Children in Research: They’re Not Just Small Adults 5/13/2018 4:06 PM Children in Research: They’re Not Just Small Adults Kelly O’Berry IRB Education & Outreach Manager Human Subjects Photo by Zachary Scott, 1981, for the New York Times © 2007 Microsoft Corporation. All rights reserved. Microsoft, Windows, Windows Vista and other product names are or may be registered trademarks and/or trademarks in the U.S. and/or other countries. The information herein is for informational purposes only and represents the current view of Microsoft Corporation as of the date of this presentation. Because Microsoft must respond to changing market conditions, it should not be interpreted to be a commitment on the part of Microsoft, and Microsoft cannot guarantee the accuracy of any information provided after the date of this presentation. MICROSOFT MAKES NO WARRANTIES, EXPRESS, IMPLIED OR STATUTORY, AS TO THE INFORMATION IN THIS PRESENTATION.

Overview Pros and Cons of Using Children as Subjects Ethical Principles Federal Regulations and Guidance Consent/Assent Resources

Children as Research Subjects Pros: Cons Risks from taking medication that has not been tested in children Regulations allow parent/guardian to grant permission Children’s Health Act of 2000 Diseases only in kids Risks from investigational medication and study procedures lack legal authority to consent for themselves Historic cases of unethical research

Ethical Principles: Respect for Persons Beneficence Justice Provisions for parental permission Considerations for the child Beneficence Discoveries that benefit children Justice Research must be done in adults before children, whenever possible Photo by Zachary Scott, 1981, for the New York Times

Regulations & Guidance Photos by Zachary Scott, 1981, for the New York Times

Subpart A (The Common Rule) Definitions Legally Authorized Representative Criteria for IRB Approval (45 CFR 46.111) Minimize Risk to Subjects Risk/Benefit Evaluation Informed Consent will be sought and documented Additional Safeguards for Vulnerable Subjects

Common Rule (continued) Obtaining Informed Consent From subject or Legally Authorized Representative Circumstances minimize coercion or undue influence Language the subject or LAR can understand Presenting the required information (elements of consent)

Expedited Review Limits amount of blood collected, based on subject’s: Age Weight Health

Subpart D: Children Definitions Limits on Exempt Research Children Parent Guardian Limits on Exempt Research NOT surveys or interviews Observation of public behavior - ONLY if researcher not participating in the activities being observed

Subpart D – Risk and Benefit The IRB Can approve studies that are: No greater than minimal risk Greater than minimal risk, but include the prospect for direct benefit Greater than minimal risk and no prospect for direct benefit, but likely to yield generalizable knowledge of subject’s disorder or condition

The IRB Cannot Approve: Studies that are more than minimal risk, no prospect for direct benefit and not likely to yield generalizable results about the subject’s condition, but opportunity to further understand, prevent or alleviate a serious problem affecting health/welfare of children

Approval Process for Studies the IRB Cannot Approve Department of Health and Human Services (HHS) Posts Protocol in Federal Register Time for Public Comment Convene an expert panel Protocol approved by the HHS Secretary 8-week process

Wards of the State Only the first 2 IRB approval categories if: Research is related to their status as a Ward Research is done in a setting where the majority of child subjects are not Wards Requires appointment of an advocate in addition to the Guardian

Subpart B: Pregnant Women, Fetuses and Neonates Scope Consent/Permission from the Woman Benefit to herself Benefit to herself and fetus No benefit (minimal risk to fetus and purpose to develop important biomedical knowledge) Permission from Both Parents Prospect of benefit only for the fetus

Subpart B (continued) Pregnant Teens Follow Subpart D (research with children) Limitations on what Researchers can do No inducements No part in decision-making No determination about viability

Subpart C: Prisoners Definitions Must comply with requirements of Subpart B and Subpart C

Informed Consent & Assent Photo by Zachary Scott, 1981, for the New York Times

Parent/Guardian Permission Granting permission – not consent All required elements of consent Voluntary agreement for child to participate

Anticipate and Address Needs Reluctance to ask questions Concerns about “experiments” & research Bad experience with health care/research Difficulty understanding words/concepts Confuse healthcare and research (therapeutic misconception Coercion or undue influence

Consent Document Use IRB template Fill in study details When to use “your child” in place of “you” Could describe both the parent and child participation in the study Could collect information about the child from a proxy (parent, teacher, other)

Documenting Parent Permission Valid IRB Approval Stamp Subject Printed Name Subject Signature & Date, if applicable Parent/Guardian Section Good: Mother, Father, Legal Guardian Questionable: Step Parent, Foster Parent, Grandparent, Aunt/Uncle, Other… Record Storage Requirements

Assent from the Child Obtain Assent Read and Sign Read and Verbal Agreement Verbal Description and Agreement No Assent Not capable Prospect for direct benefit Waiver of assent

Assent Document Template Assent Document Simpler description of the study Printed name, signature and date Edit to reflect the proposed assent process

Resources UI Investigator’s Guide Federal Regulations – HHS and FDA Family Education Rights and Privacy Act (FERPA) Guidance from the Office of Human Research Protections (OHRP) Special Protections for Children as Subjects FAQ on Research with Children Guidance from the Food and Drug Administration (FDA) General Considerations for the Clinical Evaluation of Drugs in Infants and Children Children and Clinical Studies.org

Questions/Comments? Photo by Zachary Scott, 1981, for the New York Times