1. Ethical issues with children and families in research
Julia A. Snethen, PhD, RN
Associate Professor
University of Wisconsin-Milwaukee
College of Nursing

2. Background: Historically
Limited research with children due to:
Protection-prevent research that might
harm children
Limited ability to consent
Less allocation of funds for research
with children
Fewer researchers conducting
research with children

3. Background: Historically
Limited research with children due to:
Children more likely to experience
rare diseases:
Limits number of children available
to participate in studies of unique diseases
Studies (e.g. drug) expensive if only benefits small number of children

4. Children “Persons (children) who have not attained the
legal age for consent to treatment or
procedures involved in the research,
under the applicable law of the jurisdiction
in which the research will be conducted”
45 CFR

5. 3 Basic Ethical Principles: Respect for Persons (Children)
Acknowledge that individuals have
autonomy
Protection must be provided to persons with diminished autonomy—including children.
Children must be informed of risks in research, and assent obtained
(Belmont Report, 1978)

6. Basic Ethical Principle: Beneficence
Researchers have an obligation to ensure that children are treated in an ethical manner:
respecting their opinions
and decisions
protecting them from harm,
make efforts to secure their well-being.
(Belmont Report, 1978)

7. Basic Ethical Principle: Beneficence
Researchers working with children have an obligation to follow the general rules of:
Do no harm
Maximize possible benefits to child,
minimizing any possible harm to child.
(Belmont Report, 1978)

8. Basic Ethical Principle: Beneficence
“effective ways of treating childhood diseases and
fostering healthy development are benefits that serve to
justify research involving children”
“research also makes it possible to avoid the harm that
may result from the application of previously accepted
routine practices…that may turn out to be dangerous”
(Belmont Report, 1978)

9. Basic Ethical Principle: Justice
Who ought to receive the benefits of research and bear its burdens?
An injustice occurs when a benefit the child should have is:
denied without good reason or
burden improperly imposed
Children should have the benefit of
research, not just adults (Belmont Report, 1978)

10. Basic Ethical Principle: Justice
Burdens and benefits should be distributed to each person equally, based on:
individual need,
individual effort,
societal contribution,
merit (Belmont Report)

11. Children-Vulnerable Population
Developing:
Cognitive
Psychological
Social
Haven’t reached age of
consent
Limited understanding of:
Research protocols
Risk involved in participation

12. Research with Children: Assess Benefits & Risks
Probability of harm:
Physical,
emotional,
social,
Economic
Varies from minimal to significant.
Benefit:
Valued or desired outcome

13. Minimal Risk: Federal Regulations Definition
Federal regulations only define minimal risk
“Probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests”.

14. Minimal Risk: Examples
Physical examinations
Psychological examinations
Alterations in
daily routine
Immunizations
Specimens:
Blood
Urine
Modest dietary changes

15. Protection of Children in Research
Code of Federal Regulations (CFR)
Require research be reviewed by IRB
DHHS Guidelines have 4 categories for acceptable research in children

16. Code of Federal Regulations 46.404
Research not involving greater than minimal risk.

17. Code of Federal Regulations 46.404
“no greater than minimal risk to children”
adequate provisions made for soliciting assent of children and permission of their parents or guardians,
HHS regulations at 45 CFR

18. Code of Federal Regulations 46.405
Research involving greater than minimal risk but
presenting the prospect of direct benefit to the child
Requires informed consent from parent and child assent

19. Code of Federal Regulations 46.405
Risk justified by anticipated benefits for child;
Relation of anticipated benefit for child to the risk is at least as favorable to child as that provided by available alternative approaches;
Adequate provisions made for soliciting assent of child and permission of parents or guardians HHS regulations at 45 CFR

20. Code of Federal Regulations 46.406
Research involving greater than minimal risk and
no prospect of direct benefit to the individual child involved in research,
likely to yield generalizable knowledge about child's disorder/condition.

