Pediatric Research: Challenges for Institutional Review Boards

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Pediatric Research Challenges for Institutional
Review Boards

• Summary Points
• Alexander A. Kon, MD
• University of California Davis

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Variability in IRB Review

• Major barrier to multicentered studies
• Difficulty when investigators change institutions

3
Case 1 SLE

• Close monitoring of adverse events particularly
  when problems are less obvious
• Minimize risk using inclusion/exclusion criteria
• Exclude children at excessive risk
• Must include children at some risk to preserve
  the endpoints
• Define stable on medications carefully
• Careful assessment of drug holidays/placebos
• If such a holiday would be reasonable in the
  clinical care of the patient
• Mixed vote on placebo arm

4
Case 2 Insulin Clamp

• How do we assess risk?
• 2 I.V.s is not what normal children experience
  vs.
• Clamp in an experienced unit is no riskier than
  everyday life
• Does not fall clearly under the federal
  regulations for minimal risk
• Different IRBs will make different decisions

5
Case 3 Autism Screening

• Level of risk of genetic research
• Risk beyond the actual interventions
• Consider implications of the diagnosis
• No clear consensus
• Level of risk of sedation for MRI
• Consider alternatives (e.g., no sedation)
• Sedation vs. anesthesia
• IOM report
• Mixed IRB review
• Do siblings of patients have a disorder or
  condition per 46.406?

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Case 5 Self Inflicted Injury

• Waiver of parental permission/assent/consent
• How do we do community engagement/consultation?
• Who is the community?
• Is this a life threatening circumstance?
• OHRP position that if a minor can consent to
  treatment (e.g., STDs), he/she can consent to
  study inclusion for research of that condition
• Variability in state laws

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Case 4 GBM Gene Therapy

• Off label chemotherapy in combination with
  investigative agent
• Many standard therapies in pediatrics are off
  label
• Evidence regarding prospect of direct benefit
• Pediatric specific clinical data vs. adult data
• Issues with pediatric-specific malignancies/diseas
  es
• Would tolerate greater risk if the survival with
  standard therapy is very low

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Presentations

• Support in regulations for central IRB review
• Central IRB/Local IRB roles in facilitated review
  process
• Challenges
• Consent form readability
• What constitutes research
• Determination of risk category
• Therapeutic misconception
• Confusion regarding who is in charge
• Sponsor/investigator roles in providing
  information to the IRB

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Presentations

• Inclusion of children only if essential for
  pediatric health
• Risk/benefit assessment for EACH procedure in
  each protocol
• Risk assessment based on a uniform (not relative)
  standard

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Major Difference in IRB Practice in Todays
Meeting

• Defining Minimal Risk
• Defining Minor Increase Over Minimal
• What Constitutes a Disorder or Condition

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Life is Risky

• Some have argued that since life is risky, IRBs
  ought weigh minimal risk against the appropriate
  background
• Wendler et al. demonstrated substantial risk in
  everyday life
• E.g., Driving in a car on a country road at night
  with a teen driver probably the most risky
  situation
• May be appropriate based on the benefits in life
• Likely not minimal risk as most would consider
  it

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THANK YOU

• All of our panelists, presenters, and moderators
• The members of the planning committee
• Shawn Redfern and Jim Hollahan for technical
  support
• The NCRR and the NICHD
• Dr. Steven Hirschfeld

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Slides From Today

• Slides and audio/video will be available on the
  CTSA website

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