Why persons choose to opt out of an exception from informed consent cardiac arrest trial

doi:10.1016/j.resuscitation.2013.01.030

Resuscitation

Volume 84, Issue 6, June 2013, Pages 825-830

https://doi.org/10.1016/j.resuscitation.2013.01.030 Get rights and content

Abstract

Background

We sought to characterize persons who requested to opt out of an exception from informed consent (EFIC) cardiac arrest trial and their reasons for opting out.

Methods

At one site of a multi-site, out-of-hospital, cardiac arrest EFIC trial (September 2007 – June 2009), persons who did not want to participate in the study could request an opt-out “NO STUDY” bracelet to prevent trial enrollment. We surveyed all persons who requested a bracelet by phone interview, web or mail. Opt-out bracelets were advertised in all public communication about the study, including community consultation and public disclosure efforts. Survey questions included demographics, Likert scale items about attitudes toward the trial and research in general, plus open-ended questions. We used descriptive statistics for standardized questions and qualitative analysis to identify common themes from open-ended questions.

Results

Sixty bracelets were requested by 50 individuals. Surveys were completed by 46 persons (92% response rate). Seventy percent of respondents agreed emergency research is important, but 87% objected to any research without consent. In the qualitative analysis, 5 overlapping themes emerged: questioning the ethics of EFIC research; concerns about how the study would impact end-of-life preferences; subjective emotions including sarcasm, anger, and allusions to past unethical research; negative reference to unrelated public health controversies; and objections to the study protocol based on misinformation.

Conclusions

A primary reason for opting out from this EFIC trial was opposition to all research without informed consent, despite stated support for emergency research. Understanding the demographics and beliefs of persons opting out may aid researchers planning EFIC studies and help provide clarity in future EFIC-related community education efforts.

Introduction

Informed consent is one of the basic tenets of protection for human subjects in clinical research. However, there are important, unanswered questions about the optimal treatment of people with emergent, time-sensitive conditions such as cardiac arrest and serious traumatic injuries. Because informed consent is not possible for patients with certain acute medical conditions or requiring time-sensitive interventions, the Food and Drug Administration (FDA) developed regulations creating safeguards for potential subjects in these trials, including requirements for community consultation and public disclosure.1, 2 While resuscitation research using the exception from informed consent (EFIC) regulations has become more common, researchers and regulatory bodies continue to struggle with both the ethics and logistics involved in conducting this type of research.⁹ IRB members have often found the community consultation and public disclosure regulations vague and difficult to implement; the most appropriate form of community consultation has not been defined.3, 4 The American Heart Association (AHA) has outlined steps to be taken in planning community consultation and public disclosure to allow flexibility among different communities.⁵ Studies have shown that the majority of people support resuscitation research using the EFIC, but some individuals seriously object to any interventional research without informed consent.6, 7

Although federal regulations do not specifically require investigators to provide a mechanism for people to refuse potential enrollment in EFIC studies, some local IRBs require the provision of an opt-out option.⁸ Community characteristics of persons opting out of EFIC studies have been detailed,¹⁰ yet description of individuals opting out of EFIC trials and their reasons for doing so have not been previously published. Since an important component of EFIC research is building and maintaining a level of trust between the research community and the public, characterizing this population and understanding their reasons may aid researchers and regulatory bodies in addressing community concerns about this type of research.

The purpose of this study was to characterize persons opting out of an EFIC out-of-hospital cardiac arrest trial at one site of a multi-site resuscitation network and to detail common themes cited as reasons for opting out.

Section snippets

Study design

This was a mixed-methods study using a structured survey (discrete quantitative questions and open-ended qualitative questions) administered either by phone, mail or internet. The sample included persons requesting an opt-out bracelet at a single-site participating in the Resuscitation Outcomes Consortium (ROC) Prehospital Resuscitation using an Impedance valve and Early vs. Delayed analysis (PRIMED) multi-center, out-of-hospital, cardiac arrest trial.11, 12 The study was approved by the Oregon

Results

During the 18-month study period, 60 bracelets were requested by 50 individuals. Forty-six surveys were completed and analyzed (response rate 92%). No bracelets were requested after the first year of trial enrollment and all persons requesting to opt out of the trial were approached about participation in the survey. The majority of respondents were Caucasian, female, highly educated, religious and over 50 years of age (Table 1).

Discussion

To our knowledge, this is the first study to characterize persons opting out of an EFIC study and to elucidate reasons for opting out. The views represented by this small group of respondents are unlikely to represent the views of the larger community, as evidenced by the 7 involved IRBs independently interpreting community responses as supportive of the study and allowing the trial to proceed, as well as previous studies demonstrating general support for EFIC research.15, 19 However, this

Limitations

Public perception of the PRIMED trial may have been influenced by previous press about a trauma resuscitation trial done by the same research network in this community. The trauma trial had significantly higher numbers of persons requesting to opt out, possibly because persons objecting to the PRIMED study already had a bracelet from the previous EFIC trial.23, 24 However, the same team of investigators fielded all opt-out requests from the previous EFIC trial and felt that the themes

Conclusion

Persons opting out of an EFIC trial on cardiac arrest at one site prioritized the rights of the individual over public health and the needs of the community. Respondents had concerns about the ethics of research without informed consent, regardless of subject matter or the study intervention. Additional attitudes and beliefs included concerns about infringement on end-of-life preferences and emotional responses of anger, fear and mistrust of the medical/research community. Many respondents

Conflict of interest statement

No conflicts of interest to declare.

