Establishing a global regulatory floor for children’s decisions about participation in clinical research

Establishing a global regulatory floor for children’s decisions about participation in clinical research
Special Article
Steven Joffe, Albert J. Allen, Jonathan M. Davis, Elisa Koppelman, Susan Z. Kornetsky, Grace Marie V. Ku, Victoria A. Miller, Jennifer Preston, Lesha D. Shah, Barbara E. Bierer
Pediatric Research, 28 January 2023
Enrolling children in clinical trials typically requires parental or guardian permission and, when appropriate, child assent. Aligning requirements across jurisdictions would facilitate multisite pediatric trials. Guidance from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) is the best candidate for a global standard but would benefit from additional specification.
Ethical analysis of ICH guidance for permission and assent for pediatric trials, with recommendations for clarification.
ICH guidance regarding permission and assent would be enhanced by additional detail in the following areas: (1) what information should be provided to parents, guardians, and children considering a trial, and how that information should be provided; (2) the definition of “assent,” the criteria for when assent should be required, and the need to include children in discussions even when assent is not mandated; (3) criteria for requiring children’s signatures indicating agreement; (4) greater specificity regarding children’s right to decline or withdraw; and (5) clarification of when children’s wish to decline or withdraw from participation may be overridden and of what the overriding process should entail.
ICH guidance provides a global standard for decision-making regarding children’s participation in trials. Several clarifications would facilitate the conduct of multinational pediatric research.

“Your Child Needs Surgery”: A Survey-Based Evaluation of Simulated Expert Consent Conversations by Key Stakeholders

“Your Child Needs Surgery”: A Survey-Based Evaluation of Simulated Expert Consent Conversations by Key Stakeholders
Zoe Atsaidis, Stephan Robitaille, Elena Guadagno, Jeffrey Wiseman, Sherif Emil, Dan Poenaru
Journal of Pediatric Surgery, 24 January 2023
Consent conversations in pediatric surgery are essential components of pre-operative care which, when inadequate, can lead to significant adverse consequences for the child, parents, surgeon, and others in the healthcare system. The aim of this study is to explore expert consenting practice from the key stakeholders’ perspective.
Four senior attending pediatric surgeons obtained consent from a standardized mother of a child requiring surgery in two scenarios: a low-risk elective surgery (inguinal hernia repair – Video 1), and a high-risk emergency surgery (intestinal atresia – Video 2). All sessions were recorded. Families of children who had undergone minor or major surgery, families without medical or surgical background, and healthcare professionals were invited to view and evaluate the videos using a semi-structured questionnaire.
Out of 251 distributed surveys, 56 complete responses were received. Thirty two participants (57.1%) evaluated video 1 and 24 (42.9%) evaluated. Overall, 22 (69%) respondents to video 1 and 20 (84%) respondents to video 2 were “very satisfied” with the recorded consent conversation. Qualitative responses shared common themes of valuing surgeon empathy, good surgeon communication, patient engagement, and adequate time and information. Suggestions for improvement included additional resources and visual aids, improved patient engagement, and discussion of post-operative expectations.
Our data identifies strengths and gaps in the current consent process from the perspective of patient families and providers. Identified areas for improvement in the informed consent process based on multi-stakeholder input will guide the planned development of a consenting educational video resource.

Incentives in Pediatric Research in Developing Countries: When Are They Too Much?

Incentives in Pediatric Research in Developing Countries: When Are They Too Much?
Erwin Jiayuan Khoo, Devan M. Duenas, Benjamin S. Wilfond, Luke Gelinas, Armand H. Matheny Antommaria
Pediatrics, 20 January 2023
When incentives are offered to parents and their children to partake in research, there are concerns that parents may be unduly influenced by the incentives, and the children may be exploited. We present a case from a low- and middle-income country and consider the ethical issues that arise when the children are asked to participate in a multinational, double-blind, randomized, placebo-controlled trial of the effects of a nutritional supplement on growth. The first commenter, from Malaysia, notes that their residents might not share Americans’ expectations regarding children’s role in the consent process from a cultural perspective, which may alter the analysis of the concerns. The authors of the second commentary emphasize the use of incentives that benefit the child participant rather than their parent or are provided directly to the child participant to address the concerns. The third commentator discusses the importance of minimizing the study’s risks and balancing the benefits and the risks, which attenuates the concerns.

Who decides? Consent for healthcare decisions of minors in the United States

Who decides? Consent for healthcare decisions of minors in the United States
Nichole M Stettner, Ella N Lavelle, Patrick Cafferty
Current Opinion in Pediatrics, 18 January 2023
Purpose of review
The purpose of this review is to examine when parents and legal guardians have the authority to make medical decisions on behalf of the minors in their care, when the decisions of healthcare professionals may supersede those of parents and guardians, and under what conditions minors can make healthcare decisions for themselves.
Recent findings
The coronavirus disease 2019 (COVID-19) pandemic has reignited discussion of who should make healthcare decisions for minors. Though serious adverse reactions to COVID-19 vaccines are rare, hesitancy toward pediatric COVID-19 vaccination is prevalent among parents in the United States. This has contributed to large numbers of minors who are not up-to-date or not fully vaccinated against severe acute respiratory syndrome coronavirus 2 infection. Surveys reveal a majority of minors in the United States are willing to receive a COVID-19 vaccine. A number of scholars have recommended allowing adolescents the ability to consent to COVID-19 vaccination without parental approval.
Allowing adolescents with a minimum age of 15 to consent to vaccination without parental or guardian approval will more quickly enable adolescents to receive new vaccines as they become available, such as the COVID-19 bivalent vaccine.

