A great majority of ICU patients who had consented to participate in a clinical trial during their ICU stay recalled their clinical trial participation after 10 ± 2 days. Other studies, including those on patients with acute myocardial infarction, have reported clinical trial participation recall rates similar to ours [14
]. Our rate is also similar to the rate we found in a study in which informed consent was obtained in an ideal situation, namely before ICU admission [9
Although this may seem very encouraging, only 32% of the patients who gave consent during their ICU stay recalled clinical trial components; this is in contrast to our 'ideal situation' previous study in which 75% of patients had a complete recall [9
]. The low rate of complete recall in the present study could be explained by the difficulty of some ICU patients to process information given the stress of the acute phase and possibly experiencing feelings of dependence and anguish [17
]. Our routine clinical evaluation might not detect this potential cognitive defect [18
]. The reasons why some patients are able to recall whereas others cannot therefore remain unclear.
The severity of disease, the neurological status of the patients, and the medications received in the ICU when informed consent was obtained and during the 24 hours after the informed consent procedure were similar in both groups of our patients.
Inadequate information disclosure to some patients that could explain our results can reasonably be excluded because the information procedure was well standardized. In contrast with previous reports, we found that neither age nor educational status influenced the ability to recall clinical trial components [19
]. This might reflect the fact that the information presented was not difficult to understand.
If the informed consent satisfies the three criteria specified by international guidelines, the consent is deemed valid [1
]. However, if the clinical trial has already begun and the patient is unaware of the purpose, related risks, and their participation in the clinical trial, they are obviously unable to decide mindfully whether to continue in the clinical trial or to withdraw from it at any time. In this case, we might question the respect of the participant's autonomy offered by the informed consent. This leads us to view the informed consent as a process rather than a simple procedure. The informed consent process requires, to our mind, multiple conversations on several occasions while the research is conducted.
We found simple but important factors associated with complete recall of the clinical trial components. We tried to identify factors that were easy to observe by an investigator such as 'asking questions' and 'reading the informative leaflet'. In our previous study, we found that more patients who were able to mention all clinical trial components had read the leaflet and had asked at least one question. 'Asking questions' increased the chance of recall in critically ill patients. We could speculate inversely that asking no questions could increase the potential for poor initial comprehension of the clinical trial components.
Our results are in line with Flory and Emanuel's findings [22
], which concluded that person-to-person interaction with clinical trial participants may be the most effective way of improving their understanding.
This finding revives the debate about informed consent for research in the ICU. In the past, deferred consent [23
] or waiving of consent for research in the emergency setting [24
] was considered acceptable in particular research situations. However, during the past few years, legislation has tried to enhance protection for incompetent patients. Barriers to the inclusion of ICU patients in research studies have increased, especially across Europe [2
]. We fully support the idea that oversight is necessary to ensure the uniform application of ethical standards [11
], but the most dependable safeguard for the research subject is investigator understanding and respect of the ethical requirements of clinical research.
Our study presents some limitations. First, the small number of patients enrolled was dependent on the clinical trial. This might have impeded the detection of other potential factors that could influence the recall of the clinical trial. In addition, the small clinical trial size precluded the possibility of a multivariate analysis. Second, we did not investigate the recall of patients who had refused to participate in the clinical trial on inflammation primarily because there was no consent to investigate. Perhaps the degree of recall might have been different in patients who had refused participation. Third, we did not assess patients' cognitive capacity. There is good evidence that the cognitive capacity of ICU patients, or even sick patients in general, is impaired [27
]. However, spending more time with patients to test their cognitive capacity, and interacting with them for much longer than for a 'standard' informed consent procedure, would have biased our results. It is for this same reason that we did not measure the patients' memory. Fourth, scores of severity of illness and laboratory values may suggest that patients with incomplete recall were more ill than those with complete recall. Although not statistically significant, these results do not allow for the possibility that the severity of the disease might act on recall. However, the fundamental message remains that a poor rate of recall of a clinical trial is present in ICU patients. Finally, as our patients were presumed fully competent, the study faced the best possible situation in ICU patients. We are aware that these patients do not represent the majority of ICU patients and our results may therefore not be generalizable. However, it is reasonable to speculate that the rate of recall may be even worse in usual patients in the ICU.