Communicating with Communities about Emergency Research

The challenge of effectively communicating with communities about research is particularly salient for investigators who are conducting emergency research with an exception from informed consent. The authors discuss the ethical basis for the community consultation requirement and describe the nature and extent of the consultative process required to achieve these ethical purposes. The findings of the consensus conference are summarized as follows. 1) The requirements for community consultation and public disclosure for exception from informed consent studies serve important ethical purposes and should be retained. 2) Community consultation allows investigators and institutional review boards to obtain input from the community regarding planned research. The process serves to facilitate understanding, promote trust, ensure justice, and protect research participants. 3) Community consultation is a process that requires active participation by community members; however, it does not require their approval, consent, or consensus. The practical challenges involved in conducting meaningful community consultation are also discussed: defining the community and its appropriate representatives, methods to actively engage the community, the lack of uniformity among institutional review boards in required community consultation activities, and the lack of measures to evaluate the adequacy and appropriateness of community consultation. The recommendations of the consensus conference regarding future research about community consultation are summarized. Priorities include identifying best practices; defining effectiveness and developing measures to evaluate community consultation; evaluating alternative models and potential infrastructures to facilitate, conduct, and/or oversee effective community consultation processes; and developing educational modules for community members to empower their active participation in discussions about emergency research in their communities.     

The Research on Community Consultation: An Annotated Bibliography

Community consultation is a required element of research studies that use a waiver of or exception from informed consent. Its intent is to provide an additional patient safeguard in emergency research circumstances when prospective informed consent is not possible. Investigators have reported that community consultation may be the most difficult aspect in implementing research trials using a wavier of or exception from informed consent. This article presents a brief overview of the sparse literature available on the process of community consultation since the inception of the current emergency research regulations. To determine if the process is meeting its goals, more research will be required.     

An Approach to Community Consultation Prior to Initiating an Emergency Research Study Incorporating a Waiver of Informed Consent

OBJECTIVES: In November 1996, the Food and Drug Administration (FDA) and the Department of Health and Human Services (DHHS) enacted rules allowing a narrow exception to the requirement for prospective informed consent when enrolling critically ill patients in clinical research studies of emergency treatments. These rules require that, prior to initiation of the study, the applicable institutional review board (IRB) assess the acceptability of the proposed research study to members of the community in which the research will be conducted. Specifically, the IRB must perform community consultation-a process during which community members learn about the proposed research and communicate their opinions regarding its acceptability to investigators or IRB representatives. The FDA and DHHS rules do not define specific acceptable methods for performing this community consultation. The objective of this study is to demonstrate the feasibility and utility of one proposed method for performing such community consultation. METHODS: Parents of children being seen for minor traumatic injuries in three pediatric EDs were asked to participate in a study regarding informed consent. After consent, an instructor described to the parent a prospective, randomized, placebo-controlled trial of phenytoin for the prophylaxis of posttraumatic seizures in children with severe closed head trauma. All parents were then asked whether they would have consented for their own child's participation, if their child had suffered such head injury. The parents were further asked to explain the reason(s) for their responses. RESULTS: Parents of 227 children (children's mean +/- SD age 8.0 +/- 4.8 years, 57% male) were interviewed. Sixty-six percent of parents (149/227) stated they would give consent for their child's participation. Of the 149 consenting parents, 85% (126/149) cited potential benefit to their child, 72% (107/149) cited potential benefit to other children, and 60% (90/149) cited furthering medical knowledge. Of the 78 nonconsenting parents (34% of total), 54% (42/78) cited fear of adverse effects, 39% (30/78) did not want their child to be a research subject in general, 27% (21/78) believed they needed to discuss participation with family members who were unavailable, and 26% (20/78) stated they were unable to decide unless they were in the actual situation. Parental ethnicity and household income were found to influence the consent decision, while the parent's gender, religion, language, and educational level were not associated with the consent decision. CONCLUSIONS: Community consultation regarding the acceptability of an emergency research protocol can be obtained via interview techniques in the ED. This methodology may allow investigators to obtain data on opinion from a targeted community for IRB consideration during the review of emergency research studies proposing a waiver of informed consent.     

