Human subject research
Human subject research is systematic, scientific investigation that can be either interventional (a "trial") or observational (no "test article") and involves
Human subject research is used in various fields, including research into advanced
Human subjects
The United States Department of Health and Human Services (HHS) defines a human research subject as a living individual about whom a research investigator (whether a professional or a student) obtains data through 1) intervention or interaction with the individual, or 2) identifiable private information (32 CFR 219.102). (Lim, 1990)[2]
As defined by HHS regulations (45 CFR 46.102):
- Intervention – physical procedures by which data is gathered and the manipulation of the subject and/or their environment for research purposes.
- Interaction – communication or interpersonal contact between investigator and subject.
- Private Information – information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public.
- Identifiable information – specific information that can be used to identify an individual.[2]
Human subject rights
In 2010, the National Institute of Justice in the United States published recommended rights of human subjects:
- Voluntary, informed consent
- Respect for persons: treated as autonomous agents
- The right to end participation in research at any time[3]
- Right to safeguard integrity[3]
- Protection from physical, mental and emotional harm
- Access to information regarding research[3]
- Protection of privacy and well-being[4]
From Subject to Participant
The term research subject has traditionally been the preferred term in professional guidelines and academic literature to describe a patient or an individual taking part in biomedical research. In recent years, however, there has been a steady shift away from the use of the term 'research subject' in favour of 'research participant' when referring to individuals who take part by providing data to various kinds of biomedical and epidemiological research.[5]
Ethical guidelines
In general, it can be said that experimental infections in humans are tightly linked to a history of scandals in medical research, with scandals being followed by stricter regulatory rules.[6] Ethical guidelines that govern the use of human subjects in research are a fairly new construct. In 1906 some regulations were put in place in the United States to protect subjects from abuses. After the passage of the Pure Food and Drug Act in 1906, regulatory bodies such as the Food and Drug Administration (FDA) and institutional review boards (IRBs) were gradually introduced. The policies that these institutions implemented served to minimize harm to the participant's mental and/or physical well-being.[citation needed]
The Common Rule
The Common Rule, first published in 1991, also known as the Federal Policy for the Protection of Human Subjects,[7] is dictated by the Office of Human Research Protections under the United States Department of Health and Human Services and serves as a set of guidelines for institutional review boards (IRBs), obtaining informed consent, and Assurances of Compliance[7] for human subject participants in research studies. On January 19, 2017, a final rule was added to the Federal Register[8] with an official effective date of July 19, 2018.[9]
Nuremberg Code
In 1947, German physicians who conducted deadly or debilitating experiments on concentration camp prisoners were prosecuted as war criminals in the
Declaration of Helsinki
The Declaration of Helsinki was established in 1964 to regulate international research involving human subjects. Established by the
The Declaration of Helsinki is widely regarded as the cornerstone document on human research ethics.[10][11][12]
The Belmont Report
The Belmont Report was created in 1978 by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to describe the ethical behaviors that involve researching human subjects. It is most heavily used by the current United States system for protecting human subjects in research trials.[7] By looking primarily at biomedical and behavioral research that involve human subjects, the report was generated to promise that ethical standards are followed during research of human subjects.[13] There are three standards that serve as the baseline for the report and how human subjects are to be researched. The three guidelines are beneficence, justice and respect for persons. Beneficence is described as protecting the well-being of the persons and respecting their decisions by being ethical and protecting the subjects from harm. The two rules of beneficence are maximizing the benefits of research and minimizing any possible risks.[14] It is the job of the researcher to inform the persons of the benefits as well as the risks of human subject research. Justice is important because it causes the researchers to be fair in their research findings and share what they have found, whether the information is good or bad.[14] The selection process of the subject is supposed to be fair and not separate due to race, sexual orientation or ethnic group.[15] Lastly, respect for persons explains that at any point a person who is involved in a study can decide whether they want to participate, not to participate or withdraw themselves from the study altogether. Two rules of respect for persons involve the person being autonomous and persons with diminished autonomy and entitled to protection.[13] The sole purpose of these guidelines is to ensure autonomy and to protect against those with a lesser chance to remain autonomous because of something out of their control.[13]
Ethical concerns
As science and medicine evolve, the field of bioethics struggles to keep up with updating guidelines and rules to follow. There has been an interest in revisiting the ethics behind human subject trials. Members of the health field have commented that it may be useful to have ethics classes available to students studying to be health care professionals as well as have more discussions surrounding the issues and importance of informed consent.[16] There have also been a bigger push to protect participants in clinical trials. Rules and regulations of clinical trials can vary by country.[17] Suggestions to remedy this include installing a committee to keep better track of this information and ensure that everything is properly documented.[17] Research coordinators and physicians involved in clinical studies have their own concerns, particularly that an implementation of ethics rules could potentially disrupt the logistics of preparing a research study, specifically when it comes to enrolling patients.[18][19] Another concern that research teams may have is that even if the rules are ethically sound, they may not be logical or helpful for conducting their studies.[19]
Of note currently in the research field is the manner in which researchers direct their conversations with potential human subjects for a research study.
