I. Overview: CODES OF ETHICS

Guiding all regulations on clinical investigations are ethical principles. Though we occasionally pay lip service to such codes of ethics, we rarely refer to them, re-read them, or sit and ponder what they mean to our daily activity.

The Nuremburg Code is reprinted as the first important code in American research history. It recognized the importance of informed consent.

The Belmont Report was written by the National Commission on Protection of Human Subjects of Biomedical and Behavioral Research in 1979. The principles it discusses are directly reflected in the Common Rule regulations adopted by the NIH and FDA in 1981 and revised in 1991.

The World Medical Association adopted the Declaration of Helsinki in 1964 and has revised it several times. Most protocols refer to this declaration and international research is predicated on it.

The American Medical Association's opinion on responsibilities of physicians conducting clinical investigations is for physician
investigators.

The Association of Clinical Research Professionals has a code of ethics for certified research staff.

The Institutional Review Board expects principal investigators to have read the ethical codes appropriate to their field.

II. The Nuremberg Code

In 1947 the War Crimes Tribunal meeting at Nuremberg convicted 23 German defendants, most of whom were physicians, of performing criminal experiments on human subjects. The Tribunal propounded ten standards to guide physicians in carrying out future experiments on human subjects.

1.** The voluntary consent of the human subject is absolutely essential. This means that the person involved should have legal capacity to give consent; should be so situated as to be able to exercise free power of choice, without the intervention of any element of force, fraud, deceit, duress, over-reaching, or other ulterior form of constraint or coercion; and should have sufficient knowledge and comprehension of the elements of the subject
matter involved as to enable him to make an understanding and enlightened decision.

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 or unnecessary in nature.

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 justify the performance of the experiment.

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

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.

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.

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

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.

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

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 the 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.

III. The Belmont Report

A. Respect for Persons

1. Respect for persons incorporates at least two ethical convictions; first, that individuals should be treated as autonomous agents, and second, that persons with diminished autonomy are entitled to protection. In most cases of research involving human subjects, respect for persons demands that subjects enter into the research voluntarily and with adequate information. In some situations, however, application of the principle is not obvious.

2. Beneficence
Persons are treated in an ethical manner not only by respecting their decisions and protecting them from harm, but also by making efforts to secure their well-being. Such treatment falls under the principle of beneficence. The term "beneficence" is often understood to cover acts of kindness or charity that go beyond strict obligation. In this document, beneficence is understood in a stronger sense, as an obligation. Two general rules have been formulated as complementary expressions of beneficent actions in this sense: (1) do not harm and (2) maximize possible benefits
and minimize possible harms.
The Hippocratic maxim "do no harm" has long been a fundamental principle of medical ethics.

3. Justice
Who ought to receive the benefits of research and bear its burdens? This is a question of justice in the sense of "fairness in distribution" or "what is deserved." An injustice occurs when some benefit to which a person is entitled is denied without good reasons or when some burden is imposed unduly. (1) to each person an equal share (2) to each person according to individual need, (3) to each person according to individual effort, (4) to each person according to societal contribution, and (5) to each person according to merit.

4. Informed Consent
Respect for persons requires that subjects, to the degree that they are capable, be given the opportunity to choose what shall or shall not happen to them. This opportunity is provided when adequate standards of informed consent are satisfied.

a. Information
Most codes of research establish specific items for disclosure intended to assure that subjects are given sufficient information. These items generally include: the research procedure, their purposes, risks and anticipated benefits, alternative procedures (where therapy is involved), and a statement offering the subject the opportunity to ask questions and to withdraw at any time from the research. Additional items have been proposed, including how subjects are selected, the person responsible for the research, etc.

b. Comprehension
The manner and context in which information is conveyed is as important as the information itself. For example, presenting information in a disorganized and rapid fashion, allowing too little time for consideration or curtailing opportunities for questions, all may adversely affect a subject's ability to make an informed choice. Because the subject's ability to understand is a function of intelligence, rationality, maturity and language, it is necessary to adapt the presentation of the information to the subject's capabilities.

