The Ritvo Autism Asperger Diagnostic Scale Revised (RAADS-R) A scale to assist the diagnosis of autistic spectrum disorder in adults- An international.

The Ritvo Autism Asperger DiagnosticThe Ritvo Autism Asperger DiagnosticScale Revised (RAADS-R)Scale Revised (RAADS-R)

A scale to assist the diagnosis of autistic spectrum disorder in adults-An international validation study with nine participating centers

Ariella Riva Ritvo, Ph.D., Yale Edward R. Ritvo, MD., UCLADonald Guthrie, Ph.D., UCLA

Max Ritvo, Yale UniversityDemetra Hufnagel, Yale University

Daniela Markovic, MS., UCLA

Participating Centers: Ami Klin, Ph.D., Yale; Latha Soorya, Ph.D. Mt. Sinai; William McMahon, MD, Kim Moody, U of Utah;David Mataix-Cols, Ph.D., King’s Collge; Bruce Tonge, MD, Avril Brereton, PhD, Monash University;

Trevor Clark, Ph.D, Vicki Gibbs, Fiona Aldridge, Megan Williams, ASPECT, Sydney;Tony Attwood, Ph.D, J. Eloff, Ph.D. Griffith University; Stephanie Moeser-Warren, Geneva Center, Toronto;

Lisa Andersen, Susanne Bejerot, MD, PhD. Karolinska Institute

IMFAR 2010IMFAR 2010PHILADELPHIAPHILADELPHIA

IMFAR 2010IMFAR 2010PHILADELPHIAPHILADELPHIA

© Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 2

BackgroundBackground The RAADS-R is a modified version of the Ritvo Autism Asperger

Diagnostic Scale. The rationale for its development, its method of construction, and its comparison to other similar scales have been published in JADD in 2008 .

The first version of the RAADS contained 78 questions. Published data demonstrated it had high validity, reliability, sensitivity, and specificity in a limited number of subjects.

Questions on the initial RAADS assess developmental pathology in three symptom areas: language, social relatedness, and sensory-motor (re. DSM-IV-TR). After critical review and the results of a factor analysis, a revised 80-item version was developed (the RAADS-R) with the addition of a fourth symptom area (circumscribed interests), two questions, and several word clarifications.


ObjectivesObjectives

To describe the methods and present the results of the nine university international standardization study of the new 80-item RAADS-R.


MethodsMethods1. A uniform protocol was used by all centers

2. IRB consent was obtained by each center

3. All subjects signed informed consent

Participating Subject Groups: Autism Spectrum Disorder Subjects N = 201

1. 66 subjects with a diagnosis of Autistic Disorder

2. 135 subjects with a diagnosis of Asperger’s Disorder

Comparison Subjects N = 5781. 276 subjects with no DSM-IV-TR diagnosis

2. 302 subjects with other DSM-IV-TR diagnoses


MethodsMethods ASD Subjects (groups 1 and 2 n = 201)

Uniformly diagnosed by research criteria : 1. A clinical interview (DSM-IV-TR diagnostic criteria met) 2. ADI/ADOS Scale (ADOS module IV at least) to establish

concurrent validity3. Standardized IQ test, (WAIS or WASI) full IQ of =/> 80 4. Constantino Social Responsiveness Scale-Adult (SRS-A)

to assess concurrent validity when available (69 subjects) 5. Repeat testing to assess reliability

Comparison subjects (groups 3 and 4 n = 578 ):1. Volunteers without a DSM-IV-TR diagnosis2. Volunteers with current DSM-IV-TR diagnosis other than

ASD


MethodsMethods Administration of RAADS-R:

1. ASD subjects: Following initial screening, a clinician interviewed each subject to confirm the diagnostic information and IQ data, completed the ADI/ADOS or ADOS module IV, and then introduced the scale and explained how to answer the questions. The clinician remained with each subject as the questions were being answered to offer clarifications when asked, and to make sure answers were entered in the proper columns on the Likert scale. An SRS–A scale was obtained from cooperating accompanying adults when available.

2. Comparison Subjects: All were given the RAADS-R to complete in the presence of a clinician. All comparison subjects were clinically evaluated to determine that their IQ was 80 or above.

