Good Science, Good Ethics?

1. · Good Science, Good Ethics? The Thinker Experimentation is necessary to advance knowledge In the health field, experimentation inevitably involves human subjects

2. · • Celsus was a medical author of Ancient Rome. His detailed accounts of medical practice paint a clear picture of medicine during this era. • Celsus justified experiments on condemned criminals in Egypt Aulus Cornelius Celsus (25BC-40AD) "It is not cruel to inflict on a few criminals sufferings which may benefit multitudes of innocent people through all centuries."

3. · "The Origin of the Vaccine Inoculation"(Jenner - 1801) Over 200 years ago, English physician Edward Jenner observed that milkmaids stricken with the viral disease cowpox were rarely victims of a similar disease, smallpox. In an experiment, Jenner took a few drops of fluid from a pustule of a woman who had cowpox and injected the fluid into a healthy young boy who had never had cowpox or smallpox. Six weeks later, Jenner injected the boy with fluid from a smallpox pustule, but the boy remained free of the dreaded smallpox. Smallpox caused massive disfigurement, in its worse case blindness, and in many cases killed its victims. Populations of towns and villages were eradicated.

4. · • Social Concerns that must be addressed: • The importance of honoring the basic ethical principles supporting the involvement of humans as research subjects. • The need for independent, objective review of research. • The need to preserve public trust in research involving human subjects.

5. · • Bad Science, Bad Ethics: • A poor study design provides invalid results – this is not ethical as it is disrespectful to participants • But, the trial may have a good study design yet the risk to participants is too great • Thus Good Science does not always equate with Good Ethics

6. · • At the end of World War II, 23 Nazi doctors and scientists were put on trial for the murder of concentration camp inmates who were used as research subjects. • It became clear during the trial that no accepted standards existed regarding the conduct of human research. • The court found that it could not convict the defendants of violating the rights of research subjects. • [The court did convict 15 of the 23 defendants of murder. The remaining 8 were acquitted] Nuremberg Tribunal, November 21, 1945

7. · 1949 • The Nuremberg Code includes the following guidance for researchers: • Informed consent is essential. • Research should be based on prior animal work. • The risks should be justified by the anticipated benefits. • Only qualified scientists must conduct research. • Physical and mental suffering must be avoided. • Research in which death or disabling injury is expected should not be conducted. http://ohsr.od.nih.gov/guidelines/nuremberg.html

8. · 1964 Declaration of Helsinki A code of research ethics from the World Medical Association that reinterpreted the Nuremberg Code for medical research with therapeutic intent Journal editors require that research be performed in accordance with the Declaration. This document set the stage for the implementation of Institutional Review Boards (IRB) http://ohsr.od.nih.gov/guidelines/helsinki.html

9. · 1979 The Belmont Report The Report is a summary of the basic ethical principles identified by the National Commission which met for discussions over a four year period. It is a statement of the basic ethical principles and guidelines that should be used to resolve the ethical problems that surround the conduct of research with human subjects. The Belmont Report identifies three basic ethical principles that underlie all human subject research: Respect for persons, Beneficence, and Justice http://ohsr.od.nih.gov/guidelines/belmont.html

10. Respect for Persons • This principle requires researchers to treat individuals as autonomous human beings, capable of making their own decision/choices, and not to use people as a means to an end. The principle also provides extra protection to those with limited autonomy. • Elements of autonomy include: • Mental capacity (the ability to understand and process information) • Voluntariness (freedom from the control or influence of others) Beneficence This principle requires researchers to minimize the risks of harm and maximize the potential benefits of their work. Researchers must ensure that the potential benefits justify the risks of harm. Justice The principle of justice requires us to treat people fairly and to design research so that its burdens and benefits are shared equitably. Those who benefit from the research should share in the burden of being subjects in the research. Those who serve as subjects in the research should share in the potential benefits from the research. Individuals or groups should not be selected for research participation solely because they are available, cannot say “no” or do not know that they can say “no”.

