Human Subjects Issues in Longitudinal Research with High Risk Children: Notes from the Field with Se

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Human Subjects Issues in Longitudinal Research
with High Risk Children Notes from the Field
with Selections from 2004 Presentation by Marilyn
Field (Staff for IOM Committee) John Landsverk,
Ph.D.
Child and Adolescent Services Research Center
Childrens Hospital San Diego Prepared for
the Child Health Services Research Meetings
(6/2004) Adapted for CHIPS, June 22, 2005

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Increased Focus on Pediatric Research and Ethical
Concerns

• Increased use of drug interventions with
  pediatric populations with little test of
  efficacy in those populations
• Controversy about safety of drugs tested in
  adults but not in children, e.g. SSRIs and
  suicide risk for children with depression
• IOM report estimates tripling of children
  participating in clinical trials from 1997 to
  2001
• Developing consensus regarding ethical conduct in
  pediatric research with development of
  IOM/Academies reports.

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IOM/Academies Reports

• Ethical Conduct of Clinical Research Involving
  Children (2004)
• Responsible Research (2003)
• Protecting Participants and Facilitating Social
  and Behavioral Sciences Research (2003)
• View or purchase at www.nap.edu

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REGULATORY FRAMEWORK

• Common Rule (Subpart A) basic regulations to
  protect human research participants developed by
  DHHS now applies to 17 agencies
• Subpart D protections for children also adopted
  by Dept of Education, CIA, and SSA but not, e.g.,
  HUD, EPA, etc.
• FDA similar but separate regulations

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CHARGE TO IOM COMMITTEE

• Consider definition of minimal risk for purposes
  of approving research involving children
• Assess appropriateness of regulations for
  children of different ages
• Evaluate regulatory compliance
• Consider IRB roles, responsibilities

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CHARGE (contd)

• Examine comprehension of parents and children of
  childs research participation
• Examine process for obtaining parental permission
  and child assent to research participation
• Examine appropriateness of payments to parents or
  children

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Contextual Overview for Notes from the Field
High Risk Populations

• Mission of the NIMH funded Child and Adolescent
  Services Research Center is to improve publicly
  funded mental health service delivery and quality
  of treatment for children and adolescents
  categorized as severely emotional disturbed or
  at high risk for the development of mental
  disorders
• Study participants involve children and families
  open for services in public sectors child
  welfare (dependents), juvenile justice (wards),
  mental health, school SED programs
• Center involves staff and investigators from at
  least three universities and colleges and a
  childrens hospital, all with different IRBs, and
  partners from public service sectors, all with
  gate-keeping mechanisms.
• Celia Fisher, Fordham University, as
  co-investigator with yearly seminars on
  developments in ethical issues and regulations
  for research studies involving children.

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Variation Across IRBs and Service System
Committees

• Formally constituted IRBs and service sector
  committees often have quite different functions
• Service sector committees are primarily concerned
  with impact of study on operations and the
  benefit and risk to the organization
• Federally sanctioned IRBs are primarily concerned
  with the risks and benefits for the potential
  research participants
• Most often service sector committees are not duly
  organized IRBs authorized under federal
  guidelines as are the university based IRBs with
  education and mental health likely to be closest
  to the IRB model and child welfare and juvenile
  probation least likely.

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Variation Across IRBs and Service System
Committees

• Differences between duly constituted IRBs appear
  related to
• Experience with medical studies and medical
  clinical trials or university based without much
  experience with these types of studies
• Prior experience with highly vulnerable children
  and families
• Prior experience with researchers who have
  successfully conducted studies with service
  sector participants such as dependents (child
  welfare) and wards (juvenile justice)

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Longitudinal Study Examples

• Longitudinal examples used because of the need to
  link through identifiers and most complex with
  high risk populations.
• Longitudinal Study of Child Abuse and Neglect
  (LONGSCAN) with five sites - 330 children in San
  Diego recruited from foster care between ages of
  birth and 3.5 years now ages 10 to 14
• Randomized trial of home visitation with 488
  families recruited at birth of index child
  followed to index childs 3rd birthday funded
  by NICHD (P. Fisher, OSLC, PI) for additional but
  different study at ages 7 to 9
• National Study of Child and Adolescent Well-Being
  (NSCAW) 6,000 families and children involved
  with child welfare and recruited into a three
  year cohort as a national representative sample
  at entry into child welfare system

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COMPREHENSION OF RESEARCH Findings

• Even young children can understand basic
  information about what will happen in research.
• Older adolescents similar to adults in many
  aspects of understanding.
• Education and discussion usually increase
  understanding.

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COMPREHENSION OF RESEARCHFindings

• Adultsas parents and in their own rightoften
  misunderstand research
• Therapeutic misconception believing purpose of
  clinical research is to treat rather than gain
  knowledge
• Written information is too complex
• Focus is too often on forms not communication

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Parental Consent Issues

• Who is the parent when child is in custody of
  the court
• Jurisdiction of the juvenile court
• Biological parent consent
• Substitute parent (kinship or non-kinship)
  consent
• Court order (shift from class to individual) to
  allow for consent and assent process when
  biological parent cannot be located (issue of
  best efforts to locate)
• Use of non-involved (study) child advocate for
  informing youth in circumstances when timeliness
  of study entry is issue.

