The European Clinical Trials Directive was issued in 2001 and aimed to simplify and harmonise the regulatory framework of clinical trials throughout Europe, thus stimulating European research. However, significant complexity and inconsistency remains due to disparate interpretation by EU member states. Critical care research has been particularly impacted due to variable and often restrictive consenting procedures for incapacitated subjects, with some countries requiring a court-appointed representative, while others recognise consent from family members and occasionally professional representatives. Furthermore, the absence of (...) a waiver of consent threatened to put an end to emergency research in Europe and was met with varied responses. Approval procedures by ethics committees are equally inconsistent, particularly those relating to provision of a single opinion for multi-centre trials. Although evidence is somewhat mixed, this complexity as well as a general increase in administrative and financial burden following the Directive has been shown to cause a reduction in clinical trial activity in Europe, particularly academic trials. We aim to clarify some of these inconsistent procedures, particularly those relating to informed consent of incapacitated subjects, as well as discussing some general weaknesses and possible improvements of the Directive ahead of its planned revision in 2011. (shrink)

Deception is a useful methodological device for studying attitudes and behavior, but deceptive studies fail to fulfill the informed consent requirements in the U.S. federal regulations. This means that before they can be approved by Institutional Review Boards, they must satisfy the four regulatory conditions for a waiver or alteration of these requirements. To illustrate our interpretation, we apply the conditions to a recent study that used deception to show that subjects judged the same wine as more enjoyable when they (...) believed it had a higher price. (shrink)

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the waiver (...) of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood—the standard treatment for hemorrhagic shock—is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)

Severe Traumatic Brain Injury (TBI) remains a major cause of death and disability afflicting mostly young adult males and elderly people, resulting in high economic costs to society. Therapeutic approaches focus on reducing the risk on secondary brain injury. Specific ethical issues pertaining in clinical testing of pharmacological neuroprotective agents in TBI include the emergency nature of the research, the incapacity of the patients to informed consent before inclusion, short therapeutic time windows, and a risk-benefit ratio based on concept that (...) in relation to the severity of the trauma, significant adverse side effects may be acceptable for possible beneficial treatments. Randomized controlled phase III trials investigating the safety and efficacy of agents in TBI with promising benefit, conducted in acute emergency situations with short therapeutic time windows, should allow randomization under deferred consent or waiver of consent. Making progress in knowledge of treatment in acute neurological and other intensive care conditions is only possible if national regulations and legislations allow waiver of consent or deferred consent for clinical trials. (shrink)

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the waiver (...) of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood - the standard treatment for hemorrhagic shock - is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)

In emergency research, obtaining informed consent can be problematic. Research to develop and improve treatments for patients admitted to hospital with life-threatening and debilitating conditions is much needed yet the issue of research without consent (RWC) raises concerns about unethical practices and the loss of individual autonomy. Consistent with the policy and practice turn towards greater patient and public involvement in health care decisions, in the US, Canada and EU, guidelines and legislation implemented to protect patients and facilitate acute research (...) with adults who are unable to give consent have been developed with little involvement of the lay public. This paper reviews research examining public opinion regarding RWC for research in emergency situations, and whether the rules and regulations permitting research of this kind are in accordance with the views of those who ultimately may be the most affected. (shrink)

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. (shrink)

This article focuses on emergency medical care in black urban populations, suggesting that the classification of a "community" within clinical trial language is problematic. The article references a cultural history of black Americans with pre-hospital emergency medical treatment as relevant to contemporary emergency medicine paradigms. Part I explores a relationship between "autonomy" and "community." The idea of community emerges as a displacement for the ethical principle of autonomy precisely at the moment that institutionalized medicine focuses on diversity. Part II examines (...) a clinical trial for the blood substitute PolyHeme® (Northfield Laboratories, Inc., Evanston, IL). It illustrates the ways in which bias in research paradigms and Institutional Review Board decisions attach to the notion and utility of the language of "community." The conclusion's contemporary anecdote makes apparent the vitality of the issues of prehospital emergency medical care and the ways in which decisions and practices fall too easily into a narrative of culturally biased treatment. (shrink)