c. Voluntariness
An agreement to participate in research constitutes a valid consent only if voluntarily given. This element of informed consent requires conditions free of coercion and undue influence. Coercion occurs when an overt threat of harm is intentionally presented by one person to another in order to obtain compliance. Undue influence, by contrast, occurs through an offer of an excessive, unwarranted, inappropriate or improper reward or other overture
in order to obtain compliance. Also, inducements that would ordinarily be acceptable may become undue influences if the subject is especially vulnerable.

d. Assessment of Risks and Benefits
The assessment of risks and benefits requires a careful arrayal of relevant data, including, in some cases, alternative ways of obtaining the benefits sought in the research.

e. Selection of Subjects
Just as the principle of respect for persons finds expression in the
requirements for consent, and the principle of beneficence in risk/benefit assessment, the principle of justice gives rise to the moral requirements that there be fair procedures and outcomes in the selection of research subjects.

IV. World Medical Association/The Declaration of Helsinki
Adopted by 18th World Medical Assembly, Helsinki, Finland, l964, and revised by
29th World Medical Assembly, Tokyo, Japan, l975
35th World Medical Assembly, Venice, Italy, 1983
41st World Medical Assembly, Hong Kong, 1989.

A. Basic Principles

1. Biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on adequately performed laboratory and animal experimentation and on a thorough knowledge of the scientific literature.

2. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol which should be transmitted for consideration, comment and guidance to a specially appointed committee independent of the investigator and the sponsor provided that this independent committee is in conformity with the laws and regulations of the country in which the research experiment is to be carried out.

3. Biomedical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent, medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given his or her consent.

4. Biomedical research involving human subjects cannot legitimately be carried out unless the importance of the objective is in proportion to the inherent risk to the subject.

5. Every biomedical research project involving human subjects should be preceded by careful assessment of predictable risks in comparison with foreseeable benefit to the subject or to others. Concern for the interest of the subject must always prevail over the interests of science and society.

6. The right of the research subject to safeguard his or her integrity must always be respected. Every precaution should be taken to respect the privacy of the subject and to minimize the impact of the study on the subject's physical and mental integrity and on the personality of the subject.

7. Physicians should abstain from engaging in research projects involving human subjects unless they are satisfied that the hazards involved are believed to be predictable. Physicians should cease any investigation if the hazards are found to outweigh the potential benefits.

8. In publication of the results of his or her research, the physician is obliged to preserve the accuracy of the results. Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication.

9. In any research on human beings, each potential subject must be
adequately informed of the aims, methods, anticipated benefits and potential hazards of the study and the discomfort it may entail. He or she should be informed that he or she is at liberty to abstain from participation in the study and that he or she is free to withdraw his or her consent to participation at any time. The physician should then obtain the subject's freely-given informed consent, preferably in writing.

10. When obtaining informed consent for the research project the physician should be particularly cautious if the subject is in a dependent relationship to him or her or may consent under duress. In that case the informed consent should be obtained by a physician who is not engaged in the investigation and who is completely independent of this official relationship.

11. In case of legal incompetence, informed consent should be obtained from the legal guardian in accordance with national legislation. Where physical or mental incapacity makes it impossible to obtain informed consent, or when the subject is a minor, permission from the responsible relative replaces that of the subject in accordance with national legislation. Whenever the minor child is in fact able to give a consent, the minor's consent must be obtained in addition to the consent for the minor's legal guardian.

12. The research protocol should always contain a statement of the ethical considerations involved and should indicate that the principles enunciated in the present Declaration are complied with.

V. AMA Principles of Medical Ethics 1996

A. A physician shall be dedicated to providing competent medical service with compassion and respect for human dignity.

B. A physician shall deal honestly with patients and colleagues, and strive to expose those physicians deficient in character or competence, or who engage in fraud or deception.

