Assent to Research

Assent to research is a method of expression significant for recognizing autonomy, and represents agreement to become a research subject. “Informed consent is morally valid when disclosure and comprehension of Information is discussed in the presences of voluntariness and the competence to consent” (The Nuremburg Code). A morally valid choice therefore includes the concept of “assent”, when a prospective subject lacks capacity to provide legally effective consent. Seeking assent provides the means for a person to communicate a negative preference on participating in a study..

MUHC health research conducted in populations not legally capable to provide consent is subject to Article 21 of the Civil Code of Quebec; a special provision intended to increase protections for “vulnerable” people invited to participate in research. In Quebec, only REBs designated by the Quebec Minister of Health may approve research involving children and incapacitated adults. All MUHC REBs maintain “ministerial designation” for this type of review.

Individuals with some ability to understand the proposed study may be able to express their wishes in a meaningful way by verbally or physically assenting to, or dissenting from research participation. TCPS2 identifies persons who may be capable of assent or dissent as: [To continue reading...]

Pediatric Research

The responsibility to seek assent from a child to participate in medical research was published in the Canadian Medical Research Council “Guidelines on Research Involving Human Subjects” (1987) stating: "A minor child, incapable of giving legally and ethically acceptable consent, may give assent." In Quebec, conducting health research in children is governed by the Civil Code of Quebec, Article 21 that includes the assent requirement. 

Almost all MUHC pediatric research is conducted at the Montreal Children’s Hospital (MCH) site where the child’s assent is central to the participation decision. With respect to cognitive norms and developmental maturity, a separate assent document written in language and a reading level understandable to children aged 7 to 12 years is routinely required.  If a parent “consents” to enroll their child in research but the child refuses, the negative choice should take precedence.  Mere failure to object should not be construed as agreement to participate. When study eligibility criteria include children younger than 7 years, the informed consent discussion should include the child, but only the written consent of the parent or legal guardian is necessary to enroll the child in the research. 

The Pediatric (PED) REB at the MCH is an authoritative resource concerning the ethical conduct of all research with a pediatric component at the MUHC.  If an REB reviews a study designed for an adult population that also permits enrollment of children, the REB Chair at the adult site consults the PED REB Chair to request adequate input for the ethical deliberation. When an adult research study designed to enroll children is approved at an MUHC adult site, the PED REB Chair is consulted to provide opinion on appropriate safety monitoring for the study. 

Seeking consent and assent for pediatric research is challenging, and a family-centered approach to planning the informed consent discussion is recommended.  When the discussion includes the child in the decision-making, ethical standards expected for MUHC pediatric research are met. 

Usually, subject recruitment takes longer in pediatric clinical trials and ICH GCP E11suggests only investigators with pediatric research experience should conduct studies with invasive procedures in children.  A pediatrician with broad clinical experience may not necessarily possess the specialized skill to lead the informed consent discussion involving children, and mentoring is encouraged. 

Obtaining knowledge of the effects of medicinal products in children is an important goal of pediatric research, yet the rights of a child to withdraw from a study must be respected. In certain investigational treatment studies there may be circumstances whereby, in the opinion of the investigator or parents, withdrawal from the study would jeopardize the child’s health. In this situation, continued parental or legal guardian consent should be sufficient to allow ongoing research participation. 

Written documentation of explicit consent should be obtained from research subjects enrolled in studies as minor children, once they turn 18 years old, if still participating in the study. This includes subjects whose identifiable data was collected and stored in research data repositories and tissue banks.

 

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Incapacitated Adult Research

"Respect for persons involves a recognition of the personal dignity and autonomy of individuals, and special protection of those persons with diminished autonomy." (The Belmont Report).  

In Quebec, consent to participate as a subject of health research is governed by the Civil Code of Quebec, Article 21 to safeguard the well being of individuals with transient, progressive or permanent incapacity who are subjects of research. REBs weigh the need for additional protections for vulnerable study populations that includes ensuring voluntariness of their research participation.

Adults who lack the capacity to make voluntary choices are usually recruited for research only when the knowledge to be gained cannot be obtained from competent individuals or from persons able to consent freely.  REBs strive to balance the ethical principles of Respect, Beneficence and Justice when considering a request to recruit incapacitated adults, to avoid limiting research only to those who can make informed choices. Distributive justice applied to research requires those who are to receive the benefits also to bear its burdens. In that way vulnerable members of society are not routinely denied potential benefits from participating in research.

An important ethical challenge in the informed consent discussion concerns ensuring that prospective subjects understand how participating in research differs from receiving standard medical care, to avoid the “therapeutic misconception”.  Investigators’ challenge is made more difficult when communicating such distinctions to persons with capacity impairments. It is especially critical that the informed consent discussion and the document be very clear about the differences. It is essential to address clearly if study participation would affect current efficacious care for the prospective subject. The choice of words to describe the research purpose and experimental procedures must be precise.

There is no “standard” tool, model or procedure for assessing capacity to consent to research, although the ability to assess capacity is a skill that all physicians should possess. The Investigator must determine if the person with diminished capacity has sufficient competence to consent research participation. The REB will decide whether it is appropriate that the Investigator seeking consent is also the professional who will judge the prospective subject’s capacity to consent.

The prospective subject’s level of engagement in the informed consent discussion is a key indicator of the person’s capacity to consent to research.  If following multiple attempts by the Investigator to describe the study, a subject cannot repeat back to the Investigator a simplified explanation of study participation, the person lacks capacity to consent. 

An individual not capable of providing “explicit” research consent must be asked to provide “assent” in order to participate.  Assent implies willingness; it does not imply understanding.  An interpretable statement on assent or dissent from the subject must be taken as valid regardless of the subject’s level of confusion.  Demonstrating a negative choice need not be verbal. Indications of distress such as crying or attempts to escape the situation should be taken as refusals to participate. 

Fundamental to research consent is the subject’s right to withdraw their participation.  Investigators need to be aware of verbal and non-verbal behaviour of incapacitated research subjects that may indicate their desire to participate no longer.   A clear expression to discontinue participation may be difficult to distinguish from other behaviour.  How this dilemma will be managed in context of the study should be discussed in the research protocol.

Some longitudinal studies involving progressive disorders or aging populations are designed to enroll subjects who were competent to consent at the outset of the study.  However, during the course of the research some subjects may experience progressive incapacitating effects or intermittent disorders leading to decisional impairment.  In these situations Investigators need to discuss with prospective subjects whether they should designate someone to serve as a legally authorized representative at the outset of the study; ready to step in as substitute decision-maker if the subject’s ability to assess personal needs and interests becomes compromised during the study. 

In the course of providing medical care “advance directives” in compliance with applicable law are commonly used. While advance directives concerning research participation may appear legitimate, they have no “legal standing”.  Note discussion at TCPS2, Article 3.11 about “Research Directives” to understand that Investigators and substitute decision makers must be guided by such directives during informed consent discussions.

Written documentation of explicit consent should be obtained from research subjects who were enrolled in a study while cognitively impaired, if they are still participating in the study when they regain competency. This includes subjects whose identifiable data was collected and stored in research data repositories and tissue banks.

 

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