Patients participating in the shared benefits of publicly funded health care enjoy the benefits of treatments tested on previous patients. Future patients similarly depend on treatments tested on present patients. Since properly designed research assumes that the treatments being studied are—so far as is known at the outset—equivalent in therapeutic value, no one is clinically disadvantaged merely by taking part in research, provided the research involves administering active treatments to all participants. This paper argues that, because no other practical or (...) moral considerations count decisively against so doing, we could and should oblige patients to agree to receive indicated treatment within the terms of any concurrent research protocols. This ensures their treatment will benefit not only themselves but also future patients through contributing to new knowledge. By analogy with the paying of income tax, patients should not be allowed to “veto” their social responsibility to take part in clinical research. (shrink)

Acute myocardial infarction (AMI) is a common disease in the Western world and has been the topic of much research. Conducting clinical trials with patients in the acute phase of a myocardial infarction, however, poses an ethical challenge. As patients are often under extreme stress and require urgent medical attention, the process of informed consent is severely constrained. Furthermore, the very procedure of informed consent, which is supposed to protect eligible patients, may be a cause of harm in itself due (...) to the delay in the provision of therapy which it causes. This paper describes how physicians have dealt with the informed consent process in various AMI trials and summarizes the results from empirical studies of the consent process of such trials. Finally, the ethical issues and their implications for future trials involving this particular group of patients are discussed. (shrink)

The ethics of conducting research in epidemic situations have yet to account fully for differences in the proportion and acuteness of epidemics, among other factors. While epidemics most often arise from infectious diseases, not all infectious diseases are of epidemic proportions, and not all epidemics occur acutely. These and other variations constrain the generalization of ethical decision-making and impose ethical demands on the individual researcher in a way not previously highlighted. This paper discusses a number of such constraints and impositions. (...) It applies the ethical principles enunciated by Emmanuel et al.1 to the controversial Pfizer study in Nigeria in order to highlight the particular ethical concerns of acute epidemic research, and suggest ways of meeting such challenges. The paper recommends that research during epidemics should be partly evaluated on its own merits in order to determine its ethical appropriateness to the specific situation. Snap decisions to conduct research during acute epidemics should be resisted. Community engagement, public notification and good information management are needed to promote the ethics of conducting research during acute epidemics. Individual consent is most at risk of being compromised, and every effort should be made to ensure that it is maintained and valid. Use of data safety management boards should be routine. Acute epidemics also present opportunities to enhance the social value of research and maximize its benefits to communities. Ethical research is possible in acute epidemics, if the potential challenges are thought of ahead of time and appropriate precautions taken. (shrink)

Background: In the USA, the Food and Drug Administration waiver of informed consent permits certain emergency research only if community consultation occurs. However, uncertainty exists regarding how to define the community or their representatives.Objective: To collect data on the actual preferences and values of a group—those at risk for stroke—most directly affected by the waiver of informed consent for emergency research.Design: Face to face focused interviews were conducted with 12 patients who were hospitalised with a stroke diagnosis in the previous (...) year. The interviews were audiotaped and a transcript based method was used for their analysis.Results: All 12 participants felt “that it was important that new treatments for stroke be developed”, but they were initially confused about the distinction between “research for stroke” and “emergency research for stroke”. However, after explanation, most expressed willingness to participate in the latter. In the absence of a surrogate to give informed consent in a stroke emergency situation, the majority said they would want the physician to “go ahead and enrol them in the trial”.Conclusions: This study is the first to identify the values and concerns of individuals most directly affected by stroke emergency research. Further interviews and focus groups are needed to develop and test a validated questionnaire on the preferences and values surrounding emergency research for stroke. (shrink)

The empirical results from recent randomised controlled studies on remote, intercessory prayer remain mixed. Several studies have, however, appeared in prestigious medical journals, and it is believed by many researchers, including apparent sceptics, that it makes sense to study intercessory prayer as if it were just another experimental drug treatment. This assumption is challenged by discussing problems posed by the need to obtain the informed consent of patients participating in the studies; pointing out that if the intercessors are indeed conscientious (...) religious believers, they should subvert the studies by praying for patients randomised to the control groups; and showing that the studies in question are characterised by an internal philosophical tension because the intercessors and the scientists must take incompatible views of what is going on: the intercessors must take a causation-first view, whereas the scientists must take a correlation-first view. It therefore makes no ethical or methodological sense to study remote, intercessory prayer as if it were just another drug. (shrink)