3. Each of the 9 participating centers was asked to score, review and mail in full packets of ASD subjects. Some of the participating centers contributed data to the comparison group subject pool.


TranslationsTranslations Translations took into account cultural/idiomatic variations.

Questions addressed core symptoms regardless of language, which will allow for standardization of results and assessment of validity and reliability. Some studies are well on their way (Swedish and Japanese) while others (French and Hindi) are in early stages. Standard protocol and translation methods are being followed.

Studies are being conducted in:1. Swedish: Lisa Andersen, Ph.D, Susanne Bejerot, MD,

PhD, Karolinska Institute2. Japanese: Prof. Masatsugu Tsujii, Kaori Matsumoto, Kenji

Tsuchiya, Nagoya, Japan3. Hindhi4. French


Results: DemographicsResults: Demographics

N

Males Females

Meanage

Married%

Highest grade

MeanIQN % N % High

SchoolCollege Graduate

Autistics 66 52 79.1 14 20.9 30.81 13.4 52.2 37.3 10.4 114

Asperger 135 93 68.9 42 31.1 32.01 21.5 37.8 53.3 7.4 122

ASD 201 145 72.1 56 27.9 31.45 18.9 45.0 45.3 8.9 119

No DSM-IV-TR 276 114 41.3 162 58.7 41.51 39.5 37.7 46.0 16.3 N/A

Other DSM-IV-TR 302 134 44.4 168 55.6 42.04 28.5 40.1 53.3 6 N/A

All controls 578 248 42.9 330 57.1 41.78 33.7 38.9 49.7 11.2 N/A

Total study population

779 394 44.4 386 49.5 29.9 39.9 49.4 10.3 N/A


ResultsResults Diagnostic Accuracy (Sensitivity and Specificity):

Utilizing a cut off RAADS-R score of 65, six ASD subjects from three of the nine centers scored below, and thus were in the non ASD range. They are labeled “false negatives,” yielding sensitivity for the RAADS-R of 97%. None of the comparison subjects scored above 65, so there were no false positives. Thus the specificity for the RAADS-R is 100%.

Pair-wise comparison of each of the 80 questions Post-hoc unequal variance t-tests were performed for pair-wise comparison of

each of the 80 questions. The ASD subjects differed significantly from the comparison groups on all 80 questions (p < 0.0001 for all questions).

The mean RAADS-R scores of the ASD, the Autistic, and the Asperger groups from all nine centers are significantly different (p < 0.0001) from the combined mean of the comparison groups, and the mean for each of the nine research centers.

Cronbach Alpha coefficients demonstrate good internal consistency.

© Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 10 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 10

Cronbach Alpha CoefficientsCronbach Alpha Coefficients Circumscribed Interests

9, 13, 24, 30, 32, 40, 41, 50, 52, 56, 63, 70, 75, 78 Alpha = .903

Language2, 7, 27, 35, 58, 66, 15 Alpha = .789

Sensory Motor10, 19, 4, 33, 34, 36, 46, 71, 16, 29, 42, 49, 51, 57, 59, 62, 65, 67, 73, 74 Alpha = .905

Social1, 6, 8, 11, 14, 17, 18, 25, 37, 38, 3, 5, 12, 28, 39, 44, 45, 76, 79, 80, 20, 21, 22, 23, 26, 31, 43, 47, 48,53, 54, 55, 60, 61, 64, 68, 69, 72, 77 Alpha = .923


Factor AnalysisFactor Analysis Factor Analysis was carried out using both Varimax (orthogonal) and Oblique (non

orthogonal) rotation. Results were compared between the two rotational strategies. The Oblique rotational method was chosen because we assume the underlying constructs are interrelated.

We identified four factors. To compare the model derived factors versus the assigned four subdomains (DSM-IV-TR), we computed the Pearson correlation. Factors I and IV correlated most strongly with the social construct (r =.80). Factor II correlated most strongly with circumscribed interests (r =.78), factor III with sensory motor (r =.88).

