2023.08.20 | Questions 54-55
Ethics (3/3) - Human subjects research
Hello,
This post is the third in a 3-part series on ethics. Today’s post focuses on the ethics behind human subjects research.
I am sending my best wishes to everyone who will take (or who already took) the ABGC or ABMGG exam this month.
Please feel free to email with any comments or questions about this post (daniel@studyrare.com) and to share this post with anyone who might find it useful!
-Daniel
Questions
Question 54
A researcher is conducting a study to assess the performance of a new single-gene non-invasive prenatal test (NIPT) in pregnancies affected by fetal hydrops. The target population for the study includes pregnant women receiving care at community clinics who have a reported household income below the federal poverty line. As compensation for their participation, each participant is offered $200 for each of 5 study visits (that each include a peripheral blood draw) as well as $1000 for an amniocentesis. Participants must complete all parts of the study, including the amniocentesis, in order to receive the payment. Which of the following represents the most significant ethical concern in this study?
Question 55
A 23-year-old man with 22q11.2 deletion syndrome develops new-onset hallucinations and delusions. He is subsequently diagnosed with schizophrenia. His symptoms persist despite undergoing standard medical treatment. His psychiatrist, who is the lead investigator in a Phase II, open-label study exploring the effects of electroconvulsive therapy for patients with treatment-resistant schizophrenia, is enthusiastic about the potential benefits of this study. The psychiatrist discusses the study with the patient, who then agrees to enroll in the hope that this new treatment approach will alleviate his symptoms. What is the most significant ethical concern associated with the patient enrolling in this study?
Explanation
Q54: Undue influence
Q55: Therapeutic misconception
Ethical issues with paying research participants (Question 54)
Offering financial rewards to research participants is a common practice that helps increase participant recruitment and compensates individuals for travel costs, lost wages, and (if applicable) the risks involved in the study. However, there are multiple ethical concerns surrounding the payment of research participants. One issue is the potential for undue influence (aka undue inducement) (Question 54), where incentives (often financial) influence a participant’s decision to participate in a study and lead them to make choices they might not make in the absence of payment. Financial incentives may cloud the judgment of research participants, causing them to underestimate potential harms due to the appeal of a financial reward. This concern is amplified when recruiting socioeconomically disadvantaged subjects who may be disproportionately influenced by financial incentives, as was the case in Question 54.
Undue influence should be distinguished from coercion (Choice D), which, according to the Belmont Report, “occurs when an overt threat of harm is intentionally presented” by an investigator in order to secure a person’s participation in a study. When an individual is coerced into participating in a study, informed consent is not possible. Though both coercion and undue influence compromise the process of informed consent, coercion is against the law and is a more serious ethical violation compared to undue influence. A table contrasting coercion with undue influence is below.
Deception (Choice A) involves intentionally misleading or withholding information from research participants about the true purpose or potential risks of a study. In certain contexts (e.g. certain forms of psychology research), deception may be acceptable and necessary to answer a particular research question. Deception is used when knowledge of the true purpose of the research could influence the participants’ behavior. An example of deception would be a researcher telling participants that they performed poorly on a math exam, regardless of their actual performance, to study the effects of negative feedback on heart rate and blood pressure. When deception is used as part of a study, the true purpose of the research should be disclosed to participants after the study is complete (this is called debriefing).
Conflicts of interest (Choice C) are situations where a researcher has a financial or personal relationship that may bias a researcher’s judgment when conducting or reporting research. These conflicts should be disclosed to an Institutional Review Board (discussed further below) as part of the review and approval process for research studies involving human subjects. An example of a conflict of interest is a researcher who owns stock in Pfizer and who is also a principal investigator a Phase I clinical trial that is sponsored by Pfizer. There were no mentions of conflicts of interest in this question stem.
