Intensive Care Med DOI 10.1007/s00134-014-3557-4
Antoniu O. Petris¸ Diana C. Cimpoes¸ u Didona Ungureanu
WHAT’S NEW IN INTENSIVE CA RE
What’s new in ethics of cardio-pulmonary resuscitation research: too little time and too many rules?
Received: 2 July 2014 Accepted: 9 November 2014 Ó Springer-Verlag Berlin Heidelberg and ESICM 2014 A. O. Petris¸ ()) Cardiology Clinic, ‘‘St. Spiridon’’ County Emergency Hospital, University of Medicine and Pharmacy ‘‘Grigore T. Popa’’, B-dul Independent¸ ei nr. 1, 700111 Ias¸ i, Romania e-mail: [email protected] Tel.: ?40-723597500 D. C. Cimpoes¸ u Discipline Emergency Medicine, ‘‘St. Spiridon’’ County Emergency Hospital, University of Medicine and Pharmacy ‘‘Grigore T. Popa’’, Ias¸ i, Romania D. Ungureanu Department of Immunology, ‘‘St. Spiridon’’ County Emergency Hospital, University of Medicine and Pharmacy ‘‘Grigore T. Popa’’, Ias¸ i, Romania
Nowadays, any clinical trial must fulfill the principles of ethical conduct of research involving human subjects [1]: respect for persons, beneficence and justice. The informed consent processes for cardiopulmonary resuscitation (CPR) research are carried out in time-limited and emergency circumstances involving vulnerable patients who must be protected in the best way possible, while at the same time allowing research to proceed that will improve the effectiveness of CPR. The valid informed consent consists of adequate disclosure of information, sufficient subject understanding of the information and voluntariness of the decision [2]. Common sense argues that ‘‘obtaining an informed consent in emergency conditions’’ gives rise to a contradiction in terms [3]. Compared to common medical research, obtaining an
informed consent in emergency research is quite different: it relates to an incapacitated patient or to his next-of-kin/ proxy/legal guardian who actually arrive later at the event site or in the hospital emergency department, who are often under considerable emotional stress and who do not have the opportunity to properly weigh the decision to participate or not in such research. We will review the contemporary ethical approaches related to informed consent in emergency research (Table 1). The without-consent model This presumes that, as long as welfare interests of patients are preserved, the same spplies to their autonomy interests [4]. In reality, this is not an ethical approach: it casts doubts on the principle of patient autonomy and undermines the patient’s trust in his physician. Sanders suggested that CPR research could be conducted without consent if the research used a continuous quality improvement model rather than using the randomized trial design [5]. Although this approach may be useful for some studies of CPR quality improvement, it will not allow the same degree of rigor and causal inference as using randomized trials and would relegate CPR research to a lower quality of evidence. Prospective informed consent The investigators try to identify and obtain in advance the consent from as many members of the ‘‘high-risk’’ group as possible, hoping that many of them will develop the studied emergency condition. It is a task not always easy to achieve: e.g. the HAT trial [6]: from 2003 to 2005, patients with acute myocardial infarction were randomly assigned to receive, if necessary, a standard CPR with/without home automated external defibrillator (AED). These patients revascularized in 72 % of cases had a mortality of only 2 % and not the anticipated mortality of 4 %, which has been calculated on the basis of a prior trial (1990–1993) which recruited unselected patients with ST-elevation infarction. The authors recognized that the lower-thanexpected rate of sudden death, the scarcity of shockable rhythm and the worse-than predicted outcome of the
Table 1 Contemporary ethical approaches in CPR research: advantages versus disadvantages Approach
Advantages
Disadvantages
The without-consent Fast recruitment of a great number of patients model The prospective It respects the patients’ autonomy principle. It informed consent identifies the ‘‘high-risk’’ group within which the event is most likely to occur The integrated clinical consent procedure The consent from professional legal representative The deferred informed consent
It respects the patients’ autonomy principle. It can include most of patients from the community with this emergency condition A pragmatic approach: the informed consent can be given by the patient’s professional legal representative (PLR) A pragmatic approach: obtain the consent later from patient, if recovers, or from his legally authorized representative (LAR) [8]
appropriate delivery of AED shock did not allow the validation of the HAT trial assumptions. Integrated clinical consent procedure A prospective informed consent at community scale including all people, not just those from the ‘‘high-risk’’ group. The investigators incorporate the research element into a familiar clinical conversation that makes the research protocol transparent to the patient or to his legal representative [4]. However, this approach is often difficult to achieve because it is resource-intensive, time-consuming, and may not be feasible in regions with diverse and complex communities. Authorized representative consent The Directive 2001/20/EC provides the possibility for clinical trials on incapacitated adults not able to give informed legal consent to obtain this consent from the legal representative of the patient [7]. The wording ‘‘legal representative’’ has created problems because in some countries it has been interpreted as requiring a court order as to whom the legal representative is, while in other countries proxy consent was considered good enough [8]. Furthermore, it is very problematic for medical personnel to be designated as patient legal representatives because of the built-in danger of partiality [5].