Views of Adolescents and Young Adults with Cancer and Their Oncologists Toward Patients’ Participation in Genomic Research

Views of Adolescents and Young Adults with Cancer and Their Oncologists Toward Patients’ Participation in Genomic Research
Amanda M. Gutierrez, Jill O. Robinson, Robin Raesz-Martinez, Isabel Canfield, Mary A. Majumder, Sarah Scollon, Lauren R. Desrosiers, Rebecca L. Hsu, Wendy Allen-Rhoades, D. Williams Parsons, Sharon E. Plon, Amy L. McGuire, Janet Malek
Journal of Adolescent and Young Adult Oncology, 2 January 2023
With increased use of genomic testing in cancer research and clinical care, it is important to understand the perspectives and decision-making preferences of adolescents and young adults (AYAs) with cancer and their treating oncologists.
We conducted an interview substudy of the BASIC3 Study, which enrolled newly diagnosed cancer patients <18 years of age with assent. Of 32 young adults (YAs) with cancer who reached the age of majority (AOM; 18 years) while on study, 12 were successfully approached and all consented to study continuation at AOM. Of those, seven completed an interview. Patients’ oncologists, who enrolled and participated in return of clinical genomic results, were also interviewed (n = 12). Interviews were transcribed, deidentified, and analyzed using thematic analysis.
YAs cited the possibility of helping others and advancing science as major reasons for their assent to initial study enrollment and their willingness to consent at AOM. YAs thought obtaining informed consent from research participants for study continuation at AOM was a good idea in case they changed their minds or wanted to make their own decisions, and to keep them aware of study activities. There was diversity in what YAs understood and learned from genomic testing: some recalled specific findings, while some remembered minimal information about their results. Oncologists varied in their assessment of adolescents’ engagement with the study and understanding of their results.
Given the different ways AYAs engage with genomic information, careful assessment of AYAs’ diverse communication and decision-making preferences is needed to tailor interactions accordingly.

[Prescribing Contraceptives to Minors Without Parental Consent]

[Prescribing Contraceptives to Minors Without Parental Consent]
Goldstick O, Peled-Raz M
Harefuah, 1 November 2022, 161(11) pp 709-713
The Israeli Legal Capacity and Guardianship Law, denies minors the right to decide upon medical treatment, and regards medical treatment of minors, including contraception, without parental consent as an infringement of parental autonomy. Yet, adolescent girls occasionally ask doctors to prescribe them contraceptives, while refusing parental involvement. This article reviews the relevant legal situation, examines some comparative legal stances and refers to the ethical aspects that should be considered during contraceptive advice to minors, in light of the United Nations Convention on the Rights of the Child. Seeking contraception is an example of mature behaviour, and when a minor asks for contraception, the physician has to act in her best interests. In the decision to prescribe contraceptives without parental consent or even knowledge, doctors should consider the girl’s ability to understand their advice, the risks associated with lack of parental involvement, the significance of parental autonomy infringement, the risks to the girl if the parents will be informed contrary to her request, and the girl’s risks of unintended pregnancy, associated with not using contraception. In this article we suggest means and modes of action in a situation when an adolescent needs contraception and denies any parental involvement.

Editor’s note: This a hebrew language publication

Informed Consent and Public Health: The Case of Childhood Vaccination

Informed Consent and Public Health: The Case of Childhood Vaccination
Ivana Tucak, Gordana Pelčić
European Journal of Bioethics, 4 May 2022
Informed consent, which is primarily aimed at encouraging individual patients and subjects of scientific research to make autonomous decisions, and public health measures, such as compulsory vaccination against infectious diseases, the successfulness of which implies harmonized administration of vaccines to a broad population, seem to be irreconcilable opposites at first glance. This paper deals with investigating whether these opposites can reconcile or whether informed consent can be applied in the field of public health. The first part of the paper provides a short overview of the main features of informed consent and its relevance in treating individual patients. The second part of the paper tackles the issue of immunization. If not provided with consent of their patients or having a legal obligation, physicians are believed to interfere with the bodily integrity of other people when conducting vaccination and their act can be deemed as an assault and entail non-pecuniary damage compensation. Herd immunity as a “public good” can only be achieved if all people are equally subject to public health measures. At this point, the key question is if informed consent and appertaining freedom of decision-making represent a threat to the accomplishment of this public health goal. This question should truly be answered since vaccination may, though rarely, bring to medical complications, which may then lead to high treatment costs, loss of income and extremely rare, to death. The purpose of this paper is to demonstrate that disclosure of the risks and benefits of immunization within the framework of public health programmes could contribute to putting the fundamental bioethical postulates into practice: establishing and fostering mutual trust between physicians and their patients, which can, in the end, contribute to a higher immunization rate of a population.