Using the Exception from Informed Consent Regulations in Research

This article reflects the proceedings of a breakout session, “Using the Regulations in Research” at the 2005 Academic Emergency Medicine Consensus Conference, “Ethical Conduct of Resuscitation Research.” There have been two organized studies, and a number of anecdotal reports, describing the decline in cardiac arrest resuscitation research in the United States since the implementation of the Final Rule. Paradis and colleagues found that the volume of human cardiac arrest research published in the United States was significantly less in a four‐year period after the Final Rule was adopted as compared to the earlier period. Nichol and colleagues reported that both the absolute number of US‐based randomized cardiac arrest trials and the proportion of US‐based trials (vs. foreign trials, based on the mailing address of the first author) decreased by about 15% annually. Despite the concern about a negative impact, there are at least five published trials, one in progress and one in planning that have been or are being conducted under the regulations. Those completed include the Diaspirin Cross‐Linked Hemoglobin, Public Access Defibrillation, Multicenter Vest CPR, Brain‐CPR, and Pre‐Hospital Treatment of Status Epilepticus trials. Reports of how investigators met the regulations and their experience in doing so are reviewed. A summary table of the federal regulations is provided. Participants discussed what additional information and research about using the regulations would be helpful for the promotion of quality resuscitation and emergency care research in the United States. Areas suggested for further investigation include: impact on the quality as well as quantity of such research; current level of understanding of the regulations by investigators, regulatory/IRB personnel and potential subjects (the general public); costs incurred: additional time required for preparation, approval and conducting community consultation and public disclosure; impact on research on non–life‐threatening conditions; value and cost of a registry; use of a standard reporting template for issues regarding meeting the requirements in individual clinical trials; whether more specific guidance would be helpful or restrictive; what constitutes effective community consultation and public disclosure; and whether titration of community consultation and public disclosure based on the risk of the proposed intervention to subjects is feasible and acceptable.     

Resuscitation Research Involving Vulnerable Populations: Are Additional Protections Needed for Emergency Exception from Informed Consent?

The application of basic ethical principles to resuscitation research and other research in the emergency and critical care settings presents a particular challenge. The emergency exception from informed consent (EFIC) rule (21 CFR 50.24 and 45 CFR 46.101[i]) addresses a particular vulnerability: that which occurs when persons cannot consent due to acute loss of decisional capacity. The question arises as to whether populations defined as “vulnerable” are unique within studies to which EFIC applies. This report details the proceedings of a breakout session of the 2005 Academic Emergency Medicine Consensus Conference, “Ethical Conduct of Resuscitation Research,” that dealt with this issue. Topics addressed were 1) the applicability of the term “vulnerable” in research using EFIC; 2) the relationship between vulnerability, exploitability, and capacity; 3) the significance of vulnerability in research design; 4) the adaptation of the informed consent process to the emergency setting; and 5) the role of the institutional review board. Ten consensus recommendations emerged from the discussion. Of particular importance was the endorsement of the idea that research using EFIC is as important in vulnerable populations as in the general population and that the systematic exclusion of vulnerable populations from resuscitation research is inappropriate.     

Research Conditions That Qualify for Emergency Exception from Informed Consent

Medical research involving critically ill and injured subjects unable to provide informed consent can only be conducted under federal regulations that attempt to balance the need to develop lifesaving treatments with protection of research subjects' rights. Regulators, researchers, and medical ethicists have all struggled to define the conditions under which an emergency exception from informed consent is appropriate. Although research has been successfully conducted under the current regulations, confusion remains regarding the meaning of the regulations, the applicable conditions, and the best ways to balance the needs of future patients and the rights of research subjects. In May 2005, at the Academic Emergency Medicine Consensus Conference “Ethical Conduct of Resuscitation Research,” a breakout session was held on the research conditions that qualify for the emergency exception from informed consent process. Several recommendations emerged: 1) The definition of “life‐threatening condition” should be broadly interpreted to include serious disability as well as death. 2) Existing therapies should be considered “unsatisfactory,” even if partially effective, when serious risk of morbidity or mortality remains even with the best available treatment or when the adverse effects of the best available treatment are serious. 3) Research with the emergency exception should be performed only if sufficient evidence exists that the proposed intervention has a reasonable chance of benefit. 4) More evaluation is needed to determine the degree to which the current rules impede research. 5) Application of the current regulatory framework for abbreviated or waived consent in emergency research should be encouraged. 6) Further study should also address variability among institutional review boards, the goals of community involvement, and how best to engage and educate the public in research efforts using emergency exception from informed consent.     

