Ethical aspects of child’s enrolment in clinical trial


Introduction

Clinical trials are one of the most important tools for research and for the development of new
drugs. It is the validation, demonstration of efficacy and safety of potential medicines or
treatments developed under detailed testing conditions in the laboratory. Clinical trials are
conducted before a drug is approved for marketing authorisation and before it enters the market.
Clinical trials do not always guarantee a positive outcome and sometimes carry risks. Because of
the risks, it is sometimes difficult for an adult to decide whether or not to take part in a
clinical trial. And it is particularly difficult for parents to decide when a clinical trial is
offered to their child. The aim of this essay is to highlight the ethical aspects of child
participation in clinical trials.  To determine what are the ethically correct steps to maintain
good relationships between health care professionals, parents and minor patients during clinical
trials. According to this theme, different studies and articles were compared and summarized.

1.      Basic definition and concepts of Health care ethics

Advances in medical knowledge and medical technology bring with them new and important moral
questions. Moral issues include the clinical relationship between health professional and patient,
biomedical and behavioural research on human subjects, organ harvesting and transplantation,
euthanasia, abortion and the allocation of health services. Medical ethics is a branch of applied
ethics that deals with a wide range of moral decision-making situations that arise in medical
practice in addition to the procedures and policies that are intended to guide that practice.
Understanding the most important ethical principles and methods of moral decision-making is
essential to understanding the moral issues that arise in the context of health care delivery.
Decisions are applicable to such moral issues and which serve to guide our moral decision-making.
(STEPHEN C. TAYLOR, 2018 , online)

1.1.                        An ethical problem and the procedure for solution

There are three recommended steps in solving an ethical dilemma. First, get technically clear about
what is at stake. In our case, it is the parents, the health professionals and the Child.  The
second step is to gather all possible arguments for and against. Which in our study are provided by
various studies and literature. In the last step we will try to formulate our own opinion which
will be well argued. I will summarize most of my opinions in the conclusion.  (HEŘMANOVÁ, 2012,
page 9)

2.      Communication by minor patients and their legal representatives

A number of professional studies have looked intensively at what psychological factors influence
the treatment process. Modern medicine clearly points to the fact that if a health professional can
communicate appropriately with a patient, he or she can significantly influence virtually all
aspects of the treatment process and ensure his or her satisfaction.


2.1.                       Minor patient and their rights

The period from birth to 18 years of age is the period of childhood and adolescence. Children are
considered vulnerable individuals not only because they are more vulnerable to negative factors in
their environment due to their immature bodies, but also because they do not have the physical,
cognitive and often social skills to effectively defend themselves as adults, which can lead to
harm. Ethical issues that may be related to this age period include the question of protecting the
rights of the hospitalized child, information and decision-making options for certain medical
interventions, especially for adolescents, communication between medical personnel and parents,
etc. (HEŘMANOVÁ, 2012, page 120)

In the case of a minor patient, the necessary information and the necessary decision-making are
discussed primarily with his/her legal guardians, who are usually the parents. It can also be
another person who has been appointed as the child's legal representative or an adoptive parent.
This does not mean that the doctor or other medical personnel do not communicate with the minor
patient at all and everything is discussed only with the minor's legal guardians. On the contrary,
communication with the minor is necessary and, from the point of view of the minor himself, becomes
more important as he grows older and more mature. Under Article 6 of the Convention on Human Rights
and Biomedicine, if a minor lacks legal capacity, the procedure cannot be carried out without the
consent of his or her legal guardian, an official or other person legally entitled to do so. The
opinion of the minor shall be taken into account as a factor whose severity increases with age and
level of maturity. (PTÁČEK, 2011, page 455)