The language construct was not picked up with the four factor model. However, the factor analysis is a mathematical computation of clusters and picks up on key words, missing the nuances in these questions. For instance, the question: “the phrase ‘I’ve got you under my skin’ makes me feel uncomfortable” is clearly a language construct question and targets concrete language and lack of understanding symbolic language. The factor analysis loaded it as a sensory motor question, most likely because it contained the words “skin” and “uncomfortable”.

We will report the variances accounted for by each factor and the Cronbach alpha coefficients, but upon review of the loadings, we remain confident that the original assignments of questions reflect the clinical picture with more clinical relevance. Either way, the instrument has good internal consistency.


Factor AnalysisFactor Analysis Factor I accounts for 23.9% of the variance with a Cronbach

alpha coefficient of .93

Factor II accounts for 25.0 % of the variance with a Cronbach alpha coefficient of .95

Factor III accounts for 22.4 % of the variance with a Cronbach alpha coefficient of .87

Factor IV accounts for 18.9% of the variance with a Cronbach alpha coefficient of .89


Factor AnalysisFactor Analysis Factor I: Social, containing questions related to empathy, intimacy and social language

Questions: 1, 6, 8, 11, 13, 14, 15, 16, 18, 31, 37, 38, 43, 48, 52, 53, 58, 62, 66, 68, 72, 74, 77. Alpha= .93

Factor II: Circumscribed Interests, also with questions relating to social blindnessQuestions: 3, 4, 5, 7, 9, 12, 16, 17, 20, 22, 25, 27, 28, 32, 33, 39, 41, 44, 45, 49, 50, 56, 60, 64, 76, 78, 79, 80. Alpha = .95

Factor III: Sensory motorQuestions: 2, 10, 19, 24, 29, 34, 35, 36, 40, 46, 51, 54, 57, 59, 65, 70, 71, 73. Alpha= .87

Factor IV: Social AnxietyQuestions: 21, 23, 26, 30, 42, 47, 55, 61, 63, 67, 69, 75. Alpha =.89

This factor is important. Targeting the social anxiety questions within the instrument may help the clinician differentiate social anxiety from ASD. The two are often confused diagnostically.


Test – Retest ReliabilityTest – Retest Reliability mean interval between tests = 15 months

SubjectsN

Mean RAADS-R1st Test

Mean RAADS-R2nd Test

ASD subjects 15 155 149

Comparison subjects 15 20 21


Test – Retest Data Statistical Analysis Test – Retest Data Statistical Analysis

Subject group Number Pearson r= Spearman Rho=

All subjects 30 .987 .956

Autistic 7 1.0 1.0

Asperger 8 .939 .952

Comparisons 15 .874 .764


Validity DataValidity Data

Type and number of subjects

Percent agreement

Research center’s clinical criteria (inclusion requirement)

ASD 201 100%

ADI/ADOS or ADOS module 4(inclusion requirement)

ASD 201 100%

RAADSSensitivity (6 false negatives) Specificity (0 false positives)

ASD 201COMPARISON 578

97%100%

Constantino SRS-ASensitivity (3 false negatives)

ASD 69 95.69%


Validity Data-Constantino Social Responsiveness Scale, Adult (SRS-A)Validity Data-Constantino Social Responsiveness Scale, Adult (SRS-A)

69 SRS-A were administered to a 3rd party (e.g. parent, spouse).

SRS-A cutoff t score is 59. Three subjects (4.31 percent) scored below the cutoff (55, 57 and 58). This is a 95.59% concordance rate with RAADS-R subjects.


Mean RAADS-R Scores and Ranges by Research Center: ASD SubjectsMean RAADS-R Scores and Ranges by Research Center: ASD Subjects

Research center NRAADS-R Scores

Mean Min Max

UCLA 53 146 84 222

Yale 31 115 48 178

Mount Sinai 19 123 73 166

University of Utah 7 92 72 109

Monsah University, Australia 13 138 62 172

Aspect, Sydney 14 118 58 193

Griffith University, Australia 42 146 56 227

Geneva Center, Canada 8 148 107 216

University of London 14 135 67 205


Mean RAADS-R Scores and Ranges – Autism, Asperger and, ASDMean RAADS-R Scores and Ranges – Autism, Asperger and, ASD

