Part 1 – Overview
NGHS is pleased to offer to its staff, patients and community the opportunity to participate in the pursuit of knowledge. At the same time, NGHS acknowledges the ethical and legal burden involved in research. To this end NGHS has established a Program for the Protection of Human Subjects (PPHS). The component parts of this program include:
- Establishment of an Institutional Review Board (IRB)
- A program of education of IRB members and NGHS staff
- A compliance program
The following statement is the NGHS policy for the protection of human subjects in research.
Program for Protection of Human Subjects
The protection of all human subjects participating in research is important to the board, administration, staff and patients at Northeast Georgia Health System (NGHS).
The NGHS Program for the Protection of Human Subjects is authorized by the NGHS Board of Directors and Administration. The program is responsible for :
All research involving humans as subjects conducted at or under the auspices of NGHS, is subject to the Program for Protection of Human Subjects and the policies and procedures established and implemented by the NGHS Institutional Review Board.
Several overriding principles guide the PPHS of NGHS:
- To conduct, support or participate in research as an investigator, coordinator, or as a subject is a privilege. With every privilege comes a concomitant responsibility.
- All research involving human subjects conducted at NGHS will be reviewed using the criteria for review and informed consent found in the applicable Federal Regulations (Appendix C).
- The NGHS policy includes reference to the ethical principles found in the:
- Codes of Ethics for the Association of Clinical Research Professionals,
- Belmont Report,
- Nuremberg Code, and
- Declaration of Helsinki (Appendix D)
- Investigators and staff must also be governed by the ethical codes of their individual professions.
Ethical codes guide the behavior of people. Such codes can be found based on communal, religious, or professional values. Breach of a code is not necessarily a legal breach but is, instead, normative; that is, against the accepted norms of the group.
Most professional organizations have codes of conduct. The American Medical Association guides the conduct of medical practice with some information about research and is a baseline for physicians. The Association of Clinical Research Professionals (ACRP) code guides its study coordinator and monitor members. There are also codes for nursing research, psychology, anthropology and others.
The Nuremburg Code, written by American justices following World War II, established ten principles to guide use of human subjects in research (Appendix D). Although important in history, it was not generally accepted in U.S. medical circles. The World Medical Association adopted the Declaration of Helsinki in 1964. Governing medical research in the international community, it has gone through multiple revisions.
The Belmont Report was written in 1989 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This Commission was asked to identify the ethical principles underlying human research in the United States. The report first discusses the fine line between the practice of medicine and the conduct of research. It then discusses three ethical principles. In order to approve research, the IRB shall determine that all of the following requirements are satisfied
The Belmont Report
Respect for Persons
• Informed consent will be sought from each prospective subject or the subject's legally authorized representative.
• Risks to subjects are minimized and benefits maximized
• Selection of subjects is equitable.
Every person and every organization has multiple interests. These interests can come into conflict. Most conflicts are tenable and can be lived with - without hardship to others. An untenable conflict may cause a person to act in such a way that either the subject or the study will be harmed. Admitting an interest and acknowledging conflicts among interests is a first step. The second is to know when the conflict is a problem. For this, working with the IRB, the institution and one’s peers is important.
In proposing, reviewing or conducting studies one can ask several direct questions.
- What are the interests of each party?
- Are any of those interests in conflict with another?
- Could that conflict be the source of harm to the health, safety or welfare of the subject or the study?
- How can the interests be best served?
Although IRBs and institutions tend to focus on regulations, it should not be forgotten that legal cases, regulatory interpretation, and common practices also inform the review and practice of research. Neither the regulations nor the IRB exist in a vacuum.Federal Sources of Regulation
The federal regulations are viewed as the minimum standard. They are written in very subjective terms requiring interpretation. This was deliberate in order to encourage institutions to adapt the rules to their special and local needs. The relevant enforcement offices offer further interpretation. The states and the local institution are encouraged to establish stricter requirements.
Almost every federal agency regulates the research it funds or the research on products it regulates. The Common Rule, adopted in 1991, is the baseline for all federal regulation. The Common Rule, found in 45 CFR 46, is the regulation from the Department of Health & Human Services (DHHS). When the Common Rule was adopted, 17 federal agencies signed on. Each agency, however, was allowed to publish its own deviations from the Common Rule.