Furthermore, the rights of child patients are set out in the Charter of Rights of Hospitalized
Children. The rights listed in the Charter apply to all sick children regardless of their illness,
age or disability, origin or social or cultural background, or the possible reason for treatment or
the form or place of treatment, whether they are inpatients or outpatients. The European
Association for Children in Hospitals (EACH) is an umbrella organisation for organisations that
seek to improve the living conditions of children in situations that are in some way related to
hospitalisation. EACH currently has 19 full members from 17 European countries and Japan. I would
like to mention Articles 4 and 5. Article 4 states that children and parents have the right to be
informed in a manner appropriate to their age and understanding. Measures should be taken to
alleviate physical and emotional stress. Article 5 states that children and parents have the right
to informed participation in all decisions concerning their health care. Every child must be
protected from unnecessary medical treatment and examination. The last sentence tells us that the
benefits must always outweigh the risks, and this applies to clinical trials as well. (AIF, 2022,
online and  EACH, 2022, online)

The rules of good clinical practice set out in the Convention on Biomedicine must be followed when
children enter a study in which a clinical trial of a medicinal product is being conducted. The
ethics committees of organisations that guarantee good clinical practice in a study must oversee
the appropriate ethical conduct of the investigating physicians. Efforts to treat the child
ethically should not end with the approval of the study by the ethics committee. It is important to
use non-traumatic procedures, especially when obtaining biological material. For example, when
taking blood. It is also necessary to choose painless procedures using analgosedation or at least
local anaesthesia in the form of numbing plasters or ointments. It is recommended to choose
laboratory methods that work with a minimum volume of biological material. These are the so-called
micromethods. These should not be studies that require repeated collection of tens of millilitres
of blood. There are studies that test the antibody response to the vaccine administered. ( PTÁČEK,
2011, page 155)

In a Japanese clinical study, children's ability to consent to treatment was assessed. The results
of the study say that children should be allowed to give consent and their opinions should be
respected. Involving children in decision-making promotes more open communication and transparency
between health professionals, parents and children. The researchers used the method of children
divided into three age groups (6-10 years, 11-14 years and 15-18 years) with three categories of
disease severity. Possible correlations between the number of children, the age of the children,
the level of education of the parents and the attitudes of the parents were investigated. The
method was provided by a semi-structured Internet survey on parents' opinions and attitudes and
preferences regarding involvement in medical research. Possible correlations between the number of
children, the age of the children, the level of education of the parents and the attitudes of the
parents were investigated. (FUKUDA, 2018, online)

In another clinical study, potential determinants of children's competence to consent to clinical
research and the extent to which they explain differences in judgments of competence were examined.
In the study, age was found to be the factor that explained most of the variance in children's
competence to consent, followed by intelligence. Experience of illness did not affect competence in
this study, nor did other variables. The study lasted 2 years, and pediatric patients aged 6 to 18
years, eligible for clinical research studies, were enrolled prospectively in various internal and
outpatient pediatric departments. Children's competence to consent was assessed using the MacArthur
Competency Assessment Tool for Clinical Research. Potential determining variables for children
included age, gender, intelligence, disease experience, ethnicity, and socioeconomic status. Of 209
eligible patients, 161 were included. The mean age was 10.6 years and 47.2% of the men
participated. Age, socioeconomic status, intelligence, ethnicity, complexity, parental assessment
of competence, and study participation were univariately associated with competence. Results showed
that age was a key factor explaining most of the variance in children's competence to consent. IQ
is a second important contributing factor. Other factors that could potentially contribute to
causality (gender, experience of illness, ethnicity) did not contribute significantly to the
explained variance in competence, nor did contextual factors. The high contribution of age to the
assessment of children's competence to consent complements recent findings on age. Previous work
has shown that competence to consent is unlikely for children younger than 9.6 years and competence
is likely for children older than 11.2 years. These findings offer a rationale for appropriate age
boundaries in child consent policies. (HEIN, 2015, online)

