**4.3 Consent and capacity: pediatrics**

An additional challenge that tends to be overlooked in data sharing discussions is that many patients with rare disease are minors, who are generally legally presumed to lack the capacity to consent to genetic testing, research participation, or release of personal data on their own [38]. Moreover, a number of rare diseases involve intellectual disability, which may diminish the decision making capacity of rare disease patients. Regulatory frameworks developed in the context of experimental research are traditionally protectionist, aiming to ensure vulnerable individuals are protected from harm and exploitation. These frameworks place several limitations on research involving minors. Where research is allowed, additional safeguards must be in place for minors. The guiding legal and ethical principle is the best interests of the child, though this principle is somewhat modified in the research context. A modified best interests limitation is only allowing research if it offers direct benefit to the individual or to individuals with a similar age or condition, and that the benefit is favorable vis-a-vis the individual risks, as determined by a REC. Where research is permitted, the minor is protected by parental (or legal guardian) representation, who must provide informed consent. The parent would be provided with detailed information about the research and would be asked to consent on behalf of the child.

This protectionist approach has been somewhat modified both by public health and human rights concerns. From a public health perspective, the inclusion of children in research is imperative to ensuring that the standard of care improves for conditions that predominantly affect children. Given the physiological differences between children and adults, drugs demonstrated to be safe and effective for adults may not be so for children. Human rights instruments and discussions have also highlighted the principle of non-discrimination, which argues that some attempts to protect children ultimately result in their exclusion from participation in society.

Another important human rights and ethical principle is respect for the developing autonomy of the child. Mature-minor exceptions address the developing capacity of minors to make decisions. These regimes allow exceptions for children below the age of majority to make certain their own decisions (e.g., for health care) if they demonstrate their capacity to understand information and appreciate the consequences of decisions. Regardless of who has ultimate legal capacity to consent, children should generally be given appropriate opportunities to be involved in decisions concerning them. Many health research ethics guidelines recommend that children should be involved in decisions through assent, where the child is provided with age appropriate information and asked if they would like to participate, and dissent, where a clear objection to participation must also generally be respected by researchers. Dissent is more clearly applicable in experimental research, such as distress caused by a needle, than in data-intensive research.

Based on the principle of inclusion, as well as practical implications, the GA4GH Pediatric Task Team has argued that those who generate pediatric data as part of research or clinical care have an obligation to offer minors and their parents an opportunity to share their data, so as to benefit the care of children in the future [39]. The best interests of the child are ensured in this context through the benefit–risk assessment, ongoing data governance (to maximize scientific and societal

benefits while minimizing risk), parental representation and informed consent, and the child's involvement through assent processes.
