Protection of Human Subjects
Description
Maintaining constant improvement in the emergency care system requires extensive research conducted with patients seeking
treatment in emergency care settings.1 Emergency care researchers are responsible for protecting the rights and safety of
patients who become human subjects in the context of research. This responsibility can be fulfilled by researchers through the
exercise of respect for persons, beneficence, and justice. Respect for persons is demonstrated by recognizing the rights of
individuals to decline participation in research with no adverse consequences to themselves.2 Additionally, people with
limited decision-making capacity are entitled to protection from unauthorized research participation. Researchers demonstrate
beneficence by implementing research that causes no harm, maximizes potential benefits, and minimizes risks.2 Justice is
implemented through the even-handed treatment of research subjects and by not targeting research to a vulnerable population
that is not anticipated to benefit from the results.
Vulnerable populations include pregnant women, human fetuses, neonates, prisoners, and children.3 Depending on where the
research is conducted, vulnerable populations may also include students; employees; racial, religious, or ethnic minorities;
the economically or educationally disadvantaged; and those with physical, sensory, or mental disabilities.4 Despite the best
efforts of researchers to epitomize ethical conduct in their work, some vulnerable populations may feel they are required to
participate in research. Individuals may believe they do not have the right to decline research participation or fear that
nonparticipation means they will be denied services to which they otherwise would be entitled (e.g., emergency healthcare,
employment). They may also experience a phenomenon known as therapeutic misconception, which occurs when patients
who are asked to participate in research do not recognize the difference between clinical care and a clinical trial.5 These
patients may believe that declining research participation is akin to declining clinical care.
Research subjects have the right to be informed of the actual or potential risks in any research endeavor and to refuse to
participate or withdraw from research without penalty. Nurses act as advocates to ensure that patients’ rights and safety are
protected during the consent process and the conduct of the research. This is a legal, ethical, and professional responsibility
of nurses.6,7
ENA Position
It is the position of the Emergency Nurses Association that:
1.
It is essential for emergency nurses to be knowledgeable of the tenets relating to the protection of human subjects.
2.
Emergency nurse researchers and others conducting studies in the emergency setting adhere to U.S. Department of
Health and Human Services and Federal Drug Administration regulations for the protection of human subjects in
research.
3.
The rights of research subjects are protected during the informed consent process and during and after the conduct of the
study. These include 1) the right to voluntary participation and withdrawal without loss of future benefits and 2) the right
to anonymity, confidentiality, and privacy.
4.
All research proposals undergo scientific and institutional peer review to ensure quality research and the protection of
research subjects’ rights and safety.
5.
Medical and Social/Behavioral Institutional Review Boards are interprofessional and include nurses as both scientists
and clinicians.
Background
Many advances in healthcare are the result of research. For example, research in the 1940s contributed to today’s emergency
nursing practices for the care of people with high-altitude injuries, hypothermia, or seawater inhalation. While these research
findings have strong clinical significance, the experiments were conducted by Nazi scientists on prisoners at the Dachau
concentration camp without the research subjects’ permission.8 These unethical experiments, revealed at the subsequent trial
of the Nazi scientists, led to the establishment of the Nuremberg Code, which focuses on informed consent.8 After many
years of discussion, the World Medical Association subsequently approved the Declaration of Helsinki in 1964, which has
evolved over time, with the seventh version being approved by the World Medical Association in 2013.9 The Declaration
addresses multiple aspects of the protection of human subjects: general principles; risks, burdens, and benefits; vulnerable
groups and individuals; scientific requirements and research protocols; research ethics committees; privacy and
confidentiality; informed consent; use of placebos; post-trial revisions; research registration; publication and dissemination of
results; and the use of unproven interventions in clinical practice.
