Informed consent approaches for clinical trial participation of infants with minor parents in sub-Saharan Africa: A systematic review.

BACKGROUND: Regulations are vague regarding the appropriate decision-maker and authority to consent for children of minor parents participating in clinical trials. In countries with high rates of underage mothers, such as in sub-Saharan Africa, this lack of guidance may affect the rights of potential paediatric participants already bearing increased vulnerability. It can also influence the recruitment and generalizability of the research. We provide evidence and discuss informed consent management in such cases to inform best practice. MATERIALS AND METHODS: We searched PubMed/MEDLINE, Embase, CINAHL, and Google Scholar for articles published up to March 2019. In total, 4382 articles were screened, of which 16 met our inclusion criteria. Studies addressing informed consent in clinical trials involving children with minor parents in sub-Saharan Africa were included. We performed descriptive and qualitative framework analyses. The review was registered in PROSPERO: CRD42018074220. RESULTS: Various informed consent approaches were reported. Articles supporting individual consent by minor parents based on emancipation or "mature minor" status lacked evidence in the context of research. National laws on medical care guided consent instead. When no laws or guidance existed an interpretation of the local decision-making culture, including community engagement and collaboration with local ethics committees, defined the informed consent approach. CONCLUSIONS: The review emphasises that the implementation of informed consent for children with minor parents may be variable and hampered by absent or ambiguous clinical trial regulations, as well as divergent local realities. It may further be influenced by the research area and study-specific risks. Clear guidance is required to help address these challenges proactively in clinical trial planning. We provided a set of questions to be considered in the development of an ethically acceptable informed consent approach and proposed information that should be integrated into international clinical trial guidelines.

Shortened consent forms for genome-wide sequencing: Parent and provider perspectives.

BACKGROUND: Consent forms for exome and/or genome sequencing, collectively called genome-wide sequencing (GWS), frequently contain detailed information on complex topics such as sequencing analysis and incidental findings. Considering recent endeavors by the health care community to simplify GWS consent forms, it is important to gain stakeholders' perspectives on the content, length, and use of consent forms. METHODS: Thematic analysis was conducted on data obtained from focus groups with two participant cohorts: parents who previously provided consent for trio-based GWS as part of the translational pediatric GWS CAUSES Study, and genetic health care providers (HCP) who provide pre-test counseling for GWS. RESULTS: Genetic HCP indicated that consent forms cannot replace pre-test counseling, and as such, a simplified consent form focusing on the implications of GWS would be beneficial to both patients and HCP. Although parents' primary concerns varied when considering GWS, they all highly valued information. Parents also indicated the need for community and support after the return of GWS results. Both participant cohorts recommended that consent forms be available online and include an appendix for supplementary information. CONCLUSION: It is important to include both parents and HCP in the design of GWS consent forms, and also, to help connect families who have a shared diagnosis after the post-test counseling session.

WASP (Write a Scientific Paper): Ethnography with children: Some considerations.

This paper introduces the key methodological challenges related to working with children within an ethnographic research design. After briefly identifying in-depth contextually rich data as the key aim of any ethnographic research, some of the particular challenges related to working with children are explored. These are described along two key axes: ethical issues related to power dynamics loaded in favour of the adult researcher, and practical, logistical barriers to generating data that are a true reflection of the young child's ideas and beliefs. 'Process assent' and 'ethical symmetry' are flagged as the key means of optimising ethicality, while the benefits of using the 'least adult role', and creative child centric activities are outlined as ways to generating and collecting trustworthy data.

Anticipatory Waivers of Consent for Pediatric Biobanking.

As pediatric biobank research grows, additional guidance will be needed about whether researchers should always obtain consent from participants when they reach the legal age of majority. Biobanks struggle with a range of practical and ethical issues related to this question. We propose a framework for the use of anticipatory waivers of consent that is empirically rooted in research that shows that children and adolescents are often developmentally capable of meaningful deliberation about the risks and benefits of participation in research. Accordingly, bright-line legal concepts of majority or competency do not accurately capture the emerging capacity for autonomous decision-making of many pediatric research participants and unnecessarily complicate the issues about contacting participants at the age of majority to obtain consent for the continued or first use of their biospecimens that were obtained during childhood. We believe the proposed framework provides an ethically sound balance between the concern for potential exploitation of vulnerable populations, the impetus for the federal regulations governing research with children, and the need to conduct valuable research in the age of genomic medicine.

