Cindy Munro, PhD, RN, ANP, FAAN Professor, School of Nursing, IRB Panel A Member, Virginia Commonwealth University

 examine legislation of other countries (particularly European and Asian countries, which have strong critical care research programs) regarding consent in the critical care setting, and compare those to the diversity of state legislation in the United States.

 Difficulty receiving and comprehending research study information  Difficulty communicating wishes  Difficulty differentiating research procedures from clinical care  Cognitive impairment

 Cognitive impairment can arise from ◦ therapeutic interventions (such as sedation and pain medications) ◦ pathophysiology and disease processes  Delirium is common  Level of cognition can fluctuate widely over a short period of time

 Consent for care is distinct from consent to participate in research  There is a “heterogeneity of consenting practices” for invasive non-research procedures in critical care in the United States (Manthous, et al., 2003) which affects perceptions of risk and appropriate consent practices for research

 Existing literature regarding focuses on those who will likely not regain competence  Critically ill persons are often decisionally impaired during the acute event, but may regain competence

 44 adults in intensive care unit participating in clinical trial about inflammation ◦ Glasgow Coma Scale score of 15, be fully oriented and free of mechanical ventilation, and be judged competent by both the investigator and the attending physician.  Questioned 10 days after consent

 Waiver of some or all elements of informed consent  Prospective consent  Retrospective consent  Proxy consent

 38 adults in surgical intensive care unit post cardiac surgery participating in coagulation study  Consented day before elective surgery  Questioned 10 days after consent

US Federal Code  “ legally effective informed consent of the subject or the subject's legally authorized representative” (45 CFR ). (covers all human subjects research)  defer to US state laws to define who is authorized to act (these laws vary widely) EU Directive 2001/20/EC “the written consent of the patient's legal representative, given in cooperation with the treating doctor, is necessary before participation in any such clinical trial.” (covers clinical trials of medicinal products only) defer to EU member nation laws to define who is authorized to act (these laws vary widely)

 ‘clinical trial’: any investigation in human subjects intended to discover or verify the clinical, pharmacological and/or other pharmacodynamic effects of one or more investigational medicinal product(s), and/or to identify any adverse reactions to one or more investigational medicinal product(s) and/or to study absorption, distribution, metabolism and excretion of one or more investigational medicinal product(s) with the object of ascertaining its (their) safety and/or efficacy;

 ONLY Virginia (since 1999) and California (since 2003) have specific legislation identifying who may give proxy consent  Several states specify legal representative for medical care decisions without specifically addressing research consent  Other states lack legislation addressing proxy consent for either medical care or research

 Austria ◦ Legally authorized representative appointed by a judge for proxy consent for research (all research)  Germany ◦ Legally authorized representative appointed by a judge for proxy consent for research (research involving pharmaceuticals)  France ◦ Family members who can consent to care can consent to research

 UK, Medical Health Act ◦ 2004, strict interpretation of directive, with no proxy permitted ◦ 2005, legal representative proxy  personal representative not connected with the conduct of the trial and who is suitable to act in this capacity by virtue of their relationship with the patient, and is available and willing to do so  If no personal representative is available, then a professional legal representative not connected with the conduct of the trial, who is either the doctor responsible for the patient’s treatment or someone nominated by the relevant health care provider, can be approached

 Netherlands, Dutch Directive on Medical Research Involving Human Subjects ◦ 1998, only spouse or life companion may give proxy consent for research ◦ 2006, broadened to parents, children, siblings

 In both cases (US and EU), implementation and interpretation of the overarching documents are delegated to the member entities.  In both cases (US and EU), the implementation and interpretations vary widely.  “The legal and ethical acceptability of third party permission for nonbeneficial research is jurisdiction specific, which is a source of ongoing debate and is often subject to inconsistent directives.” (Shaul, 2005)