No autonomy: patients are unaware that they have been included in a clinical trial [4] It is difficult to achieve the 1:100:10,000 ratio (to identify one case of the ‘‘high risk’’ group it is necessary to recruit 100 cases and must obtain the consent of 10,000 subjects) [3]. It may alter subjects’ behavior (the Hawthorne effect) This approach is resource-intensive, time-consuming, and may not be feasible in regions with diverse and complex communities Different interpretations on the definition of PLR. Builtin danger of partiality [5] It requires consent to something that has already happened. Concerns if LAR really know patients’ wishes [3]
Deferred informed consent Investigators start to recruit suitable subjects later obtaining consent from the patient, if he recovers, or from his legally authorized representative. The deferred consent approach is accepted as a substitute for informed consent in approximately half of the EU member states [8]. The EU Commission proposed a regulation which would replace the directive 2001/20, with the main aim to simplify and speed up the process of authorization and conduct of clinical trials, according to which deferred consent in emergency situations is acceptable [9]. Achieving progress in cardiac arrest research is only possible if national legislations allow deferred consent for clinical trials. It is the right and the responsibility of the community to support but also to constantly check (‘‘trust and vigilance’’) how the trials will take place in major emergencies. Acknowledgement Scientific research was funded by the University of Medicine and Pharmacy ‘‘Grigore T. Popa’’ Ias¸ i, based on the contract No. 1851/05.02.2013. Conflicts of interest
None.
References 5. Sanders AB (2011) Cardiac arrest and 1. Vollmer SH, Howard G (2010) Statistical 3. Booth MG (2007) Informed consent in the limitations of clinical trials. N Engl J emergency research: a contradiction in power, the Belmont Report, and the Med 365:850–851 terms. Sci Eng Ethic 13:351–359 ethics of clinical trials. Sci Eng Ethic 6. Bardy GH, Lee KL, Mark DB et al 4. Kim SYH, Miller FG (2014) Informed 16:675–691 (2008) Home use of automated external consent for pragmatic trials—the 2. Silverman HJ, Lemaire F (2006) Ethics defibrillators for sudden cardiac arrest. integrated consent model. N Engl J Med and research in critical care. Intensive N Engl J Med 358:1793–1804 370:769–772 Care Med 32:1697–1705
http://ec.europa.eu/health/files/eudralex/ 9. Matei M, Kompanje EJO, Maas AIR, 7. Directive 2001/20/EC of the European Menon DK, Lemaire F (2013) Clinical vol-1/dir_2001_20/dir_2001_20_en.pdf parliament and of the council of 4 April research into the ICU: clouds at the 2001 on the approximation of the laws, 8. Kompanje EJO, Maas AIR, Menon DK, horizon, once again. Intensive Care Med Kesecioglu J (2014) Medical research in regulations and administrative provisions 39:1479–1480 emergency research in the European of the member states relating to the Union member states: tensions between implementation of good clinical practice theory and practice. Intensive Care Med in the conduct of clinical trials on 40:496–503 medicinal products for human use. Off J Eur Commun L121:34–44.