Therapeutic misconception (Question 55)
The most likely ethical concern with the study in Question 55 is therapeutic misconception. Therapeutic misconception occurs when a research participant or investigator inaccurately attributes therapeutic intent to research procedures. Said another way, a patient thinks that by enrolling in a research study, they will clinically improve. The potential for therapeutic misconception is especially important to consider when enrolling patients living with conditions that are progressive and/or degenerative (e.g. amyotrophic lateral sclerosis) or refractory to treatment (e.g. metastatic cancer). In question 55, the patient living with treatment-refractory schizophrenia was eager to enroll in the study and expressed hope that his symptoms would improve as a result of being in the trial. In these cases, a principal investigator may wish to hire a research ethicist to witness the consent process and “curb the enthusiasm” that both patient and clinician express related to participation in the study.
The distinction between receiving individualized care and being a participant in a study designed to answer a research question is fundamental. In clinical care, the physician’s role is to promote the well-being of the patient, whereas in research, the primary aim is to produce generalizable knowledge, regardless of whether the participants in the study benefits from the intervention or not. It is the responsibility of the research team to ensure that the patient fully understands the nature of a clinical trial, including potential risks and benefits, the experimental nature of the treatment (if applicable), and that the primary purpose of the trial is to generate scientific data. In the setting of therapeutic misconception, undue weight may be given to the potential benefits without full consideration of the risks. A complete and balanced understanding of the risks and benefits of a study is critical for ensuring truly informed consent.
Incorrect answers (Question 55)
Protocol deviations (Choice A) occur when an investigator does not implement or follow some aspect of a research study as approved by the IRB. An example of a protocol deviation would be enrolling a participant who did not meet all the inclusion criteria for a study. Research misconduct (Choice B) refers to the fabrication, falsification, or plagiarism in proposing, performing, or reviewing research, or in reporting research results. Privacy violations (Choice C) involves the unauthorized access, use, or disclosure of a research subject’s personal information.
Historical Context Behind Human Subjects Research Ethics
Human subjects research (HSR) refers to scientific investigations that involve human beings as research participants. HSR includes interventional clinical trials that assess the safety and efficacy of medical interventions (e.g. drugs, vaccines, & medical devices), as well as observational studies that seek to understand various aspects of human health and behavior without intervention.
There was a time in the recent past when informed consent and voluntary participation in research studies was not standard practice. Within the last century, unethical human experimentation has been conducted and sponsored by institutions and governments around the world, including in the United States, Japan, and Germany. As a result of these abuses, multiple public and private institutions around the world have developed ethical standards and regulations that govern human subjects research. Ethical standards for human subjects research comes from institutions that conduct research (e.g., hospitals, universities), governments, professional societies, and organizations that fund research.
In the United States, HSR is overseen by an institutional review board (IRB). The IRB is composed of medical professionals, statisticians, researchers, and community advocates. Most institutions that conduct HSR, like hospitals and academic medical centers, have their own IRB to oversee studies conducted within their facilities. The primary role of an IRB is to review human research protocols and to ensure that the benefits of the research outweigh the risks, informed consent is obtained from participants, and the research does not discriminate against any group. The National Research Act, enacted in 1974, requires all federally-funded research to undergo review by an IRB.
Learning objective
Human subjects research is a highly regulated type of research that has faced ethical concerns both in the past and in the present day. These issues include the ethical implications of financial incentives for research participants, the possibility of undue influence, and therapeutic misconception. In the U.S., Institutional Review Boards (IRBs) are responsible for ensuring that research protocols involving human subjects meet commonly accepted ethical standards and adequately protect research participants.
2023 ABMGG General Exam Blueprint | X. Genetic Counseling → c) Ethical issues (page 5)
2023 ABGC Exam Content Outline | Domain 5. Financial/Reimbursement Issues, Resources and Services for Clients, Legal and Regulatory Requirements, and Professional Frameworks → C. Legal and Regulatory Requirements → 5. Standards and regulations for human-subjects research
References
When Does the Amount We Pay Research Participants Become “Undue Influence”?
Bioethical Issues in Providing Financial Incentives to Research Participants