Implementing the Food and Drug Administration's Final Rule for Waiver of Informed Consent in Certain Emergency Research Circumstances

In 1996, the Food and Drug Administration released its Final Rule for Waiver of Informed Consent in Certain Emergency Research Circumstances (the Final Rule). The Department of Health and Human Services (DHHS) also released an update of its regulations related to waiver of informed consent in emergency research. These new regulations allow resuscitation research to proceed with a waiver of informed consent under very narrow and specific clinical research circumstances. Waiving informed consent for research participation has profound ethical and scientific implications. However, in unpredictable life-threatening clinical situations for which current therapy is unproven or unsatisfactory, patients usually are unable to consent on their own behalf to participate in clinical trials of potentially beneficial but experimental interventions. Because of the time-dependent nature of most resuscitation interventions, it is usually not feasible to identify and contact the legally authorized representative who can speak on behalf of the patient within the presumed therapeutic window of the intervention under investigation. For such clinical trials to proceed, a waiver of informed consent is usually necessary. Patients who are critically ill or injured and unable to provide meaningful prospective informed consent because of their current life-threatening condition are vulnerable and require additional protections beyond those for research subjects who can speak on their own behalf. The Final Rule and the DHHS-updated regulations incorporate a number of additional patient safeguards that must occur if a clinical trial is to proceed with waiver of informed consent. Specific means of adequately meeting these requirements are not described in the regulations. Although this was intentional on the part of the federal regulators so that individual protocols and research environments would direct the development of these patient safeguards, the lack of specific guidance has led to confusion on the appropriate implementation of the new regulations. This article reviews some of the key concepts of the Final Rule, with suggestions on their purpose and meaning. It also reviews the studies that have been approved to date to proceed with waiver of informed consent, and offers suggestions for the process of implementing the requirements of the Final Rule for research involving patients who are unable to give prospective informed consent.     

Attitudes of Emergency Department Patients and Visitors Regarding Emergency Exception from Informed Consent in Resuscitation Research, Community Consultation, and Public Notification

OBJECTIVE: To assess public views on emergency exception to informed consent in resuscitation research, public awareness of such studies, and effective methods of community consultation and public notification. METHODS: A face-to-face survey was conducted in two academic Level I trauma center emergency departments (EDs) in Oregon and Minnesota from June through August 2001. RESULTS: Five hundred thirty people completed the survey, with an 82% response rate. The mean age of the respondents was 41 years (range 18-95) with a standard deviation of 14.5; 46% were female and 64% white. Most (88%) believed that research subjects should be informed prior to being enrolled, while 49% believed enrolling patients without prior consent in an emergency situation would be acceptable and 70% (369) would not object to be entered into such a study without providing prospective informed consent. Informing and consulting the community as a substitute for patient consent in emergency research was thought to be reasonable by 45% of the respondents. Most respondents would prefer to be informed about a study using emergency exception from informed consent by radio and television media (42%). Two hundred fifty-eight respondents (49%) stated they would attend a community meeting; the less educated were more likely to attend than those with college degrees (OR = 0.53; 95% CI = 0.33 to 0.85, p = 0.008). However, only 5% knew of ongoing studies in their community using emergency exception from informed consent. CONCLUSIONS: Most respondents disagreed with foregoing prospective informed consent for research participation even in emergency situations; however, many would be willing to participate in studies using emergency exception from informed consent. Most respondents would not attend community meetings, and would prefer to rely upon the media for information. Very few were aware of emergency exception from informed consent studies in their community. This suggests that current methods of community notification may not be effective.     

Community attitudes towards emergency research and exception from informed consent

Objective

To determine public attitudes towards emergency research, exception from informed consent (EFIC) and a specific proposed clinical trial using EFIC.

Methods

As part of a planned community consultation activity, a survey was conducted at a popular public venue. Participants answered demographic questions and then were asked their opinions on specifically described consent circumstances in emergency research, including the proposed EFIC trial. Multiple logistic and linear regression were used to determine respondent characteristics associated with specific attitudes.

Results

1901 surveys were completed. The majority of respondents supported emergency research (88%) and the concept of surrogate consent by a legally authorized representative (78%). The concept of EFIC was less well supported (35%) but the application of EFIC was more accepted, especially when EFIC was applied to the respondent themselves (51%). The community believed the proposed EFIC study was acceptable (82%); a minority had concerns but most were related to patient safety and not to EFIC. Respondents with less education and lower incomes were less likely to express opinions about the consent and research concepts described.