Federal regulation, possible only if backed by a Congressional mandate found in a law, is implemented through two channels: regulation of federally funded studies; and, regulation of federally regulated products.
a) Federally Regulated Studies
The Food and Drug Administration (FDA) adopted very similar rules on the same date in 1991. These are found in Title 21 of the Code of Federal Regulations, Parts 50, and 56 (Appendix A). As the FDA is a regulatory agency instead of a funding agency, its rules apply to the studies of a regulated product that lead to an application for a permit to put the product on the market. The FDA does not regulate the institution. It regulates and inspects the various participants in the research process including sponsors, investigators and IRB’s.
Within the FDA structure is a set of rules which, taken together, form "Good Clinical Practices". Any investigator seeking to conduct FDA regulated activity is responsible for knowing the responsibilities of a principal investigator, the requirements for drug accountability, protection of human subjects and monitoring (Appendix C).
- 21 CFR 50.20 General Requirements for Informed Consent
- 21 CFR 54 Financial Disclosure
- 21 CFR 56 Institutional Review Boards
- 21 CFR 312 Investigational New Drugs
- 21 CFR 812 Investigational Devices
b) Federally Funded Studies
The federal government funds grants to institutions and not to individuals. The Office for Human Research Protections (OHRP), representing the DHHS, requires institutions assure their compliance with "The Common Rule". The institution must sign a Federal-Wide Assurance (FWA), a binding assurance agreement stipulating the method(s) by which the institution will protect the personal rights and welfare of human research subjects. Other federal agencies that fund human studies either accept the FWA negotiated with the DHHS or negotiate their own assurances. OHRP conducts IRB inspections.
Currently Georgia has no additional requirements specific to research. Rules that are applicable from other areas include:
a) Age of consent – for medical care or research
b) Persons who may be a legally authorized representative for consent purposes.
c) Use of controlled substances
The International Conference on Harmonization (ICH) guidance E.6 was published as an FDA guide. Any company intending to develop data for submission to the FDA regulatory equivalent in Japan or the European Union must comply with the ICH. The NGHS IRB is in compliance with ICH.Institutional Requirements
All research conducted by or at NGHS would be subject to IRB review.
NGHS IRB has a Federal-Wide Assurance in which it assures the OHRP that all research at NGHS will be in compliance with 45 CFR 46.
NGHS IRB is registered with the FDA. All FDA regulated products must also meet the requirements of 21 CFR 56.
Research within NGHS are regulated by both sets of requirements.Regulatory Requirements Common To All
All of the above requirements have common elements or threads.
A Program of Human Subjects Protection.
The institution must have a program of protection. The NGHS program includes education, IRB review, and a compliance program.
A High Level of Authority
A program that is not endorsed at the highest levels and that is not a part of the institutional culture is no program. NGHS accepts responsibility for the ethical conduct of research. The program’s authority emanates from the highest institutional level.
A review – external to the study management – helps assure that external values are added. The NGHS IRB policies help assure that it is independent from the study management.
An IRB must have a diverse membership in order to introduce opinions from outside the field. The NGHS IRB has community membership and persons from a variety of fields.
As change and progress are inevitable, re-review must occur on a periodic basis. The regulations set one year as the maximum.
Respect for Persons
In addition to assuring a community in which subject protection is paramount and in which justice and beneficence are considered by the reviewers, the regulations and NGHS put reliance on subject autonomy and informed consent with a concomitant responsibility on investigator obligation to assure that consent is gained.
Education : Research Integrity
A National Institutes of Health (NIH) policy that requires all who are involved in research using human subjects/participants to participate in education related to human research protections went into effect in October, 2000. This policy is based on a commitment to ensure that researchers receive basic instruction in the key elements of responsible research and are familiar with basic regulatory requirements. From time to time Cooperative Groups (e.g. SWOG, NSABP, ECOG) require the submission of documentation of education/training on the protection of human subjects in research to maintain affiliation with them.
Researchers and research staff are encouraged to take advantage of the continuing education opportunities (i.e. periodicals, articles, speakers) that are available via the NGHS IRB Office. However, the responsibility of acquiring research education/training by individuals involved with the design, review or conduct of research within NGHS is that of those desiring to conduct research within NGHS.
When you attend or participate in educational programs with research related content you should forward to the IRB Office a copy of: your attendance certificate; the program’s objectives; and/or, an outline of the program’s content.