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.     

Confronting the Ethical Challenges to Informed Consent in Emergency Medicine Research

The Society for Academic Emergency Medicine believes that protection of human subjects is vital in emergency medicine research and that, whenever feasible, informed consent is at the heart of that protection. At the same time, the emergency setting presents unique barriers to informed consent both because of the time frame in which the research is performed and because patients in the emergency department are a vulnerable population. This report reviews the concept of informed consent, empirical data on patients' cognitive abilities during an emergency, the federal rules allowing exemption from consent under certain circumstances, issues surrounding consent forms, and the new Health Insurance Portability and Accountability Act regulations as they relate to research. The authors conclude that, in many circumstances, informed consent is possible if the researcher is diligent and takes time to adequately explain the study to the potential subject. In cases in which it is possible to obtain consent, precautions must be taken to ensure that subjects have decision-making capacity and are offered time to have their questions answered and their needs met. Sometimes resuscitation and other emergency medicine research must be conducted without the ability to obtain consent. In these cases, special protections of subjects under the exception from consent guidelines must be followed. Protection of research subjects is the responsibility of every researcher in emergency medicine.     

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.     

Improving the Proficiency of Research Consent Administrators

Objective:

To describe the development and testing of a module to improve consent administrators’ skills when obtaining research consent from culturally and linguistically diverse and low literacy populations.

Design:

Development and psychometric testing of video module including community vignettes.

Methods:

Following initial content, face, and construct validity testing by experts, a field trial was conducted with pre‐ and postknowledge tests and satisfaction surveys completed by 112 consent administrators.

Results:

Mean score out of a possible 10 on pretest was 8.6 (±standard deviation [SD], 1.55) and on posttest was 9.1 (±SD, 1.2; paired t‐test 95% confidence interval of difference: –0.18 to –0.88; two‐tailed p = 0.003). The average years of experience with obtaining consent was 6.42 years (range: 0–35), but years of experience was not significantly associated with either pre‐ or posttest scores (p = 0.82 and 0.44, respectively). Most user evaluations were positive, although suggestions for improvements were made.

Conclusion:

Although pretest scores were relatively high, training needs of research consent administrators for consenting diverse and low literacy populations may be unmet. We urge that institutional review boards, researchers, policymakers, educators, and bioethicists address the training needs of research consent administrators and we offer this training module as one potential resource and adjunct to such training.     

Current Status of Research on the Federal Guidelines for Performing Research Using an Exception from Informed Consent

In order to set the stage for the later discussion of future directions, this Consensus Conference began by reviewing some of the existing research on conducting resuscitation studies using an exception from informed consent. That research is described in this article. The authors conclude that, based on the experiences reported by researchers and institutional review boards, resuscitation research may be ethically and legally conducted under the current regulations, but such research requires substantial effort, financial resources, and personnel. Federal regulations have set the bar appropriately high, and this may pose significant difficulties for small sponsors and individual investigators. However, further study of the experiences of subjects, researchers, and the regulatory process is warranted.     

Issues of Informed Consent in Conducting Medical Research Involving People with Intellectual Disability

Background People with severe intellectual disability are considered vulnerable to exploitation in research. Discovery of exploitative practices in recent history has motivated the development of guidelines for informed consent and proxy decision‐making procedures when involving these individuals in research. Methods Issues for determining capability to provide informed consent and the proxy decision process are reviewed according to the literature, current ethics guidelines and recent legislature in Victoria, Australia. Results The complex process of involving in research people with severe intellectual disability who are particularly vulnerable by virtue of their institutionalized residential status is discussed within the context of a recent project into examining potential nutritional determinants of Pica behaviour (i.e. the eating of inedible items). Conclusions This example serves to highlight the role of legislation, various government bodies and researchers in balancing principles of protection of vulnerable groups and rights to self‐determination.     