Research in rural communities
Recently there has been a shift from conducting research studies at research institution facilities or academic centers to rural communities. There is concern surrounding the topics addressed during the discussions with this specific demographic of participants, particularly having to do with funding, overall efficacy of the treatment being studied, and if conducting such studies is done to the highest ethical standard.[citation needed]
Ann Cook and Freeman Hoas from the University of Montana's Department of Psychology conducted a study[18] to gain more understanding about what influences potential candidates to consent to participation in any given clinical trial. They published their findings in February 2015. Cook and Hoas asked for the perspectives of the researchers and whether they would consent to being a subject in a clinical trial. To assess the shift to rural communities, they surveyed 34 physicians or researchers and 46 research coordinators from states that have "large rural populations and have historically demonstrated limited participation in clinical research."[18] Proper consent forms were provided and signed at the start of the study. Of the physicians and research coordinators that participated in this study, 90% were from hospital centers or worked in a hospital-clinic setting. Of all the participants, only 66% of research coordinators and 53% of physicians received training in research methods, while 59% of the coordinators received any ethics training. Only 17% of the physicians had ethics research training prior to this study.[citation needed]
Hoas and Cook categorized their findings into the following main topics:[citation needed]
- source of funding
- morally nagging and challenging issues
- willingness to join a research study
The role of funding
Cook and Hoas found that funding played a significant role in participant selection. One of Hoas's and Cook's participants commented that "in his practice, the income from conducting pharmaceutical trials sometimes [is] used to offset the losses of conducting scientifically interesting but poorly funded federal studies,"[18] and most other participants administered trials because "reimbursements generated from such trials made it possible to maintain a financially viable, as well as profitable, practice."[18] Cook and Hoas found that most of the physicians and coordinators could not explain directly if they actually told their patients or subjects about any financial compensation they received. Respondents worry that discussing funding or compensation would affect enrollment, effectively swaying participants from joining a research study. In most respondents' experience, most patients do not even ask for that information, so they assume that they do not have to discuss it with them and not jeopardize enrollment. When asked if information about funding or compensation would be important to provide to patients, one physician replied "...certainly it may influence or bring up in their mind questions whether or not, you know, we want them to participate because we're gonna get paid for this, you know, budget dollar amount. But, you know, when you talk about full disclosure, is that something that we should be doing? That's an interesting question."[18]
Morally nagging or challenging issues
Respondents more often pointed out practical or logistical issues with the overall process rather than ethical issues. There was a general consensus that the whole practice of conducting research studies was more focused on the business aspects like funding and enrolling participants in the study in time. A physician commented that "[industry] relationships are very important because of cash flow."[18]
Typical ethical issues that arise in this type of research trials include participant enrollment, the question of coercion if a physician refers their own patients, and any misunderstandings regarding treatment benefits. Patients are more likely to enroll in a trial if their primary care physician or a provider that they trust recommends the study. Most respondents seem to[
There was a large amount of respondents who thought that research participants did not read or understand the documents provided for informed consent.[18] However, those respondents did not believe that was an ethical or moral concern.[citation needed]
Willingness to join a research study
