Consent In Emergency Research Research Articles

Context and principles must drive alternatives to consent in emergency research

Context and principles must drive alternatives to consent in emergency research

Abstract 391: Variation in Time to Notification After Enrollment in Trials Conducted Under Exception From Informed Consent for Emergency Research

Context: Research in an emergency setting is challenging because the window of opportunity to treat may be short, and preclude time to obtain informed consent from the patient or their representative. Such research can be conducted under exception from informed consent (EFIC) if specific criteria are met. In the United States, this includes notification of an enrolled subject or their representative as soon as feasible after enrollment so that they have autonomy to opt out from ongoing study participation. To date, there is limited empiric information about time to notification (TTN). Objective: To describe variation in TTN among sites participating in randomized trials conducted under exception from informed consent for emergency research. Methods: Notification strategies were determined at each site prior to initiation of subject enrollment, and approved by a local institutional review board or equivalent. TTN was summarized overall, as well as stratified by site and clinical outcome among patients enrolled in multiple trials conducted by the Resuscitation Outcomes Consortium (ROC). Results: Included were 34,868 patients enrolled in four trials. Of these, 33,805 had with out-of-hospital cardiac arrest; and 1,063 had life-threatening traumatic injury. TTN varied (Table). Conclusions: There is large variation in TTN in trials conducted under EFIC for emergency research. Early notification is difficult; delayed notification may reduce the autonomy of patients or their representative.

A 20-year Review: The Use of Exception From Informed Consent and Waiver of Informed Consent in Emergency Research.

Due to the acuity and time-sensitive needs of their clinical condition, patients presenting with certain emergent pathologies may lack capacity to provide meaningful prospective informed consent to participate in clinical research. For these reasons, these populations have often been excluded from research investigations. To mitigate this, regulations allowing exception from informed consent (EFIC; 21 CFR 50.24) or waiver of informed consent (WIC; 45 CFR 46.101) were developed in 1996. The purpose of this study was to identify trends in the utilization of EFIC and WIC in emergency research. We also sought to describe the disclosure of necessary prestudy regulatory requirements and justification for the use of EFIC/WIC as reported in completed EFIC/WIC clinical trials. This study is a review of 20 years of published trials using EFIC or WIC as the primary method of patient consent. Studies were identified using a MEDLINE search; ClinicalTrials.gov; queries to emergency and resuscitation researchers, research directors, department chairs, and principal investigators of acute care research networks; clinical review papers; and a query of the Federal Drug Administration (FDA) docket. All eligible studies were reviewed by three investigators and study data of interest were abstracted. Data are presented descriptively. We identified 45 potentially eligible studies; 11 were ongoing (with no data yet available), four were completed (with no publications or data available), and two did not use EFIC or WIC. Of the remaining 28 studies, 24 (86%) used EFIC and four used WIC. The most common pathologies under study were cardiac arrest (10), hemorrhagic shock (six), and traumatic brain injury (five). Completion of the prestudy regulatory requirements was reported as follows: FDA investigational new drug/investigational device exemption application (for FDA regulated studies; 14, 50%), community consultation (13, 46%), public disclosure (10, 36%), and opt-out procedures if requested by the institutional review board (seven, 25%). The justification of the need for the use of EFIC or WIC in the reported clinical trial, as defined as mention of at least one of the eight established criteria, was described in the text of 13 (46%) publications. Since their implementation in 1996, the EFIC/WIC regulations have allowed progress in research aimed at determining optimal care for devastating life-threatening conditions. However, consistent and rigorous report of regulatory prestudy requirements and justification of the use of EFIC/WIC is lacking in clinical trial publications or on websites such as ClinicalTrials.gov. Since research without consent is an ethically sensitive issue and not widely understood, better justification of its needs within the presentation of the research itself may educate the general medical community and also reduce concerns about whether or not the regulations are being properly applied.

Qualitative evaluation of a deferred consent process in paediatric emergency research: a PREDICT study

BackgroundA challenge of conducting research in critically ill children is that the therapeutic window for the intervention may be too short to seek informed consent prior to enrolment. In specific...

Does proximity to violence negatively influence attitudes toward exception from informed consent in emergency research?