Systematic Bias Introduced by the Informed Consent Process in a Diagnostic Research Study

Objectives:  To determine population characteristics, outcomes, and reasons for unsuccessful enrollment among potential study subjects approached for written, informed consent in a minimal-risk emergency department (ED) study. The authors hypothesized that the prevalence of venous thromboembolism (VTE) would be lower among study participants and that medical acuity and refusal to provide a blood sample would be the most common reasons for nonparticipation.
Methods:  The authors requested prospective, written, informed consent for a blood sample and follow-up from consecutive ED patients undergoing evaluation for pulmonary embolism (PE) and recorded spontaneously stated reasons for refusal. VTE was diagnosed or excluded using a combination of D-dimer testing and selective computed tomography (CT) angiography of the chest with venography of the lower extremities. The primary outcome was defined by the number of CT scans positive for VTE among ED patients evaluated for PE.
Results:  Over 16 weeks, 260 of 287 (91%, 95% confidence interval [CI] = 87 to 94%) eligible patients were approached and consent was obtained from 183 patients (64%, 95% CI = 58% to 69%). The prevalence of VTE was 6% among participants and 13% among nonparticipants (95% CI [of the difference] = 1% to 15%). The proportions of African Americans, uninsured, and Medicaid patients were significantly higher among nonparticipants. No significant differences were found in the proportions of nonparticipants who disliked or distrusted research or desired financial reimbursement, compared to those not enrolled due to medical acuity or refused a blood sample.
Conclusions:  These data implicate the written, informed consent process as a significant source of bias on estimated disease prevalence.     

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.     

产前超声检查中知情同意的应用价值

目的探讨医院产前超声检查中应用知情同意书的价值。方法对2002年1月一2010年1月经产前超声常规筛查并分娩出生缺陷儿（均为基层医院常规超声筛查难以显示或无法诊断的先天性异常）的产妇,按实行知情同意前后分为两组：实施前的有21例（A组）,实施后的有19例（B组）,比较两组出生缺陷儿产妇对产后结果的反映情况。结果B组产妇对产前超声筛查理解13例,可以理解4例,难以理解2例;A组理解3例,可以理解5例,难以理解13例,两组理解程序差异有统计学意义（Z=-3．741,P=O．000）。结论知情同意书是产前超声检查过程中孕妇对医方理解及对孕妇负责的必要手段。     

病人安全进展与挑战——知情同意与告知

“告知”是医务人员在实施临床诊疗、提供医疗服务过程中积极主动的行为，是知情同意原则履行中的关键。随着人们维权意识的逐渐增强，因轻视或忽视告知义务，侵犯病人知情同意，引发的事件逐渐上升。本文就告知的概念、意义及其内容、程序进行了探讨，并讨论了知情同意与告知的关系。     

Capacity of People with Intellectual Disabilities to Consent to Take Part in a Research Study

Background Within the context of current legislation relating to mental capacity in adults, the capacity of people with intellectual disabilities to consent to take part in research studies and the impact of different forms of information provision was experimentally investigated. Materials and methods A questionnaire measure of ability to consent to take part in this research study was administered individually to participants. A total of 102 participants with intellectual disabilities were recruited from three day services for adults with intellectual disabilities. Consent information appertaining to taking part in an actual research project was presented to participants and their capacity assessed using a questionnaire. Three experimental conditions were used:

• • Control (n = 34) – consent information was presented followed by the questionnaire.
• • Section (n = 34) – consent information was broken into sections and the appropriate questions were asked following each section.
• • Photograph (n = 34) – consent information was accompanied by six colour photographs, followed by the questionnaire.

Participants also completed measures of memory ability, verbal ability and non‐verbal problem‐solving ability. Results Seventeen participants withdrew from the study at some point. Of the remaining 85 participants, no significant differences in ability to consent scores were found between the experimental conditions. Using this measure, only five participants (5.9%) were deemed able to consent, i.e. scored the minimum required on each aspect of consent. Conclusions The validity and usefulness of the current dichotomous concept of consent is challenged as only a small proportion of participants were deemed able to consent.     

Does the Emergency Exception from Informed Consent Process Protect Research Subjects?

