Seven Ethical Requirements, continued
Valueless research includes the following:
 Non-generalizable knowledge
 A trifling hypothesis
 Results that are unlikely to be disseminated
 An intervention that cannot be practically implemented
 Substantial or total overlap of already proven results
Unfortunately, valueless research diverts resources, such as funds and personnel, from more
worthy social pursuits and often exploits subjects, exposing them to potential harm without
important resulting social or scientific benefit.
Ethical Requirement #2 - Scientific Validity
To be valid, research must:
 Be conducted in a methodologically rigorous manner that is practically feasible
 Have a clear scientific objective
 Be designed using accepted principles, methods and reliable practices
 Have sufficient power to definitively test the objective
 Offer a plausible analysis plan
 Be possible to execute
 Have an honest null hypothesis when comparing therapies
Invalid research includes underpowered studies, studies with biased end points, instruments,
or statistical tests, and studies that cannot enroll sufficient subjects.
If research doesn't result in data that is important and useable, then it places people at risk for
no reason--it is invalid.
#1 Social Validity
To be valuable, clinical research must lead to improvements in health or advancement in
generalizable knowledge.
Valueless research includes the following:
 Non-generalizable knowledge
 A trifling hypothesis
 Results that are unlikely to be disseminated
 An intervention that cannot be practically implemented
 Substantial or total overlap of already proven results
Unfortunately, valueless research diverts resources, such as funds and personnel, from more
worthy social pursuits and often exploits subjects, exposing them to potential harm without
important resulting social or scientific benefit.
#3 Fair subject selection
To select a human subject fairly, the following should be considered:
 The scientific objectives of the study, not the vulnerability or privilege of the subject,
should guide the inclusion criteria and targeted populations.
 Subjects should not be chosen merely because they are convenient.
 Groups cannot be excluded without scientific reasons. For example, women as a class
cannot be peremptorily excluded. However, higher risk is a valid reason to exclude
certain groups.
 Except under special circumstances, participating groups who are susceptible to the
condition being researched and who assume risk, should benefit if the research provides a
positive result, such as a new treatment.
Fair subject selection helps insure the following:
 Equals are treated fairly.
 The benefits and burdens generated by social cooperation and activities such as clinical
research are distributed fairly.
#4: Favorable Risk-Benefit ratio
Clinical research can be justified only when it is conducted in a manner consistent with the
standards of clinical practice. Risks to individual subjects must be minimized while the
potential benefits must be enhanced. Overall, the potential benefits to subjects and society
must equate to, or outweigh the risks.
4-step evaluation of favorable risk-benefit ratio.
#5 Independent review
Independent review helps to minimize the influence of potential conflicts of interest that you
will encounter as a Principal Investigator and it also assures society that your study will not
benefit from the abuse of your subjects.
As mentioned previously, you will have many goals that may conflict with each other as a
Principal Investigator. Your goals include conducting high-quality research, completing your
research expeditiously, protecting research subjects, obtaining funding and advancing your
career.
Diverse interests can divert even the best-intentioned investigators. It can become easy to
resort to shortcuts and convenience in research design, conduct and analysis. Independent
review helps to minimize these potential conflicts.
Many people are aware of the Tuskegee incident and the atrocities that led to the Nuremberg
Code. The nightly news tells the general public about incidents like deaths in gene transfer
trials. That same public needs to be confident that abuses are not taking place in clinical
research.
Independent review helps assure society that human subjects will be treated ethically. Review
also assures the human subjects in clinical research that the trial is ethically designed and the
risk-benefit ratio is favorable.
In the United States, independent review is conducted by a number of groups, including
granting agencies, local Institutional Review Boards (IRBs) and data and safety monitoring
boards (DSMBs).
#6 Informed consent
Informed consent is an ethical requirement for the following reasons:
 It shows respect for your subjects' autonomy.
 Informed consent lets individuals decide whether they want to be subjects in a clinical
trial, participating only when the research is consistent with their values, interests and
preferences.
 For those who cannot consent, such as children and mentally impaired subjects, research
must fit with their interests.
Informed consent requires:
 Disclosure of relevant information to the subject
 Understanding of the information by the subject
 Voluntary (uncoerced) decision-making by the subject
A truly informed consent means that human research subjects have been accurately informed
of the purpose, methods, risks, benefits and alternatives to the research.
They must understand the information and its impact on their own clinical situation.
It means they make a completely voluntary decision about whether to participate or not.
What happens if one or more of your subjects are unable to sign an informed consent?
Children and subjects impaired by conditions such as stroke, Alzheimer's disease or other
impairments are usually represented by a proxy decision maker. In emergency settings, where
it is not possible to secure informed consent from subjects or proxy, research can proceed
without consent when the research is conducted under strict guidelines.
Federal regulations require eight elements be included in each informed consent document.
They are as follows:
 Purpose and duration of participation
 Risks
 Alternatives
 Benefits
 Confidentiality of records
 Compensation for injuries
 Person to contact for answers to questions
 Voluntariness and right to withdraw without penalty
#7 Respect for human subjects
Ethically, respecting your subjects is a top priority. You are required to respect both their
autonomy and their welfare. Specifically:
 Demonstrate your respect by protecting their confidentiality and permitting them to
withdraw without penalty.
 Monitor their welfare and provide appropriate treatment.
 Provide your subjects with new information, even after they are enrolled, such as
information about new risks.
 Finally, inform your subjects of what was learned from the research.
Another of the requirements to respect subjects at the NIH involves educating subjects about
Advance Care Directive. Introducing and discussing the directives with subjects are the
responsibilities of the Principal Investigator, and it's important to remember that these
directives are not just about treatment for someone who is terminally ill and becomes
incompetent.
The NIH Advance Care Directive permits the following:
1. The designation of a substitute decision maker or proxy
2. The specification of preferences for participation in research
3. The specification of preferences for end-of-life care