Conclusions

Emergency research and the proposed EFIC trial is supported in this community. The concept of EFIC is less well supported but is more acceptable when a specific trial is described or when respondents consider EFIC for themselves. Specific respondent characteristics are associated with attitudes about research; this can assist in development of meaningful community consultation activities.     

Emergency Medicine and the Development of the Food and Drug Administration's Final Rule on Informed Consent and Waiver of Informed Consent in Emergency Research Circumstances

This article reviews the federal regulations for emergency and acute resuscitation research in effect prior to October 1996, the historical issues that contributed to the development of these regulations, the controversies that arose surrounding the application of these regulations to emergency research circumstances, and the methods by which the regulations were changed. The new regulations introduced by the U.S. Food and Drug Administration (FDA) also are reviewed.     

Informed Consent and Ethical Issues in Military Medical Research

Informed consent in military research shares many of the same fundamental principles and regulations that govern civilian biomedical research. In fact, much of modern research ethics is grounded in events that occurred in the context of war or government‐sponsored research. Despite these similarities and common origins, research in the military has additional requirements designed to preserve service members' informed consent rights. The special nature of the superior–subordinate relationship in the military necessitates careful protections to avoid perceptions of coercion or undue influence on a military subject. Additionally, current legal and regulatory requirements for advanced informed consent significantly restrict the flexibility of the military to conduct research using waiver of consent. This has implications on the ability of the nation to develop effective medical treatments for the global war on terrorism. Nevertheless, work is under way to realign defense research policy with the norms of civilian biomedical practice. Future directions include the adoption of waivers for military emergency research, and the cautious introduction of human subject studies on the battlefield. This paper discusses historical background, regulatory differences, and concerns and challenges of some of these regulatory differences for research personnel that apply to informed consent and waiver of said informed consent for emergency research conducted by the U.S. military.     

Exception from Informed Consent: Viewpoint of Institutional Review Boards—Balancing Risks to Subjects, Community Consultation, and Future Directions

Differences in interpretation of the Final Rule for exception from informed consent (EFIC) requirements for emergency research result in inconsistencies in implementation and difficulties for some institutional review boards (IRBs) to approve such research. During a consensus workshop organized by the editorial board of Academic Emergency Medicine, participants discussed how IRBs balance the risks to human subjects in EFIC research, the conduct of community consultation and its role in IRB decision making, and future directions to improve and research EFIC effects. Areas of consensus and diversity of opinion were identified. During the workshop, the National Institutes of Health model of consensus building was used to develop statements pertaining to specific questions of the effects, directions, implementation, and ultimate goals for emergency research using EFIC. The program was composed of an overview of the history and issues related to EFIC or Final Rule research and presentations of viewpoints of experts in this area of research. A final consensus was developed regarding the major topics, including IRB perspective, effective community consultation (often considered the main difficulty in implementing EFIC research), and goals for future directions and research on the topic. Roundtable discussions and breakout sessions involving interested parties were used as a format. In regard to how IRBs balance risks, by consensus it was agreed the regulations stipulate that EFIC studies must involve treatment that is unproven or unsatisfactory. The committee agreed that resuscitation rates are currently unsatisfactory, and thus current treatments are unsatisfactory. Many treatments currently used as standard care have never been proven to be effective. IRBs and the public need education that resuscitation research is needed. The same can be said for other conditions to which this rule applies. Because IRB expertise differs across the country, a group of peer reviewers to act as consultants should be available to help IRBs determine if current treatment for a condition is unproven or unsatisfactory. In regard to community consultation, the experiences of others are important and helpful as guidance. The amount and formats of community consultation should correspond to the amount of risk involved in the study proposed. In regard to future directions, communities should be asked how they define “success” of community consultation and public disclosure. Research on community attitudes is critical. Ways to continue/add to research include the following: research including major National Institutes of Health/Centers for Disease Control and Prevention funding acquisition for evaluation of the clinical impact of EFIC research; education for research funding agencies about emergency research, including current outcomes (e.g., survival rates); participation of emergency medicine researchers in meetings of research ethicists/IRB members (Public Responsibility in Medicine and Research/Applied Research Ethics National Association); publication of experiences and of the effects of EFIC research; future update meetings such as this one at the Society for Academic Emergency Medicine meeting; and more membership on IRBs of emergency physicians. While IRBs must approve EFIC research based on their own local environment, additional guidelines from regulatory agencies may be helpful. In general, current treatments for EFIC conditions are unsatisfactory and many are unproven. A group of peer reviewers can act as consultants to IRBs that do not have this expertise.     