Most of the coordinators and researchers showed some hesitation when they were asked if they would enroll as a subject in a clinical trial, not necessarily their own, but any study. When asked to elaborate on their hesitation, many said that they would be "concerned about the motivations behind the study, its purpose, its funding, as well as expectations of what participation might entail."[18] Ultimately, only 24% of the respondents said they would be willing to participate with a majority of them stating they would need full transparency and an indication that there would be some personal benefit in order for them to even consider participating. Some had a list of criteria that had to be met. Eleven percent indicated that they would not at all be willing to enroll in a research study. One respondent commented "If it involved taking a medication, no. Never. I would be in a clinical trial if there was something, like...track [your] mammogram…[something] I am already subjecting myself to."[18] Cook and Hoas stated that these answers were "particularly puzzling" because "these respondents still reported that their patient/participants received 'optimal care'" from clinical trials.[18]
Clinical trials
Clinical trials are
Depending on product type and development stage, investigators initially enroll volunteers and/or patients into small pilot studies, and subsequently conduct progressively larger scale comparative studies. Clinical trials can vary in size and cost, and they can involve a single research center or multiple centers, in one country or in multiple countries. Clinical study design aims to ensure the scientific validity and reproducibility of the results.[citation needed]
Trials can be quite costly, depending on a number of factors. The sponsor may be a governmental organization or a
Human subjects in psychology and sociology
Stanford prison experiment
A study conducted by Philip Zimbardo in 1971 examined the effect of social roles on college students at Stanford University. Twenty-four male students were assigned to a random role of a prisoner or guard to simulate a mock prison in one of Stanford's basements. After only six days, the abusive behavior of the guards and the psychological suffering of prisoners proved significant enough to halt the two-week-long experiment.[22] The goal of the experiment was to determine whether dispositional factors (the behavior of guards and prisoners) or positional factors (the social environment of prisons) are the major cause of conflict within such facilities. The results of this experiment showed that people will readily conform to the specific social roles they are supposed to play. The prison environment played a part in making the guards behavior more brutal, due to the fact that none of the participants showed this type of behavior beforehand. Most of the guards had a hard time believing they had been acting in such a way. The evidence concludes this to be positional behavior, meaning the behavior was due to the hostile environment of the prison.[23]
Milgram experiment
In 1961, Yale University psychologist Stanley Milgram led a series of experiments to determine to what extent an individual would obey instructions given by an experimenter. Placed in a room with the experimenter, subjects played the role of a "teacher" to a "learner" situated in a separate room. The subjects were instructed to administer an electric shock to the learner when the learner answered incorrectly to a set of questions. The intensity of this electric shock was to be increased for every incorrect answer. The learner was a confederate (i.e. actor), and the shocks were faked, but the subjects were led to believe otherwise. Both prerecorded sounds of electric shocks and the confederate's pleas for the punishment to stop were audible to the "teacher" throughout the experiment. When the subject raised questions or paused, the experimenter insisted that the experiment should continue. Despite widespread speculation that most participants would not continue to "shock" the learner, 65 percent of participants in Milgram's initial trial complied until the end of the experiment, continuing to administer shocks to the confederate with purported intensities of up to "450 volts".[24][25] Although many participants questioned the experimenter and displayed various signs of discomfort, when the experiment was repeated, 65 percent of subjects were willing to obey instructions to administer the shocks through the final one.[26]
Asch conformity experiments
Psychologist
Robber's Cave study
A classic advocate of
Bystander effect
The
Cognitive dissonance