Trauma research has been limited by perceived patient reluctance to participate in exception from informed consent (EFIC) studies. We hypothesized that race, socioeconomic status, and proximity to violence influence willingness to participate in and perception of EFIC research among at-risk populations. Trauma patients, families, and community members ranked statements regarding attitude toward EFIC in the context of an upcoming trial and willingness to participate in emergency research using a 5-point Likert scale during a community consultation. Higher total scores reflected a more positive attitude regarding EFIC (range, 6-30; neutral, 18) and willingness (range, 23-115; neutral, 69). Subject zip code was used to calculate median income, as an estimate for socioeconomic status, and proximity to the five most violent city zip codes. Linear regression, Spearman's correlation, and Kruskal-Wallis tests (p < 0.05) were used to evaluate relationships between estimated socioeconomic status, race, mechanism of injury, proximity to violence, and attitudes toward EFIC. A total of 179 subjects participated including trauma patients (n = 99), families (n = 33), and community members (n = 47). Overall, participants were supportive of EFIC and reported high scores in willingness to participate (median, 24; interquartile range, 21-25; median 89, interquartile range, 82-95, respectively). Proximity to violence did correlate with race (p = 0.03) but was not associated with violent mechanism of injury, perception of EFIC, or willingness to participate in emergency research. Estimated socioeconomic status and race did not correlate with perception of or willingness to participate in EFIC. Based on our data, there is no correlation between either proximity to violence or estimated socioeconomic status and willingness to participate in EFIC research. Given this lack of correlation, researchers should partner with at-risk communities to conduct EFIC studies without concern for limited participation. Epidemiologic/prognostic study, level III.

Creating an infrastructure for comparative effectiveness research in emergency medical services.

Emergency medical services (EMS) providers deliver the initial care for millions of people in the United States each year. The Institute of Medicine noted a deficit in research necessary to improve prehospital care, created by the existence of data silos, absence of long-term outcomes, and limited stakeholder engagement in research. This article describes a regional effort to create a high-performing infrastructure in southwestern Pennsylvania addressing these fundamental barriers. Regional EMS records from 33 agencies in January 2011 were linked to hospital-based electronic health records (EHRs) in a single nine-hospital system, with manual review of matches for accuracy. The use of community stakeholder engagement was included to guide scientific inquiry, as well as 2-year follow up for patient-centered outcomes. Local EMS medicine stakeholders emphasized the limits of single-agency EMS research and suggested that studies focus on improving cross-cutting, long-term outcomes. Guided by this input, more than 95% of EMS records (2,675 of 2,800) were linked to hospital-based EHRs. More than 80% of records were linked to 2-year mortality, with more deaths among EMS patients with prehospital hypotension (30.5%) or respiratory distress (19.5%) than chest pain (5.4%) or nonspecific complaints (9.4%). A prehospital comparative effectiveness research infrastructure composed of patient-level EMS data, EHRs at multiple hospitals, long-term outcomes, and community stakeholder perspectives is feasible and may be scalable to larger regions and networks. The lessons learned and barriers identified offer a roadmap to answering community and policy-relevant research questions in prehospital care.

Waiver of Consent for Low-Risk Studies

Waiver of Consent for Low-Risk Studies

Waiver of Informed Consent in Prehospital Emergency Health Research in Australia

Informed consent is a vital part of ethical research. In emergency health care research environments such as ambulance services and emergency departments, it is sometimes necessary to conduct trial interventions or observations without patient consent. At times where treatment is time critical, it may be impossible or inappropriate to seek consent from next of kin. Emergency medicine is one of the few areas where the process of informed consent can be waived to allow research to proceed without patient consent. This article will explore the ethics of informed consent in the prehospital emergency research context. This will include an overview of current Australian guidelines for ethical research, and recent changes in law internationally which have affected the conduct of international emergency health research. An overview of the ethical reasoning behind the waiver of informed consent in emergency research is presented, also addressing issues relating to emergency health research such as proxy consent, unconscious patients, and patient decision making capacity. The unusual circumstances encountered in the prehospital ambulance environment will also be discussed, including the dependent and coercive relationship between patients and ambulance professionals, and a lack of alternatives for care and transport for patients who refuse consent. The conflict arising from differences in medical culture and values between patients and health care professionals will also briefly be discussed. It will be argued that, while emergency care research should not require informed consent due to the restrictions of time and dependent nature of the relationship between patient and health professional, emergency health researchers still have a responsibility to consider the patients' perspective when considering the ethical issues of an emergency research project, particularly in the prehospital environment.