N

RAADS-R Scores

Mean Min Max

All ASD subjects 201 133.8 44 227

All Autistic subjects 66 138.5 44 227

All Asperger subjects 135 131.5 52 225


Mean RAADS-R Scores and Ranges – Comparison SubjectsMean RAADS-R Scores and Ranges – Comparison Subjects

N

RAADS

Mean Min Max

No DSM-IV-TR diagnosis 275 22 0 64

Other DSM-IV-TR diagnoses 302 30 0 65

Total All Comparison subjects 578 25 0 65


Characteristics of the only 6 ASD subjects (3%) whose mean RAADS-R scores Characteristics of the only 6 ASD subjects (3%) whose mean RAADS-R scores were below 65 (false negatives) Sorted by RAADS-R scores (mean age = 19.9)were below 65 (false negatives) Sorted by RAADS-R scores (mean age = 19.9)

Center Diagnosis N Sex School SRS IQ RAADS-R

Yale Asperger 19 M HS 120 52

Griffith Asperger 23 M HS 90 117 56

Aspec Autistic 18 M HS 116 58

Griffith Asperger 19 M HS 122 58

Yale Asperger 20 M COL 116 59

Yale Asperger 19 M COL 116 60


ConclusionsConclusions No difficulties were reported in administration even though subjects were evaluated at

nine medical centers on three continents.

The RAADS-R proved to be highly accurate in discriminating between subjects with ASD and those without a DSM-IV-TR diagnosis and with another DSM-IV-TR diagnosis (Sensitivity = 97%. Specificity = 100).

Mean RAADS-R scores were significantly different (p < 0.0001) between ASD and comparison subjects at each of the nine centers and in all centers combined.

All eighty questions significantly differentiated between ASD and comparison subjects. The fact that this was true even when the comparison cases had a variety of DSM-IV-TM diagnoses other than ASD makes the RAADS-R particularly useful in adult clinic clinical settings.

The RAADS-R also demonstrated high test – retest reliability (Pearson Correlation Coefficient = .987, Spearman Correlation Coefficients = .956).

Concurrent validity with ADI/ADOS was 100% and with Constantino SRS-A concordance rate was 95.59%.


ConclusionsConclusions Cronbach alphas were good for the four DSM-IV-TR domains, suggesting a good

internal consistency of the RAADS-R.

Factor analysis with oblique rotation to account for assumed correlation between constructs yielded four factors, also with good internal consistency.

Because ASD is a behaviorally defined syndrome with subtle nuances and factor analysis is mathematically based, picking up key words, we prefer to remain with the original question assignment, which reflects the clinical picture more accurately. That being said, the Cronbach alpha coefficients are good either way, and the original subdomains as well as the factors differentiate ASD from non-ASD subjects in a statistically significant way. The instrument was designed to be used as a whole, and all questions ultimately have one measurement—ASD symptomatology.


SummarySummary The results from nine medical centers, based on 201

ASD subjects and 578 comparison subjects, demonstrated that the RAADS-R is highly valid, highly reliable, and it is easy to administer and to score. Thus we conclude that it can serve as a valuable asset to assist clinicians diagnosing ASD in adults eighteen years and older.


Clinical Implications of RAADS ScoresClinical Implications of RAADS Scores

66OR ABOVE

HIGHLY LIKELYTO HAVE ASD

65OR BELOW

HIGHLY UNLIKELYTO HAVE ASD

Sensitivity = 97% (6 false negatives)Specificity = 100% (no false positives)


The Ritvo Autism Asperger Diagnostic Scale-R The Ritvo Autism Asperger Diagnostic Scale-R R

AA

DS

SC

OR

ES

ASD N = 201 OTHER DX N = 302NO OTHER DX N = 276

SENSITIVITY = 97% SPECIFICITY = 100%

MEAN134

MEAN22

MEAN30

65

© The Ritvo Autism Asperger Diagnostic Scale Revised (RAADS-R) 2010

Thank you.

The Ritvo Autism Asperger Diagnostic Scale Revised (RAADS-R) A scale to assist the diagnosis of autistic spectrum disorder in adults- An international.

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