Human subjects have been commonly used in experiments testing the theory of cognitive dissonance after the landmark study by Leon Festinger and Merrill Carlsmith.[31] In 1959, Festinger and Carlsmith devised a situation in which participants would undergo excessively tedious and monotonous tasks. After the completion of these tasks, the subjects were instructed to help the experiment continue in exchange for a variable amount of money. All the subjects had to do was simply inform the next "student" waiting outside the testing area (who was secretly a confederate) that the tasks involved in the experiment were interesting and enjoyable. It was expected that the participants would not fully agree with the information they were imparting to the student, and after complying, half of the participants were awarded $1 (roughly the same as $10 now), and the others were awarded $20 (like $209 now). A subsequent survey showed that, by a large margin, those who received less money for essentially "lying" to the student came to believe that the tasks were far more enjoyable than their highly paid counterparts.[31]
Vehicle safety
This section relies largely or entirely upon a single source.(December 2020) ) |
In the automotive industry, research has shown that civilian volunteers decided to participate in vehicle safety research to help automobile designers improve upon safety restraints for vehicles. This research allows designers to gather more data on the tolerance of the human body in the event of an automobile accident, in order to better improve safety features in automobiles. Some of the tests conducted ranged from sled runs evaluating head–neck injuries, airbag tests, and tests involving military vehicles and their restraint systems. From thousands of tests involving human subjects, results indicate no serious injuries were persistent. This is largely due to the preparation efforts of researchers to ensure all ethical guidelines are followed and to ensure the safety and well-being of their subjects. Although this research provides positive contributions, there are some drawbacks and resistance to human subject research for crash testing due to the liability of injury and the lack of facilities that have appropriate machinery to perform such experiments. Research with live persons provides additional data which might be unobtainable when testing with cadavers or crash test dummies.[32]
Social media
The increased use of social media as a data source for researchers has led to new uncertainties regarding the definition of human subject research. Privacy, confidentiality, and informed consent are key concerns, yet it is unclear when social media users qualify as human subjects. Moreno et al. conclude that if access to the social media content is public, information is identifiable but not private, and information gathering requires no interaction with the person who posted it online, then the research is unlikely to qualify as human subjects research.[33] Defining features of human subject research, according to federal regulations, are that the researchers interact directly with the subject or obtain identifiable private information about the subject.[2] Social media research may or may not meet this definition. A research institution's institutional review board (IRB) is often responsible for reviewing potential research on human subjects, but IRB protocols regarding social media research may be vague or outdated.[33]
Concerns regarding privacy and informed consent have surfaced regarding multiple social media studies. A research project by Harvard sociologists, known as "Tastes, Ties, and Time", utilized data from Facebook profiles of students at an "anonymous, northeastern American university" that was quickly identified as Harvard, potentially placing the privacy of the human subjects at risk.[34] The data set was removed from public access shortly after the issue was identified.[35] The issue was complicated by the fact that the research project was partially funded by the National Science Foundation, which mandates the projects it funds to engage in data sharing.[35]
A study by
Moreno et al.'s recommended considerations for social media research are: 1) determine if the study qualifies as human subject research, 2) consider the risk level of the content, 3) present research and motives accurately when engaging on social media, 4) provide contact information throughout the consent process, 5) make sure data is not identifiable or searchable (avoid direct quotes that may be identifiable with an online search), 6) consider developing project privacy policies in advance, and 7) be aware that each state has its own laws regarding informed consent.[33] Social media sites offer great potential as a data source by providing access to hard-to-reach research subjects and groups, capturing the natural, "real-world" responses of subjects, and providing affordable and efficient data collection methods.[33][40]
