Autism Spectrum Disorders: A Review of Measures for Clinical, Health Services and Cost-Effectiveness Applications

Nalin Payakachat; J Mick Tilford; Erica Kovacs; Karen Kuhlthau


Expert Rev Pharmacoeconomics Outcomes Res. 2012;12(4):485-503. 

In This Article

Abstract and Introduction


Autism spectrum disorders (ASDs) are characterized by impairments in social interaction, communication and behavioral functioning that can affect the health-related quality-of-life outcomes of the affected child and the family. ASDs have increased in prevalence, leading to a demand for improved understanding of the comparative effectiveness of different pharmacologic, behavioral, medical and alternative treatments for children as well as systems for providing services. This review describes outcome instruments that can be used for clinical, health services and cost–effectiveness applications. There is a pressing need to identify the most appropriate instruments for measuring health-related quality-of-life outcomes in this population. Studies evaluating the cost–effectiveness of interventions or treatments for children with ASDs using the cost per quality-adjusted life year metric are lacking. Researchers have the potential to contribute greatly to the field of autism by quantifying outcomes that can inform optimal treatment strategies.


Autism spectrum disorders (ASDs) are complex neurodevelopmental conditions that involve impairments in social interaction, communication and behavioral functioning such as repetitive and stereotyped behaviors.[1,2] While individuals with ASDs are characterized by a core set of symptoms, there is wide heterogeneity in the severity of the disorder. Three subtypes are typically used to classify ASDs that include autistic disorder, Asperger's disorder and pervasive developmental disorder – not otherwise specified (PDD-NOS). Whether such categorical distinctions should be made is debatable and the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders criteria is likely to exclude this classification in favor of a single diagnostic category.[201] However, there is agreement that children with ASDs differ according to age and type of onset, severity and comprehensiveness of symptoms, and extent of language delay and intellectual disability.[3]

Diagnosis of ASD subtypes requires a full understanding of a child's profile of abilities including developmental/cognitive, speech, language, communication, social, adaptive, sensorimotor and behaviors.[4] Owing to the wide range of abilities and limitations across clinical characteristic, clinicians may not reliably agree on the diagnostic subtypes of ASD – that is, clinicians may apply the specific diagnostic labels (autistic disorder, Asperger's disorder and PDD-NOS) differently across sites even when standardized clinical instruments are used.[5] Children who meet full diagnostic criteria for ASD are likely to be categorized as autistic disorder or classic autism, which typically is the most severe form.[1] Children with some symptoms of ASD but not enough to be diagnosed with autistic disorder are often diagnosed as having PDD-NOS. Asperger's disorder is the least severe ASD subtype and may be referred to as high-functioning autism. Children with Asperger's disorder have social impairments and autistic behaviors such as repetitive or restrictive patterns, but have intact cognitive ability (absence of intellectual disability) and no delays in early language development.[6]

Autism is generally a lifelong condition beginning in childhood and affecting outcomes in adulthood. Outcomes describing difficulties or issues in finance, employment and socialization for adults with ASDs have been described previously.[7–9] Findings from these studies indicate substantial progress in the care and treatment of persons with ASDs, allowing individuals to participate more fully in community life with reduced burden on families. Despite these advances, living with autism can be difficult,[10] particularly during developmental transition and critical need periods of childhood. While all children with ASDs exhibit one or more of the core symptoms (impairments in social interaction, communication and behavioral functioning), some children may have associated problems with mood and affect. They can exhibit severe tantrums, noncompliance, destructiveness and self-injury.[11–13] Children with ASDs may sleep less and awake frequently during the night.[14–17] Many parents report a regression in sociability, language and play during their child's toddler or preschool years. Therefore, parenting for some children with ASDs can be challenging and can severely impact family functioning as well as the health and wellbeing of caregivers and other family members.[18,19] Clearly, successful interventions for children with ASDs have the potential to greatly affect health outcomes for the child and can have extensive economic benefits by contributing to the child's independence into adulthood.

