European legislation impedes critical care research and fails to protect patients' rights

Abstract

The European Clinical Trials Directive requires an informed consent from the patient or a proxy in drug trials. Although informed consent is a valuable tool to protect patients' rights in clinical trials, this requirement largely impedes research in critical care settings, and if pursued in this context, it does not provide the patient with adequate protection. Instead of insisting on informed consent, we suggest that the focus should be shifted towards two other ethically relevant elements in human experimentation: risk assessment and selection of research subjects. When reviewing protocols in which a waiver of consent is deemed necessary, the Ethical Review Board should ensure that non-therapeutic risks are minimal, that the research is specifically designed to benefit critically ill patients, and that it cannot be conducted under circumstances where an informed consent can be obtained. If the European Directive is changed accordingly, this permits clinical trials in critical care settings, while adequate protection from risky non-therapeutic procedures is ensured and exploitation of the patient as an easily accessible research subject is prevented.

Exceptions to the rule of informed consent for research with an intervention

“…For example, severely ill patients who are focused on their treatment and recovery [ 41 ], and who may already be quite anxious [ 42 ], may find it disturbing to be informed about a study. Similarly, the stressfulness of the medical situation is thought to inhibit potential study participants from grasping the rationale of the study, especially in emergency research [ 36 , 37 , 43 ], for example when patients have suffered an acute myocardial infarction [ 36 ]. Others have argued that patients might also be negatively affected by the knowledge that their physician does not know which treatment is best [ 44 , 45 ].…”

“…Emergency research is the most often mentioned example in all contexts described, and it is the most notable research discipline in which practical problems are forwarded as the primary reason why the informed consent requirement should be waived. This is because it is simply impossible to ask (temporarily) incapacitated patients for informed consent [ 1 , 5 , 23 , 33 , 34 , 36 , 38 , 40 , 43 , 45 , 47 – 95 ]. Patient populations often mentioned in this context are those with acute head or brain injuries [ 5 , 25 , 34 , 38 , 39 , 74 , 96 ], and comatose, unconscious or sedated patients [ 49 , 92 ], although a much wider range of relevant patient populations has also been named [ 40 , 58 , 60 , 63 , 65 , 66 , 97 – 105 ].…”

An ethical analysis of proxy and waiver of consent in critical care research

“…At best, they may assess whether the protocol violates the patient's best interest from a clinical point of view, an assessment that has already been made by the research ethical committee. Thus, so‐called proxy consent in the form of a signature from a health professional or a lawyer represents a legal formalism that fails to protect the patient's basic rights, while impeding critical care research where immediate intervention is required …”

“…If this protection is not achievable by proxy consent, other means should be instituted. To obey the categorical imperative, the focus must therefore be shifted from the consent procedure to other ethically relevant aspects of the research practice, namely the incremental risk imposed by research participation and the selection of research subjects . Thus, the non‐therapeutic risk imposed by research participation must comprise no more than a minimal risk .…”

“…According to national legislation in some countries, a waiver is only permitted if the therapeutic intervention in the study has the prospect of benefiting the individual patient. However, based on the componential risk assessment, it is clear that such a distinction is ethically irrelevant, as long as the non‐therapeutic risk constitutes no more than a minimal risk …”