Briefly describe a specific question, or set of related questions, about a health care test or treatment that this program should consider.

What is the comparative effectiveness of genetic and other diagnostic tests to identify and treat intellectual and developmental disabilities caused by genetic mutations in post-natal to early childhood populations?

Does your question include a comparison of different health care approaches? (If no, your topic will still be considered.)

yes

If yes, explain the specific technologies, devices, drugs, or interventions you would like to see compared:

Genetic and clinical tests for the following:

Angelman syndrome

Genetic tests:

Methylation analysis of 15q11.2-q13

FISH analysis of 15q11.2-q13

Other 15q11.2-q13 deletion/duplication analysis (e.g., quantitative PCR)

Uniparental disomy study

UBE3A sequencing and/or deletion/duplication analysis

Clinical tests:

Wechsler Preschool and Primary Scale of Intelligence (WPPSI)

Wechsler Intelligence Scales for Children (WISC III)

Stanford-Binet Intelligence Scale

Kaufman Assessment Battery for Children

McCarthy Scales of Children's Abilities

Differential Abilities Scales

Leiter International Performance (tests non-verbal abilities)

Inventory for Client and Agency Planning (ICAP)

Scales of Independent Behavior (SIB-R)

Vineland Adaptive Behavior Scales _____________________________________________________________________________________

Austim Spectrum Disorder (ASD)

Genetic tests:

Oligo- or SNP-based Chromosomal Microarray (CMA)

High-resolution G-banded karyotype

FMR1 testing for fragile X syndrome (see below)

Other available tests

Clinical tests:

Autism Behavior Checklist (ABC)

Autism Diagnostic Interview-Revised (ADI-R)

Autism Observation Scale for Infants (AOSI)

Checklist for Autism in Toddlers (CHAT)

Childhood Autism Rating Scale (CARS)

Gilliam Autism Rating Scale-2nd Edition (GARS-2)

Autism Diagnostic Observation Schedule-Generic (ADOS-G)

Autism Diagnostic Observation Schedule-Toddler Module (ADOS-T) _____________________________________________________________________________________

Fragile X syndrome

Genetic tests:

CGG expansion detection in FMR1 via PCR or Southern blot

Methylation analysis of FMR1 promoter region

AGG trinucleotide repeat gen

What patients or group(s) of patients does your question apply to? (Please include specific details such as age range, gender, coexisting diagnoses, and indications for therapy.)

Children with intellectual and developmental disabilities and their families

Are there subgroups of patients that your question might apply to? (For example, an ethnic group, stage or severity of a disease.)

Siblings of children with intellectual and developmental disabilities

Describe the health-related benefits you are interested in. (For example, improvements in patient symptoms or problems from treatment or diagnosis.)

• Early identification of children with a genetic cause for their intellectual or developmental disability Improved classification for earlier and better treatment
• Earlier implementation of appropriate medical, behavioral, nutritional, or physical support interventions
• Improved developmental and health outcomes
• Identification of medical co-morbidities

Describe any health-related risks, side effects, or harms that you are concerned about.

• Social stigmatization
• No/poor genetic counseling
• Delay in treatment during critical early childhood developmental 'windows of opportunity'
• Risk of incorrect evaluation and classification leading to inappropriate treatment and/or individualized supports

Appropriateness for EHC Program

Does your question include a health care drug, intervention, device, or technology available (or likely to be available) in the U.S.?

yes

Which priority area(s) and population(s) does this topic apply to? (check all that apply)

EHC Priority Conditions (updated in 2008)

• Depression and other mental health disorders
• Developmental delays, attention-deficit hyperactivity disorder, and autism
• Functional limitations and disability

AHRQ Priority Populations

• Children
• Individuals with special health care needs, including individuals with disabilities or who need chronic care or end-of-life health care

Federal Health Care Program

• Medicaid
• State Children's Health Insurance Program (SCHIP)
• Other

Importance

Describe why this topic is important.

The Arc, the largest US advocacy organization for people with intellectual and developmental disabilities, estimates that "4.6 million Americans have an intellectual or developmental disability (1). Prevalence studies may not identify all people with intellectual disabilities. Many school age children receive a diagnosis of learning disability, developmental delay, behavior disorder, or autism instead of intellectual disability." (from http://www.thearc.org/page.aspx?pid=2448).

The number of possibilities for tests is increasing at a rapid rate, and it is important to understand the clinical utility of these tests versus other options. Determining this would address uncertainty policymakers and clinicians feel regarding the utility of genetic testing for intellectual or developmental disabilities. One Medicaid director stated, "We have seen a significant number of claims for genetic testing in children with alleged and/or proven intellectual or developmental disabilities. Many of these children have well defined genetic syndromes. Our average reimbursement is approximately $1750.00 for this microarray testing. We feel that in many instances it is abuse of the Medicaid system and has little to no clinical utility."

1. Larson, S.L. et al. (2000). Prevalence of mental retardation and/or developmental disabilities: Analysis of the 1994/1995 NHIS-D. MR/DD Data Brief. Minneapolis, MN: Institute on Community Integration, University of Minnesota

What specifically motivated you to ask this question? (For example, you are developing a clinical guideline, working with a policy with large uncertainty about the appropriate approach, costly intervention, new research you have read, items in the media you may have seen, a clinical practice dilemma you know of, etc.)

This question was prioritized by stakeholders engaged in the Topic Identification project conducted by the Oregon Evidence-based Practice Center for the Medicaid Medical Directors Learning Network.

Does your question represent uncertainty for clinicians and/or policy-makers? (For example, variations in clinical care, controversy in what constitutes appropriate clinical care, or a policy decision.)

yes

If yes, please explain:

In most states there is no minimum standard set of genetic and/or clinical diagnostic tests resulting in variations in clinical care. For policy-makers the issue centers on whether genetic tests should be covered. It is also unclear which tests are the most likely to correctly identify specific intellectual and/or developmental disabilities.

Potential Impact

How will an answer to your research question be used or help inform decisions for you or your group?

This report would help identify effective genetic diagnostic tests for children at risk for intellectual and/or developmental disabilities, which would inform differential diagnosis, treatment stratification to improve developmental outcomes, and identification of potential medical co-morbidities.

Describe the timeframe in which an answer to your question is needed.

There is no specific timeframe.

Describe any health disparities, inequities, or impact on vulnerable populations your question applies to.

Medicaid populations Children with special health care needs

Nominator Information

Other Information About You: (optional)

Please choose a description that best describes your role or perspective: (you may select more than one category if appropriate)

This report would help identify effective genetic diagnostic tests for children at risk for intellectual and/or developmental disabilities, which would inform differential diagnosis, treatment stratification to improve developmental outcomes, and identification of potential medical co-morbidities.

Are you making a suggestion as an individual or on behalf of an organization?

Organization

Please tell us how you heard about the Effective Health Care Program