Although subject protection is the cornerstone of medical ethics, when considered in the context of research using emergency exception from informed consent, its success is debatable. The participants of a breakout session at the 2005 Academic Emergency Medicine Consensus Conference discussed the issues surrounding subject protection and advanced the following recommendations. 1) There are no outcome measures that define “protection”; therefore, it is not currently known whether or not subjects are protected under the current rules. 2) Care must be taken to protect not only the individual from harm during research but also to protect society from unregulated research in other countries and an inability to appropriately advance medical knowledge. 3) Some surrogate markers/methods of protection whose efficacies are debatable include data safety monitoring board activity, the community consultation and public notification (CC/PN) process, and institutional review board approval. 4) Minimal‐risk studies should be held to different standards of protection than those that involve more significant risk to the subject. 5) A handful of studies have been published regarding community consultation and notification, and the majority are case studies. Those that are specifically designed to discover the most successful methods are hindered by a lack of formal outcomes measures and tend to have negative results. 6) Follow‐up data from the CC/PN process should be disclosed to the Food and Drug Administration and incorporated into study designs. 7) Focus groups and/or random‐digit dialing have been suggested as promising methods for fulfilling the CC/PN requirements. 8) Studies need to be funded and performed that formally investigate the best means of CC/PN. 9) More funding for this research should be a priority in the emergency medicine and critical care communities. More data regarding terminated studies should be made available to the research community. 10) Quantifiable markers of success for CC/PN must be validated so that research may determine the most successful methods. 11) Data regarding subjects' and family members' experiences with exception from informed consent studies need to be obtained.     

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.     

Ethics and research in critical care

Background The past few years have witnessed several controversies regarding the ethics of conducting research involving critically ill patients, and such research is ethically challenging.Discussion Research ethics is a changing field, one that is influenced by empirical data, contemporary events, and new ideas regarding aspects of clinical trial design and protection of human subjects. We describe recent thoughts regarding several aspects of research ethics in the critical care context.Conclusion The ability of the research community to conduct research ethically and to maintain public trust would benefit from heightened awareness to the principles and requirements that govern such research.     

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.     

Research without Consent: Community Perspectives from the Community VOICES Study

Objective: To explore community attitudes toward the federal regulations that allow investigators to conduct emergency research without obtaining informed consent from participants. Methods: Focus‐group participants were recruited from residential sites in New York City that were enrolled in the Public Access Defibrillation (PAD) Trial. The PAD Trial, a National Institutes of Health–funded, randomized trial in which laypersons were trained to treat cardiac arrest, was granted an exception from informed consent under these rules. Community residents and those who had been trained as lay responders in the PAD Trial were asked about the ethical issues raised by the conduct of research without consent (RWC), their definition of community, and appropriate methods of community consultation regarding RWC studies. Grounded theory content analyses were conducted on focus‐group data. Results: Seventeen (40%) men and 25 (60%) women from 15 buildings participated in six focus groups: four in English; two in Spanish. Definitions of “community” varied widely among and across groups; no strategy for community consultation was consistently endorsed by the participants. There were significant support and occasional adamant opposition to conducting RWC; participants often recounted specific personal experiences as the basis for both positive and negative opinions. Individuals with negative attitudes toward RWC often voiced strong support for specific RWC scenarios. Conclusions: There is no consensus regarding the definition of “community” or appropriate methods of consultation. Community members' attitudes toward RWC are often shaped by their personal experiences, and their general attitudes often differ from their reactions to specific RWC protocols.     

Community Consultation Methods in a Study Using Exception to Informed Consent

Objective. The most effective means of community consultation is unknown. We evaluated differences in community opinion elicited by varying means of consultation. Methods. We compared responses with a cross-sectional, standardized survey administered as part of the community consultation for the Resuscitation Outcomes Consortium (ROC) hypertonic saline trial. Surveys were obtained from four sources: two sets of random-digit dialing phone surveys, paper surveys from community meetings, andweb-based surveys. Results. Three hundred sixty-one usable surveys were obtained: 186 from phone survey 1; 86 from phone survey 2 (using slightly modified wording); 54 from community meetings (8 from open forums; 46 from existing meetings); and35 from a web site. Demographics were similar between the sets except that the surveys obtained from community meetings had the highest minority representation (63.3% nonwhite). Community meeting respondents were more willing than phone or web respondents to receive experimental treatment for themselves (93.6% vs. 77.5% overall) andfor a family member (95.2% vs. 74.9% overall). The web-based survey generated the least feedback andhad the most higher-income responders. Conclusions. Responses varied by method of consultation. The open forums were very poorly attended, despite heavy advertising by investigators. Furthermore, attendees at those meetings provided the least objection to proposed research without informed consent. Phone surveys elicited the most objections. We suggest that an efficient method of community consultation is random-digit dialing supplemented with discussion at already scheduled events to target special populations.