Funding

This publication was made possible with support from the following sources: Oregon Clinical and Translational Research Institute (#UL1 RR024140, the National Center for Research Resources, a component of the NIH, and NIH Roadmap for Medical Research); and the Resuscitation Outcomes Consortium (ROC) Training Grant (#U01/HL-04-001, National Heart, Lung and Blood Institute), and the ROC cooperative grants. The ROC is supported by a series of cooperative agreements to 10 regional clinical centers

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Cited by (19)

European Resuscitation Council Guidelines 2021: Ethics of resuscitation and end of life decisions
2021, Resuscitation
Citation Excerpt :
In contrast, a strict requirement for pre-enrolment consent may delay the initiation of an experimental intervention, thereby hampering its potential benefit to the patient.327 Another ethically acceptable and legally supported consent model comprises exception to informed consent (EIC) with prior community consultation (and a possibility of prospective opt out for community members).328–335 The EIC model also mandates obtaining post-enrolment consent.317
These European Resuscitation Council Ethics guidelines provide evidence-based recommendations for the ethical, routine practice of resuscitation and end-of-life care of adults and children. The guideline primarily focus on major ethical practice interventions (i.e. advance directives, advance care planning, and shared decision making), decision making regarding resuscitation, education, and research. These areas are tightly related to the application of the principles of bioethics in the practice of resuscitation and end-of-life care.
Approaches to community consultation in exception from informed consent: Analysis of scope, efficiency, and cost at two centers
2018, Resuscitation
Citation Excerpt :
In fourteen prior studies, eight [7,15–21] showed no relationship of age or educational level to study approval, however three [7,15,21] did note racial differences in EFIC approval. Two trials [11,22] showed greater EFIC acceptance among younger and more educated patients while two other trials [23,24] showed increased acceptance with increasing age, one [25] showed increased acceptance with less education, and several [26,27] showed increased acceptance with middle age, and less acceptance in the young and elderly groups as well as a racial difference in acceptance. Soliciting and obtaining an online group of respondents was the most expensive method of community consent at $15.63 per completed survey and was not time-efficient.
Community consultation (CC) is fundamental to the Exception from Informed Consent (EFIC) process for emergency research, designed to inform and receive feedback from the target study population about potential risks and benefits. To better understand the effectiveness of different techniques for CC, we evaluated EFIC processes at two centers participating in a trial of early cardiac catheterization following out-of-hospital cardiac arrest.
We studied the Institutional Review Board-approved CC activities at Maine Medical Center (MMC) and University of Arizona (AZ) in support of NCT02387398. In Maine, the public was consulted by survey at a professional basketball game and in the emergency department waiting room (in-person group), by multimedia direction to an online website (online group), and by mail (mailing group). Arizona respondents were either approached at a county fair (in-person group) or were directed to an online survey (online group) via social media advertising.
Among 2185 survey respondents, approval rates were high for community involvement and personal participation without individual consent. Community consultation using in-person, online, and mailed surveys offered slightly different approval rates, and the rate of responses by modality differed by age and education level but not ethnicity. Print advertising was the least cost effective at $442 per completed survey.
Canvassing at public events was the most efficient mode of performing CC, with approval rates similar to mailings, online surveys, and canvassing in other locations. Print advertisements in local papers had a low yield and cost more than other approaches.
Evolution of medical ethics in resuscitation and end of life
2016, Trends in Anaesthesia and Critical Care
Medical ethics has evolved from paternalistic to patient-centred. Emergency and end-of-life situations are frequently associated with inability to make informed decisions. Respect for advance directives, proxy informed consent for therapeutic/research interventions, do-not-attempt resuscitation orders, and withdrawal of life-sustaining treatment focus on autonomy and nonmaleficence. Beneficence is increasingly interpreted in terms of “achieved quality of life” following emergency treatment/resuscitation. Justice pertains to equality of access to best available care, which depends on patient age, comorbidity, preferences, socioeconomic status, race, ethnicity, and religion. Dignity includes the concept of “dignified death;” the still-debated practice of physician-assisted death is gaining ground. Honesty/transparency augments patient participation in shared decision-making and treatment selection. A still-prominent, international variation in bioethical principles interpretation mandates continuous effort for harmonization.
Evolution of European Union legislation on emergency research
2015, Resuscitation
Citation Excerpt :
Family autonomy is generally considered as “the best possible substitute” to the individual autonomy of an incapacitated patient. A possibly improved alternative to deferred consent could be exception to informed consent (EFIC) with prior community consultation, and in conjunction with the option for community members to opt out from an EFIC study by wearing “NO STUDY” bracelets.18 Emergency research involving EFIC [19, Appendix I] or deferred consent,20 and collectively, exception to pre-enrolment consent seems generally acceptable by the public in North America and the European Union (EU),21–28 particularly when research interventions pose minimal risk.23,28
