Informed consent provides research subjects a mechanism to protect themselves. Such a protection mechanism is necessary, because unlike in the clinical setting in which the interests of patients and doctors converge, researchers' interests in obtaining valid scientific data can conflict with their obligation to protect the rights and welfare of the research participants.
Critical care investigators face a difficult task of recruiting research subjects who may have diminished capacity to understand information, appreciate the situation they are in, and to make complex decisions. Indeed, studies have shown that patients with acute illnesses may have limitations in their decision-making capabilities due to a number of factors, including the presence of delirium, their underlying illness, or the use of sedatives and analgesics [11–16]. The presence of these factors does not necessarily translate into incapacity to provide a valid informed consent to research. Indeed, two types of errors can occur in the setting of obtaining informed consent from critically ill patients. One, surrogate consent is obtained for patients who are capable of providing consent, thus depriving such patients their autonomy rights to choose for themselves. The opposite error occurs when investigators obtain informed consent from patients who lack decisional capacity, thus making them vulnerable to exploitation. Several studies have documented that many enrolled subjects have limited understanding of the research to which they provided consent [17–20].
Another issue with the proper obtainment of informed consent involves the ability of research participants to distinguish between research and clinical care . "Therapeutic misconception" (TM) is used to describe this phenomenon, a term first reported by Appelbaum and colleagues in 1982 during interviews with patients with psychiatric disorders who participated in clinical trials . Indeed, several empirical studies have shown that individuals participating in clinical research misconstrue a therapeutic intention to the research procedures in a study [23–26].
Investigators have identified two ways in which TM can be manifested: 1) when research participants fail to recognize that decisions regarding randomization or certain aspects of the research procedures (e.g., dosages and duration of administered drugs) will not be individualized to their personal needs (TM1); or 2) when research participants hold an unreasonable appraisal of the nature or likelihood of medical benefit from their study participation (TM2) . Essentially, research participants might hold mistaken beliefs about how the research will be executed (TM1) or is designed in a manner to ensure direct benefits to them (TM2) .
Investigators have explored the frequency and the factors (both participant- and study-related) that might underlie the existence of TM in clinical research [23, 25–27]. In a study involving patients in different types of clinical trials, those with greater age, lower levels of education, poorer health and functional status, and those with greater optimism about their health in the future were at higher risk for manifesting TM . In another study involving early-phase gene transfer trials, participants with cancer or vascular diseases exhibited TM more frequently than those with inherited or infectious diseases. Also, the presence of TM was significantly less in patients who received a consistent message that benefits were unlikely compared with those who did not receive any such messages . Finally, in a study involving more than 270 patients enrolled in clinical trials, TM was present in 70% of respondents and it presence was positively associated with the acuteness and severity of the disease .
The presence of TM might be explained by participants' knowledge gap regarding how clinical research and patient care differ in their purpose, characteristic methods, and justification of risks . Alternatively, it might be due to participants' misplaced trust in researchers, thinking that they will act as their physicians who will protect them, as well as promote their individual health interests . Finally, the conduction of research studies in the clinical setting might reinforce the presence of treatment relationships and individualized care. Accordingly, many patients who enroll in research might think that their care will still be individualized to match their personal medical needs even in the context of a research study . Such perceptions might be enhanced by the use of certain language found in consent forms (such as "doctor" instead of "investigator," and "treatment" instead of "intervention"), the "therapeutic" discourse used by nurses and physicians conducting clinical trials , or the recruitment of patients into clinical trials by investigators who also their primary physicians.
There are two major ethical concerns with the TM. First, failure to appreciate correctly the risks and benefits of research participation raises concerns regarding the validity of informed consent [21, 23]. Second, the presence of TM reflects the very real possibility that research participants will see the investigator's role as that of the physician and view an invitation to enroll in research as a professional recommendation that is intended to serve their individual treatment interests. Such inappropriate enrollment of patients into research reflects a concern with exploitation .