Case Study 3: Screening for autism spectrum disorders in infants

1. Case Study 3: Screening for autism spectrum disorders in infants Moderator: Dr. Rosemary Higgins, NIH/NICHD

2. Case Study 3: Screening for autism spectrum disorders in infants • Moderator:Rosemary Higgins, NIH/NICHD • Panelists: • Michael Cotten, Duke University • Allyn McConkie-Rosell, Duke University • Kathleen Kennedy, University of Texas • Benjamin Handen, University of Pittsburgh • Richard Guido, University of Pittsburgh • Sudha Kashyap, Columbia University • Description of the case: • Autism spectrum disorders affect an estimated half a million people under the age of 19 in the United States. The characteristics include abnormalities of social interaction and communication, a narrow spectrum of interests and highly repetitive behavior. • Diagnosis is usually made by the age of 3 years with some children manifesting symptoms at about 18 months. Interventions vary and include medications to treat symptoms and environmental adjustments. The rapid growth and learning that occurs prior to 18 months may provide an opportunity to impact the outcome in children who are likely to develop any of the autism spectrum disorders. • An ability to identify at risk children would allow testing of potential interventions. A combination of imaging, genetic, and biochemical tests will be used in this study to determine if autism spectrum disorders can be predicted.

3. Details of Case Study # 3 • Objective: Determine the predictive value of brain imaging, genetic and biochemical testing for autism spectrum disorders • Hypothesis: A combination of imaging, genetic and biochemical tests can predict for expression of an autism spectrum disorder • Population: All infants admitted to a level II nursery in community hospitals • Design: Single arm with single set of assessments with longitudinal follow up • Therapeutic Intervention: None • Assessments: Imaging (Magnetic Resonance Imaging of brain), additional use of blood taken for clinical care. The MRI will require sedation, which carries associated risks. Each type of blood test will be performed by a different research group at a different institution, with each independently funded. The genetic samples will be stored in a repository that has a policy for multiple interrogation of its inventory. • Primary Outcome: Diagnosis of autism spectrum disorder

4. Key Issues for Case Study # 3 • How should IRB’s approach issues of genetic research? How much variability exists among IRB’s across clinical sites? What are the scientific merits versus the risk to the study subject? At what point should assent be obtained if samples are retained indefinitely? How is ownership of discovery determined in individual patient samples? • What are the potential risks and possible benefits of participating in this descriptive study? How much blood is allowed for “research purposes” per study subject? Specifically, since an MRI requiring sedation constitutes more than minimal risk, what are the pros and cons of the study? • How will positive screening of children enrolled in the study be addressed? For example, chromosomal and non-chromosomal diagnoses may be made. What is the plan in place in the protocol to deal with an incidental or clinically relevant finding and who and how will parents be informed? • Will the study be performed in a targeted or high risk population? For example, familial or genetic risk factors or children enrolled in a high risk developmental clinic?

5. Question for Audience • Would you allow an MRI scan of the brain if it did not involve sedation for research purposes in this study? • Individual Yes Votes: 23 • Multiple Person Yes Votes: 11 • Individual No Votes: 2 • Multiple Person No Votes: 1