EXECUTIVE SUMMARY

Researchers do not always justify use of exception from informed consent, found a recent study. Other findings include:

• not all studies reported completion of the prestudy regulatory requirements;

• only half of studies reported the FDA investigational new drug/investigational device exemption application;

• less than half reported community consultation and public disclosure.


Obtaining informed consent isn’t possible for patients with life-threatening conditions such as cardiac arrest, hemorrhagic shock, or traumatic brain injury. Thus, these patients often have been excluded from clinical research.

To mitigate this, regulations allowing Exception From Informed Consent (EFIC) or Waiver of Informed Consent (WIC) were developed in 1996.

But how are these actually being used in emergency research? To answer this question, researchers analyzed 28 studies using EFIC or WIC.1

“The motivation for this study was to determine how often and how well EFIC has been used since its availability. 2016 marked the 20th anniversary,” says Michelle H. Biros, MD, MS, professor of emergency medicine and interim chair in the department of emergency medicine at University of Minnesota Medical School in Minneapolis.

The researchers wanted to see if investigators explained why EFIC is justified to answer the study questions. “Research without prospective consent is a sensitive issue,” says Biros. “It is important for investigators to show that EFIC was carefully considered and appropriately applied.”

Not all studies reported completion of prestudy regulatory requirements. Only half of studies reported the FDA investigational new drug/investigational device exemption application. Less than half reported community consultation (46%) and public disclosure (36%). Justification of the need for the use of EFIC and WIC was described in only 46% of publications.

“Although logistical aspects of the EFIC requirements are frequently discussed in primary research papers, the justification for its use is not so well-described,” concludes Biros.

Research using EFIC needs to balance competing ethical principles.

“Two alternative safeguards were created to substitute for prospective informed consent: public notification and community consultation,” says Terri Schmidt, MD, MS, professor emeritus in the department of emergency medicine at Oregon Health & Science University in Portland. The intent was to balance protection of potential subjects with the greater public good of improving care.

“The devil is in the details,” says Schmidt. “We still struggle with the best ways to do community consultation and public notification to meet the intent.” As both an emergency researcher and a healthcare ethicist, Schmidt attended a community consultation meeting for the first study performed at OHSU using EFIC.

“Despite our best efforts, only four people attended the meeting,” says Schmidt. The IRB head indicated that he planned to approve the study, but that better ways to engage the community were needed. “I agreed, and have done a few studies looking at other ways of doing it,” says Schmidt.2,3

Impossible to Attain

Ideally, research participants receive a thorough explanation of risks and benefits, have adequate time to consider these in light of their own personal values and goals, and have any questions answered in a respectful and thoughtful manner.

“There are multiple issues facing the patient and the researcher in the emergency medicine setting that make that ideal impossible to attain,” says Roger J. Lewis, MD, PhD, FACEP, a professor and chair in the department of emergency medicine at Harbor-UCLA Medical Center in Torrance, CA.

The ethical challenge for researchers working in this area is to balance the goals of providing information and fostering patient autonomy, yet still allow important research to be conducted.

“It’s an inconvenient truth that in order to improve the care of patients with acute medical conditions, you have to do research on patients with acute medical conditions,” says Lewis.

Both the patient, who is a prospective research participant, and the population that in the future suffers from the acute condition, have the potential for improved care. “Failing to do the research simply means we are condemning all future generations to receiving the same unproven therapies that we often use today,” says Lewis.

Other ethical issues include the following:

• The patient’s condition may be distracting, anxiety-provoking, or otherwise affect the ability to think clearly.

This is true even for medical conditions that do not directly affect cognition. “This makes it difficult even for the patient to apply their own values to the decision,” says Lewis.

• The dual role of the clinician/investigator in providing care and conducting research makes it difficult to maintain the clear boundaries between clinical care and research that ideally would exist.

• The time frame for treatment may be relatively short.

“This makes it necessary to make a decision quickly about participation, versus receiving standard care for their condition,” says Lewis.

Gaps in Regulations

The regulations specifically state that they are intended for the investigation of therapies for diseases without effective treatments, or where treatments are unproven. “That language, while I believe intentionally vague, has been interpreted by many as not allowing this provision of the regulations to be used when a treatment is often successful, but we are trying to make more modest improvements in outcomes,” says Lewis.

The ethical question: Should regulations apply if effective treatment does exist, but researchers want to further improve outcomes? An example would be a traumatic injury with an 80% survival rate with current treatment. The way the regulations are written, it is unclear whether the EFIC can be used to evaluate a therapy intended to improve the survival rate to 90%.

“There is a tremendous need for clarity in determining the types of therapies for which the exception can be used,” says Lewis. This would allow researchers to broaden its use, to evaluate therapies that are potentially more effective than current treatment.

Whether EFIC can be applied in settings where patients are at substantial risk of poor outcome or death, but most do well, currently is unclear.

“It’s up to the IRB, informed by the processes of community consultation, to determine when the risk/benefit ratio of subjects is sufficiently neutral or positive so it makes sense,” says Lewis.

In some cases, the FDA decided that EFIC could not be used because the majority of people do well with existing therapy, even though there was significant room for improvement in outcomes. “That has made proposed trials infeasible using consent limited to legally authorized representatives,” says Lewis.

At the time the regulations were being drafted, there was a general consensus that it was very important that their use be restricted to the most dire situations. “Researchers now have over two decades of experience with the application of the regulations,” notes Lewis.

A relatively small number of subjects enrolled under the exceptions withdraw or are dissatisfied with their participation. In light of this, argues Lewis, “It’s time to consider broadening the scope of therapies that can be evaluated under the exceptions.”

REFERENCES

1. Klein L, Moore J, Biros MA. 20 year review: The use of exception from informed consent and waiver of informed consent in emergency research. Acad Emerg Med 2018 Apr 21. doi: 10.1111/acem.13438. [Epub ahead of print]

2. Bulger EM, Schmidt TA, Cook AJ, et al. The random dialing survey as a tool for community consultation for research involving the emergency medicine exception from informed consent. Ann Emerg Med 2009; 53(3):341-350.

3. Nelson M, Schmidt TA, Delorio NM, et al. Community consultation methods in a study using exception to informed consent. Prehosp Emerg Care 2008; 12(4):417-425.

SOURCES

• Michelle H. Biros, MD, MS, Professor, Emergency Medicine/Interim Chair, Department of Emergency Medicine, University of Minnesota Medical School, Minneapolis. Phone: (612) 626-5961. Email: biros001@umn.edu.

• Roger J. Lewis, MD, PhD, FACEP, Chair, Department of Emergency Medicine, Harbor-UCLA Medical Center, Torrance, CA. (310) 222-6741. Email: roger@emedharbor.edu.

• Terri Schmidt, MD, MS, Professor Emeritus, Department of Emergency Medicine, Oregon Health & Science University, Portland. Phone: (505) 494-8311. Email: schmidtt@ohsu.edu.