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Parental Consent Issues

• Continuous right of child to assent to
  participate in study
• Re-consenting when custody status of child
  changes over the course of longitudinal study
• Child is reunified with biological parent
• Substitute parent becomes guardian
• Biological parental rights are severed and child
  is adopted

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Change of Study Focus

• Under original focus of longitudinal study, right
  of parent and child to withdraw from
  participation reasserted at each longitudinal
  data point
• New study question added to original study (e.g.,
  focus on neglect or biological markers added) due
  to new funding initiative or new/additional
  sponsor center requires re-consenting
• Follow-up study after completion of original
  study center requires full new recruitment into
  secondary study and re-consenting

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Assent is not informed consent

• Seeking assent is respectful.
• My daughter will be nine years old and she needs
  some kind of input in whats going on. Shes
  presently in a study and I need for her to be
  able to understand what shes getting herself
  into . . . Shes at the point where she asks a
  lot of questions.
• Andrell Vaughn, parent, 2003

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PERMISSION AND ASSENT Recommendations

• Focus on process not forms
• It has to be very interactive process. After I
  was asked this entire list of questions, I began
  to question my own first response. Just giving a
  kid a piece of paper--no matter how
  comprehensible--is not effective. I think the kid
  needs to be prompted with questions.
• Sarah, research participant at age 13

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Permission as ongoing process

• There is never enough time in those situations
  to make an informed decision. We signed the
  form because thats what you do.
• Its always at the worst time to be reading this
  type of material . . . Parents arent in control
  nor is the child.
• Joseph Lilly, parent, 2003

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Change of Service Sector Procedures / IRB
Regulations

• Child welfare and juvenile court shift from court
  order under class coverage to individualized
  court order e.g., LONGSCAN project required
  best efforts to find biological parents and
  re-consenting for participation of child in
  longitudinal study
• Linkage to administrative data bases under HIPPA
  requires new IRB review and consent for use of
  PHI or waiver process especially important for
  services research studies

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Experience with HIPPA Regulations

• CASRC provides service under contract to service
  sectors by preparing a mental health system
  report each year that requires linkage to
  administrative data bases and across databases
• Under HIPPA, CASRC operates in a well-defined
  business associate relationship to SD County
  Mental health and other agencies
• Within CASRC, use of administrative data
  containing PHI is strictly controlled and
  monitored for use in pilot studies leading to
  collaborative research projects and applications
  between CASRC investigators and agencies

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PAYMENTS TO PARENTS OR CHILDREN

• Concern some payments may distort parents or
  childs decisions and lead to choices that are
  not in the childs best interests.
• Findings limited data but evidence of
  considerable variability in practices
• Findings lack of explicit IRB policies and
  guidance for investigators

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Assent and Use of Incentives

• Level of payment or honorarium is sensitive to
  socio-economic status of potential study
  participant variation in coercive level e.g.,
  home visitation study where parents called in for
  subsequent interview because of need for payment
  to provide birthday resources or basic family
  needs
• Need for study investigators to use focus groups
  and other qualitative strategies to involve class
  of potential study participants in determination
  of coercive level of incentive and appropriate
  type of incentive bring this data to IRB as
  part of the application

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PAYMENTS TO PARENTS OR CHILDREN Recommendations

• Okay reasonable reimbursement for expenses of
  being in research
• Okay tokens of appreciation
• Scrutinize carefully payments for childs time
  and inconvenience for research w/o prospect of
  benefit
• Never okay payments to parent or child for
  increased research risk

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PAYMENTS TO PARENTS OR CHILDREN Recommendations

• IRBs should adopt explicit policies on acceptable
  payment practices.
• To equalize access to research participation,
  IRBs, agencies, sponsors should encourage
  investigators to accommodate parental work and
  family commitments.

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DEFINITION Minimal Risk

• Definition in Subpart A
• probability and magnitude of harm or discomfort
  anticipated in research are not greater . . .
  than those ordinarily encountered in daily life
  or . . . in routine physical or psychological
  examinations or tests.

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DEFINITION Minimal Risk

• Interpretation What is minimal risk is same for
  healthy and ill children
• It is not acceptable to approve higher risk in
  research because children to be studied research
  face higher risk in their daily lives (e.g.,
  unsafe homes) or in their medical care (e.g.,
  painful tests or treatments)

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Minimal Risk with High Risk Child Populations

• Current experience of re-calibration of minimal
  risk from original IRB review on multiple studies
  with shift to higher than minimal risk at annual
  IRB review no change in protocol, no change in
  federal statutes, and no change in subjects
  change in time and committee members
• Issue of whether minimal risk is perceived
  differentially between IRBs and between IRB
  members and members of high-risk study
  populations
• Minimal risk within well-educated and middle to
  upper class communities and high crime, poverty,
  and diverse communities need for research

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Child Question Content

• Issue of sensitivity of IRB members to type of
  and level of vulnerability among very high risk
  children
• Is administration of scale on child depression a
  risk for increased depression in high risk
  children lack of experience of IRB member
  rather than change in threshold by level of
  vulnerability
• Importance of prior use by investigator or other
  studies or use of pilot study data
• Sensitivity to distress due to re-questioning
  about abuse and neglect specifics may be
  increased distress leading to non-use of
  questions in that area.

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Conclusions

• Studies with especially vulnerable children are
  both critical to do and feasible to accomplish
• Need for empirical studies that inform the
  complex human subjects issues
• Research on mandating reporting and its effect
  on longitudinal study participation (NSCAW data
  available)
• Research on IRB and diverse study family
  participants in definition of and acceptability
  related to minimum risk
• Research on true informed consent processes

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Practical Guidelines for the New Investigator

• Get to know your IRB staff and materials for
  prior discussion of complex study issues.
• Locate university based ethicist with experience
  in research studies involving children
• Understand preparation of the IRB application is
  necessary and time-consuming process.
• Review NIH and IRB applications from successful
  examples related to your own work.
• Understand the NIH review and funding process
  regarding human subjects comments and concerns.