21. Code of Federal Regulations 46.406
Procedure likely to provide generalizable knowledge about child’s condition vitally important for understanding or improving condition
Adequate provisions made for obtaining assent of child and permission of both parents/ guardians --HHS regulations at 45 CFR
Risk of research minor increase over minimal risk;
Intervention/procedure reasonably equal with child’s medical, dental, psychological, social, or educational situations

22. Code of Federal Regulations 46.407
Research not otherwise approvable which
presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health and welfare of children
Requires informed consent from both parents and child assent

23. Code of Federal Regulations 46.407
Secretary of HHS determines
(following expert panel consultation and public input)
Research reasonable opportunity to further understanding, prevention, or alleviate serious health problem affecting children
Research conducted in accordance with sound ethical principles
--HHS regulations at 45 CFR

24. Parental Permission (Diekma, 2006)
Agreement of parent(s) or guardian to the participation of their child or ward in research
45 CFR
Permission obtained through “informed consent”

25. Informed Consent: Research Participation
Ensures that participants (or their legal representatives) be given the opportunity to choose what they participate in, or choose not to participate in
(Belmont Report, 1978)

26. Informed Consent
Children (under 18 years of age) not legally considered able to provide informed consent
Parents or legal guardian required to make the decision to choose whether their children participate in research or not (Belmont Report)

27. Informed Consent: Information
Research procedure
Purpose
Risks
Anticipated benefits
Alternative procedures
Statement offering opportunity to ask questions
Opportunity to withdraw at any time
(Belmont Report, 1978)

28. Informed Consent: Comprehension
How is the information being presented to children and their family?
Time:
Adequate for completely sharing information
Appropriate time allowed for questions and responding to questions?
(Belmont Report)

29. Informed Consent: Comprehension (Kopelman, 2006)
Organized sharing and ensuring understanding of information
Children
Family
(Belmont Report, 1978)

30. Informed Consent: Voluntariness
Consent and/or assent for participation must be
voluntarily given, free of:
Coercion
Undue influence.

31. Assent: Broome, 1999; Broome & Stieglitz, 1992
“Child’s voluntary affirmative agreement to participate in research” 45 CFR
IRB required to ensure children assent obtained.
Failure to object should not, without agreement, be construed as assent 45 CFR

32. Child Assent Exceptions (Diekema, 2006)
Limited capability of child to provide assent
Research intervention or procedure has direct benefit to well-being of child, that is only available through the research
Adequate provisions for informed consent from parents or guardian still required.
45 CFR

33. Issues of concern: Assent Broome & Stieglitz, 1992; Diekema, 2006; Lindeke et al., 2000)
Age
No specific age required
Children: 7-18 years of age
Written
Verbal
Children ability to assent dependent on:
Maturity
Psychological
Social
Cognitive

34. Issues of Concern: Dissent Broome, 1999; Broome & Stieglitz, 1992
Child’s decision against participation in research.
Failure to object should not be construed as assent
Can happen at anytime, even if child has already provided assent.

35. Coercion and Undue Influence Belmont Report, 1978; CPS, 2008
Undue influence: Reward
for research participation:
excessive,
unwarranted,
Inappropriate
ordinarily acceptable for adult may become undue influences for child
Coercion
threat of harm intentionally presented to obtain compliance.

36. Coercion: Healthcare provider relationship Belmont Report, 1978; CPS, 2008
Child and their parents may agree to participate because of their relationship with healthcare provider.
May be more challenging for the child and parents to say ‘no’ to health care provider

37. Coercion-Compensation Belmont Report, 1978; CPS, 2008
Compensation for child participation.
Monetary
Non-monetary

38. Coercion-Compensation Belmont Report, 1978; CPS, 2008
Monetary Compensation
Gift cards
Cash amounts
Concerns:
Adults: Insignificant amount
Children: Significant amount

39. Coercion-Compensation
Non-monetary
Trips: (e.g. fieldtrips)
Costly equipment or supplies
(e.g. diabetes blood glucose meter)
Program (e.g. weight control)