Emergency research is necessary to prevent exposure of patients to unvalidated clinical practice (nonmaleficence), and to improve the dismal prognosis of disorders requiring emergent treatment such as cardiac arrest (beneficence). Regulations that govern clinical research should conform to bioethical principles of respect for nonmaleficence, beneficence, autonomy, and justice. Our objectives are to review the evolution of European Union (EU) legislation on emergency research, and to identify potentially remaining problems.
EU legislative sources on clinical research and medical literature describing the impact of EU Regulations on emergency research.
Article 5 of EU Directive 2001/20/EC required consent before enrolment in a research study to ensure the autonomy of potentially incapacitated research subjects. However, obtaining such consent is often impossible in emergency situations. Directive 2001/20/EC was criticized for potentially preventing emergency research. Several EU Member States addressed this problem by permitting deferred consent. International ethical guidelines supporting deferred consent were also cited by Good Clinical Practice Directive 2005/28/EC. However, Directive 2001/20/EC was not revised to achieve harmonization of EU emergency research, thus resulting in ongoing “ambiguity” as regards to emergency research legitimacy. This will be definitively addressed by applying EU Regulation No. 536/2014 and repealing Directive 2001/20/EC. The new EU Regulation permits using deferred consent under clearly specified conditions, and may foster emergency research that evaluates interventions posing minimal risk relative to standard practice.
Legislation related to emergency research in Europe has evolved to increase concordance with bioethical principles so as to increase evidence-based improvements in emergency care.
International variation in policies and practices related to informed consent in acute cardiovascular research: Results from a 44 country survey
2015, Resuscitation
Citation Excerpt :
Importantly, relatives of patients with OHCA are unlikely to be present on scene or able to understand the explanation of informed consent.12 Individuals who sought to opt out of participation in an emergency research trial agreed that such research was important.29 However, they questioned the ethics of EFIC, as well as whether such research conflicted with patient preferences, and raised unrelated public health controversies.
Research in an emergency setting such as that with an acute cardiovascular event is challenging because the window of opportunity to treat may be short and may preclude time to obtain informed consent from the patient or their representative. Some perceive that requiring informed consent in emergency situations has limited improvements in care. Vulnerable populations including minorities or residents of low-income countries are at greatest risk of need for resuscitation. Lack of enrollment of such patients would increase uncertainties in treatment benefit or harm in those at greater risk of need for resuscitation. We sought to assess international variation in policies and procedures related to exception from informed consent (EFIC) or deferred consent for emergency research.
A brief survey instrument was developed and modified by consensus among the investigators. Included were multiple choice and open-ended responses. The survey included an illustrative example of a hypothetical randomized study. Elicited information included the possibility of conducting such a study in the respondent's country, as well as approvals required to conduct the study. The population of interest was emergency physicians or other practitioners of acute cardiovascular event research.
Usable responses were obtained from 44 countries (76% of surveyed). Community opposition to EFIC was noted in 6 (14%) countries. Emergency Medical Services (EMS) providers in 8 (20%) countries were judged unable or unwilling to participate. A majority of countries (36, 82%) required approval by a Research Ethics Committee or similar. Government approval was required in 25 (57%) countries.
There is international variation in practices and polices related to consent for emergency research. There is an ongoing need to converge regulations based on the usefulness of multinational emergency research to benefit both affluent and disadvantaged populations.
The inadequacies of community consultation in emergency medicine research: A proposal for revising the rule
2015, American Journal of Emergency Medicine

View all citing articles on Scopus

^☆: A Spanish translated version of the summary of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.01.030.

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Clinical paperWhy persons choose to opt out of an exception from informed consent cardiac arrest trial☆

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Study design

Results

Discussion

Limitations

Conclusion

Conflict of interest statement

Funding

Ann Emerg Med

Am J Emerg Med

Resuscitation

Resuscitation

Resuscitation

Ann Emerg Med

Am J Med Sci

Ann Epidemiol

Soc Sci Med

Health and Human Services policy for protection of human subjects research--HHS. Final rule

Fed Regist

A qualitative study of Institutional Review Members’ experience with reviewing proposals for exception from informed consent in resuscitation research

J Med Ethics

Community consultation methods in a study using exception to informed consent

Prehosp Emerg Care

Conducting empirical research on informed consent: challenges and questions

IRB

Clinical paper
Why persons choose to opt out of an exception from informed consent cardiac arrest trial☆