ETHICAL GUIDELINES FOR RESEARCH INVOLVING MINORS

OR CHILDREN
1. Definitions

1.1. Children
1.1.1. RA 9344 (Juvenile Justice and Welfare Act of 2006)
and The United Nations Convention of the Rights of
the Child define children as a “human being below
the age of 18 years unless, under the law applicable
to the child, majority is attained earlier.”

1.1.2. RA 7610 (Special Protection of Children Against

Abuse, Exploitation, and Discrimination Act) defines
“children" as those persons younger than 18 years
of age or those older but are unable to fully take
care of themselves or protect themselves from
abuse, neglect, cruelty, exploitation, or
discrimination because of a physical or mental
disability or condition.

1.2. Minors are defined as those who have not reached the age
of majority (< 18 years) as defined by Republic Act 6809 (An
Act Lowering the Age of Majority from Twenty-One to
Eighteen Years) (RA 6809, 1989).

2. The following features that speak of the uniqueness of the child as

a research participant must be considered, particularly in drug trials.
It should be realized that the child is not simply a small adult. These
features include:

2.1. Non-translatability and non-applicability of research

findings from adults are due to:

2.1.1. Differences in disease susceptibility

2.1.1.1. Children are at risk for infectious diseases
due to the immaturity of their immune
system; thus, most vaccine-preventable
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 illnesses are more common among
children.

2.1.1.2. Congenital illness and genetic conditions

are often first appreciated upon birth or
early childhood.

2.1.1.3. Some diseases predominantly affect

children, such as dengue or Zika virus.

2.1.2. Children often being unwilling victims or collaterally

affected in disasters and wars with the effects that
could scar them for a lifetime;

2.1.3. Children being affected by or may be the victims of

family or sexual violence, poverty, or crime; and

2.1.4. Children as a class being susceptible to malnutrition

and developmental disorders.

2.2. Differences in physiology and pharmacokinetics

• stage of development
• nutritional status
• pathology

2.3. Heterogeneity of the population

2.3.1. There are several birthweight categories, each with
different disease susceptibilities.
• ELBW (< 1000 g)
• VLBW (< 2000 g)
• LBW (< 2500 g)

2.3.2. There are different gestational age categories with

varying clinical risks and prognoses.
• Preterm (< 37 weeks)
• Term (3–42 weeks)
• Post term (> 42 weeks)

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 2.3.3. There are different child developmental stages with
their unique developmental, and among
adolescents, social issues.
• Neonates (0–28 days)
• Early infancy (28 days to 12 mos.)
• Late infancy (12–24 mos.)
• Pre-school (2–5 yrs.)
• Primary school (6–11 yrs.)
• Adolescents (12–18 yrs.)

2.4. Vulnerability

2.4.1. Young children are incapable of understanding the

consent assent process.
2.4.2. Children may have a situational vulnerability, such
as victims of violence, war, or crimes.
2.4.3. Children have a relational vulnerability to adults.

3. Existing guidelines regarding children as research participants are

concerned with the responsibilities of the persons, institutions, and
authorities involved in biomedical research. These include the WMA
Declaration of Helsinki, the ICH-GCP guidelines, the EU directives on
the implementation of GCP, the CIOMS guidelines, and our National
Ethical Guidelines.

Gil (2004) suggests that in addition to existing guidelines, the

following principles should be considered in doing research among
children.

3.1. Aim of clinical studies

3.1.1. The aim of studies should focus on clinically or
socially relevant conditions affecting children.
Children should not be used as research objects on
behalf of adults.
3.1.2. Children should not be involved in research that
serves only scientific interests, especially if the
research has no benefit to them.

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 3.2. Integrity of the child and respect for autonomy

3.2.1. The Convention of the Rights of the Child

guarantees child protection. The protection of the
child’s integrity must be considered in all life stages.

3.2.2. Children need special protection because of their

vulnerability.

3.2.3. To respect the child’s autonomy is to involve them

in the assent process whenever possible.

