researcher has consulting contracts with the drug company
sponsoring the study?
 Do videos improve the quality of understanding in informed
consent?

26. • First, there are descriptive studies. The first area
in which such studies occurred and became
methodologically rigorous was end-of-life care.
• A major issue in end-of-life care related to proxy
decision making. When patients become
incompetent and cannot make decisions about
medical interventions.

27. • A second type of research involves elucidating predictors of an outcome such as a
decision or behavior.
• In such research, a certain outcome is described and univariate and multivariate
analyses indicate whether certain factors are significantly associated with the
outcome.
• This has been done effectively in the area of conflicts of interest.
• There has been extensive discussion and debate about this point.
• Many defenders of physicians have argued that receiving money for medical
services does not affect their medical judgment.
• An important series of studies demonstrated that there is a link between
physician investment in medical facilities and a higher use of the services provided
by those facilities.
• One of the most important studies was conducted by Hillman et al., who
compared the frequency and costs of diagnostic radiologic imagining between
physicians who have diagnostic radiologic facilities in their offices and physicians
who refer patients to radiologists for diagnostic imaging. The results ?
 Physicians who self-referred that is, utilized radiologic services in their offices
performed diagnostic imaging 4 to 4.5 times more often than physicians who
referred patients to outside radiologists.

28. • There are many studies of conflict of interest among clinical
researchers.
• Probably the most important is a study by Stelfox and colleagues. In
the mid-1990s,
• it was controversial whether the use of calcium channel
antagonists as antihypertensive medications was safe.
• Stelfox and colleagues assessed whether financial ties to drug
companies that manufactured calcium channel antagonists
influenced researchers’ judgments.

29. 5) Policy Analysis
• Policy analysis can take a variety of forms, but one that has been useful in
relationship to bioethical issues is akin to meta-analysis.
• It is the collection, summary, and analysis of data on a potential policy
choice.
• An example in which this has been done relates to cost savings from use
of hospice care.
• It has been commonly argued that spending for dying patients is
extremely high and that use of a hospice can produce substantial cost
savings.
• the analysis suggests that during the last year of life, hospice use is
associated with a saving of 10% in total costs.

30. SPECIAL CONSIDERATIONS IN
BIOETHICAL RESEARCH

31. • First, few clinical researchers have any training or experience in the
methods of historical research, such as using original sources and
archival material.
 Collaboration with people who have expertise in these areas can
provide a way of obtaining the skills.
• Second, The more precise the concepts, the better the empirical
research.
 if one wanted to do research on voluntariness in informed consent,
then it is important to understand what is essential to voluntariness
not feeling pressure from the researcher, being able to refuse
enrollment, and being able to withdraw.
• Third, creating validating outcome measures. To overcome bias.
• Finally, a problem that is common in bioethical empirical research is
small numbers and low power. Many studies have been conducted
at single institutions with small numbers of participants.

32. Reference :
• Principles and Practice of Clinical Research -
Gallin, John .
• IPPCR Course by NIH Clinical Center .