C. A physician shall respect the law and also recognize a responsibility to seek changes in those requirements which are contrary to the best interest of the patient.

D. A physician shall respect the rights of patients, of colleagues, and of other health professionals, and shall safeguard patient confidences within the constraints of the law.

E. A physician shall continue to study, apply and advance scientific
knowledge, make relevant information available to patients, colleagues, and the public, obtain consultation, and use the talents of other health professionals when indicated.

F. A physician shall, in the provision of appropriate patient care, except in emergencies, be free to choose whom to serve, with whom to associate, and the environment in which to provide medical services.

G. A physician shall recognize a responsibility to participate in activities contributing to an improved community.

Section 2.07 Clinical Investigation: The following guidelines are intended to aid physicians in fulfilling their ethical responsibilities when they engage in the clinical investigation of new drugs and procedures.

1. A physician may participate in clinical investigation only to the extent that those activities are a part of a systematic program competently designed, under accepted standards of scientific research, to produce data which are scientifically valid and significant.

2. In conducting clinical investigation, the investigator should demonstrate the same concern and caution for the welfare, safety, and comfort of the person involved as is required of a physician who is furnishing medical care to a patient independent of any clinical investigation.

3. Minors or mentally incompetent persons may be used as subjects in clinical investigation only if:

a. The nature of the investigation is such that mentally competent adults would not be suitable subjects.

b. Consent, in writing, is given by a legally authorized representative of the subject under circumstances in which informed and prudent adults would reasonably be expected to volunteer themselves or their children as subjects.

4. In clinical investigation primarily for treatment:

a. The physician must recognize that the physician-patient relationship exists and that professional judgment and skill must be exercised in the best interest of the patient.

b. Voluntary written consent must be obtained from the patient, or from his legally authorized representative if the patient lacks the capacity to consent, following:

i. disclosure that the physician intends to use an investigational drug or experimental procedure,

ii. a reasonable explanation of the nature of the drug or procedure to be used, risks to be expected, and possible therapeutic benefits,

iii. an offer to answer any inquiries concerning the drug or procedure, and

iv. a disclosure of alternative drugs or procedures that may be available.

c. Physicians should be completely objective in discussing the details or the drug or procedure to be employed, the pain and discomfort that may be anticipated, known risks and possible hazards, the quality of life to be expected, and particularly the alternatives.

5. In clinical investigation primarily for the accumulation of scientific knowledge --

a. Adequate safeguards must be provided for the welfare, safety and comfort of the subject. It is fundamental social policy that the advancement of scientific knowledge must always be secondary to primary concern for the individual.

b. Consent, in writing, should be obtained from the subject, or from his legally authorized representative if the subject lacks the capacity to consent following: (a) disclosure of the fact that an investigational drug or procedure is to be used, (b) a reasonable explanation of the nature of the procedure to be used and risks to be expected, and (c) an offer to answer any inquiries concerning the drug or procedure.

6. No person may be used as a subject in clinical investigation against his or her will.

7. The overuse of institutionalized persons in research is an unfair distribution of research risks. Participation is coercive and not voluntary
if the participant is subjected to powerful incentives and persuasion.

8. The ultimate responsibility for the ethical conduct of science resides within the institution (academic, industrial, public, or private) which conducts scientific research and with the individual scientist. These guidelines should ensure that

a. the process used to resolve allegations of fraud does not damage science,

b. all parties are treated fairly and justly with a sensitivity to reputations and vulnerabilities,

c. the highest degree of confidentiality is maintained,

d. the integrity of the process is maintained by an avoidance or real or apparent conflicts of interest,

e. resolution of charges is expeditious,

f. accurate and detailed documentation is kept throughout the process, and

g. responsibilities to all involved individuals, the public, research sponsors, the scientific literature, and the scientific community are met after resolution of charges.