3.2.4. Involvement of the child in the assent consent

process is developmentally determined and will
differ for different populations and cultures. In
keeping with the child’s capacity, the present
guidelines for assent include the following:

• < 7 y/o – no need for assent

• 7 to < 12 y/o – verbal assent
• 12 to < 15 y/o – simplified written assent
• 15 to < 18 y/o – the minor can co-sign the
consent signed by the parents

3.2.5. According to CIOMS (2016), if children reach the

legal age of maturity during long-term studies, their
consent to continued participation should be
obtained.

3.2.5.1. Children less than 12 y/o, who during the

research turn older than 12 but younger
than 15 years, should sign an assent form.

3.2.5.2. Children aged between 12 and 15 years,

who during the research turn older than 15
years, should co-sign the consent form
signed by their parent or LAR.

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 3.2.5.3. Children younger than 18 years, who during
the research turn 18 y/o, should sign a
newly administered consent form (apart
from what was signed by their LAR or
parents).

3.2.6. In general, the refusal of a child or adolescent to

participate or continue in the research must be
respected unless continued participation in the
research is in the best interest of the child,
considering their medical condition.

3.2.7. The child’s dissent should be upheld and respected.

3.3. Study design: Observational research vs. Interventional

research

3.4. Benefits vs. risks

3.4.1. The goal of research among children should be to

improve the welfare of the child or to reduce
suffering.

3.4.2. The predicted benefits must always outweigh the

recognizable risks of participation.

3.4.3. The risk must be minimized by all available means.

3.4.4. Should the objectives be realized through

observational studies, this should be preferred over
interventional studies.

3.5. Investigator qualifications in investigational provisions

3.5.1. Only studies that are properly planned and

conducted by competent researchers are ethically
justified. The study should be conducted or

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 supervised by child experts such as pediatricians
whenever possible.

3.5.2. Study protocols and study designs should be child-

specific and not simple modifications of study
protocols originally designed for adults.

3.5.3. Clinical trials and other interventional studies

should be carried out in a facility that provides a
child-friendly atmosphere.

3.6. Timing of the involvement of children in clinical trials (Gill,

2004):

3.6.1. For diseases exclusively affecting children, trials

involving children may be carried out even without
previous adult exposure.

3.6.2. For diseases mainly affecting children or graver in

children or having a different natural history in
comparison with adults, trials are needed at an
early stage following evidence of efficacy in adults

3.6.3. For diseases occurring in both adults and children

with no or limited treatment, trials are needed at an
early stage following evidence of efficacy in adults.

3.6.4. For diseases occurring in adults and children for

which sufficient treatment exists, trials in children
should follow the completion of adult trials.

3.7. Minimizing risks

3.7.1. Adequate pre-clinical toxicity studies and safety

data from adult studies should be available.

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 3.7.2. The sample size should be the smallest to affect the
least number of participants but be large enough
for statistical inference.

3.7.3. Doses used for clinical trials should be the lowest

therapeutic dose.

3.7.4. The number and extent of interventions (especially

invasive) should be minimum.

3.7.5. The methods for laboratory tests should use the

smallest blood sample volumes possible.

3.7.6. The study should be reviewed and approved by an

ethics committee with the necessary expertise in
childcare (e.g., the presence of a pediatrician or
developmental psychologist).

3.8. Minimizing discomforts

3.8.1. Every effort must be made by research institutions

and staff to minimize pain, discomfort, and fear
through preparations, play facilities, and a child-
friendly environment.

4. In reviewing research involving children and minors, the following

assessment items should be reviewed by the members of the
Research Ethics Committees.

4.1. The investigator and the study team must be qualified to

conduct of research among children. These qualifications
may be assessed by reviewing the resumé. The proponent
is qualified by his education, training, and experience.

4.2. In therapeutic trials, the reviewer should note the results of

existing studies done among adults. These can be assessed
by reviewing the investigators’ brochures.

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 4.3. The social value of the study considers the burden of illness,
equipoise, and whether it addresses an important unmet
need.

4.4. The risk-benefit ratio should be favorable, and the benefits

should far outweigh the risk considering that the child is
vulnerable.

4.5. The reviewer should pay particular attention to risk

mitigation procedures, monitoring details, and withdrawal.

4.6. The reviewer should ensure that the assent consent is

comprehensive and written in a language that will be
understood, considering the age of the children to be
recruited.

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