Unethical human experimentation
Unethical human experimentation violates the principles of
Nazi Germany performed human experimentation on large numbers of prisoners (including children), largely
During World War II,
From the 1950s-60s, Chester M. Southam, an important virologist and cancer researcher, injected HeLa cells into cancer patients, healthy individuals, and prison inmates from the Ohio Penitentiary. He wanted to observe if cancer could be transmitted as well as if people could become immune to cancer by developing an acquired immune response. Many believe that this experiment violated the bioethical principles of informed consent, non-maleficence, and beneficence.[49]
In the 1970s, the Indian government implemented a large-scale
Some pharmaceutical companies have been accused of conducting clinical trials of experimental drugs in Africa without the informed consent of participants or without providing adequate access to healthcare. These practices raise questions about the exploitation of vulnerable populations and the prioritization of commercial interests over the rights of participants.[51]
The COVID-19 pandemic has sparked debates surrounding the ethical implications of vaccination efforts. While vaccines are hailed as a crucial tool in combating the spread of the virus, ethical concerns arise when considering issues such as vaccine distribution, access, and equity. In some cases, wealthier nations have been accused of hoarding vaccine doses, exacerbating global disparities in access to essential healthcare resources. Additionally, the emergence of vaccine misinformation and conspiracy theories has further complicated efforts to achieve widespread vaccination. Moreover, the prioritization of certain demographics for vaccination, such as healthcare workers and elderly populations, has raised questions about fairness and social justice. Furthermore, the rapid development and approval of vaccines have led to concerns regarding safety and efficacy, especially in the context of emergency use authorization. The pressure to achieve herd immunity has sometimes resulted in inadequate attention to informed consent and transparent communication about potential risks and benefits. These ethical dilemmas underscore the need for a thoughtful and equitable approach to vaccination during the pandemic, ensuring that public health interventions prioritize the well-being and rights of all individuals.[53]
- Nuremberg Trials)
- Duplessis Orphans
- Genie (feral child)
- Human radiation experiments
- Institutional review board
- Japanese human experimentations
- Medical torture
- Military medical ethics
- Nazi human experimentation
- Non-human primate experiments
- Chester M. Southam's Cancer Injection Study
- Statistical unit
- Unethical human experimentation in the United States
- Vivisection
References
- ^ a b "Definition of Human Subject Research". Research Administration, University of California, Irvine. Retrieved 2012-01-04.
- ^ a b c "What is Human Subjects Research?". University of Texas at Austin. Archived from the original on 2012-02-07. Retrieved 2012-01-04.
- ^ a b c Perlman D (May 2004). "Ethics in Clinical Research a History Of Human Subject Protections and Practical Implementation of Ethical Standards" (PDF). Society of Clinical Research Associates. Retrieved 2012-03-30.
- ^ Human Subject & Privacy Protection, National Institute of Justice, 2010-04-20, retrieved 2012-03-30
- PMID 25790380.
- )
- ^ a b c "Federal Policy for the Protection of Human Subjects ('Common Rule". HHS.gov. 2009-06-23. Retrieved 2019-04-30.
- ^ "Federal Policy for the Protection of Human Subjects". Federal Register. 2017-01-19. Retrieved 2019-04-30.
- ^ "Revised Common Rule". HHS.gov. 2017-01-17. Retrieved 2019-04-30.
- ^ "WMA Press Release: WMA revises the Declaration of Helsinki. 9 October 2000". Archived from the original on September 27, 2006.
- ^ Snežana B (2001). "The declaration of Helsinki: The cornerstone of research ethics". Archive of Oncology. 9 (3): 179–84.
- PMID 17642902.
- ^ a b c "The Belmont Report". HHS.gov. 2010-01-28. Retrieved 2017-04-03.
- ^ a b "MSU Authentication | Michigan State University". ovidsp.tx.ovid.com.proxy2.cl.msu.edu. Retrieved 2017-04-03.
- ^ "The Belmont Report | Institutional Review Board". www2.umf.maine.edu. Retrieved 2017-04-24.
- PMID 27086370.
- ^ a b Shuchman, Miriam. "Protecting Patients in Ongoing Clinical Trials." CMAJ: Canadian Medical Association Journal 182, no. 2 (2010): 124-126.
- ^ S2CID 25139037.
- ^ S2CID 27295875.
- ^ "Clinical Trials" (PDF). Bill and Melinda Gates Foundation.
