Although informed consent is important in clinical research, questions persist regarding when it is necessary, what it requires, and how it should be obtained. The standard view in research ethics is that the function of informed consent is to respect individual autonomy. However, consent processes are multidimensional and serve other ethical functions as well. These functions deserve particular attention when barriers to consent exist. We argue that consent serves seven ethically important and conceptually distinct functions. The first four functions pertain (...) principally to individual participants: (1) providing transparency; (2) allowing control and authorization; (3) promoting concordance with participants' values; and (4) protecting and promoting welfare interests. Three other functions are systemic or policy focused: (5) promoting trust; (6) satisfying regulatory requirements; and (7) promoting integrity in research. Reframing consent around these functions can guide approaches to consent that are context sensitive and that maximize achievable goals. (shrink)

In accordance with ethical principles and standards, researchers conducting studies with children are expected to seek assent and respect their dissent from participation. Little attention has been given to assent and dissent in research with toddlers, who have limited cognitive and emotional capabilities. We discuss research with toddlers in the context of assent and dissent and propose guidelines to ensure that research with toddlers still adheres to ethical principles. These guidelines include designing engaging studies, monitoring refusal and distress, and partnering (...) with parents. Research with toddlers requires flexibility and creativity to respect toddlers in the context of their developmental capabilities. (shrink)

Although law is established on a strong presumption that persons younger than a certain age are not competent to consent, statutory age limits for asking children’s consent to clinical research differ widely internationally. From a clinical perspective, competence is assumed to involve many factors including the developmental stage, the influence of parents and peers, and life experience. We examined potential determining factors for children’s competence to consent to clinical research and to what extent they explain the variation in competence judgments.

Medical care of critically ill and injured infants and children globally should be based on best research evidence to ensure safe, efficacious treatment. In South Africa and other low and middle-income countries, research is needed to optimise care and ensure rational, equitable allocation of scare paediatric critical care resources.

Assent is an important ethical and legal requirement of paediatric research. Unfortunately, there are significant differences between the guidelines on the details of assent.

We systematically reviewed contemporary literature to create an evidence-informed framework for research studies involving children and adolescents who can assent to participate. We searched seven citation indices to locate peer-reviewed research published in English language journals between 2000 and 2012. After screening 1,231 titles and abstracts for relevance, we assessed levels of evidence, extracted information, and analysed content from 87 articles. Most articles narrowly focused on paediatric assent barriers and facilitators for decision-making about research participation. No articles provided a single, (...) comprehensive ethical framework to guide the development and review of research assent protocols. We developed a 6-step framework that provides guidance to: prepare the child for the assent process; assess the child’s readiness to engage in decision making; discuss the elements of informed consent to the greatest extent possible; seek an initial assent decision; monitor and affirm assent; and respect the child’s role as a research participant. The PAeDS-MoRe framework also supports the creation of process models that address the unique, developmental needs of paediatric sub-groups, and guides the operationalization of jurisdictional requirements for ethical research involving children who are unable to provide free, informed and ongoing consent. (shrink)

In order to involve children in the decision-making process about participation in medical research it is widely recommended that the child’s assent be sought in addition to parental consent. However, the concept of assent is fraught with difficulties, resulting in confusion among researchers and ethics committees alike.

There is an increased focus on, and evidence of, children's capability to both understand and make decisions about issues relating to participation in medical research. At the same time there are divergent ideas of when, how and to what extent children should be allowed to decide for themselves. Furthermore, little is known about parents' views on these matters, an important issue since they often provide the formal consent. In this questionnaire study of 2500 families in south-east Sweden (with and without (...) research experience) we explored parents' views on issues relating to information, consent and research data. We found that parents are generally positive about supplying their child with individual information (93.3%; median age 7) and assuring the child's consent/assent to participation (74.3%; median age 12). However, parents' views vary regarding the extent to which children should influence research data: as many as 47–61% of our sample were opposed to children's rights to decide about the use and storage of biological samples and natural history data. Parents who are opposed to child consent and a wider influence on their research participation argue that parental authority and research quality are two important factors opposing enhanced child influence. Drawing on this, we underline the need to discuss how to balance children's rights against parental autonomy and research interests before implementing any standardized protocols granting children the right to consent and revoke data in long-term research. (shrink)