A didactic approach to presenting verbal and visual information to children participating in research protocols: the comic book informed assent.

OBJECTIVE: When children participate in research protocols, consent (by a parent or legal guardian) and assent (by the children) must be given. Understanding research protocols can be challenging for an adult and even more difficult for a child. The aim of this study was to describe the development of a comic book created to facilitate children's understanding of informed assent with clear and simple language. METHODS: Five researchers with scores above seven according to the Fehring criteria developed the comic book, avoiding the use of technical terminology. Twenty children between 7 and 12 years old, and enrolled in a larger study, responded using a Likert scale and questions about the clarity of texts and illustrations. The final version met National Health System Resolutions (Resoluções do Conselho Nacional da Saúde - CNS n° 196/1996 and 466/2012). RESULTS: The comic book assent presents a short story containing information about a real study: the invitation to participate, objectives, methods, instruments, procedures, risks, benefits, and the researchers' contact information. Most of the participants answered that they perceived the content of the text to be "Excellent" (40%) and "Very good" (40%), and the illustrations were perceived as "Excellent" (45%) and "Very good" (55%). CONCLUSION: The construction of a simple and clear model of informed assent is possible, and this model should be used in experiments with children.

A didactic approach to presenting verbal and visual information to children participating in research protocols: the comic book informed assent

OBJECTIVE: When children participate in research protocols, consent (by a parent or legal guardian) and assent (by the children) must be given. Understanding research protocols can be challenging for an adult and even more difficult for a child. The aim of this study was to describe the development of a comic book created to facilitate children's understanding of informed assent with clear and simple language. METHODS: Five researchers with scores above seven according to the Fehring criteria developed the comic book, avoiding the use of technical terminology. Twenty children between 7 and 12 years old, and enrolled in a larger study, responded using a Likert scale and questions about the clarity of texts and illustrations. The final version met National Health System Resolutions (Resoluções do Conselho Nacional da Saúde - CNS n° 196/1996 and 466/2012). RESULTS: The comic book assent presents a short story containing information about a real study: the invitation to participate, objectives, methods, instruments, procedures, risks, benefits, and the researchers' contact information. Most of the participants answered that they perceived the content of the text to be "Excellent" (40%) and "Very good" (40%), and the illustrations were perceived as "Excellent" (45%) and "Very good" (55%). CONCLUSION: The construction of a simple and clear model of informed assent is possible, and this model should be used in experiments with children.

A randomized study of a method for optimizing adolescent assent to biomedical research.

PURPOSE: Voluntary consent/assent with adolescents invited to participate in research raises challenging problems. No studies to date have attempted to manipulate autonomy in relation to assent/consent processes. This study evaluated the effects of an autonomy-enhanced individualized assent/consent procedure embedded within a randomized pediatric asthma clinical trial. METHODS: Families were randomly assigned to remain together or separated during a consent/assent process; the latter we characterize as an autonomy-enhanced assent/consent procedure. We hypothesized that separating adolescents from their parents would improve adolescent assent by increasing knowledge and appreciation of the clinical trial and willingness to participate. RESULTS: Sixty-four adolescent-parent dyads completed procedures. The together versus separate randomization made no difference in adolescent or parent willingness to participate. However, significant differences were found in both parent and adolescent knowledge of the asthma clinical trial based on the assent/consent procedure and adolescent age. The separate assent/consent procedure improved knowledge of study risks and benefits for older adolescents and their parents but not for the younger youth or their parents. Regardless of the assent/consent process, younger adolescents had lower comprehension of information associated with the study medication and research risks and benefits, but not study procedures or their research rights and privileges. CONCLUSIONS: The use of an autonomy-enhanced assent/consent procedure for adolescents may improve their and their parent's informed assent/consent without impacting research participation decisions. Traditional assent/consent procedures may result in a "diffusion of responsibility" effect between parents and older adolescents, specifically in attending to key information associated with study risks and benefits.

