Human Subjects Regulations

Human subjects research: regulations and the shifting interpretation of “justice”. Phil 133 – Ethics in Science San José State University

Medicine and science.
Science is aimed at knowledge-building (often to build knowledge to help people)
Medicine is focused on caring for patients (and involves explicit duties to patients)
How have physicians and patients understood these obligations historically?

The Hippocratic Oath
The Hippocratics, in Ancient Greece, aimed to make medicine more “scientific” (sought understanding , not just ways to heal)
Established standards to professionalize medicine (and to “create a climate of opinion favorable to learned medicine”)

I swear by Apollo the healer, by Aesculapius, by Health and all the powers of healing, and call to witness all the gods and goddesses that I may keep this Oath and Promise to the best of my ability and judgment.

I swear by Apollo the healer, by Aesculapius, by Health and all the powers of healing, and call to witness all the gods and goddesses that I may keep this Oath and Promise to the best of my ability and judgment.
It’s a serious oath.

I will pay the same respect to my master in the Science as to my parents and share my life with him and pay all my debts to him. I will regard his sons as my brothers and teach them the Science, if they desire to learn it, without fee or contract.

I will pay the same respect to my master in the Science as to my parents and share my life with him and pay all my debts to him. I will regard his sons as my brothers and teach them the Science, if they desire to learn it, without fee or contract.
Debt to professional community, those who taught you.
Duty to educate next generation of profession.

I will hand on precepts, lectures and all other learning to my sons, to those of my master and to those pupils duly apprenticed and sworn, and to none other.

I will hand on precepts, lectures and all other learning to my sons, to those of my master and to those pupils duly apprenticed and sworn, and to none other.
Keeping trade secrets secret.

I will use my power to help the sick to the best of my ability and judgment; I will abstain from harming or wronging any man by it.
Duty to patients.
(Do no harm.)

I will not give a fatal draught to anyone if I am asked, nor will I suggest any such thing. Neither will I give a woman means to procure an abortion.

I will not give a fatal draught to anyone if I am asked, nor will I suggest any such thing. Neither will I give a woman means to procure an abortion.
No euthanasia or abortion.
(Note that other writings in the Hippocratic corpus indicate that physicians in this tradition did participate in such procedures)

I will be chaste and religious in my life and in my practice.

I will be chaste and religious in my life and in my practice.
Conduct yourself as a good person.
(Reputation of whole profession connected to reputation of individual practitioners.)

I will not cut, even for the stone, but I will leave such procedures to the practitioners of that craft.

I will not cut, even for the stone, but I will leave such procedures to the practitioners of that craft.
No surgery.
(Note that other writings in the Hippocratic corpus indicate that physicians in this tradition did participate in such procedures)

Whenever I go into a house, I will go to help the sick and never with the intention of doing harm or injury.

Whenever I go into a house, I will go to help the sick and never with the intention of doing harm or injury.
Awareness of power and responsibilities that come with it.

I will not abuse my position to indulge in sexual contacts with the bodies of women or men, whether they be freemen or slaves.

I will not abuse my position to indulge in sexual contacts with the bodies of women or men, whether they be freemen or slaves.
Power, responsibility, reputation of the profession again.

Whatever I see or hear, professionally or privately, which ought not to be divulged, I will keep secret and tell no one.

Whatever I see or hear, professionally or privately, which ought not to be divulged, I will keep secret and tell no one.
Patient privacy?
More likely trade secrets, again.

If, therefore, I observe this Oath and do not violate it, may I prosper both in my life and in my profession, earning good repute among all men for all time. If I transgress and forswear this Oath, may my lot be otherwise.

If, therefore, I observe this Oath and do not violate it, may I prosper both in my life and in my profession, earning good repute among all men for all time. If I transgress and forswear this Oath, may my lot be otherwise.
It’s a serious oath.

The Nuremberg Code
Direct response to Nazi medical experiments
Focus on the most appalling features of those experiments (harms to human subjects and lack of consent from subjects)

The Nuremberg Code
1. The voluntary consent of the human subject is absolutely essential.

The Nuremberg Code
1. The voluntary consent of the human subject is absolutely essential.
Description of legal requirements for voluntary consent.
Consent must be informed.

The Nuremberg Code
1. (cont’d) The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.

