If someone is in the ED with cardiac arrest or severe traumatic injury, he or she is unlikely to be able to make well-reasoned decisions about study participation. Thus, some clinical trials in the emergency setting are conducted under an exception from informed consent (EFIC).
“Research is needed to help improve outcomes in patients with terrible conditions, such as cardiac arrest, strokes, and profound trauma, where it’s simply not possible to obtain consent for research interventions that have to be delivered quickly due to patients’ clinical needs,” says Jeremy Sugarman, MD, MPH, MA, professor of bioethics and medicine at the Johns Hopkins University Berman Institute of Bioethics.
Any research conducted under the EFIC falls under many strict requirements. Anyone who is included in an EFIC study (or their legally authorized representative) must be notified about their enrollment as soon as it is feasible. This gives the enrolled patient the chance to either consent to continued participation or opt out.
Sugarman and colleagues analyzed data from 35,442 patients enrolled in five trials over a 12-year period conducted under the EFIC.1 They found wide variation in time to notification. “IRBs made different interpretations regarding when and how notification may happen, perhaps due to local norms and practices or their interpretation of the relevant regulations,” Sugarman reports.
For 33,805 patients who experienced cardiac arrest, time to notification ranged from a median of six to 28 days. For 1,636 patients with traumatic injury, time to notification ranged from zero days to 36 days. “While some of this variability may be reduced with single IRBs, understanding local contexts and being sensitive to the clinical situation of patients is essential,” Sugarman stresses. Investigators conducting research under EFIC must plan for the notification process and ensure they have adequate resources to do it.
Only 7.7% of patients with traumatic injury withdrew from studies after they were notified. For patients with cardiac arrest, the rate was just 0.3%. “It was comforting to see that only a small proportion of those who were enrolled under EFIC opted out of continued participation,” Sugarman shares.
The most challenging ethical question with emergency research centers on the patient’s ability to adequately understand the voluntary nature, risks, and potential benefits of participating, according to Roger J. Lewis, MD, PhD, a professor in the department of emergency medicine at Harbor-UCLA Medical Center. Even if patients are awake and can participate in a consent discussion, “their ability to truly think about their decision regarding participation may be severely impacted by their concerns regarding their emergent medical condition,” Lewis says.
Previous research demonstrated that patients undergoing evaluation for potentially life-threatening emergencies (including traumatic injuries and myocardial infarction) have markedly diminished cognitive capacity.2
“Thus, I see a large risk in the consent processes related to studies for emergency conditions in which there is the appearance of voluntary informed consent, but the patient is sufficiently compromised,” Lewis says.
If patients worry declining to participate could affect their treatment negatively, this creates a coercive environment. “Investigators and IRBs alike should think carefully about alternative consent procedures,” Lewis argues.
Researchers could give markedly reduced quantities of information to prospective participants, and follow up with more comprehensive information on the research study later. “IRB members, especially those who haven’t personally participated in the consent process in true emergency situations, may not appreciate the difficulty in communicating the key elements of informed consent in that setting,” Lewis notes.
That causes some IRBs to fall back on the “default” of insisting everyone use standard consent procedures. “In doing so, the IRB can give the false impression of an ethical consent process that simply isn’t,” Lewis cautions.
IRBs must determine if clinical trials meet EFIC criteria. “The regulations, which I personally believe are brilliant in the way they’re worded, lay out key elements to be considered by the IRB,” Lewis says.
To meet EFIC criteria, studies must involve therapies for truly life-threatening conditions for which there is no acceptable and generally effective therapy. There must be a detailed plan in place for obtaining consent for continued participation from a legally authorized representative (when one is available in time) and also for obtaining consent from participants (should they recover and be able to participate in a consent discussion for continued participation).
“In my view, these regulations lay out a very clear path through which IRBs can consider the benefits, risks, and ethical balance of research in emergency settings, and, therefore, reach reasonable decisions even when the patient cannot participate in the discussion,” Lewis offers.
But there is an important gap. Emergent conditions can make it impossible for patients to participate meaningfully in a consent discussion; sometimes, the condition does not meet the specific requirements of EFIC. This happens with acute myocardial infarction, severe traumatic injuries, stroke, and extremely painful conditions.
EFIC regulations require the condition to be life-threatening. Existing therapies must be ineffective or unproven. “That latter requirement is a bit subjective, but many consider our treatments for traumatic injuries; myocardial infarction; and, more recently, stroke to be established and demonstrated to be at least partially effective,” Lewis notes.
The EFIC regulations envision a person who is unconscious because of illness or injury. For some medical conditions, people may appear to be awake and able to participate in a discussion regarding enrollment. “But more careful examination shows that you aren’t really processing the information and making an informed decision the way consent is supposed to work in non-emergency settings. This is, I think, the biggest challenge for IRBs considering emergency research protocols,” Lewis says.
The task for IRBs is to find research consent processes that protect and preserve patients’ autonomy to the extent possible, while also allowing medical progress to occur and giving participants access to potentially beneficial therapies. IRB members often want everything to fit neatly into the regulations so there is no question the law supports the consent process.
“But some things don’t fit, and figuring out how to apply ethical principles appropriately for the benefit of society requires a more creative process than just following the rules,” Lewis says.
The rules do allow IRBs to alter the consent process based on the risk level and potential benefits of the trial (e.g., orally presenting information from a short form consent document). “The regulations actually give the IRB quite a bit of flexibility,” Lewis observes. “The difference is whether IRBs choose to use that flexibility or to pretend they don’t have it.”
REFERENCES
- Nichol G, Zhuang R, Russell R, et al. Variation in time to notification of enrollment and rates of withdrawal in resuscitation trials conducted under exception from informed consent. Resuscitation 2021;168:160-166.
- Dickert NW, Fehr AE, Llanos A, et al. Patients’ views of consent for research enrollment during acute myocardial infarction. Acute Card Care 2015;17:1-4.
Find consent processes that protect and preserve patients’ autonomy to the extent possible, while also allowing medical progress to occur and giving participants access to potentially beneficial therapies. Doing so may require
a more creative process than just following the rules.
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