Ethical and Legal Issues in Emergency Research: Barriers to Conducting Prospective Randomized Trials in an Emergency Setting

As in any area of medicine, clinical trials are crucial to the advancement of trauma care and the establishment of evidence-based guidelines. This work identifies consent regulations that impede advances in trauma resuscitation research and examines several ethical issues underlying current policies in the United States which regulate how clinical trials are conducted in an emergency setting. Trauma is a leading cause of mortality in the U.S. Minorities and those in low socioeconomic groups are subject to a disproportional amount of traumatic injuries and have worse treatment outcomes than non-minority individuals. Current regulations guiding consent requirements in emergency research were enacted to protect such vulnerable populations from exploitation. Ironically, these same regulations also serve as barriers to clinical trials in trauma research, thus depriving these same vulnerable groups from the benefits of advances in trauma care. A literature review was conducted on areas affecting emergency medical research including: informed consent, socioeconomic and racial disparities, federal regulations in trauma research and biomedical ethics. In the ten year period following the passage of the FDA's Common Rule (21 CFR 50.24) in 1995, 21 published emergency research studies were conducted under the waiver of informed consent. Misconceptions regarding federal regulations and cumbersome internal review board approval processes are frequently cited as significant barriers to conducting prospective randomized trials in the emergency setting. Given the history of past abuses in medical research, the principle of maintaining autonomy of choice is of paramount importance. However, trauma resuscitation is unique in that patients are either unconscious or of limited mental capacity at the time treatment is required, and thus the standard of informed consent is unable to be achieved as in other areas of medicine. While this paradox was recognized by the FDA in 1995 with the creation of an exception to the requirement for informed consent in emergency research (the "Common Rule"), the wording of this exception is ambiguous, and has consequently deterred trauma investigators from pursuing valuable research endeavors. In particular, the language requiring "community consultation" and demonstration that existing treatments are "unproven or unsatisfactory" have been identified as the most problematic terms to satisfactorily address by those aiming to conduct trauma research. It is imperative that the current exemptions to the Common Rule be more thoroughly operationalized, so that greater advancement in emergency medicine research can be promulgated, while concurrently maintaining a high standard of protection for the rights of trauma patients.

Community meetings for emergency research community consultation*

To survey attendees at community meetings for an emergency research protocol and determine whether these meetings aid participants' understanding and decision to support the proposed emergency research. Postmeeting questionnaire. Three community meetings for the PolyHeme study in San Antonio area. One hundred fifty community meeting attendees. PolyHeme research team representatives made a study presentation concerning exception to informed consent regulations. In addition, institutional review board (IRB) members attended these meetings and made a separate presentation about the IRB approval of research and the exception to informed consent in emergency research. The IRB members requested attendees to voluntarily complete an additional Community Consultation Survey assessing demographics, community meeting satisfaction, and impact of the community meeting on their attitudes toward emergency research studies. Feedback to the PolyHeme investigators with their validation questions indicated that 35% of the respondents objected to research without prior consent, but 82% gave approval for the study in the local community; 137 attendees completed the additional Community Consultation Survey. The average score on the adequacy of information provided about the PolyHeme study was 0.58 on a 5-point Likert scale (-2 to +2). Adequacy of IRB background information on human subjects research received an average score of 0.56, and the overall clarity of the information on community consultation was 0.91. Although 80% of respondents felt there was a potential benefit from PolyHeme, <67% would either want to participate or enroll their family members with or without prior consent. The majority of community meeting attendees understand basic concepts and regulations of emergency research without prior consent. Despite an 82% concurrence with the study in their community, approximately 30% of persons would not willingly choose to participate in emergency research or provide consent for their family members despite knowledge about the process.

