|
Ethical
Foundations
of Clinical Research
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Research ethics is shared norms, values and practices
rooted in
Respect for Persons
Nonmaleficence
(Do No Harm)
Beneficence
(Do Good)
Justice
It progressively evolves from 'Social Conventions'
to 'Professional Codes' to 'Law'.
Respect for Persons
| |
Ethical Consideration |
Policy and Requirements |
| Self-determination |
| • |
Human right |
| • |
The decision making capacity,
rather than the outcome, is important … even if decision is seemingly
not in favor of one's own interest |
|
| • |
Voluntary participation,
with great emphasis on informed
consent |
| |
- |
Free from misrepresentation,
duress and undue influence |
| |
- |
Right to withdraw at any
time without reprisal |
| |
- |
No exculpatory clause |
| |
- |
Consent form and subsequent
changes must be approved by REC |
| |
- |
ICH GCP has detailed requirements |
|
| Human Dignity |
| • |
Do unto others as you would
have them do unto you |
| • |
Respect privacy |
| • |
Honesty |
|
| • |
Do not exploit
research subjects |
| • |
Ensure data confidentiality |
| • |
Adhere to consent granted |
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Nonmaleficence (Do No Harm)
| |
Ethical Consideration |
Policy and Requirements |
| Utilitarianism |
| • |
Utilitarianism |
| • |
Beware that unchecked utilitarianism
could infringe human right and contradict other principles of ethics |
|
| • |
Study has a reasonable expectation
in improving health, HC or furthering knowledge |
| • |
Considerations related to
the well-being of trial subjects should take precedence over the interests
of science and society |
|
| Scientific Validity |
| • |
Without validity, a research
cannot generate benefit to justify its risk |
|
| • |
Equipoise
exists between therapies to be compared |
| • |
Methodology is scientifically
valid and practically feasible |
| • |
Hypothesis is testable (i.e.
falsifiable) |
| • |
Objectives and research
questions are clear |
| • |
Design reduces bias and
confounders |
| • |
Statistically sound, sufficient
power to test research objectives |
|
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Beneficence (Do Good)
| |
Ethical Consideration |
Policy and Requirements |
| Favorable
Risk-benefit Ratio |
| • |
Anticipated benefits should
outweigh risks |
|
| • |
Design must minimize risk
to participants and other individuals |
| • |
Not only must the risk be
reasonable in relation to the potential benefits but even reasonable
risks must be minimized to the extent possible |
| • |
Do not include vulnerable
subjects unless research is necessary to promote the health of the
population represented and it cannot be otherwise performed |
|
| Competence |
| • |
Study performed with necessary
competence |
|
| • |
Investigators are qualified
in scientific and ethical capacities |
| • |
Study sites are adequately
equipped |
| • |
Among other responsibilities, investigators
must
|
| |
- |
monitor participants'
well-being throughout study |
| |
- |
manage record
and data to preserve accuracy of reporting, interpretation and verification
of research data |
| |
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safe custody
of study articles, especially unlicensed drugs |
|
| Availability of Study Article after
Study |
| • |
Subjects are
entitled to receive appropriate medical care after completion of study |
|
| • |
A study article that benefits
the subjects should continue to be available after study until it
is commercially available |
| • |
If it is foreseeable that
an effective (but expensive) Rx may not be financed by the PHS, the
possible consequence must be explained & documented in the consent |
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Justice
| |
Ethical Consideration |
Policy and Requirements |
| Avoid Conflict of Interest |
| • |
This concerns people who
discharge duty as a result of holding an office or act in an official
/ professional capacity, so that those relying on him have legitimate
expectation |
|
| • |
Investigators and reviewers
need to address conflict
of interest |
| • |
Declare interest, refrain
from activity if conflict is considered serious |
|
| Distributive justice |
| • |
Fair subject selection |
| • |
Fair use of resources |
|
| • |
Neither privilege nor vulnerability,
but suitability and equity, should drive the recruitment and allocation
process |
| • |
Besides ethical approval,
study must be endorsed by supervisor and heads of other departments
providing support to study |
| • |
Prompt and appropriate dissemination
of results |
|
| Independent Review and Study Oversight |
| • |
Independent review is a
cornerstone in research subject protection |
| • |
Reviewers act on behalf
of research subjects |
|
| • |
Mandatory ethics review
and study oversight by REC
(with lay participation) |
| • |
REC has authority to examine
all aspects of study and intervene, even terminating a study |
| • |
REC performance subject
to independent monitoring |
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Relevant Reading:
Emanuel EJ, Wendler D, Grady C. What
makes clinical research ethical? JAMA 2000; 283: 2701-2711
The article delineates 7 requirements for
determining whether a research trial is ethical: social or scientific value,
scientific validity, fair subject selection, favorable risk-benefit ratio, independent
review, informed consent, respect for potential and enrolled subjects.
Edwards SJL, Lilford RJ, Braunholtz DA, Jackson
JC, Hewison J, Thornton J. Ethical
issues in the design and conduct of randomised controlled trials. Health
Technology Assessment 1998; 2(15)
A review on (a) ethical arguments put forward
in the literature on randomised, controlled trials with particular focus on
uncertainty as an underpinning issue, and (b) empirical data (from comparative,
observational and qualitative studies) bearing relevance to the ethics of conducting
trials.
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Last update: 3 August 2007