The Nuremberg Code
1. (cont’d) The duty and responsibility for ascertaining the quality of the consent rests upon each individual who initiates, directs, or engages in the experiment. It is a personal duty and responsibility which may not be delegated to another with impunity.
Free informed consent non-negotiable.

The Nuremberg Code
2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.

The Nuremberg Code
2. The experiment should be such as to yield fruitful results for the good of society, unprocurable by other methods or means of study, and not random and unnecessary in nature.
Benefit to society
No other way to get that benefit

The Nuremberg Code
3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.

The Nuremberg Code
3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment.
Probability of benefit must be maximized (since you’re risking harms to subjects)

The Nuremberg Code
4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.

The Nuremberg Code
4. The experiment should be so conducted as to avoid all unnecessary physical and mental suffering and injury.
Harms are serious, and must be minimized

The Nuremberg Code
5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.

The Nuremberg Code
5. No experiment should be conducted where there is an a priori reason to believe that death or disabling injury will occur; except, perhaps, in those experiments where the experimental physicians also serve as subjects.
The line you cannot cross with human subjects

The Nuremberg Code
6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.

The Nuremberg Code
6. The degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment.
Even if you don’t cross the line, benefit must outweigh harms.

The Nuremberg Code
7. Proper preparation should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.

The Nuremberg Code
7. Proper preparation should be made and adequate facilities provided to protect the experimental subject against even remote possibilities of injury, disability, or death.
Taking care not to cross the line accidentally

The Nuremberg Code
8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.

The Nuremberg Code
8. The experiment should be conducted only by scientifically qualified persons. The highest degree of skill and care should be required through all stages of the experiment of those who conduct or engage in the experiment.
Skill further increases chance of benefit, decreases likely harms

The Nuremberg Code
9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where the continuation of the experiment seemed to him to be impossible.

The Nuremberg Code
9. During the course of the experiment the human subject should be at liberty to bring the experiment to an end if he has reached the physical or mental state where the continuation of the experiment seemed to him to be impossible.
Subject autonomy – gets to stop at any point.

The Nuremberg Code
10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.

The Nuremberg Code
10. During the course of the experiment the scientist in charge must be prepared to terminate the experiment at any stage, if he has probable cause to believe, in the exercise of good faith, superior skill and careful judgment required of him that a continuation of the experiment is likely to result in injury, disability, or death to the experimental subject.
Scientist’s duty to avoid harms

Declaration of Helsinki
Recognition that experiments with humans are necessary to medical progress
Concept of research in a clinical setting, potentially benefiting the human subject directly.
In clinical setting, can’t decouple duties of physician to patient from duties of physician to science.

Declaration of Helsinki (1989 version) (points paraphrased)
1. Experiment must “conform to generally accepted scientific principles,” be grounded in a literature search and appropriate animal experiments.

1. Experiment must “conform to generally accepted scientific principles,” be grounded in a literature search and appropriate animal experiments.
Better preparation, knowledge increases chance of benefit, decreases likely harms

2. Experimental protocol must be formulated and evaluated by “a specifically appointed committee independent of the investigator and the sponsor.”

2. Experimental protocol must be formulated and evaluated by “a specifically appointed committee independent of the investigator and the sponsor.”
Requirement for Institutional Review Board (IRB)
Investigator can’t trust self to be objective in weighing risks and benefits.

3. Experiment must be conducted by qualified scientists and clinicians.

3. Experiment must be conducted by qualified scientists and clinicians.
Skill increases chance of benefit, decreases likely harms

4. Can’t do the experiment unless benefit is in proportion to potential harm to the subject.

5. Must assess predictable risks and foreseeable benefits before the experiment.

6. Must protect the subject’s integrity, minimizing physical and mental impacts, impacts on personality, impacts on privacy.

6. Must protect the subject’s integrity, minimizing physical and mental impacts, impacts on personality, impacts on privacy.
Duty to well-being of subjects, to increase chance of benefit, decrease likely harms (and not just physical ones)

7. Can’t do experiment if hazards are unpredictable (and must halt experiment in which they turn out to be so).

7. Can’t do experiment if hazards are unpredictable (and must halt experiment in which they turn out to be so).
Minimum level of knowledge/control required. Below that level, human subject research cannot be ethical.