This article focuses on emergency medical care in black urban populations, suggesting that the classification of a ?community? within clinical trial language is problematic. The article references a cultural history of black Americans with pre-hospital emergency medical treatment as relevant to contemporary emergency medicine paradigms. Part I explores a relationship between ?autonomy? and ?community.? The idea of community emerges as a displacement for the ethical principle of autonomy precisely at the moment that institutionalized medicine focuses on diversity. Part II examines (...) a clinical trial for the blood substitute PolyHeme? (Northfield Laboratories, Inc., Evanston, IL). It illustrates the ways in which bias in research paradigms and Institutional Review Board decisions attach to the notion and utility of the language of ?community.? The conclusion's contemporary anecdote makes apparent the vitality of the issues of prehospital emergency medical care and the ways in which decisions and practices fall too easily into a narrative of culturally biased treatment. (shrink)

Background: In the USA, the Food and Drug Administration waiver of informed consent permits certain emergency research only if community consultation occurs. However, uncertainty exists regarding how to define the community or their representatives.Objective: To collect data on the actual preferences and values of a group—those at risk for stroke—most directly affected by the waiver of informed consent for emergency research.Design: Face to face focused interviews were conducted with 12 patients who were hospitalised with a stroke diagnosis in the previous (...) year. The interviews were audiotaped and a transcript based method was used for their analysis.Results: All 12 participants felt “that it was important that new treatments for stroke be developed”, but they were initially confused about the distinction between “research for stroke” and “emergency research for stroke”. However, after explanation, most expressed willingness to participate in the latter. In the absence of a surrogate to give informed consent in a stroke emergency situation, the majority said they would want the physician to “go ahead and enrol them in the trial”.Conclusions: This study is the first to identify the values and concerns of individuals most directly affected by stroke emergency research. Further interviews and focus groups are needed to develop and test a validated questionnaire on the preferences and values surrounding emergency research for stroke. (shrink)

The ethical concept of Informed Consent provides individuals with the right and the opportunity to approve of events that will occur regarding his or her own person. In medicine, informed consent is obtained for treatment and for research participation. However, under some circumstances, prospective informed consent cannot be obtained because of the devastating clinical condition of the patient. In emergency circumstances, treatment is never withheld if obtaining informed consent from a critically ill person is not possible or if a delay (...) while seeking surrogates would further endanger life. In emergency research circumstances, waiving informed consent for study participation is fraught with additional ethical considerations. This article will review a presentation given at the June 2, 2006 conference entitled “The Ethics of Research in Emergency Medicine”. (shrink)

OBJECTIVE: To apply component analysis, a structured approach to the ethical analysis of risks and potential benefits in research, to published emergency research using a waiver of/exception from informed consent. The hypothesis was that component analysis could be used with a high degree of interrater reliability, and that the vast majority of emergency research would comply with a minimal-risk threshold. METHODS: A Medline search and manual search were done to identify studies using a waiver of/exception from informed consent published between (...) July 1996 and December 2000. A review panel of physicians and bioethicists independently classified nontherapeutic procedures in each study as minimal risk, probably minimal risk, or probably more than minimal risk. RESULTS: Seventy studies using a waiver of/exception from informed consent were identified. A majority of reviewers classified nontherapeutic procedures in 62 studies (88.6%) as minimal risk. Reviewers classified nontherapeutic procedures in six studies (8.6%) as minimal risk or probably minimal risk. In two studies (2.9%), nontherapeutic procedures were classified as probably more than minimal risk. The intraclass correlation coefficient was 0.89 (95% CI = 0.85 to 0.93), indicating very high interrater reliability. CONCLUSIONS: Component analysis can be used with high reliability to review emergency research and may improve the consistency of institutional review board review of emergency research. The vast majority of published emergency research performed using a waiver of/exception from consent complies with a properly-applied minimal-risk threshold. A minimal-risk threshold for nontherapeutic procedures protects subjects better than current U.S. regulations while permitting important emergency research to continue. (shrink)