Finding family for prospective consent in emergency research

Innovative approaches are needed to allow for research in the emergency setting while not compromising either the rights or the interests of the subjects enrolled in such research. The emergency consent exception was developed to meet this need. The goal was to describe the timing of initial contact with relatives and the timing of obtaining informed consent for a research study in patients with severe traumatic brain injury. The study was designed as a prospective, observational study of 129 patients enrolled in an emergency study of traumatic brain injury conducted under the emergency consent exception. Detailed descriptive information was collected both about the availability of relatives of patients enrolled in a study of traumatic brain injury to give prospective consent within the time period required for entering the study and about the extent to which they did give prospective consent during that time period. The number of patients with relatives who could be contacted by research staff increased with time after injury, with 3% (95% CI=0 to 6%), 25% (95% CI=18 to 32%), and 43% (95% CI=35 to 52%) having family at 1, 3, and 6 h, respectively postinjury. An additional 15% were available within the next 6 h. The median time after injury to the initial family contact by the research staff was 2.0 h for patients who had relatives already present at the hospital and 5.7 h for patients whose family had already been contacted by the hospital. The percentage of family members actually giving prospective research consent was much smaller; only 18% actually gave prospective consent within 6 h postinjury. The proportion of critically ill patients with family available to give prospective consent for enrollment in emergency research studies depends primarily on the time period allowed for enrollment in the individual study and the length of the transition from initial contact to completed prospective consent. The study was performed in a specific patient population and may not be generalizable to other settings. Careful attention should be paid by investigators and IRBs as to whether the emergency consent exception is really required for a particular study, or whether the study could proceed using only prospective consent with a longer recruitment period, more research sites, and a higher yield of available family members giving prospective consent. Measures that could shorten the time between initial contact and obtaining informed consent (for example, allowing consent over the phone rather than requiring written consent) might decrease the need for the emergency consent exception.

Recommendations for Implementation of Community Consultation and Public Disclosure Under the Food and Drug Administration’s “Exception From Informed Consent Requirements for Emergency Research”

In addition to the usual requirement of appropriate study design and institutional review board (IRB) approval, research studies performed under the Food and Drug Administration (FDA) and Department of Health and Human Services regulations regarding “Informed Consent and Waiver of Informed Consent Requirements in Certain Emergency Research” (21 CFR §50.24)1 require community consultation and public disclosure. This special report discusses the general issues related to consent in emergency circumstances and provides a template to help IRBs implement community consultation and public disclosure appropriately. A portion of the material in this special report was presented as testimony by Dr Halperin on October 11, 2006, at the FDA’s public hearing on “Draft Guidance for Institutional Review Boards, Clinical Investigators, and Sponsors: Exception From Informed Consent Requirements for Emergency Research.” More than 300 000 Americans die each year due to catastrophic medical and surgical emergencies.2,3 New interventions based on sound research could save lives. These research studies must be done within an ethical framework that traditionally includes obtaining prospective informed consent from the research subject. The ethical framework for the conduct of human research began with the development of the Nuremberg Code4,5 in 1949. This code states that (1) informed consent of volunteers must be obtained without coercion of any form, (2) human experiments should be based on prior animal experiments, (3) the anticipated scientific results should justify the experiment, (4) only qualified scientists should conduct medical research, (5) physical and mental suffering should be avoided, and (6) no expectation of death or disabling injury should be expected from the research study. The Declaration of Helsinki6 was issued in 1964 and defines rules for clinical research. It repeats the ethical concerns stated in the Nuremberg Code but also gives a provision for enrolling certain patients in clinical research without …

Informed Consent in Acute Stroke

To the Editor: The process of informed consent is an integral component in the daily practice of medicine. Ongoing debate reflecting varying societal issues across wide geographical locales, medicolegal sophistication and evolving regulations have shaped this process. Increasingly complex medical decisions are formulated through this interaction between patients and doctors, opting for established surgical procedures, concocting medication regimens for off-label use, or choosing investigational approaches. Although a dedicated document may not be used in every scenario, the process embodies a universal doctrine designed to protect the patient. Elaborate algorithms or language considerations are often devoted to protect specific populations, yet this process also protects the doctor by noting patient consent. When consent is not established, many providers now document informed refusal.1 Discussions of risks, benefits, and alternatives have culminated in informed consent or refusal documents spanning up to 20 pages. Such documentation may not be feasible and the process may be entirely waived under specific emergency circumstances. The US Food and Drug Administration recently held public hearings to update stipulations for waiver of consent in emergency research. Clinical trialists have actively engaged in these forums, yet paradoxically, public interest and participation in these discussions that may decisively influence their future …

Informed Consent in Emergency Research: A Contradiction in Terms

Improving the treatment of life threatening emergency illness or disease requires that new or novel therapies be assessed in clinical trials. As most subjects for these trials will be incapacitated there is some controversy about they might best protected whilst still allowing research to continue. Recent European and UK clinical trials legislation, which has effectively stopped research into emergency conditions, is discussed. Possible changes to these regulations are proposed.