2.2.                       Parents

An autonomous person is capable of conscious autonomous action, which is crucial to the fulfilment
of the principle of autonomy in relation to the acceptance or refusal of medical care, unlike
parents who decide according to the duty of responsibility whether or not their child should
participate in a clinical trial. This fundamental difference between trials in adult and pediatric
medicine, relatively little is known about how the specific role of parents influences
communication about the trial. Most parents want what is best for their child, but not knowing what
the best course of action is can affect their response to a clinical trial. To the investigator,
this may appear to be a misunderstanding of the rationale for the trial because parents are
constructing the situation in a way that is acceptable to their need to protect their child. Some
parents will see the trial as a threat to their child or fear that they will regret their decision,
while others will see the trial as a hope for better treatment for their child. Almost all parents
value their role in protecting their children and want to ensure the best outcome for them, but
many recognise the complexity of the medical and research context and how this limits their ability
to fulfil this role. Conducting studies with children can benefit from a better understanding of
the special situation of parents and their particular need for support to enable them to maintain a
sense that they have protected their child's interests. (SHILLING, 2009, online)

The Brazilian study by Carvalho and Costa also confirms that parents are not sufficiently informed.
They aimed to understand how mothers perceived the processes of informed consent and randomization
in a randomized control trial that divided uncooperative children into three intervention groups
(physical restraint, sedation, and general anesthesia) for dental rehabilitation. Mothers'
perceptions of the processes of informed consent and randomization in the clinical trial are
characterized by a lack of understanding of these research steps, vulnerability in accepting the
randomized intervention, conflicting feelings of belief, fear, helplessness, coercion, and a
tendency to overlook their feelings to ensure the completion of their children's dental treatment.
Participants in their study were mothers of children younger than 3 years who were recruited in
randomized clinical trials to receive dental care under physical restraint, mild sedation, or
general anesthesia. The children had early childhood caries, a severe oral disease that causes
primarily pain and chewing difficulties, and their oral problems were not addressed by other public
or private dental care services. Dental treatment with physical restraint and without sedation is
considered ethical in Brazil due to the unavailability of facilities that provide pharmacological
behavioral management. (CARVALHO, 2013, online)

2.3.                       Health care professionals

Health professionals who are in frequent contact with the parents of a hospitalized child must find
a balance between a friendly and impersonal approach. A balanced relationship is a professional
one, one that inspires trust in the parents, but also respect for the work of the health
professionals and the whole team. The health worker can be sensitive to the parents, encouraging,
educating and listening to their concerns, but aware of the purpose and goal of their shared care
for the sick child. The health worker must maintain a professionally balanced relationship, which
they must also maintain with the children. This requires not only a good knowledge of paediatric
nursing but also of the laws of psychomotor development. He must not take patients' reactions
personally and it is important that he does not avoid negative reactions from children. The
principle of fairness must be applied in the provision of care. Every patient must be treated
equally. (HEŘMANOVÁ, 2012, page 130)

Improper practice or malpractice in the exercise of a health care professional's profession can
lead to patient harm. This includes the odd choice of communication. In the case of a clinical
trial, inadequate explanation and disclosure of information regarding the clinical trial may lead
to the patient or parents not consenting to participate in the trial. Healthcare professionals must
have high moral credit and continually cultivate their personality. Negligence can only be
prevented if morality is internalized. (KUTNOHORSKÁ, 2009, page 62-63)

3.      Informed consent

According to Ptáček, informed consent is a practical application of the principle of the aspect of
human autonomy. Treatment without informed consent is an unethical and illegal interference with
the patient's physical and mental integrity, even if it is successful. The denial of informed
consent is not a denial of the right to medical care, but of the right to make a free decision. In
practice, an ethical dilemma can lead to conflict between two or more people who hold opposing
views. Abandonment of the principle of beneficence is characterised by an ethical crisis.
Beneficence is perceived as benefiting the patient. The solution is valid informed consent. It
represents a compromise between conflicting principles and prevents ethical conflicts, including
frustration on the part of the patient that can lead to complaints and lawsuits. (PTÁČEK, 2011,
page 111)

In contrast to Ptáček, bioethicists and others point out that informed consent did not evolve to
protect autonomy; rather, its primary purpose is to preserve well-being. Allmark and Spedding
suggest that parental consent for clinical trials is important as a social recognition of the role
of parents, but offers little additional protection for children beyond that provided by
appropriate ethical, safety monitoring and research governance procedures. From this perspective,
the quality of parental consent may be less critical. (ALLMARK, 2007, page 318-323)