11. 1991 U.S. Code of Federal Regulations 45CFR46 – ‘Common Rule’ Federal Policy for the Protection of Human Subjects Defined the role of the IRB (Institutional Review Board): To review all proposed research involving human subjects to ensure that subjects are treated ethically and that their rights and welfare are adequately protected Definition of research: A systematic investigation to develop or contribute to generalizable knowledge http://ohsr.od.nih.gov/guidelines/45cfr46.html

12. IRB Membership • 5+ members • one member who is a non-scientist • one member who is ‘scientific’ • one member who is unaffiliated with the institution • [One member can represent more than one role, such as a clergyman who may fill the roles of both the community (unaffiliated) member and non-scientist] • Members must be diverse in race, gender and cultural background, and be sensitive to local community issues • If an IRB receives research protocols in which the subjects are members of a vulnerable population (e.g., children, prisoners, the mentally handicapped), the IRB must have a member who is knowledgeable and experienced in working with the vulnerable population

13. Types of Review: (1) Exempt If a study is exempt, it will NOT need to go through IRB review (This determination is made by IRB Chair) • Research conducted in educational settings, involving normal educational practices • Research involving use of educational tests, survey procedures, interview procedures or observation of public behavior unless: • (i) information obtained is recorded in such a manner that human subjects can be identified, directly or through identifiers linked to subjects; and (ii) any disclosure of the human subjects' responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation. • Research involving the collection or study of existing data, documents, records, pathological specimens, or diagnostic specimens – • If these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through indentifiers linked to the subjects • Research and demonstration projects which are designed to study evaluate, or otherwise examine public benefit or service programs -- conducted by or subject to the approval of department or agency heads • Taste and food quality evaluation and consumer acceptance studies

14. Types of Review: (2) Expedited An expedited review procedure is for research with ‘minimal risk’ to subjects and consists of a review of by the IRB chairperson or by one or more experienced reviewers designated by the chairperson from among members of the IRB (This determination is made by IRB Chair) • Common examples of ‘minimal risk’: • Collection of blood samples by finger stick, heel stick, ear stick, or venipuncture when certain conditions are met (i.e., minimal risk and non-vulnerable populations) • Collection of data through noninvasive procedures (not involving general anesthesia or sedation) routinely employed in clinical practice, excluding procedures involving x-rays or microwaves. • Research on individual or group characteristics or behavior or research employing survey, interview, oral history, focus group, program evaluation, human factors evaluation, or quality assurance methodologies.

15. Types of Review: (3) Full-Board Review This type of review is carried out for studies that pose greater than minimal risk to subjects. (This determination is made by IRB Chair)

16. When reviewing a proposal, the goals are to:  • Identify the risks involved in the study (e.g., physical, psychological, legal, and social). • Identify how the risks are minimized. • Assess whether the risks are reasonable in relation to the anticipated benefits and, if the risk is more than minimal, assess whether the benefits outweigh or are in-balance with the risks. • Assess the adequacy of the privacy and confidentiality procedures. For example, if the investigator is conducting studies on a sensitive topic, such as spousal abuse or illegal drug use, have precautions been taken to protect the identity  and confidentiality of the participants? • Assess, when appropriate, that the study addresses how the data will be monitored to ensure the safety of enrolled subjects. For example, do the investigators propose to have an independent, ‘real time’ analysis of the data performed to assess if subjects in one treatment arm are responding significantly better or worse than the other? Or, perhaps the study’s risk/benefit analysis is acceptable for approval, but the IRB would feel more comfortable reviewing the data themselves after a certain period of time, or after a certain # of subjects has been run. • Determine if subject selection is equitable: • Has the investigator used appropriate inclusion and exclusion criteria? • Does the study target the appropriate population?  Populations of convenience should be avoided. For example, investigators should not target a population just because of “easy access,” or a population that will not benefit from the research, whether individually or as a social group. • Is the selection free of coercion? Is there an authoritative relationship between the person who is recruiting and the potential participant, such as teacher/student, physician/patient, and employer/employee? Have procedures been put into place to minimize possible coercion?

17. Responsible Conduct of Research at ASU http://researchintegrity.asu.edu/humans

18. http://www.sciencemag.org/cgi/reprint/329/5989/274-a.pdf Ethics: Researchers to Return Blood Samples to the Yanomamö http://www.sciencemag.org/cgi/content/full/328/5983/1218 Whose Blood Is It? http://www.insidehighered.com/news/2008/12/01/blood

19. Assignment #2 – due Sept. 6 Complete the CITI training: https://www.citiprogram.org/Default.asp Under curriculum, take the Human Subjects Modules. Select the course to take based on your field of research: Biomedical (Group 1 Basic) or Social & Behavioral (Group 2 Basic)