Informed Consent Procedure for Clinical Trials in Emergency Settings: The Polish Perspective

Setting reasonable and fair limits of emergency research acceptability in ethical norms and legal regulations must still adhere to the premise of well-being of the research subject over the interests of science and society. Informed consent of emergency patients to be enrolled in clinical trials is a particularly difficult issue due to impaired competencies of patients' to give consent, short diagnostic and therapeutic windows, as well as the requirement to provide detailed information to participants. Whereas the Declaration of Helsinki, Good Clinical Practice guideline, Additional Protocol to the European Bioethical Convention concerning Biomedical Research, as well as appropriate regulations adopted by the Food and Drugs Administration (USA) allow waivers from participants' consent or deferred consent for emergency research, the regulations of most European Community countries following the Clinical Trial Directive (2001/20/EC) do not give space for a deferred consent or a waiver from consent for adult patients (unless surrogate consent is made use of). This is even more confusing in case of Poland, where conflicting regulations on a waiver from a participant's consent in emergency research exist and the regulations on surrogate consent of temporarily incompetent adults are too restrictive and authorise only the guardianship courts to consent, which is not or hardly feasible in practice. European Community regulations need to be amended to allow for implementation of the deferred consent or waivers from consent for emergency research in order to enable ethical research of emergency conditions that should become a large part of important public health priorities.

Unproven or Unsatisfactory Versus Equipoise in Emergency Research with Waived Consent

Like the authors of the open letter (Kipnis, King and Nelson 2006), I support the waiver of informed consent for emergency research detailed at 21 CFR 50.24, commonly referred to as the “Final Rule...

The Spectrum of Informed Consent in Emergency Psychiatric Research

I evaluate the variation in requirements for informed consent in studies evaluating chemical tranquilization of agitated patients. A computer-assisted literature search of the National Library of Medicine was performed. Additional use of the references listed in the articles identified with the search yielded 144 citations. Studies performed outside the United States were excluded, as were studies performed before the current US Food and Drug Administration regulations came into effect. Research not yet published but presented at national meetings was included, as was one study currently under way but otherwise meeting the inclusion criteria. Authors were contacted for further clarification in cases in which information was ambiguous or unavailable in print. Twelve studies were identified, and the approach to informed consent varied widely. The primary method of enrollment was informed consent in 7 studies. Three studies used a waiver of informed consent, but in these cases the federal regulations underlying these waivers varied. One study implied that neither consent nor a waiver of consent was needed. In one case, the primary method for consent was not specified. There is poor agreement about the application of current regulations about informed consent in emergency psychiatric research. Regulations are understood in such a variety of ways that they are effectively irrelevant. There needs to be much greater clarity about the use of waivers of informed consent in emergency research in general and emergency psychiatry in particular.

The Ethical Conduct of Resuscitation Research: Setting the Stage for Change

Academic Emergency MedicineVolume 12, Issue 11 p. 1015-1016 Free Access The Ethical Conduct of Resuscitation Research: Setting the Stage for Change Michelle H. Biros MD, MS, Corresponding Author Michelle H. Biros MD, MS(biros001@umn.edu), Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MNSearch for more papers by this author Michelle H. Biros MD, MS, Corresponding Author Michelle H. Biros MD, MS(biros001@umn.edu), Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MNSearch for more papers by this author First published: 28 June 2008 https://doi.org/10.1197/j.aem.2005.07.020Citations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Biros MH, Runge JW Lewis RJ. Emergency medicine and the development of the Food and Drug Administration's Final Rule in informed consent and waiver of informed consent in emergency research circumstances. Acad Emerg Med. 1998; 5: 359– 68. Biros MH, Lewis RJ Olson CM, et al. Informed consent in emergency research. Consensus statement from the Coalition of Acute Resuscitation Researchers. JAMA. 1995; 273: 1283– 7. 3. Protection of human subjects; informed consent and waiver of consent requirements in certain emergency research; final rules. (Codified at 21 CFR .50, et al, 45 CFR .46). Fed Reg. 1996; 61(192): 51500– 33. Schmidt TA, Baren JM, Mann NC, Richardson LD. Executive summary: The 2005 AEM Consensus Conference on ethical conduct of resuscitation research. Acad Emerg Med. 2005; 12: 1017– 8. Mann NC, Schmidt TA Richardson LD. Confronting the ethical conduct of resuscitation research: a consensus opinion. Acad Emerg Med. 2005; 12: 1078– 81. Citing Literature Volume12, Issue11November 2005Pages 1015-1016 ReferencesRelatedInformation

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.

Waiving consent for emergency research

Waiving consent for emergency research