Ethical Concerns for Study Participants with Opioid Use Disorder

By Stacey Kusterbeck

Individuals with opioid use disorder are a vulnerable population who face some unique risks when participating in research.

However, protections for study participants with opioid use disorder are rarely mentioned in institutional review board (IRB) oversight, according to a recent paper.¹

“Working for this patient population with opioid use disorder and/or with pain, has been my life’s work. Discussing their vulnerabilities was a catalyst for writing this article,” says Barbara St. Marie, PhD, AGPCNP, FAANP, FAAN, an associate professor at University of Iowa’s College of Nursing.

Thus far, vulnerabilities have been defined in federal regulations to include children, prisoners, individuals with impaired decision-making capacity, or economically or educationally disadvantaged individuals. The authors wanted to draw attention to the vulnerabilities of the population with opioid use disorder and how these risks of vulnerability can be mitigated in research.

“What we do not want is an increase in burden resting on the participants with opioid use disorder with very little benefit to their population,” says St. Marie. Consent-based vulnerabilities exist in people with opioid use disorder when there is impaired rational decision-making, or if it is assumed that everyone within this population has impaired rational decision-making. “Everyone is unique and decisional capacity needs to be individually determined. What we do not want is to stigmatize or create marginalizing images of individuals with opioid use disorder,” says St. Marie.

People with opioid use disorder must be included as participants in research because they are the ultimate stakeholders who can benefit from findings from these scientific investigations, emphasizes co-author Esther Bernhofer, PhD, MA, RN, an associate professor at Frances Payne Bolton School of Nursing.

Nurse practitioners may be recruiting their own patients for research studies, which raises some additional ethical concerns, the authors add. Researchers who recruit from their own patients should be aware of any coercion or undue influence.

“There is a power imbalance between healthcare provider and patient, and healthcare providers who perform research and recruit from their own patients need to be aware of the power imbalance,” says Bernhofer. Patients may feel obligated to volunteer for the study to please the provider.

“The goals of clinical care and of research are different regarding the patient with opioid use disorder,” notes Bernhofer. However, in either situation the well-being and safety of the individual patient/participant is the priority. The authors suggest that IRBs ask these questions when reviewing study protocols:

• Is the opportunity to participate equal for everyone who could qualify for the study?

• Do prospective participants feel that the relationship with their healthcare provider will change if they do not volunteer for participation?

• Who is doing the recruitment and enrolling in the study?

• Is the provider/researcher blinded to the identity of those who participate?

• Would it help to involve people with opioid use disorder, or people in recovery, in the design of the study?

Stigma can result in people concealing opioid use disorder when enrolling in a clinical trial. “Great progress has been made in destigmatizing this disorder and passing laws that do not criminalize the disorder itself,” acknowledges Ryan Spellecy, PhD, Ursula von der Ruhr professor of bioethics and director of the Human Research Protection Program at Medical College of Wisconsin. However, persons with opioid use disorder still face legal risks in some jurisdictions. Disclosing their disorder in the course of research could increase those legal risks. This raises safety concerns, since research staff will have an inaccurate medical history for the participant. There could be drug interactions, side effects, and other safety precautions in the study.

Coercion is another ethical concern. “If clinicians enroll their own patients as participants in a research study, the risk of the perception of coercion is high,” says Spellecy. According to the Common Rule, researchers are obligated to ensure that there is not even a perception of coercion from the person enrolling in the study.²

Some patients might feel compelled to participate if their clinician is trying to recruit them into a study, for fear of being discharged from treatment.

“This can be difficult, given how hard it can be to find treatment for opioid use disorder,” says Spellecy. To mitigate this, clinicians should be very clear that the patient’s current care will not be affected in any way based on the decision of whether to participate in the study.

IRBs should be looking closely at these factors, says Spellecy:

• Who is obtaining consent. If possible, clinicians should have someone else approach the patient about enrolling in the study. “It is common for research staff members to do this, to keep the distinction between research and clinical care as clear as possible,” says Spellecy.

• The setting in which it is obtained. If possible, the consent conversation should take place somewhere other than where the patient received clinical care. “Simply moving from a clinical exam room to a small conference room down the hall can help preserve those lines between research and clinical care,” Spellecy suggests.

• How much time potential participants will have to decide. Ideally, people can take the consent form home and discuss it with friends or family, for instance.

Ethical concerns over patients feeling pressured by their clinicians to participate in a clinical trial is not unique to people with opioid use disorder. For instance, concerns have been raised that patients with cancer may be hesitant to decline participation if their own oncologist asks them to be in a clinical trial.³

Researchers also need to determine if it is appropriate to exclude people with opioid use disorder from participating. For studies on addiction treatment interventions or studies looking at whether certain medications have addiction potential, people with opioid use disorder are the most appropriate population to include, says Lindsay McNair, MD, MPH, principal consultant at Equipoise Consulting.

For other clinical trials, there are safety concerns because of the potential for drug interactions, non-adherence to the study drug regimen, or the study visit schedule. “But if safety is not an issue, then people with opioid use disorder should be considered as possible study participants and not automatically excluded, especially if the intervention being tested is one that will likely be used in people with opioid use disorder,” says McNair.

McNair advises that researchers take these steps to ensure ethical informed consent of potential study participants with opioid use disorder:

• Specify that no potential participants should be approached about the study, or asked to consent to participation, when they are intoxicated or going through withdrawal. Study protocols should state that research staff will screen potential participants for symptoms of intoxication and withdrawal. “This may also apply to specific points in the study where consent is required for invasive tests or other procedures,” says McNair.

• Recognize that while persons with opioid use disorder may have periods of diminished capacity and decisional impairment, that does not mean that they have lost their right to autonomy.

• Avoid incentives that could force certain behaviors from persons with opioid use disorder. For example, researchers should not block or decrease compensation or limit the methods of compensation (such as payment by grocery store gift cards instead of cash) to try to prevent participants from making what the IRB considers to be bad decisions about how money is spent. “This is paternalistic and inconsistent with the Belmont Report’s principle of respect for persons,” explains McNair.

REFERENCES

1. St Marie BJ, Bernhofer EI. Ethical considerations for nurse practitioners conducting research in populations with opioid use disorder. J Am Assoc Nurse Pract 2024; Apr 24. doi: 10.1097/JXX.0000000000001020. [Online ahead of print].
2. 45 CFR 46.116.
3. Morain SR, Barlevy D, Joffe S, Largent EA. Physician-investigator, research coordinator, and patient perspectives on dual-role consent in oncology: A qualitative study. JAMA Netw Open 2023;6:e2325477.