8. Experimental results must be published accurately. Experiments not following these principles shouldn’t be published.

8. Experimental results must be published accurately. Experiments not following these principles shouldn’t be published.
Avoiding unnecessary duplication (unnecessary additional risk)
Punishing researchers for ignoring ethical requirements.

9. Informed consent is required. Patient may opt out.

9. Informed consent is required. Patient may opt out.
Finally, informed consent and patient autonomy.

10. Need to ensure that the consent is freely given, not obtained under duress.

11. Consent from subject’s legal guardian is possible.

11. Consent from subject’s legal guardian is possible.
Important for research with children, the mentally disabled, etc.

12. Research protocol must address ethical considerations and must explicitly adhere to these principles.

12. Research protocol must address ethical considerations and must explicitly adhere to these principles.
Research with human subjects not a right but a privilege.
Ethical considerations as part of experimental design.

Declaration of Helsinki (1989 version) Clinical Research (points paraphrased)
1. New techniques acceptable if they might save life or health, or alleviate suffering.

2. Must be a cost/benefit analysis of new method vs. existing methods.

2. Must be a cost/benefit analysis of new method vs. existing methods.
Unless there’s good reason to think new method will be better for the patient’s outcome than existing methods, must use existing methods.

3. All subjects (including controls) “should be assured of the best proven diagnostic and therapeutic method.”

3. All subjects (including controls) “should be assured of the best proven diagnostic and therapeutic method.”
Same duties to subjects as to patients who are not experimental subjects

4. Opt-out by patient shouldn’t interfere with patient – physician relationship.

4. Opt-out by patient shouldn’t interfere with patient – physician relationship.
Ceasing to be a subject doesn’t mean researchers can cut you out of continued medical care

5. “If the physician considers it essential not to obtain informed consent, the specific reasons for this proposal should be stated in the experimental protocol for transmission to the independent committee.”

5. “If the physician considers it essential not to obtain informed consent, the specific reasons for this proposal should be stated in the experimental protocol for transmission to the independent committee.”
Deception in research

6. Research in clinical setting needs to be justified by “potential diagnostic or therapeutic value for the patient”.

6. Research in clinical setting needs to be justified by “potential diagnostic or therapeutic value for the patient”.
Otherwise, duty to provide standard treatment

Declaration of Helsinki (1989 version) Non-therapeutic research (paraphrased)
1. Duty to protect life and health of subject.

1. Duty to protect life and health of subject.
Even though research not expected to directly benefit subject, you have a duty to well-being of the subject, and there’s a line you cannot cross.

2. Subjects must be volunteers and healthy, or at least suited to the experimental design.

3. Researchers must stop experiment if continuing it would be harmful to the subject.

3. Researchers must stop experiment if continuing it would be harmful to the subject.
Even though research not expected to directly benefit subject, you have a duty to well-being of the subject, and there’s a line you cannot cross.

4. Well-being of subject outweighs interests of science and society.

Belmont Report
Direct response to uproar about the Public Health Service’s Tuskegee syphilis experiment
Focus on addressing most glaring ethical violations of that experiment
Shift from adding more duties to list to focusing on “spirit of the law”

Belmont Report Ethical principles summarized
1. Respect for persons . Individuals to be treated as autonomous agents; requirement to protect those with diminished autonomy.

1. Respect for persons . Individuals to be treated as autonomous agents; requirement to protect those with diminished autonomy.
Informed consent (or consent by guardian looking out for best interests of subject).
Ability to opt out.

2. Beneficence . Make efforts to secure people’s well-being. Maximize possible benefits and minimize possible harms.

2. Beneficence . Make efforts to secure people’s well-being. Maximize possible benefits and minimize possible harms.
Weighing of risks and benefits.

3. Justice . Research subjects must not be asked to take on an unfair burden. New knowledge and techniques ought to be distributed fairly. People ought not to be deprived of the opportunity to participate in research.

3. Justice . Research subjects must not be asked to take on an unfair burden. New knowledge and techniques ought to be distributed fairly. People ought not to be deprived of the opportunity to participate in research.
Who takes on risks? Who gets benefits? Fairness in wake of Tuskegee Experiment.

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Human Subjects Regulations

by Janet Stemwedel on Mar 18, 2010

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Human Subjects Regulations — Presentation Transcript