Interest in measuring health outcomes for children with ASDs has increased in recent years owing to reports of increasing prevalence. The prevalence of ASDs increased over the last two decades from four to ten per 10,000 children between the 1980s and early 1990s, and then to 30 to 50 per 10,000 children in the early 2000s.[20–25] In the USA, the Autism and Developmental Disabilities Monitoring Network reported an average of 1% or one child in every 110 had an ASD (males 1:70; females 1:315) in 2006.[26] Indeed, the Interagency Autism Coordinating Committee calls the increasing prevalence of autism a 'national medical emergency'.[202] A recent population-based study found high prevalence rates of ASDs, with 3.7% in males and 1.5% in females in school-age children in a South Korean community that included samples from special-needs schools and regular school settings.[27] They reported that two-thirds of ASD cases in the overall sample were undiagnosed and did not receive any special services, suggesting that there are undiagnosed children with ASDs in regular classrooms. While much discussion has concerned the causes of the increasing prevalence of ASDs such as increased public awareness of ASDs, broadening ASD diagnostic criteria, increased availability of educational services and better identification, there is clear evidence that the burden of ASDs is large. School systems and medical care systems require increasing resources to treat the growing population of children diagnosed with ASDs. Therefore, there is a considerable need for research on treatment strategies that ensure that children with ASDs achieve optimal outcomes.

Despite advances in medicine, no medication is approved for an ASD indication owing to the lack of benefits on the core symptoms of ASD.[28–30] Only risperidone and aripiprazole demonstrated improvement in parent-reported measures of challenging behaviors such as repetitive behavior, hyperactivity and noncompliance. However, there are significant side effects that may limit the use of these drugs to patients with severe impairment or risk of injury.[31] There is evidence of efficacy for early intensive behavioral interventions (EIBIs) based on applied behavioral analysis.[32] EIBI is a comprehensive treatment approach that includes a minimum of 20 h per week of behavioral interventions from clinicians initiated at an early age (toddlers and preschool-aged children), and also involves parent training and parent delivery of at least 5 h per week.[28] The approximate annual costs of EIBI range from US$20,000 to $60,000 per child.[33] Owing to the cost of EIBI and knowledge gaps among providers, there is substantial variation in whether children receive recommended levels of therapy across geographic regions. Therefore research is needed to describe the impact of variations in treatment on outcomes of children with ASDs. Achieving this goal and obtaining the best information from randomized trials of pharmaceutical inter­ventions requires an understanding of the various approaches for measuring health outcomes and selecting appropriate instruments suitable to the population of children with ASDs.

This article provides a review of health outcome measures for children with ASDs including clinical and behavioral measures, health-related quality-of-life (HRQL) measures and preference-based HRQL measures. The term 'health outcome measures' has been used to describe a broad range of instruments that can be used for clinical, health services and economic applications. In all of the applications, the instruments and the terminology reflect measures that can be used to study health outcomes from clinical trial settings or population-based registries. The review includes a discussion of preference-based measures to facilitate discussion of cost–effectiveness analysis – an approach that remains under­developed with respect to child health interventions.[34–36] Finally, new methods for cost–effectiveness analysis based on economic models that account for health outcomes of the family have been considered. Owing to the burden of ASDs on families, measures for estimating cost–effectiveness of interventions for the child with autism that account for impacts on the family have been included because both improvements in child and family health contribute to economic welfare.[37]

Health outcome measurement in child populations is often accomplished by asking the parent to report on their perceptions of the child, owing to concerns that the child may not be able to respond reliably. A growing body of literature provides evidence for obtaining health outcome responses, or patient-reported outcomes, directly from the child.[38] Such an approach in autism is complicated as children (and adults) may lack a theory of mind that allows them to communicate health outcomes as measured by the instruments described in this review.[39] Theory of mind deficits are thought to underlie the core social and communication impairments that are characteristic of individuals with ASDs. Since children with autism may have theory of mind deficits and thus be less able to report health outcomes, recent research has examined whether adolescents with autism can report their quality of life (QoL) validly and reliably.[40] Initial findings for high-functioning adolescents indicate that it is feasible to get QoL responses directly from the adolescent. Additional research indicates that parent reports of QoL were closer to adolescents when parents were asked to report as they thought the child might respond.[41] Researchers interested in measuring health outcomes for children with ASDs need to consider these issues more fully, as parent proxy reporting is likely to be necessary for younger children and lower functioning children with autism who are more likely to have theory of mind deficits. This review focuses on the descriptions of health outcome measures and the studies that have employed them, recognizing that more work needs to be focused on the issues associated with proxy reporting of child health states in autism owing to the potential theory of mind deficits.

The authors acknowledge that there are multiple health outcome measures that can be used to study ASDs in children, and that any selection of instruments covering clinical, health services and cost–effectiveness applications is likely to be incomplete. The outcome measures selected for this review were based on instruments that have been used in recent randomized clinical trials and/or collected in ongoing registries of children with autism. Despite limitations in our ability to address a comprehensive listing of instruments, it is believed that readers will appreciate the potential for including all three types of measures in research studies involving children with ASDs.