Antoniu O. Petris¸ Diana C. Cimpoes¸ u Didona Ungureanu
WHAT’S NEW IN INTENSIVE CA RE
What’s new in ethics of cardio-pulmonary resuscitation research: too little time and too many rules?
Received: 2 July 2014 Accepted: 9 November 2014 Ó Springer-Verlag Berlin Heidelberg and ESICM 2014 A. O. Petris¸ ()) Cardiology Clinic, ‘‘St. Spiridon’’ County Emergency Hospital, University of Medicine and Pharmacy ‘‘Grigore T. Popa’’, B-dul Independent¸ ei nr. 1, 700111 Ias¸ i, Romania e-mail: [email protected] Tel.: ?40-723597500 D. C. Cimpoes¸ u Discipline Emergency Medicine, ‘‘St. Spiridon’’ County Emergency Hospital, University of Medicine and Pharmacy ‘‘Grigore T. Popa’’, Ias¸ i, Romania D. Ungureanu Department of Immunology, ‘‘St. Spiridon’’ County Emergency Hospital, University of Medicine and Pharmacy ‘‘Grigore T. Popa’’, Ias¸ i, Romania
Nowadays, any clinical trial must fulfill the principles of ethical conduct of research involving human subjects [1]: respect for persons, beneficence and justice. The informed consent processes for cardiopulmonary resuscitation (CPR) research are carried out in time-limited and emergency circumstances involving vulnerable patients who must be protected in the best way possible, while at the same time allowing research to proceed that will improve the effectiveness of CPR. The valid informed consent consists of adequate disclosure of information, sufficient subject understanding of the information and voluntariness of the decision [2]. Common sense argues that ‘‘obtaining an informed consent in emergency conditions’’ gives rise to a contradiction in terms [3]. Compared to common medical research, obtaining an
informed consent in emergency research is quite different: it relates to an incapacitated patient or to his next-of-kin/ proxy/legal guardian who actually arrive later at the event site or in the hospital emergency department, who are often under considerable emotional stress and who do not have the opportunity to properly weigh the decision to participate or not in such research. We will review the contemporary ethical approaches related to informed consent in emergency research (Table 1). The without-consent model This presumes that, as long as welfare interests of patients are preserved, the same spplies to their autonomy interests [4]. In reality, this is not an ethical approach: it casts doubts on the principle of patient autonomy and undermines the patient’s trust in his physician. Sanders suggested that CPR research could be conducted without consent if the research used a continuous quality improvement model rather than using the randomized trial design [5]. Although this approach may be useful for some studies of CPR quality improvement, it will not allow the same degree of rigor and causal inference as using randomized trials and would relegate CPR research to a lower quality of evidence. Prospective informed consent The investigators try to identify and obtain in advance the consent from as many members of the ‘‘high-risk’’ group as possible, hoping that many of them will develop the studied emergency condition. It is a task not always easy to achieve: e.g. the HAT trial [6]: from 2003 to 2005, patients with acute myocardial infarction were randomly assigned to receive, if necessary, a standard CPR with/without home automated external defibrillator (AED). These patients revascularized in 72 % of cases had a mortality of only 2 % and not the anticipated mortality of 4 %, which has been calculated on the basis of a prior trial (1990–1993) which recruited unselected patients with ST-elevation infarction. The authors recognized that the lower-thanexpected rate of sudden death, the scarcity of shockable rhythm and the worse-than predicted outcome of the
Table 1 Contemporary ethical approaches in CPR research: advantages versus disadvantages Approach
Advantages
Disadvantages
The without-consent Fast recruitment of a great number of patients model The prospective It respects the patients’ autonomy principle. It informed consent identifies the ‘‘high-risk’’ group within which the event is most likely to occur The integrated clinical consent procedure The consent from professional legal representative The deferred informed consent
It respects the patients’ autonomy principle. It can include most of patients from the community with this emergency condition A pragmatic approach: the informed consent can be given by the patient’s professional legal representative (PLR) A pragmatic approach: obtain the consent later from patient, if recovers, or from his legally authorized representative (LAR) [8]
appropriate delivery of AED shock did not allow the validation of the HAT trial assumptions. Integrated clinical consent procedure A prospective informed consent at community scale including all people, not just those from the ‘‘high-risk’’ group. The investigators incorporate the research element into a familiar clinical conversation that makes the research protocol transparent to the patient or to his legal representative [4]. However, this approach is often difficult to achieve because it is resource-intensive, time-consuming, and may not be feasible in regions with diverse and complex communities. Authorized representative consent The Directive 2001/20/EC provides the possibility for clinical trials on incapacitated adults not able to give informed legal consent to obtain this consent from the legal representative of the patient [7]. The wording ‘‘legal representative’’ has created problems because in some countries it has been interpreted as requiring a court order as to whom the legal representative is, while in other countries proxy consent was considered good enough [8]. Furthermore, it is very problematic for medical personnel to be designated as patient legal representatives because of the built-in danger of partiality [5].