Many drugs used in paediatric medicine are off-label. There is a rising call for the use of adaptive clinical trial designs in responding to the need for safe and effective drugs given their potential to offer efficiency and cost-effective benefits compared with traditional clinical trials. ADs have a strong appeal in paediatric clinical trials given the small number of available participants, limited understanding of age-related variability and the desire to limit exposure to futile or unsafe interventions. Although the ethical value (...) of adaptive trials has increasingly come under scrutiny, there is a paucity of literature on the ethical dilemmas that may be associated with paediatric adaptive designs. This paper highlights some of these ethical concerns around safety, scientific/social value and caregiver/guardian comprehension of the trial design. Against this background, the paper develops a non-static conceptual lens for understanding PADs. It shows that ADs are epistemically open and reduce some of the knowledge-associated uncertainties inherent in clinical trials as well as fast-track the time to draw conclusions about the value of evaluated drugs/treatments. On this note, the authors argue that PADs are ethically justifiable given they have multiple layers of safety, exposing enrolled children to lesser potential risks, create social/scientific value generally and for paediatric populations in particular, specifically foster the flourishing of paediatric populations and can significantly improve paediatric trial efficiency when properly designed and implemented. However, because PADs are relatively new and their regulatory, ethical and logistical characteristics are yet to be clarified in some jurisdictions, the cooperation of various public and private stakeholders is required to ensure that the interests of children, their caregivers and parents/guardians are best served while exposing paediatric research subjects to the most minimal of risks when they are enrolled in paediatric trials that use ADs. Data sharing not applicable as no datasets generated and/or analysed for this study. Not applicable. (shrink)

:To what extent, if any, should minors have a say about whether they participate in research that offers them no prospect of direct benefit? This article addresses this question as it pertains to minors who cannot understand enough about what their participation would involve to make an autonomous choice, but can comprehend enough to have and express opinions about participating. The first aim is to defend David Wendler and Seema Shah’s claim that minors who meet this description should not be (...) offered a choice about whether they participate. The second aim is to show, contra Wendler and Shah, that the principle of nonmaleficence requires more with respect to giving these minors a say than merely respecting their dissent. Additionally, it requires that investigators obtain affirmation of their non-dissent. This addresses intuitive concerns about denying children a choice, while steering clear of the problems that arise with allowing them one. (shrink)

Abstract:Human and animal research both operate within established standards. In the United States, criticism of the human research environment and recorded abuses of human research subjects served as the impetus for the establishment of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and the resulting Belmont Report. The Belmont Report established key ethical principles to which human research should adhere: respect for autonomy, obligations to beneficence and justice, and special protections for vulnerable individuals and (...) populations. While current guidelines appropriately aim to protect the individual interests of human participants in research, no similar, comprehensive, and principled effort has addressed the use of (nonhuman) animals in research. Although published policies regarding animal research provide relevant regulatory guidance, the lack of a fundamental effort to explore the ethical issues and principles that should guide decisions about the potential use of animals in research has led to unclear and disparate policies. Here, we explore how the ethical principles outlined in the Belmont Report could be applied consistently to animals. We describe how concepts such as respect for autonomy and obligations to beneficence and justice could be applied to animals, as well as how animals are entitled to special protections as a result of their vulnerability. (shrink)