Concurrent with the research at Dachau, violations of human subjects’ rights were occurring in the United States. For
example, the Syphilis Study at Tuskegee involved the enrollment, without informed consent, of African-American men, some
with syphilis.10 Long after effective treatment for syphilis became available, it was withheld from the research subjects with
the disease. The study began in the 1930s and continued until 1972 when its details were revealed in a news story. In 1979,
following an investigation, the United States Department of Health and Human Services published the Belmont Report,2
which established:
-boundaries between practice and research;
-basic ethical principles of respect for people, beneficence, and justice;
-application of the informed consent process in research;
-assessment of risks and benefits; and
-subject selection process
Along with the Belmont Report, policies now regulate the qualifications of investigators as well as the review, approval,
conduct, and emergency use of drugs, biologics, and medical devices in research on human subjects.11–17 “Emergency
research” is an exception to the informed consent investigation process. Such research investigations “involve human
subjects who have a life-threatening medical condition that necessitates urgent intervention (for which available treatments
are unproven or unsatisfactory), and who, because of their condition (e.g., traumatic brain injury) cannot provide informed
consent. The research must have the prospect of direct benefit to the patient and must involve an investigational product that,
to be effective, must be administered before informed consent from the subject or the subject’s legally authorized
representative can be obtained and in which there is no reasonable way to identify prospectively individuals likely to become
eligible for participation.”14 Title 21, Code of Federal Regulations, Section 50.24 (21 CFR 50.24) was developed to guide the
development, conduct and oversight of such investigations. Updates in 2013 provided additional flexibility by permitting the
use of an independent data-safety monitoring committee (DMC) for oversight.14 Emergency nurses in cases of emergency
research are responsible for advocating on behalf of their patients by informing the physician scientist initiating the
emergency research once a patient or representative is capable of being informed of the research in which the patient is
participating.
Despite U.S. federal regulations, however, violations persist. In 2012, DuBois, Anderson, and Chibnall surveyed U.S.
medical schools and comprehensive doctoral institutions; 129 institutions responded.18 Over a two-year period, the
researchers found the majority of institutions indicated multiple violations in the conduct of research on human subjects.
These included violations of consent and privacy regulations, misconduct, conflicts of interest, and fraud. Even in the
Veterans Administration healthcare system, 15% of researchers participating in the research process in 2010 self-reported
being pressured to disregard the regulations and practices of ethical research.19 The persistence of violations today
necessitates continued vigilance to ensure the protection of human subjects.
Resources
Code of Federal Regulations (CFR) Title 45 Part 46: Protection of Human Subjects: http://www.ecfr.gov/cgi-bin/textidx?tpl=/ecfrbrowse/Title45/45cfr46_main_02.tpl
Collaborative Institutional Training Initiative (CITI) at the University of Miami: https://www.citiprogram.org/
Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects:
http://www.wma.net/en/30publications/10policies/b3/index.html
Food and Drug Administration’s Information Sheet Guidance Documents:
http://www.fda.gov/ScienceResearch/SpecialTopics/RunningClinicalTrials/GuidancesInformationSheetsandNotices/ucm113
709.htm
ENA’s Institute for Emergency Nursing Research (IENR): https://www.ena.org/practiceresearch/research/Pages/Default.aspx
The Belmont Report: http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html
References
1.
National Institutes of Health, National Institute of General Medical Sciences, Office of Emergency Care Research. (2014). Retrieved from
http://www.nigms.nih.gov/About/Overview/OECR/Pages/default.aspx
2.
U.S. Department of Health and Human Services. (1979). The Belmont Report. Retrieved from
http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html
3.
U.S. Department of Health and Human Services. (2010). Protection of Human Subjects, 45 C.F.R. pt. 46 (2009). Retrieved from
http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html.
4.
DuBois, J. M. (2006). Vulnerability in research. In E. A. Bankert, & R. J. Amdur (Eds.), Institutional review board: Management and function (2nd
ed., pp. 337–340). Sudbury, MA: Jones and Bartlett Publishers.
5.
Lidz, C. W., Albert, K., Appelbaum, P., Dunn, L. B., Overton, E., & Pivovarova, E. (2015). Why is therapeutic misconception so prevalent?
Cambridge Quarterly of Healthcare Ethics, 24(2), 231–241. doi:10.1017/S096318011400053X
6.
American Nurses Association. (2015). Code of ethics for nurses with interpretive statements. Silver Spring, MD: Author.
7.
Emergency Nurses Association. (2015). ENA code of ethics. Retrieved from https://www.ena.org/about/Documents/CodeofEthics.pdf
8.
Shuster, E. (1997). Fifty years later: The significance of the Nuremberg Code. The New England Journal of Medicine, 337(20), 1436–1440.
9.