El consentimiento informado en el menor de edad en España: mayoría de edad, representación y teorías determinantes de la minoría de edad / Informed consent in minor in Spain: age of majority, representation, and determining theories minority

La minoría de edad, así como las situaciones y las figuras jurídicas que la acompañan, ocupan un lugar destacado a la hora de estudiar el consentimiento informado. La actuación del personal sanitario deberá ser muy distinta si estamos ante una persona considerada como menor o mayor de edad (AU)

The minority and legal situations and accompanying figures prominently when informed consent study the place. The performance of health workers must be very different if we have a person considered as a minor or an adult (AU)

Whole-exome sequencing in pediatrics: parents' considerations toward return of unsolicited findings for their child.

Parents' preferences for unsolicited findings (UFs) from diagnostic whole-exome sequencing (WES) for their children remain largely unexplored. Our aim was to gain insight into parental considerations favoring acceptance/decline of UFs pertaining to their child. We conducted 20 qualitative, semistructured interviews with parents (n=34) of children with a developmental delay, aged <1 to 17 years, after consenting to WES, but before feedback of results. Key findings from our study were that all parents favored acceptance of UFs for medically actionable conditions in childhood, but that preferences and considerations diverged for UFs with no medical actionability, or only in adulthood, and regarding carrier-status. Sometimes non-medical utility considerations (considerations of usefulness of knowing UFs, not rooted in (preventive) medical treatment or controls) were given in favor of disclosure of UFs. Sometimes the child's future autonomy formed a reason to withhold UFs at present, despite an unfavorable prognosis concerning the child's cognitive capabilities. Some parents only preferred receiving UFs if these findings were directly related to their reasons for seeking a diagnosis. These findings are essential for developing morally responsible policy and for counseling. Further research should focus on whether considerations of non-medical utility alone can justify disclosure of UFs and whether reasons for seeking a diagnosis place further constraints on what UFs may be returned/withheld. How parents can be aided in contemplating different scenarios regarding their child's future development also deserves further inquiry.

Legal approaches regarding health-care decisions involving minors: implications for next-generation sequencing.

The development of next-generation sequencing (NGS) technologies are revolutionizing medical practice, facilitating more accurate, sophisticated and cost-effective genetic testing. NGS is already being implemented in the clinic assisting diagnosis and management of disorders with a strong heritable component. Although considerable attention has been paid to issues regarding return of incidental or secondary findings, matters of consent are less well explored. This is particularly important for the use of NGS in minors. Recent guidelines addressing genomic testing and screening of children and adolescents have suggested that as 'young children' lack decision-making capacity, decisions about testing must be conducted by a surrogate, namely their parents. This prompts consideration of the age at which minors can provide lawful consent to health-care interventions, and consequently NGS performed for diagnostic purposes. Here, we describe the existing legal approaches regarding the rights of minors to consent to health-care interventions, including how laws in the 28 Member States of the European Union and in Canada consider competent minors, and then apply this to the context of NGS. There is considerable variation in the rights afforded to minors across countries. Many legal systems determine that minors would be allowed, or may even be required, to make decisions about interventions such as NGS. However, minors are often considered as one single homogeneous population who always require parental consent, rather than recognizing there are different categories of 'minors' and that capacity to consent or to be involved in discussions and decision-making process is a spectrum rather than a hurdle.

Usual Care and Informed Consent in Clinical Trials of Oxygen Management in Extremely Premature Infants.