Obtaining informed consent is also important for taking photographs of underage patients for
medical research and experimentation. They are valuable material because they enrich teaching,
research and advocacy and in many cases are necessary, but they can also have negative
consequences. Children's safety and privacy could be compromised if compromising photographs
identify children and their location, given that the images, if not adequately protected, could
then reappear in the public press.  Caution must always be exercised to avoid harm, the rights of
the child being the paramount consideration. (DEVAKUMAR, 2013, online)

Conclusion

The aim of this essays was to highlight the ethical aspects of enrolling a child in a clinical
trial, which are described in several points from the perspective of health professionals, parents
and children. Various scientific articles and literature show that it is necessary to respect
children's rights, to provide them with sufficient information in a clear and age-appropriate
manner, and it is important not to neglect the child's wishes and decisions during the clinical
trial. Children, and even parents, cannot make independent decisions. Parents are burdened with a
duty of responsibility.  The role of the health professional is to provide parents and their child
with truthful and sufficient information so that they are able to make rational decisions on the
basis of that information. Inadequate information provided around clinical trials is a common
problem, according to the articles. For this reason, every clinical trial should begin with
informed consent in order to avoid communication errors, ethical crises and ensure patient welfare.
When photographing patients, especially children, for clinical trials, we must be careful not to do
so without the patient's informed consent as well. The most important argument is that the benefits
of a clinical trial should always outweigh the risks.


References

Articles:

ALLMARK, P; SPEDDING, M. Clinical trials in neonates: ethical issues. In: Seminars in Fetal and
Neonatal Medicine. WB Saunders, 2007. p. 318-323.

CARVALHO, A.A., COSTA, L.R. Mothers’ perceptions of their child’s enrolment in a randomized
clinical trial: Poor understanding, vulnerability and contradictory feelings. BMC Med Ethics 14, 52
(2013). https://doi.org/10.1186/1472-6939-14-52

DEVAKUMAR, D., BROTHERTON, H., HALBERT, J. et al. Taking ethical photos of children for medical and
research purposes in low-resource settings: an exploratory qualitative study. BMC Med Ethics 14, 27
(2013). https://doi.org/10.1186/1472-6939-14-27

FUKUDA, Y., FUKUDA, K. Parents’ attitudes towards and perceptions of involving minors in medical
research from the Japanese perspective. BMC Med Ethics 19, 91 (2018).
https://doi.org/10.1186/s12910-018-0330-1

HEIN, I.M., TROOST, P.W., LINDEBOOM, R. et al. Key factors in children’s competence to consent to
clinical research. BMC Med Ethics 16, 74 (2015). https://doi.org/10.1186/s12910-015-0066-0

SHILLING, V., YOUNG, B. How do parents experience being asked to enter a child in a randomised
controlled trial?. BMC Med Ethics 10, 1 (2009). https://doi.org/10.1186/1472-6939-10-1

Literature:

PTÁČEK RADEK, BARTŮNĚK PETR, Etika a komunikace v medicíně, Praha: Grada Publishing, a.s. v Praze,
2011. ISBN 978-80-247-3976-2

HEŘMANOVÁ JANA a kolektiv, Etika v ošetřovatelství praxi, Praha: Grada Publishing, a.s. v Praze,
2012. ISBN 978-80247-3469-9

KUTNOHORSKÁ JANA, Etika v ošetřovatelství, Praha: Grada Publishing, a.s. v Praze, 2007. ISBN
978-80-247-2069-2

Webpages:

AIFP, Klinické studie: otázky a odpovědi [online] 2022 Accessible from:
https://www.aifp.cz/cs/klinicke-studie-otazky-a-odpovedi/

EACH, Promoting children’s right and welfare in healthcare [online] 2022 Accessible from:
https://each-for-sick-children.org/each-charter/

NADAČNÍ FOND KLÍČEK, Co je EACH Charter? [online] 2008 Accessible from:

http://detivnemocnici.cz/charter/

STEPHEN C. TAYLOR, Health Care Ethics, [online] 2018 Accessible from:

https://iep.utm.edu/h-c-ethi/


Student name: Ishizaki Takayuki

Personal number: M210155