No autonomy: patients are unaware that they have been included in a clinical trial [4] It is difficult to achieve the 1:100:10,000 ratio (to identify one case of the ‘‘high risk’’ group it is necessary to recruit 100 cases and must obtain the consent of 10,000 subjects) [3]. It may alter subjects’ behavior (the Hawthorne effect) This approach is resource-intensive, time-consuming, and may not be feasible in regions with diverse and complex communities Different interpretations on the definition of PLR. Builtin danger of partiality [5] It requires consent to something that has already happened. Concerns if LAR really know patients’ wishes [3]
Deferred informed consent Investigators start to recruit suitable subjects later obtaining consent from the patient, if he recovers, or from his legally authorized representative. The deferred consent approach is accepted as a substitute for informed consent in approximately half of the EU member states [8]. The EU Commission proposed a regulation which would replace the directive 2001/20, with the main aim to simplify and speed up the process of authorization and conduct of clinical trials, according to which deferred consent in emergency situations is acceptable [9]. Achieving progress in cardiac arrest research is only possible if national legislations allow deferred consent for clinical trials. It is the right and the responsibility of the community to support but also to constantly check (‘‘trust and vigilance’’) how the trials will take place in major emergencies. Acknowledgement Scientific research was funded by the University of Medicine and Pharmacy ‘‘Grigore T. Popa’’ Ias¸ i, based on the contract No. 1851/05.02.2013. Conflicts of interest
None.
References 5. Sanders AB (2011) Cardiac arrest and 1. Vollmer SH, Howard G (2010) Statistical 3. Booth MG (2007) Informed consent in the limitations of clinical trials. N Engl J emergency research: a contradiction in power, the Belmont Report, and the Med 365:850–851 terms. Sci Eng Ethic 13:351–359 ethics of clinical trials. Sci Eng Ethic 6. Bardy GH, Lee KL, Mark DB et al 4. Kim SYH, Miller FG (2014) Informed 16:675–691 (2008) Home use of automated external consent for pragmatic trials—the 2. Silverman HJ, Lemaire F (2006) Ethics defibrillators for sudden cardiac arrest. integrated consent model. N Engl J Med and research in critical care. Intensive N Engl J Med 358:1793–1804 370:769–772 Care Med 32:1697–1705
http://ec.europa.eu/health/files/eudralex/ 9. Matei M, Kompanje EJO, Maas AIR, 7. Directive 2001/20/EC of the European Menon DK, Lemaire F (2013) Clinical vol-1/dir_2001_20/dir_2001_20_en.pdf parliament and of the council of 4 April research into the ICU: clouds at the 2001 on the approximation of the laws, 8. Kompanje EJO, Maas AIR, Menon DK, horizon, once again. Intensive Care Med Kesecioglu J (2014) Medical research in regulations and administrative provisions 39:1479–1480 emergency research in the European of the member states relating to the Union member states: tensions between implementation of good clinical practice theory and practice. Intensive Care Med in the conduct of clinical trials on 40:496–503 medicinal products for human use. Off J Eur Commun L121:34–44.