- ^ United States, Congress, Office of the Legislative Auditor, and James Nobles. A Clinical Drug Study at the University of Minnesota Department of Psychiatry: The Dan Markingson Case. www.auditor.leg.state.mn.us/sreview/markingson.pdf.
- ^ Zimbardo, P.G. (2007). The Lucifer Effect: Understanding How Good People Turn Evil. New York: Random House.
- ^ "Stanford Prison Experiment | Simply Psychology". www.simplypsychology.org. Retrieved 2017-04-03.
- PMID 5724528.
- S2CID 18309531. Archived from the original(PDF) on June 11, 2011.
- ^ Asch SE (1951). "Effects of group pressure on the modification and distortion of judgments". In Guetzkow H (ed.). Groups, Leadership and Men. Pittsburgh, PA: Carnegie Press. pp. 177–190.
- .
- ^ Whitley BE, Kite ME (2010). The Psychology of Prejudice and Discrimination. Belmont, CA: Wadsworth. pp. 325–330.
- ^ ISBN 9780313318214.
- ^ a b Cooper, Joel (2007). Cognitive Dissonance, Fifty Years of a Classic Theory. SAGE Publications.
- ^ Bradford LL (May 1973). Vehicle safety research integration: symposium. Washington: proceedings. Washington: USGPO. pp. 87–98.
- ^ PMID 23679571.
- ^ "Harvard's Privacy Meltdown". The Chronicle of Higher Education. 2011-07-10. Retrieved 2018-04-23.
- ^ S2CID 24881139.
- ^ PMID 24889601.
- ISSN 0362-4331. Retrieved 2018-04-23.
- ^ a b Grimmelmann J (2014-09-23). "Illegal, Immoral, and Mood-Altering". James Grimmelmann. Retrieved 2018-04-23.
- ^ Yarkoni T (2014-06-29). "In defense of Facebook". Retrieved 2018-04-23.
- ^ Watts DJ (2014-07-07). "Stop complaining about the Facebook study. It's a golden age for research". The Guardian. Retrieved 2018-04-23.
- ^ Федоров, Юрий. "Живущие в стеклянном доме". Радио Свобода (in Russian). Retrieved 2015-08-31.
- ^ "Angel of Death: Josef Mengele". Auschwitz website. Retrieved 11 March 2013.
- ^ Mitscherlich A, Mielke F (1992). "Epilogue: Seven Were Hanged". In Annas GJ, Grodin MA (eds.). The Nazi Doctors And The Nuremberg Code - Human Rights in Human Experimentation. New York: Oxford University Press. pp. 105–107.
- ^ ISBN 978-0-8048-3565-7.
- ^ "Hidden history of US germ testing". BBC News. 2006-02-13. Retrieved 2010-05-04.
- PMID 17242525.
- ^ Gray, Fred D. The Tuskegee Syphilis Study, Montgomery: New South Books, 1998.
- United States Department of Health, Education and Welfare
- ^ Skloot R (2010). The Immortal Life of Henrietta Lacks. New York: Broadway Paperbacks. p. 128.
- ^ "India's dark history of sterilisation". BBC News. 2014-11-14. Retrieved 2024-03-23.
- PMID 29736462.
- PMID 29460160.
- PMC 10052847.
Further reading
- AFP (October 31, 2007). "A life haunted by WWII surgical killings". THE BRUNEI TIMES. Archived from the original on 13 December 2014. Retrieved 16 May 2014.
- AFP (Oct 28, 2007). "Japanese veteran haunted by WWII surgical killings". AFP. Archived from the original on March 17, 2014. Retrieved 16 May 2014.
External links
- "Human Research Report" - a monthly newsletter on protecting human subjects
- Nuremberg Code
- Belmont Report
- Declaration of Helsinki, 6th edition
- Universal Declaration on Bioethics and Human Rights by UNESCO
- Hungry Canadian aboriginal children used in government experiments during 1940s Toronto Star, 2013