A parent’s worst nightmare comes true: their child is diagnosed with a serious illness. In the flood of emotions that follow such a diagnosis, a parent is asked to make complex decisions about medical care. They may also be asked to give permission for their child to participate in a research study, an activity which may hold out greater hope for disease mitigation but which also presents a less certain outcome than standard of care. How can a parent in the throes of such distress make an informed and rational choice about their child’s participation in a clinical research study?
The informed consent process is considered to be the cornerstone of human subject protection. The validity of the process rests upon a number of criteria, including 1) presenting the subject with complete and accurate information; 2) allowing adequate time for consideration of the information; 3) assessing comprehension; and 4) ensuring that the subject’s decision to participate is made voluntarily, that is, autonomously and free from coercion.
In the case of a young child who lacks the cognitive ability to understand complex medical and scientific information, the criterion of ensuring the subject’s comprehension cannot be met. Similarly, a young child has not developed full autonomy or authority over their own decisions. Thus, the parent stands as facilitator and surrogate for many aspects of the process: to comprehend what their child cannot, to protect as far as possible their child’s autonomy, and to act as the authority for the child’s decision.
If the child is considered capable, he or she is asked to provide assent, a threshold set by the regulations as “… a child’s affirmative agreement to participate in a clinical investigation.” In addition, the parent is asked to provide permission (“permission” as distinct from an adult consenting to their own participation in a research study) for their child’s participation. The four criteria elaborated above must be met for parental permission to be considered valid. Assuming that the first criterion is met through an IRB-approved permission document, how can the remaining three be assured?
Parents who felt they had insufficient time to consider research information scored lower on measurements of voluntariness, and “giving parents more time to make their decision” is one of the suggestions most commonly made for improving the permission process. How much time is enough time? The answer depends on a multitude of factors, including the parents’ familiarity with medical and scientific concepts, their level of trust in the person presenting the information (unfamiliar principal investigator? trusted pediatrician?), the complexity of the proposed research, and the severity of their child’s illness. The judgement is best made by assessing subjective (emotional state) and objective (comprehension of information) parameters, and best done by someone familiar with the individual parent(s).
How then can comprehension be gauged? Validated instruments such as the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR) and the University of California, San Diego Brief Assessment of Capacity to Consent (UBACC) probe an individual’s grasp of both study-specific information (purpose, procedures, risks, and benefits) and more general questions pertaining to research participation. In the latter category are questions regarding the therapeutic misconception as well as the voluntary nature of participation, and freedom to withdraw from the study. Additionally, quizzes on study-specific information can be administered to the parents during the initial permission process and periodically thereafter as a means both of evaluating comprehension and reinforcing understanding.
Voluntariness of action (that is, making a choice of one’s free will as opposed to as a result of coercion or duress) becomes significantly more complicated in the scenario of a parent giving permission on behalf of their sick child. Sources of perceived and/or felt coercion acting on the parent include (a fractional list) fear of displeasing medical personnel; lack of understanding alternatives to participation; being presented with too much or too little information; and the anticipation of regret about failing to protect one’s child. A validated instrument called the Decision-Making Control Instrument (DMCI) has been developed, predicated on the assumption that while voluntariness of action cannot be directly measured, a person’s subjective perception of whether they have acted voluntarily can be captured semi-quantitatively. Lower scores on the DMCI are associated with a parent’s perception of increased external influence, time pressure, concern that their child’s care will suffer if they decline, and a perception that they did not receive the right amount of information.
Continuous consent is a process that stands to improve the quality of permission in many domains. The gist of the process is to foster an ongoing communicative relationship with the parent spanning the life of the study, to present research-related information at multiple time points to improve assimilation and to seek renewal of consent each time the information is given. This process has been shown to improve competence, comprehension, and voluntariness scores, as well as to communicate to parents that the researchers view the informed consent process as important.
All the validated instruments in the world, gratifying as they are, do not supplant the principles of compassion and patience that must be brought to bear in these difficult situations. The validity of permission obtained from a newly traumatized parent may be increased by:
- Presenting an amount and complexity of information calibrated to avoid overwhelming the parent; while the threshold requirements must certainly be met at the initial point of obtaining permission, more information can be added post signature;
- Allowing additional and sufficient time for consideration, understanding that emotional trauma decreases a parent’s ability to absorb and understand vital information;
- Testing for comprehension by repeated administration of study-specific quizzes as well as validated instruments;
- Monitoring for and minimizing therapeutic misconception;
- Reinforcing the voluntary nature of participation; and
- Cultivating open communication with the parent over the life of the study.
 21 CFR 50.20
 21 CFR 50.3
 Roth-Cline M and Nelson RM (2013). Parental Permission and Child Assent in Research on Children. Yale J Bio Med 86: 291-301
 Eder M, Yamokoski AD, Wittman PW, and Kodish ED (2007). Improving Informed Consent: Suggestions from Parents of Children with Leukemia. Pediatrics 119(4):849-59
 Shilling V and Young B (2009). How Do Parents Experience Being Asked to Enter a Child in a Randomised Controlled Trial? BMC Med Ethics 10:1
 Jeste DV, Palmer BW, Appelbaum PS, Golshan S, Glorioso D, Dunn LB, Kim K, Meeks T, and Kraemer HC (2007). A New Brief Instrument for Assessing Decisional Capacity for Clinical Research. Arch Gen Psych 64 (8): 966-974
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