‘Yesterday, We Included Your Son in a Clinical Trial’ Conducting Research in Critically Ill Patients, Without Prior Consent

‘Yesterday, We Included Your Son in a Clinical Trial’ Conducting Research in Critically Ill Patients, Without Prior Consent

  • Issue 64

Marjolein Timmers, Erwin J.O. Kompanje | Department of intensive Care, Erasmus MC University Medical Center, Rotterdam, The Netherlands
erwinkompanje@me.com

The mortality and morbidity rates in patients with acute, life-threatening conditions such as severe traumatic brain injury, cardiac arrest, severe sepsis, and stroke are high. Therefore, an ethical imperative exists to develop and test new therapeutic strategies for these conditions. Conducting research in emergency and critical care settings provokes several unique ethical, legal, and practical concerns: the emergency nature of the intervention, the incapacity of the patients (and their relatives) to give informed consent before inclusion, short therapeutic time windows, and a relatively high risk-benefit ratio that may be acceptable in view of an already bad prognosis. The issue of conducting research in emergency settings, without prior patient or proxy consent, is an especially challenging one. Stating that prior informed consent is absolutely necessary would mean that it is almost impossible to conduct emergency research.

For good reason, (inter)national regulations on principles of good clinical practice are applied to all medical research. In addition, ethical principles include respect for autonomy of the subject; protection against discomfort, risk, and exploitation; preventing harm; and the prospect of potential benefit.1 Obtaining prior informed consent respects these basic principles. However, informed consent can seldom be obtained from patients in emergency and critical care settings. Most institutional review boards have pragmatically accepted that proxies should then provide prior informed consent. Nevertheless, these proxies are not always available in a timely manner or are, in the acute phase, too overwhelmed by the serious patient condition to understand the provided information in order to give a valid judgment.1 So, can we include patients in research projects without prior consent in the acute phase? In most European countries it is nowadays legal to defer (patient and proxy) consent, but this issue is not always settled in domestic law. With deferred consent, patients are included in a trial without prior consent. After inclusion, the patient or his/her representatives should be informed as soon as ethically feasible and subsequent consent should be requested.1 This principle of ‘act first and ask later’ is ethically, legally, and practically defendable.2 From the patients’ point of view, they can profit from the presumed benefit of the trial drug or intervention. From the representatives’ point of view, they will be spared the burden of setting their mind on deciding to consent or refuse inclusion of their loved one in acute medical research. From a practical point of view, researchers do not have to wait with a possibly beneficial treatment until the moment it is ethically valid to approach the proxies of the acutely ill patient for the consent procedure. As long as the mortality and morbidity of severely ill or traumatized patients are high and the benefit of standard treatment is low, we have to keep on searching for additional and effective treatments.3 Deferred consent is an ethically valid solution to such research; so, in many European countries, the family of a critically ill patient in intensive care can be asked for consent for inclusion in a trial starting the question with ‘Yesterday, we included your son in a clinical trial’.

References
1 Jansen TC, Kompanje EJO, Bakker J. Crit Care Med 2009;37(1 Suppl.):65-8.
2 Kompanje EJO, Maas AIR. Intensive Care Med 2004;30:168–9.
3 Kompanje EJO, Bernstein M. Consent in Emergency Clinical Research, in: Ammar A, Bernstein M (eds.). Neurosurgical Ethics in Practice: Value-based Medicine. Springer: Berlin Heidelberg, 2014;17:191-200.