Risk Assessment in Pediatric Research

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Risk Assessment in Pediatric Research

• Sumeeta Varma,
• National Institutes of Health

The views expressed are my own. They do not
represent any policy or position of the NIH,
DHHS, or US government.
2
Pop Quiz

• Researchers propose to study precursors to Type
  II diabetes in children.
• Healthy subjects age 8-10
• Physical exam and IV glucose tolerance test,
  repeated 2 years later.
• IVGTT involves IV infusion of glucose solution
  followed by serial blood sampling from the same
  IV catheter.
• Does the IV glucose tolerance test
• pose minimal or more than minimal risk?

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Outline

• Why have risk guidelines for research with
  children?
• What are the guidelines and what do they mean?
• Do they get it right?

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Need for Risk Guidelines in Pediatric Research

• Guidelines needed to balance two important aims
• Conduct research necessary to improving
  childrens health
• Protect children from excessive risks
• taking into account that children (in general)
  cant give consent

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Current Guidelines

• Research with children that does not offer the
  subjects a chance of clinical benefit is
  controversial
• To determine when this type of research is
  acceptable, HHS and FDA guidelines rely on the
  concept of minimal risk
• Determination that research involves more than
  minimal risk triggers greater scrutiny, up to and
  including 407 review

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Minimal Risk Defined

• Minimal risk is defined in terms of the risks
  of daily life
• 45 CFR 46 Minimal risks are risks 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

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Interpreting the Definition

• Procedural interpretation
• A procedure is minimal risk if it is a procedure
  children undergo in their daily lives
• Relative interpretation
• A procedure is minimal risk if it does not exceed
  the level of risk in the daily lives of the
  particular subjects
• Objective interpretation
• A procedure is minimal risk if it does not exceed
  the level of risk in the daily lives of average,
  healthy children

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Making Risk Assessments

• IRBs typically lack data on risks in research
  daily life, and must rely on their perceptions of
  risk
• Individuals make systematic errors in assessing
  risks based on perception

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Data for Making Risk Assessments

• Data can help in making more systematic
  comparisons between risks of research procedures
  and risks encountered in daily life
• Existing data on risks of daily life and of
  research procedures are limited, but some are
  available from current databases

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Using Data to Apply the Minimal Risk Standard

• Sometimes a research procedure poses a chance of
  a harm also found in daily life
• E.g. risk of death
• This is the easy case
• Sometimes, research procedures pose a chance of a
  harm not found in daily life
• E.g. research bronchoscopy poses a chance of
  airway bleeding
• Comparing different types of risks is complex,
  but doable
• Take the bus to school or ride a bike?

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Comparative Analysis

• Identify potential harms
• E.g., Bronchoscopy might cause airway bleeding
• Determine magnitude of potential harm
• E.g., Classify airway bleeding as a minor harm

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Magnitude of Harms
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Comparative Analysis, continued

• Determine likelihood of potential harm
• Probability of airway bleeding is X
• Determine likelihood of comparable harm in daily
  life
• Probability of minor harm in daily life is Y

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Likelihood of Harms in Daily Life
Wendler D, Varma S. Minimal risk in pediatric
research. J Pediatr 2006 Dec149(6)855-61.
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Comparative Analysis, continued

• Compare likelihoods
• Is X (chance of airway bleeding from
  bronchoscopy) greater than 30,000 per million
  (chance of minor harm in daily life)?
• If X is greater ? procedure is greater than
  minimal risk
• If X is NOT greater ? procedure is NOT greater
  than minimal risk

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Pop Quiz Revisited

• Does IVGTT in healthy 8-10 year olds pose
• minimal or more than minimal risk?

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Does relying on the risks of daily life allow
too much risk?

• Existing data suggest the current minimal risk
  standard allows greater risk than many assume is
  appropriate for children
• In that case
• Have we been too conservative in assessing
  research risks?
• Is the risks of daily life standard too
  permissive?