OBJECTIVE: The adequacy of informed consent in the Surfactant, Positive Pressure, and Pulse Oximetry Randomized Trial (SUPPORT) has been questioned. SUPPORT investigators and publishing editors, heads of government study funding agencies, and many ethicists have argued that informed consent was adequate because the two oxygen saturation target ranges studied fell within a range commonly recommended in guidelines. We sought to determine whether each oxygen target as studied in SUPPORT and four similar randomized controlled trials (RCTs) was consistent with usual care. DESIGN/PARTICIPANTS/SETTING: PubMed, EMBASE, Web of Science, and Scopus were searched for English articles back to 1990 providing information on usual care oxygen management in extremely premature infants. Data were extracted on intended and achieved oxygen saturation levels as determined by pulse oximetry. Twenty-two SUPPORT consent forms were examined for statements about oxygen interventions. RESULTS: While the high oxygen saturation target range (91 to 95%) was consistent with usual care, the low range (85 to 89%) was not used outside of the SUPPORT trial according to surveys and clinical studies of usual care. During usual care, similar lower limits (< 88%) were universally paired with higher upper limits (≥ 92%) and providers skewed achieved oxygen saturations toward the upper-end of these intended ranges. Blinded targeting of a low narrow range resulted in significantly lower achieved oxygen saturations and a doubling of time spent below the lower limit of the intended range compared to usual care practices. The SUPPORT consent forms suggested that the low oxygen saturation arm was a widely practiced subset of usual care. CONCLUSIONS: SUPPORT does not exemplify comparative effectiveness research studying practices or therapies in common use. Descriptions of major differences between the interventions studied and commonly practiced usual care, as well as potential risks associated with these differences, are essential elements of adequate informed consent.

Comprehension of a simplified assent form in a vaccine trial for adolescents.

INTRODUCTION: Future HIV vaccine efficacy trials with adolescents will need to ensure that participants comprehend study concepts in order to confer true informed assent. A Hepatitis B vaccine trial with adolescents offers valuable opportunity to test youth understanding of vaccine trial requirements in general. METHODS: Youth reviewed a simplified assent form with study investigators and then completed a comprehension questionnaire. Once enrolled, all youth were tested for HIV and confirmed to be HIV-negative. RESULTS: 123 youth completed the questionnaire (mean age=15 years; 63% male; 70% Hispanic). Overall, only 69 (56%) youth answered all six questions correctly. CONCLUSIONS: Youth enrolled in a Hepatitis B vaccine trial demonstrated variable comprehension of the study design and various methodological concepts, such as treatment group masking.

Consentimiento informado: algo más que una firma / Informed consent: more than just a signature

El consentimiento informado (CI) es la explicación que el médico o profesional sanitario da al paciente de la naturaleza de su enfermedad y del balance entre los efectos y los riesgos de las intervenciones diagnósticas y terapéuticas. Esta información debe estar adaptada al nivel de comprensión y a las características individuales del paciente. En el caso de los menores de edad, su opinión debe tenerse en cuenta y su madurez debe ser valorada por el médico. El CI debe considerarse un proceso de asistencia en la toma de decisiones y no la mera firma de un formulario. Se presenta el caso de una niña de 12 años con escoliosis idiopática en la que se indica una intervención quirúrgica que fue inicialmente rechazada tanto por la madre como por la niña. La intervención del equipo del centro de salud fue decisiva en este caso para una correcta toma de decisiones por parte de la familia (AU)

The informed consent (IC) is the explanation that the doctor or health professional gives to the patient on the nature of his disease and on the balance between the benefits and risks of the diagnostic and therapeutic interventions. This information must be adapted to the level of understanding and to the patient’s individual characteristics. In the case of the minors, his opinion must be taken into account and his maturity valued by the doctor. The IC must be considered as a process of assistance in the making of decisions and not as the mere signature of a form. The case report of a 12-year-old girl with severe idiopathic scoliosis is presented. The orthopedic team indicated a surgical intervention that was initially rejected both by the mother and the girl. The intervention of the Primary care staff was decisive in this case for a correct decisions making by the family (AU)

A guide for health care practitioners in the assessment of young people's capacity to consent to treatment.

The Health Care Consent Act, 1996, states that every person in Ontario, regardless of age, is presumed to be capable of consenting to or refusing medical treatment unless he or she is found incapable with respect to a specific treatment or plan of treatment. Health care practitioners may find it especially challenging to apply the legal test of capacity to young people. As an aid to assessment, a guide incorporating both legal and medical perspectives has been developed. This article describes the background and context of the development of the guide and explains how it helps practitioners to conduct a simpler, more focused evaluation of capacity in youth. The guide, along with an introduction and comments for parents, is included in an appendix.