Understanding Exception from Informed Consent in Planned Emergency Research

Many of the current accepted treatment practices provided to patients in the first critical hour after a traumatic injury, stroke, or cardiac arrest have not been rigorously tested in clinical research trials. The inability to obtain informed consent is often a barrier to research in emergency, time-sensitive situations in which the patient is not able to provide informed consent nor is their family member immediately available to provide consent on behalf of the patient. Planned emergency research, often with exception from informed consent, is a type of research study that involves a patient with a life-threatening medical condition that requires urgent interventions, wherein the current treatments may be unproven or suboptimal, and who, because of their current condition, is unable to provide informed consent. This article summarizes the necessary components for using exception from informed consent in planned emergency research. Understanding the research design, particularly research processes specific to time-critical emergency situations, will ensure that the care provided by stretcher-side emergency nurses will result in optimal patient outcomes and is an integral aspect of emergency nursing practice.     

Informed Consent for Research: Current Practices in Academic Emergency Medicine

Background:  The emergency department (ED) environment presents unique barriers to the process of obtaining informed consent for research.
Objectives:  The objective was to identify commonalities and differences in informed consent practices for research employed in academic EDs.
Methods:  Between July 1, 2006, and June 30, 2007, an online survey was sent to the research directors of 142 academic emergency medicine (EM) residency training programs identified through the Accreditation Council for Graduate Medical Education (ACGME).
Results:  Seventy-one (50%) responded. The average number of simultaneous clinical ED-based research projects reported was 7.3 (95% confidence interval [CI] = 5.53 to 9.07). Almost half (49.3%) of respondents reported that EM residents are responsible for obtaining consent. Twenty-nine (41.4%) participating institutions do not require documentation of an individual resident's knowledge of the specific research protocol and consent procedure before he or she is allowed to obtain consent from research subjects.
Conclusions:  It is common practice in academic EDs for clinical investigators to rely on on-duty health care personnel to obtain research informed consent from potential research subjects. This practice raises questions regarding the sufficiency of the information received by research subjects, and further study is needed to determine the compliance of this consent process with federal guidelines.     

The Informed Consent Process and the Use of the Exception to Informed Consent in the Clinical Trial of Diaspirin

In the clinical trial of diaspirin crosslinked hemoglobin (DCLHb), optimal therapy required the immediate enrollment of patients with severe, uncompensated, traumatic hemorrhagic shock. When it was not feasible to obtain prospective consent, an exception to informed consent was used according to FDA regulation 21 CFR 50.24. Objectives: To examine the informed consent process and the use of the consent exception and consent to continue (CTC), and to describe the patients for whom this process was used. Methods: This was a multicenter, randomized, controlled, single-blinded efficacy trial of DCLHb as an adjunct to standard therapy in the treatment of severe, traumatic hemorrhagic shock. Patients with unstable vital signs or a critical base deficit were treated, with a primary study endpoint of 28-day mortality. Results: During the 11-month study period, 112 patients were randomized in 18 U.S. trauma centers, and data from 98 of the infused patients were analyzed. Prospective consent was obtained from two patients, three family members, and one legally authorized representative (LAR) (6%). Consent to continue was requested for 89 patients (89%), and full participation was granted for 87 of these patients (98%). Consent to continue was provided by 54 (98%) of the 55 patients approached. The mean number of days for family/LAR CTC was 1.1 ± 3.8 days, and 50% of the time it was obtained on the day of study enrollment. Patient CTC was obtained in an average of 13 ± 23 days, with a median of four days. Patients treated in this protocol were more likely to have sustained penetrating trauma than the overall trauma patient population treated in these trauma centers (44% vs 21%, p = 0.002). Conclusions: Informed consent in this study of an emergent therapy most often involved the use of the consent exception and consent to continue, the latter of which occurred in a timely manner. Nearly all of those who were approached for CTC approved full participation in the study, suggesting acceptance of the process outlined in the new regulations. Patients treated in a hemorrhagic shock clinical trial may differ from the general trauma patient population.