Researchers who are examining opioid use in pregnant patients face significant ethical complexities when designing study protocols. A group of ethicists examined these issues and concluded an embedded approach to address ethical implications of these studies is needed.1
These researchers are planning a longitudinal investigation, the HEALthy Brain and Child Development (HBCD) Study. This investigation includes pregnant women from regions of the country significantly affected by the opioid crisis.2 Researchers will examine childhood neurocognitive outcomes over a 10-year period after they were exposed to opioid use during pregnancy.
The authors are part of a working group charged with considering the ethical, legal, and social implications of the study. “We began a conversation about how bioethicists can be involved in research, and our discussions led to conceptualizing this paper,” says Camille Nebeker, EdD, MS, co-founder and executive director of the UC San Diego Research Center for Optimal Digital Ethics.
Phase I involved an 18-month planning period to develop the research design and test the feasibility of proposed approaches, including participant recruitment. “The amount of stigma that people experience if they have substance use disorders in pregnancy is substantial,” says Marielle S. Gross, MD, MBE, assistant professor in the department of obstetrics, gynecology, and reproductive services at the University of Pittsburgh Center for Bioethics and Health Law.
Gross says raising important ethical questions is the purpose of the study, such as who is at risk and who is going to benefit. Participants might not realize the study is not going to provide them, or their children, any direct benefit. Since the study is observational, it is viewed as minimal risk, yet the children would undergo MRIs and other longitudinal data collection. “We need to challenge our fundamental assumptions about what is minimal risk research,” Gross asserts.
To make this type of research more ethical, Gross says an intervention should be offered to the participants, since there are known evidence-based interventions to mitigate harm. “Otherwise, we are standing by and observing what happens without providing the known intervention,” Gross says.
As a practicing OB/GYN, Gross finds it ethically problematic to recruit participants for observational studies. The patient may agree to participate because he or she likes and trusts their clinician, or because they feel guilt and shame about their substance use. “The question is: What is it achieving for the population being studied?” Gross asks.
The patients might have been drug-screened without their knowledge, which leads to Child Protective Services visiting their hospital room or home to evaluate their fitness as a parent.
“Anything you do to [patients], such as getting them involved in a study that they believe will benefit their children but really doesn’t, can end up making that person more distrustful and that much less likely to show up to their next visit when they could need a critical clinical intervention or blood pressure monitoring,” Gross cautions.
For the authors, the HBCD study underscores the importance of maintaining a holistic mindset when conducting research on a vulnerable population. “Research ethics does not equal the IRB approval process,” Gross says. “Ethics should be embedded at every level of research.”
The authors wanted to educate researchers about what a research ethicist can offer. “Ethicists can clarify researcher’s obligations and ethical tradeoffs to help determine when the design of study should be modified,” says Seema K. Shah, JD, director of research ethics at Lurie Children’s Hospital in Chicago.
For example, the HBCD study creators needed to ensure they can help participants receive the care and services they need, without confusing participants about the difference between research and clinical care. To do this, each site created a robust referral network for participants’ likely needs.
“Participants should also be told about the contributions to society they can make if they enroll, as that is the one of the main reasons for enrolling in a study like this,” Shah says.
It is important to make the distinction between the role of the IRB and the research ethicist. “We can help IRBs to consider the ethical and social implications, and provide consultation that can lead to a more informed assessment of study risks and appropriate approaches to obtaining informed consent,” Nebeker says.
Studies of participants with opioid use disorders “can be ethically complicated, especially when combined with participants who are pregnant and considered to be a vulnerable population,” says WCG Chief Medical Officer Lindsay McNair, MD, MPH, MSB, co-author of a paper on research about participants living with opioid use disorder.3
Researchers can address several ethical concerns through the informed consent process by carefully designing study protocols. McNair offers these examples:
• Study protocols should outline what steps will be taken to ensure potential participants are not decisionally impaired at the time of the consent discussion. Protocols may specify drug testing to identify substance use that is recent enough to affect mental status and decision-making ability.
“If testing is not feasible, or is negative, clinical assessments should be used to determine that a potential participant comprehends the information provided and is providing voluntary consent,” McNair says.
• Research staff should ask participants to explain study components, or give comprehension quizzes, periodically during the investigation. “This ensures that consent is ongoing,” McNair explains.
• Researchers should avoid fostering paternalism and suppressing the autonomy of potential participants. It is entirely appropriate to make sure participants can make decisions that are free of undue influence or coercion. However, overprotection can occur when researchers limit choices so participants can choose only options that are considered “good,” McNair says.
For example, researchers might provide compensation for study participants’ time and effort. “In a study that includes persons who use opioids, providing that compensation only in the form of grocery store gift cards so that the money can only be used for what the researchers consider ‘good’ purchases is overprotecting a competent adult,” McNair says.
• Study protocols should describe the consent process. Simply providing the consent document is insufficient, according to McNair. Protocols should provide answers to these questions: How are potential participants identified? Where are they approached? How is decisional ability assessed? Who is engaging in the consent discussion?
• Study protocols should address post-study medical risks. For example, in a study of potential opioid use treatment regimens, a participant might use fewer pills during the study, lowering their tolerance level. If the person returns to their previous dosage levels after the study is completed, this could be dangerous.
“IRBs should review all of these issues, as well as the plans to maintain participant privacy and data confidentiality,” McNair says.
REFERENCES
1. Shah SK, Gross M, Nebeker C. Optimizing ethics engagement in research: Learning from the ethical complexities of studying opioid use in pregnancy. J Law Med Ethics 2022;50:339-347.
2. National Institutes of Health. HEALthy Brain and Child Development Study.
3. Anderson E, McNair L. Ethical issues in research involving participants with opioid use disorder. Ther Innov Regul Sci 2018;52:280-284.
Researchers who are examining opioid use in pregnant patients face significant ethical complexities when designing study protocols. A group of ethicists examined these issues and concluded an embedded approach to address ethical implications of these studies is needed.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content