Academic institutions must be capable of, and committed to, implementing effective procedures for examining allegations of scientific fraud. No system of external monitoring should replace the efforts of an institution to set its own standards which fulfill its responsibility for the proper conduct of science and the training of scientists.

9. With the approval of the patient or the patient's lawful representative, physicians, should cooperate with the press and media to ensure that medical news concerning the progress of clinical investigation or the patient's condition is available more promptly and more accurately than would be possible without their assistance. On the other hand, the Council does not approve of practices designed to create fanfare, sensationalism to attract
media attention, and unwarranted expressions of optimism because of short-term progress, even though longer-range prognosis is known from the beginning to precarious. With the approval of the patient or the patient's family, the Council, however, encourages the objective disclosure to the press and media of pertinent information. If at all possible, the identity of the patient should remain confidential if the patient or the patient's family so desires. The situation should not be used for commercial ends of participating physicians or the institutions involved.

VI. Association of Clinical Research Professionals Code of Ethics

A. As a member of the Association of Clinical Research professionals shall:

. Strive to conduct myself and my work with objectivity and integrity.

. Hold as inviolate that credible science is fundamental to all clinical research.

. Seek to communicate information concerning subject health and safety in a timely and responsible manner, with due regard for the significance and credibility of the available data.

. Present my scientific statements or endorsements with full disclosure of whether or not factual supportive data are available.

. Abstain from professional judgments influenced by conflict of interest and, insofar as possible, make full and complete disclosure in situations that may imply a conflict of interest.

. Observe the spirit as well as the law, regulation, and ethical standards with regard to the rights and welfare of human participants involved in research procedures.

. Practice high standards of occupational health and safety for the benefit of human participants involved in research procedures, my so-workers and other personnel.

Concerns regarding ethics violations shall be communicated in writing to the ACRP Central Office. All questions of ethical concerns will be referred to ACRP's Board of Directors, and, if appropriate to ACRP's legal counsel for review and recommendations.

VII. IRB Review Criteria:

A. Risks to subjects are minimized by (i) using procedures consistent with sound research design and which do not unnecessarily expose subjects to risk, and (ii) whenever appropriate, by using procedures already being performed on the person for diagnostic or therapeutic reasons.

B. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may be expected to result.

C. Selection of subjects is equitable. In making this assessment, the IRB should take into account the purposes of the research and the setting in which the research will be conducted and should be particularly cognizant of the special problems of research involving vulnerable populations, such as children, prisoners, pregnant women, handicapped or mentally disabled persons, or economically or educationally disadvantaged persons.

D. Informed consent will be sought from each prospective subject or the subjects legally authorized representative, in accordance with and to the extent required by 21 CFR Part 50. Waiver from the obligation to gain consent may be approved under 21 CFR 50.23.

E. Informed consent will be appropriately documented, in accordance with and to the extent required by 21 CFR 50.27, "Documentation of Informed Consent."

F. Where appropriate, the research plan makes adequate provisions for monitoring the data collected to ensure the safety of subjects.

G. Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of files.

*Reproduced with the kind permission of the author, Larry Lachman, PsyD
Presented originally as:
FIELD QUALITATIVE RESEARCH METHODS/SOC 401
Chapman University, Monterey Campus Summer 2001
Instructor: Dr. Larry Lachman

Dr. Larry Lachman is an undergraduate psychology instructor for Monterey Peninsula College
where he teaches Abnormal Psychology, Social Psychology, Health Psychology and Adult Development & Aging. He is also a graduate psychology instructor at Chapman University's Monterey Campus, where he teaches Research & Bibliographic Methods.

Contact:
P.O. Box 22151
Carmel, Ca. 93922
Ph: (831) 643-2635
Fx: (509) 472-1768
DrLarry@SeasonsOfSurvival.com; dociam3@hotmail.com
http://www.seasonsofsurvival.com
http://www.blackboard.com

**The numbering in this discussion as presented on this website has been altered for the sake of consistency between the various sources.