Usually, there is plenty of time for patients or families to decide if they want to be involved in a clinical trial, and there is adequate time for a thorough informed consent process. “It’s a bit different in the ICU,” says Trevor Lane, MD, pulmonologist and critical care fellow at the University of Colorado.

A family member suddenly goes on a ventilator, and the family is immediately asked, “Do you want CPR if the patient goes into cardiac arrest?”

“Then, hours later, they are asked about participation in a research study,” Lane says. “People have information overload.”

What makes it even more challenging is patients often are unconscious and lack decision-making capacity. Therefore, the decision on whether to enroll falls to the patient’s surrogate decision-maker. “The whole process of how informed consent is undertaken in the ICU is very variable,” Lane observes.

Lane and colleagues interviewed surrogates of critically ill patients on ventilators about participation in hypothetical research studies.1 “The motivation is to create the most optimal, ethical informed consent situation,” Lane explains.

In this study, 21 out of 34 surrogates approached agreed to participate. If someone declined to participate, busy research coordinators quickly moved to someone else. “Our study highlights the need to capture more data on why people decline consent,” Lane offers. “This would be tremendously helpful.”

The study’s findings suggest trust is a major factor in decision-making. One surrogate put it this way: “We’ve gone to this hospital for a long time, and if you think it’s a good idea, we’re on board.”

Others said they decided to participate based on the fact the inpatient team thought it was OK for the researchers to approach the family (the treating physician gave permission for the research team to approach the patient or family).

Some surrogates talked about trusting the research would in some way help their loved ones. This revealed a common misconception: If the patient participated, he or she will get better care.

“Of course, we hope that the research we do will result in that. The reality is that often times it doesn’t,” Lane laments. To clear this up, researchers explained it is possible the patient will be randomized to the control group or receive a placebo.

Other surrogates based their decision on the severity of the patient’s condition. “ICU patients are quite sick, and some are near death. The family may think, ‘if there’s a Hail Mary out there, I want to try it.’ Or, they might not want to take any additional risk because things are already so dicey,” Lane says.

Still others wanted to learn about the researchers before deciding. “One surrogate talked about not wanting to be just a number,” Lane recalls.

Sadly, time does not permit this. Participation decisions usually need to be made in one or two days. “Many ICU studies need data from the first day or two of the ICU stay, when patients are first put on ventilators or sepsis patients are first given fluids or antibiotics,” Lane explains.

Many participants expressed a strong sense of altruism. One surrogate talked about how she benefited from research as a pediatric cancer patient, and would not be alive today if it was not for others consenting to research. “We heard from different people that ‘If it’s not very high risk, then it makes sense for me to give back,’” Lane says.

The goal is not to just increase consent rates. “It’s to ensure that this is truly an ethical process, and that surrogates can make the best decision with substituted judgment for the patient,” Lane says.

Surrogate decision-makers are not always immediately available to give consent. Some just do not feel comfortable making the decision to enroll their loved one in clinical research. “Because trial interventions must be started quickly in some cases, decision-making can be further complicated by considerable time pressure,” says William B. Feldman, MD, DPhil, MPH, member of the ethics committee at Brigham and Women’s Hospital in Boston.

Clinical trial investigators must ensure patients and surrogates have ample time to ask questions and understand the proposed research. “Respecting individual autonomy in these acute settings requires both skill and commitment by clinical trial investigators,” Feldman says.

If the potential patient/subject is incapacitated, investigators “need to recognize this subject requires special protections by virtue of their inability to express their autonomous decisions to participate and/or voluntarily withdraw from a study,” says Julie M. Aultman, PhD, director of the medical ethics and humanities program at Northeast Ohio Medical University in Rootstown.

Considering the vulnerability of this population, Aultman recommends these practices for investigators and institutional review boards:

  • The risks and benefits of the study should be weighed carefully, determining whether risks to potential subjects are ethically justified and whether benefits are therapeutically beneficial to subjects.
  • If a study might produce direct, therapeutic benefits, and the patient/subject can consent, he or she should be fully informed about possibly losing capacity at some point to ask questions or voluntarily withdraw. “Then, in such cases, the subject ought to decide whether to permit investigators to continue the therapeutic study while they are incapacitated,” Aultman says.
  • If the subject wishes to participate when he or she becomes incapacitated, there should be a process by which investigators use a waiver of consent or involve a proxy or surrogate decision-maker.
  • If a subject never had capacity to consent at the start of a study, but the study involves interventions that provide direct benefits with minimal risks or risks that are reasonable in relation to the anticipated benefits, then a waiver of consent (for emergency, urgent, or time-critical situations) and/or a designated proxy should be involved.
  • If there is a designated proxy or surrogate decision-maker, that individual should be fully informed at the start of the study and participate in the consent process.
  • It should be noted that next of kin or a surrogate decision-maker may not be able to provide informed consent due to emotional or psychological distress associated with a loved one staying in the ICU. “Some are simply not readily and physically available,” Aultman notes. “Thus, investigators should be mindful that a study might not be able to continue for these reasons.”
  • Investigators should ensure the proxy is acting on behalf of the patient/subject, using substituted judgment or the best interest standard. “The surrogate should not be making decisions based on their own values and interests,” Aultman underscores. 

REFERENCE

  1. Lane T, Brereton E, Nowels C, et al. Surrogate informed consent: A qualitative analysis of surrogate decision-makers’ perspectives. Ann Am Thorac Soc 2021; Feb 2. doi: 10.1513/AnnalsATS.202007-851OC. [Online ahead of print].