Comparison of Spanish-Speaking Parental Understanding Using Two Alternative Consent Pathways

Comparison of Spanish-Speaking Parental Understanding Using Two Alternative Consent Pathways
Homa Amini, Andrew Carranco, Paul S. Casamassimo, Dennis McTigue, Jin Peng
Pediatric Dentistry, November-December 2022; 44(6) pp 400-403
The purpose of this study was to assess the understanding of Spanish-speaking caregivers consenting to dental core using general anesthesia (GA) utilizing two consent-delivery pathways.
Seventy-eight parents of children who never had GA were randomly assigned to one of two groups: (0) interpreter; or (2) video: they completed o survey to evaluate comfort level with GA and comprehension of areas of informed consent.
Most parents in both groups understood the risks associated with GA (89 percent in the interpreter group and 90 percent in the video group). The majority of families had difficulty understanding indications for GA (64 percent in the interpreter group versus 60 percent in the video group). Overall, 97 percent of participants believed they sufficiently understood the information presented about GA. The mean score for comfort level with GA was 7.03 for the interpreter group and 6.82 for the video group.
Consent pathways used in this study were not significantly different for risk understanding and acquisition of consent-related knowledge.

Adolescent Capacity to Consent to Participate in Research: A Review and Analysis Informed by Law, Human Rights, Ethics, and Developmental Science

Adolescent Capacity to Consent to Participate in Research: A Review and Analysis Informed by Law, Human Rights, Ethics, and Developmental Science
Ben Mathews
Laws, 23 December 2022; 12(1)
Contemporary societies pose major challenges for adolescents and it is essential to conduct research with them to understand their experiences, identify their needs, and discover solutions to major social problems. Social science, humanities and health-related research into violence, technology, and climate change exemplify vital research endeavours requiring adolescent participation to advance Sustainable Development Goals and enhance individual lived experience and societal flourishing for current and future generations. International and national research ethics guidelines emphasise the necessity to conduct research to advance societal benefit, while upholding principles of autonomy and justice, and promoting participant welfare and avoiding harm. International human rights instruments promote adolescents’ freedom of expression and right to participate in matters affecting them. The rapid generation of robust research findings is essential, but it remains commonly assumed that adolescents cannot provide their own consent to participate in research studies, and the belief that parental consent is required can impede and impair the entire research process. Debate continues about the proper interpretation of legal principles and research ethics guidelines about who may provide consent. Continuing confusion about who must provide consent, and why, impedes the protection of adolescents’ interests and the advancement of society. This article adds to knowledge by providing a multidisciplinary overview of evidence from developmental science, social science, law, human rights, and bioethics about decision-making capacity and entitlements in the context of research participation, and an updated evidence-based analysis of adolescents’ capacity to provide their own consent to participate in social, humanities and health-related research. A conservative application of knowledge from these domains both individually and collectively supports conclusions that adolescents aged 16 are able to provide their own consent to participate in research, and no legal or ethical principle requires the provision of parental consent on their behalf. Practical considerations may support parental involvement in conversations about participation, and some types of research require trauma-informed approaches, but adolescents are developmentally, legally and ethically entitled to make their own decision about whether or not to participate.

Disability or Death: A Focused Review of Informed Consent in Pediatric Neurosurgery

Disability or Death: A Focused Review of Informed Consent in Pediatric Neurosurgery
Nathan A. Shlobin, John Paul G. Kolcun, Brian D. Leland, Laurie L. Ackerman, Sandi K. Lam, Jeffrey S. Raskin
Seminars in Pediatric Neurology, 22 December 2022
The management of pediatric neurosurgical disease often requires families to choose between long-term disability and premature death. This decision-making is codified by informed consent. In practice, decision-making is heavily weighted toward intervening to prevent death, often with less consideration of the realities of long-term disability. We analyze long-term disability in pediatric neurosurgical disease from the perspectives of patients, families, and society. We then present a pragmatic framework and conversational approach for addressing informed consent discussions when the outcome is expected to be death or disability. We performed a focused review of literature regarding informed consent in pediatric neurosurgery by searching PubMed and Google Scholar with search terms including “pediatric neurosurgery,” “informed consent,” and “disability.” The literature was focused on patients with diagnoses including spina bifida, neuro-oncology, trauma, and hydrocephalus. Patient perspective elements were physical/mental disability, lack of autonomy, and role in community/society. The family perspective involves caregiver burden, emotional toll, and financial impact. Societal considerations include the availability of public resources for disabled children, large-scale financial cost, and impacts on global health. Practical conversational steps with patients/caregivers include opening the discussion, information provision and acknowledgement of uncertainty, assessment of understanding and clarifying questions, decision-making, and decision maintenance, all while remaining sensitive to the emotional burden commensurate with these decisions. The “death or disability” paradigm represents a common challenge to informed consent in pediatric neurosurgery. Patient, family, and societal factors that inform surrogate decisions vary and sometimes conflict. Pediatric neurosurgeons must use a comprehensive approach to address the informational and relational needs of caregivers during the informed consent process.