This document discusses ethical considerations in pediatric research. It notes that children are considered a vulnerable population due to their developing decision-making capacity and dependence on others. Key ethical principles for research with children include beneficence, non-maleficence, justice, respect for consent/assent, and privacy. Research risks to children must be justified by potential benefits and should not disadvantage children. Assent from children and consent from parents are also required, with standards varying based on the study's risk level.

1. ETHICAL CONSIDERATIONS IN PEDIATRIC RESEARCH
-Dr. Ravikiran H M
ADMO/CH/MLG/NF Railway
Children are defined in FDA regulations as “persons who have not attained the legal age for
consent to treatments or procedures involved in clinical investigations, under the applicable law
of the jurisdiction in which the clinical investigation will be conducted”
Vulnerability of children is based on:
1. their decision-making capacity may be immature,
2. their lives are still subject to the authority of others,
3. their underlying dissent may be masked for fear of upsetting authority figures, and
4. their rights and interests may be undervalued by society
Ethical principles that serve as a framework for human subject’s research:
Beneficence Applying evidence-based care generated from research specific to children
Non-maleficence Avoiding harmful therapies extrapolated from adult patient data or
experience. Prevent or remove possible harm (primum non nocere).
Distributive justice Allowing research benefits to be available to all populations
Respect for informed
consent
Supporting developing autonomy in children considering research
participation
Respect for privacy
and confidentiality
Providing confidentiality within the limits of legal requirements
Scientific necessity Children should not be enrolled in a clinical investigation unless necessary
to achieve an important scientific and/or public health objective
concerning the health and welfare of children
Paternalism, is the belief that an individual is incapable of making an informed decision and
that a surrogate must make the decision in the best interest of the individual. A classic example
of the struggle of autonomy versus paternalism lives in the house of every teenager.
Parent Legal Guardian Foster Parents
 Biological
 Legally Adoptive
Legal Guardianship has been
established under state law,
which includes a written
provision documenting the
guardian's ability to consent
for the child's medical care
and any other activities
Generally do not have
authority to consent to medical
care
 Considered under the care
of Children and Youth
Service (Foster Care)
 Considered wards for

2. ETHICAL CONSIDERATIONS IN PEDIATRIC RESEARCH
-Dr. Ravikiran H M
ADMO/CH/MLG/NF Railway
contemplated by the research research purposes
Can provide consent Can provide consent with a
copy of the appropriate court
order filed with the consent
form
Cannot provide consent
Balance of Risk and Potential Benefit:
1. First, the risks to which children would be exposed must be low if there is no prospect of
direct therapeutic benefit (PDB) to the enrolled children.
2. Second, children should not be placed at a disadvantage by being enrolled in a clinical
trial, either through exposure to excessive risks or by failing to get necessary health care.
Risk gap: either an acceptably low risk of the experimental intervention or a sufficient PDB to
justify the risks of the intervention.
Clinical equipoise is commonly defined as “genuine uncertainty on the part of the expert
medical community about the comparative therapeutic merits of each arm of a clinical trial.”
Advocates of clinical equipoise argue that it “provides a clear moral foundation to the
requirement that the health care of subjects not be disadvantaged by research participation”
Placebo-controlled trial is not ethical or practical, there are several alternatives that may reduce
or eliminate the exposure to placebo. In a randomized withdrawal trial, all eligible patients
with a particular disease are initially treated with the experimental drug. Patients that have a
successful initial response are then randomized in a double-blind fashion to remain on the drug
or be switched to placebo (or lower doses).
Rights of Pediatric Assent:
1. Conducting the process in a manner and location that ensures participant privacy
2. Giving adequate information about the study in a language understandable to the
participant
3. Providing adequate opportunity for the participant to consider all options
4. Responding to the participant’s questions
5. Ensuring the participant has understood the information provided
6. Obtaining the participant’s voluntary agreement to participate
7. Continuing to provide information as the participant or research requires

3. ETHICAL CONSIDERATIONS IN PEDIATRIC RESEARCH
-Dr. Ravikiran H M
ADMO/CH/MLG/NF Railway
Characteristics Assent Consent
Meaning Agreeing with something,
a request, or to participate
in an activity.
Giving permission to be
involved in an activity
Age Obtained from people who
are not of legal age to give
a consent
Obtained from adults
(people above the legal
age)
In research Willingness to participate
in a study
Legally entered agreement
for a subject to participate
in a study
In law Not a legally binding
permission
Legally binding
permission
Risk Categories in Pediatric Research
45 CFR 46
Code
Description Examples Consent
404 Research involving no greater
than minimal risk
Venipuncture Chest
radiograph Psychological risk
Classroom observation
One parent
Child assent
405 Research involving greater than
minimal risk but presenting the
prospect of direct benefit
Shortened course of therapy
compared with conventional
practice
One parent
Child assent
406 Research involving greater than
minimal risk and no prospect for
direct benefit
Urine catheterization Skin or
bone marrow biopsy
Radiocontrast with sedation
Both parents
Child assent
407 Research otherwise not
approvable
Research not approvable by
previous sections but presents
an opportunity to understand,
prevent, or alleviate a serious
problem
116 Waiver of consent or assent

4. ETHICAL CONSIDERATIONS IN PEDIATRIC RESEARCH
-Dr. Ravikiran H M
ADMO/CH/MLG/NF Railway

5. ETHICAL CONSIDERATIONS IN PEDIATRIC RESEARCH
-Dr. Ravikiran H M
ADMO/CH/MLG/NF Railway

6. ETHICAL CONSIDERATIONS IN PEDIATRIC RESEARCH
-Dr. Ravikiran H M
ADMO/CH/MLG/NF Railway
References:
1. Oulton, K., Gibson, F., Sell, D., Williams, A., Pratt, L., & Wray, J. (2016). Assent for
children’s participation in research: why it matters and making it meaningful. Child: Care,
Health and Development, 42(4), 588–597.
2. Anthony T. Podany. Ethical Considerations in Pediatric Research. PedSAP 2017 Book 1.
3. Differencebetween.net
4. Ethical issues in health research in children. Paediatr Child Health. 2008 Oct;13(8):707-20.
doi: 10.1093/pch/13.8.707. PMID: 19436527; PMCID: PMC2606083.
5. Roth-Cline M, Gerson J, Bright P, Lee CS, Nelson RM. Ethical considerations in conducting
pediatric research. Handb Exp Pharmacol. 2011;205:219-44. doi: 10.1007/978-3-642-20195-
0_11. PMID: 21882114.