Debates on morally acceptable and lawful end-of-life practices in pediatrics were reignited by the recent amendment in Belgian law to allow euthanasia for minors of any age who meet the criteria for capacity. Euthanasia and its legalization in pediatrics are often opposed based on the availability of aggressive palliative sedation. For terminally ill patients, this type of sedation is often identified as continuous and deep sedation until death. We demonstrate that this reasoning is based on flawed assumptions: CDS is a (...) morally preferable alternative to euthanasia; CDS can meet the same patient needs as euthanasia; children lack the capacity and experience to make EOL decisions; unlike euthanasia, CDS does not raise capacity issues. Our aim is not to reject CDS as a valid option at the EOL, nor to offer a clear-cut defense of euthanasia for minors, but to emphasize the ethical issues with both practices. (shrink)

Background: Understanding is an important goal of the informed consent process in research. We sought to assess the interrater reliability (IRR) and concurrent validity of two measures of understanding in child and young adult subjects and their parents. Methods: We conducted a cross-sectional survey and interview-based study of children and young adults participating in a clinical trial for cancer, along with one parent per child or young adult subject. We estimated the IRR of the Semi-Structured Comprehension Interview (SSCI) and the (...) MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). We also estimated concordance between the SSCI, the MacCAT-CR, and the Quality of Informed Consent (QuIC). Results: For our sample of 32 subjects (16 parent–child pairs), IRR estimates were high for total score on the SSCI (intraclass correlation coefficient [ICC] = 0.88, 95% confidence interval [CI] = 0.76–0.94), as well as on the understanding (ICC = 0.93, 95% CI = 0.86–0.97) and reasoning (ICC = 0.97, 95% CI = 0.94–0.98) subscales of the MacCAT-CR. IRR was lower for the appreciation subscale of the MacCAT-CR (ICC = 0.70, 95% CI = 0.47–0.84). Scores on the SSCI were strongly correlated with scores on the understanding subscale of the MacCAT-CR (Spearman's rho = 0.72, 95% CI = 0.48–0.85) and the QuIC (Spearman's rho = 0.66, 95% CI = 0.24–0.87). Mean administration time for the SSCI was 3.1 minutes (95% CI = 2.7–3.5 minutes). Conclusions: The SSCI is a valid and reliable measure of understanding for use with both pediatric and adult research participants. It is easy to administer and score consistently, even by nonprofessional raters. The SSCI is a promising tool for use by clinician-investigators to study, detect, and correct deficiencies in understanding among children, adolescents, and adults making decisions about research participation. (shrink)

Research involving children or other incompetent subjects who are deemed unable to provide informed consent is complex, particularly in the case of research that does not directly benefit the research subjects themselves. The Helsinki Declaration, the World Medical Association's landmark document for research ethics, therefore states that incompetent research subjects must not be included in such research unless it entails only minimal risk and minimal burden. In this paper, we argue that now that research in these groups is expected to (...) expand, this undifferentiated minimal risk and burden requirement does not suffice any more. In the upcoming revision of the Declaration, the paragraph at stake should be refined in such a way that it is not unnecessarily restrictive or more permissive than can be ethically justified. Our first recommendation is to stimulate research ethics committees to identify more accurately those risks and burdens that the research subjects must undergo solely for research purposes by distinguishing between two types of study procedures instead of between two types of studies. Our second recommendation is to allow for exceptions to the minimal risk and burden requirement in cases of exceptionally valuable studies that involve subjects who can give their assent to participate in the study and that involve at most a minor increase over minimal risk and/or burden. (shrink)

Assent to medical research or treatment may be an intuitively attractive way to address the area between incapacity and capacity that might otherwise be subject to a best interests assessment. Assent has become a widely disseminated concept in law, research, and clinical ethics, but little conceptual work on assent has so far occurred. An exploration of use of assent in treatment and research in children and people with dementia suggests that at least five claims are made on behalf of assent. (...) Since at least some of these may lead to tensions with others, assent requires firmer conceptual underpinning. Whether assent remains primarily a local approach to research in children in the United States, where it appears to fit with legal background conditions, or develops its promise to overturn the dominant, binary, approach to (in)capacity will depend on the strength of future philosophical work to improve the theoretical foundations to assent. (shrink)