Consent is both an ethical and a legal concept. Legal guidelines for consent usually restrict children under a certain age from consenting to their own participation in research, although the age at which they may assume this role varies internationally. However, these legal guidelines are based on the ethical concept that some children are not yet mature enough to make autonomous decisions to assume the risk involved in research, and this maturity does not necessarily correlate with age. When children are not able to provide their consent, either because they are not yet old enough or not yet mature enough, parents are usually recognized as having the authority to provide this consent. Once parents give their consent, children are often asked whether they would like to participate, since their willing participation is important for both the safety of the child and the successful conduct of research. When parents have the authority to consent to their child's participation, if the child agrees he or she is said to assent to participation.
Even though parents are usually considered to be the appropriate adults to consent to their children's participation in research, their authority to do so is not absolute. This is a significant difference between research in adults and research in children. Adults are generally free to give their consent to participate in research that is approved by the appropriate research ethics panel. Parents are similarly free to give their consent to their children's participation when the risks posed by the study are low. When the risks are higher, parental consent is balanced with extra protections [6
]. The underlying ethical concept is that the autonomy of adults to agree to take on risk is extensive, but the autonomy of adults to agree for their child to take on risk is limited by the best interests of the child [6
Not all research requires that investigators obtain the informed consent of potential participants. Biobanks based on the third or fourth biobank model, because they fall under the nonhuman subjects category, do not need to obtain informed consent before including biological samples or health information. A sample from an adult can be included without that person's consent, and a sample from a child can be included without his or her parent's consent. In this context, samples from children and samples from adults are treated the same.
There is no international consensus, however, on which types of research can be conducted without informed consent [7
]. The investigators who developed BioVU solicited input from patients through a mail survey and focus groups and also consulted with the medical center's clinical ethics committee and legal counsel. As a result of the input they received, they decided to offer patients the opportunity to ‘opt-out’ from having their blood sample included in the biorepository [5
]. More recently, a population-based survey we conducted in the Nashville (TN, USA) area demonstrated that support for a biobank that utilizes left over clinical samples and deidentified medical record information is 93.9% as long as patients are able to opt-out. When asked for their opinion about a hypothetical biobank which collects samples without asking for written permission, only 45.5% of respondents expressed support [Brothers KB, Morrison DR, Clayton EW, Unpublished data].
This survey was not specific to pediatric biobanking. In a separate study, we have explored parent support for extending BioVU to include children through semistructured interviews. In our discussions, parents were generally favorable to including children in BioVU. Many of them acknowledged the importance of conducting medical research to improve pediatric medical care, and liked that BioVU does not involve additional needle sticks. Most parents seemed to assume that they would have a choice about whether their child's information would be included, and gave their conditional support on being given this option. Even those parents who would allow their child's sample to be included wanted to be given the opportunity to choose [Brothers KB, Clayton EW, Unpublished data]. Given the importance of both respect for persons inherent in any medical research project and the importance of building trust in research, choosing an opt-out model for human nonsubjects biobanking seems very important.
However, informed consent and the opportunity to opt-out are not equivalent. The most obvious difference is that research utilizing an informed consent process requires that participants make an affirmative act to agree to participate; research based on an opt-out assumes that participants agree to be included unless they act to opt-out.
The role of authority is another important difference. Informed consent involves the expression by the participant of his or her values. The participant values the research being conducted, and therefore, is willing to assume the risks that are entailed by being a human subject in a research study. In order for this agreement to be meaningful, the person giving permission must have an adequate understanding of the risks involved and must have the legal and moral authority to make such a decision. In the case of a competent adult, that authority is held by the subject themself. In the case of a child, that authority is usually held by the parent.
Authority plays a different role in research utilizing an opt-out. In this case, the risk involved in being included in the study must be very low and the research being conducted must be consistent with the values of most patients. If this is the case, the vast majority of patients will be willing to participate. Offering the opportunity to opt-out of the research is a way to express respect for the wishes of those people who do not want to be included, so the opt-out procedure should be easy for patients to complete. In the case of BioVU, a check box is included on standard clinic check-in forms ().
The opt-out form used in BioVU, Vanderbilt University Medical Center's (TN, USA) biorepository
No specific legal authority is required to opt a patient out of the biobank by checking this box. In fact, seeking to confirm the authority of a person wishing to opt a patient out would serve only to complicate the opt-out procedure for patients. When the patient is a child then any family member bringing the child for medical care is allowed to opt him/her out of the biobank. In fact, even the child themself, whether 10 or 17 years old, is able to choose to exercise an opt-out.
These procedures to make opting-out easy for patients minimize the chances that a patient will be included in the biobank when he or she prefers to be excluded. The cost is that some patients will be excluded when the person with legal authority to make legal decisions for them would have allowed them to be included. This trade-off is acceptable because there is no significant risk to a patient when he or she is opted out, and the scientific goals of a biobank should be attainable even if some patients are not included.
These procedures are particularly favorable in pediatric biobanking because they introduce flexibility for mature children. An opt-out model does not entail the same consent/assent distinction that is so important in research based on an informed consent. Instead, either parent or child may choose to exercise an opt-out. In this way, mature children are able to have a say in their research participation regardless of age at the same time that parents are able to protect their children from inclusion in a research resource to which they object.
Another corollary of the opt-out model is the need for oversight. Because the opt-out approach does not involve the robust exchange of information present in formal informed consent, investigators cannot assume that those patients whose samples have been included in the biobank are aware of the scope of the research being carried out. This is true even if the biobank has made efforts to notify the public of the studies being performed using the resource. Because the information included is health information, and samples are collected in the clinical setting, it is reasonable to assume that patients expect samples will be used for research to improve health and medical care. Also, since their choice not to opt-out is clearly an act of trust, investigators have a duty to carefully utilize samples for research that meets these patient expectations. To put it more simply, research on topics that are controversial or have social implications beyond improving health and healthcare is best performed using samples from individuals who explicitly approve of this use of their samples.
BioVU has chosen to implement a review process for all studies that will utilize samples. This process includes, among other elements, an ethics review intended to ensure that research being performed is targeted at equitably improving the health of patients, does not have controversial or discriminatory social implications and does not stigmatize specific groups. Patients who choose not to opt-out trust that their samples will be put to positive use; oversight of the resource attempts to ensure that this trust is well-placed. In order to further build trust, BioVU has plans to develop mechanisms to inform patients and the public about the types of research that are being performed using the resource.