Nicogossian, A., Kloiber, O., & Stabile, B. (2014). The revised World Medical Association’s Declaration of Helsinki 2013: Enhancing the protection
of human research subjects and empowering ethics review committees. World Medical & Health Policy, 6(1), 1–3. doi:10.1002/wmh3.79
10. National Institutes of Health, Office of Extramural Research. (n.d.). Protecting human research participants: Historical events – The Syphilis
Study at Tuskegee. Retrieved from https://phrp.nihtraining.com/history/05_history.php
11. U.S. Department of Health and Human Services, Food and Drug Administration, Center for Devices and Radiological Health. (2006). Information
sheet guidance for IRBs, clinical investigators, and sponsors: Frequently asked questions about medical devices. Retrieved from
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf
12. U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Office of Good Clinical Practice. (2010). Information sheet
guidance for sponsors, clinical investigators, and IRBs: Frequently asked questions – statement of investigator (Form FDA 1572). Retrieved from
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM214282.pdf
13. U.S. Department of Health and Human Services, U.S. Food and Drug Administration, Office of Good Clinical Practice. (2013). Guidance for
institutional review boards, clinical investigators, and sponsors: Exception from informed consent requirements for emergency research. Retrieved
from http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM249673.pdf
14. U.S. Department of Health and Human Services, U.S. Food and Drug Administration. (2014). A guide to informed consent – information sheet.
Retrieved from http://www.fda.gov/RegulatoryInformation/Guidances/ucm126431.htm
15. U.S. Department of Health and Human Services, U.S. Food and Drug Administration. (2014). Recruiting study subjects – information sheet. Retrieved
from http://www.fda.gov/RegulatoryInformation/Guidances/ucm126428.htm
16. U.S. Department of Health and Human Services, U.S. Food and Drug Administration. (2014). Treatment use of investigational drugs – information
sheet. Retrieved from http://www.fda.gov/RegulatoryInformation/Guidances/ucm126495.htm
17. U.S. Department of Health and Human Services, U.S. Food and Drug Administration. (2014). Emergency use of an investigational drug or biologic –
information sheet. Retrieved from http://www.fda.gov/RegulatoryInformation/Guidances/ucm126491.htm
18. DuBois, J. M., Anderson, E. E., & Chibnall, J. (2013). Assessing the need for a research ethics mediation program. Clinical and Translational Science
Journal, 6(3), 209–213. doi:10.1111/cts.12033
19. Pearlman, R. A., Cohen, J. H., Foglia, M. B., & Fox, E. (2013). Perceptions of research ethics practices: IntegratedEthicsTM staff survey data from the
VA Health Care System. AJOB Primary Research, 4(1), 34–43. doi:10.1080/21507716.2012.752417
Authors
Authored and Reviewed by the Position Statement Committee
Diane Gurney, MS, RN, CEN, FAEN, Chair
Katie Bush, MA, RN, SANE-A
Gordon Lee Gillespie, PhD, DNP, RN, CEN, CPEN, CNE, PHCNS-BC, FAEN
Robin Walsh, MS, BSN, RN
E. Marie Wilson, MPA, RN
ENA 2015 Board of Directors Liaison
Sally Snow, BSN, RN, CPEN, FAEN
ENA Staff Liaisons
Dale Wallerich, MBA, BSN, RN
Developed: 2015.
Approved by the ENA Board of Directors: May 1989.
Revised and Approved by the ENA Board of Directors: August/September 1993.
Revised and Approved by the ENA Board of Directors: December 1995.
Revised and Approved by the ENA Board of Directors: September 1997.
Revised and Approved by the ENA Board of Directors: December 1999.
Revised and Approved by the ENA Board of Directors: December 2001.
Revised and Approved by the ENA Board of Directors: September 2003.
Revised and Approved by the ENA Board of Directors: September 2015.
©Emergency Nurses Association, 2015.
This position statement, including the information and recommendations set forth herein, reflects ENA’s current position with respect to the subject matter discussed herein based on current knowledge at the
time of publication, is only current as of the publication date, and is subject to change without notice as new information and advances emerge. The positions, information and recommendations discussed
herein are not codified into law or regulations. Variations in practice and a practitioner’s best nursing judgment may warrant an approach that differs from the recommendations herein. ENA does not approve or
endorse any specific sources of information referenced. ENA assumes no liability for any injury and/or damage to persons or property arising from the use of the information in this position statement.