40. Undue Influence: Factors to consider Belmont Report, 1978; CPS, 2008
Healthcare Provider relationship with child and their parents
Compensation for participation
Offer of a reward to the child that is:
excessive
unwarranted,
inappropriate or
improper

41. Issues of Concern:Conflict of Interest (CPS, 2008)
Academic
Financial
Personal

42. Conflict of Interest-Academic
Publish or perish
Current research foundational to obtaining future grant funding

43. Conflict of Interest: Financial Kopelman, 2006)
Researcher(s) have
financial interest in:
Product
Medication
Treatment
protocol
Success of research
financially benefits
researcher(s):
Salary increases
Incentives from organization

44. Conflict of Interest: Personal
Clinical relationship between child and healthcare provider
Long-standing relationship with researcher

45. Sharing Findings: Participants (CPS, 2008)
Consent process increasingly includes offering to share the findings with participants.
However, it is important when sharing the findings to consider:
Benefits
Risks

46. Sharing Findings: Participants (CPS, 2008)
Benefits:
Helpful to inform participants on future health care choices
May help to improve care of children and families.

47. Sharing of Findings (CPS, 2008)
Risks:
When the findings are adverse to participants
Whether resources are in place to limit or ensure no negative outcomes from sharing the information.

48. Minimal Risk: Age of Children (Wendler, 2009).
Probability and magnitude
of harm or discomfort
ordinarily encountered in
daily life or during
performance of routine
physical or psychological
examinations or tests can
vary by the age of child
Example:
Adolescents more likely to be higher risk takers then younger children
Infants more dependent and potentially more vulnerable

49. Research Scenario: Name that Ethical Issue
Young child donating bone
marrow to sibling with
cancer.
Child states they do not
want to donate to the
sibling:
They have had to donate before and:
It hurts
They were told by their
parent that they have
to donate because if they don’t, their sibling
will die

50. What ethical issues have you experienced in your research?

51. Ethical Issues
What has been the most effective way, in your own research, for obtaining informed consent/assent with children and their parents/ guardians?

52. References
Berg, S. L. (2007). Ethical challenges in cancer research in children. The Pediatric Oncologist, 12,
Bioethics Committee, Canadian Paediatric Society (2008). Ethical issues in health research in children. Paediatric Child Health, 13,
Broome, M. E. (1999). Consent (assent) for research with pediatric patients. Seminars in Oncology Nursing, 15,
Broome, M. E. & Stieglitz, K. A. (1992). The consent process and children. Research in Nursing & Health,15,

53. References
Diekema, D. S. (2006). Conducting ethical research in pediatrics: A brief historical overview and review of pediatric regulations. The Journal of Pediatrics, 149, S3-S11.
Department of Health, Education, & Welfare (1979).Belmont Report: Ethical Principles and Guidelines for the protection of human subjects of research. DHEW Publication No. (OS) U.S. Government Printing Office, Washington, D.C.
Department of Health and Human Services (2005). Code of Federal Regulations, Title 45-Public Welfare, Department of Health and Human Services, Part 46, Protection of Human Subjects.
Ford, J. S. & Reutter, L. I. (1990). Ethical dilemmas associated with small samples. Journal of Advanced Nursing, 15,

54. References
Jonsen, A. R. (1978). Research involving children: Recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. Pediatrics, 62,
Kopelman, L. M. (2006). Children as research subjects: Moral disputes, regulatory guidance, and recent court decisions. The Mount Sinai Journal of Medicine, 73,
Linkeke, L. Hauch, M. R., & Tanner, M. (2000). Practical issues in obtaining child assent for research. Journal of Pediatric Nursing, 15,
 Stroustrup, A., Kornetsky, S., & Joffe, S. (2008). Knowledge of Regulations Governing Pediatric Research: A Pilot Study. IRB: Ethics and Human Research, 30, 1-7. 
Wendler, D. (2009). Minimal risk in pediatric research as a function of age. Archives of Pediatric & Adolescent Medicine, 163,