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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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Presentation on theme: "The Ritvo Autism Asperger Diagnostic Scale Revised (RAADS-R) A scale to assist the diagnosis of autistic spectrum disorder in adults- An international."— Presentation transcript:

1 The Ritvo Autism Asperger Diagnostic 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., UCLA Donald Guthrie, Ph.D., UCLA Max Ritvo, Yale University Demetra 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 2010 PHILADELPHIA

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

3 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 3 Objectives  To describe the methods and present the results of the nine university international standardization study of the new 80- item RAADS-R.

4 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 4 Methods 1. 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 = subjects with a diagnosis of Autistic Disorder subjects with a diagnosis of Asperger’s Disorder  Comparison Subjects N = subjects with no DSM-IV-TR diagnosis subjects with other DSM-IV-TR diagnoses

5 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 5 Methods  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 validity 3. Standardized IQ test, (WAIS or WASI) full IQ of =/> 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 diagnosis 2. Volunteers with current DSM-IV-TR diagnosis other than ASD

6 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 6 Methods  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.

7 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 7 Translations  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 Institute 2. Japanese: Prof. Masatsugu Tsujii, Kaori Matsumoto, Kenji Tsuchiya, Nagoya, Japan 3. Hindhi 4. French

8 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 8 Results: Demographics N MalesFemales Mean age Married % Highest grade Mean IQ N%N% High School CollegeGraduate Autistics Asperger ASD No DSM-IV-TR N/A Other DSM-IV-TR N/A All controls N/A Total study population N/A

9 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 9 Results  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 < 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 < ) 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.

10 © 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 Coefficients  Circumscribed Interests 9, 13, 24, 30, 32, 40, 41, 50, 52, 56, 63, 70, 75, 78  Alpha =.903  Language 2, 7, 27, 35, 58, 66, 15  Alpha =.789  Sensory Motor 10, 19, 4, 33, 34, 36, 46, 71, 16, 29, 42, 49, 51, 57, 59, 62, 65, 67, 73, 74  Alpha =.905  Social 1, 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

11 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 11 Factor 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.

12 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 12 Factor 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

13 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 13 Factor 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 blindness Questions: 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 motor Questions: 2, 10, 19, 24, 29, 34, 35, 36, 40, 46, 51, 54, 57, 59, 65, 70, 71, 73.  Alpha=.87  Factor IV: Social Anxiety Questions: 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.

14 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 14 Test – Retest Reliability  mean interval between tests = 15 months Subjects N Mean RAADS-R 1 st Test Mean RAADS-R 2 nd Test ASD subjects Comparison subjects152021

15 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 15 Test – Retest Data Statistical Analysis Subject groupNumberPearson r=Spearman Rho= All subjects Autistic71.0 Asperger Comparisons

16 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 16 Validity Data Type and number of subjectsPercent agreement Research center’s clinical criteria (inclusion requirement) ASD % ADI/ADOS or ADOS module 4 (inclusion requirement) ASD % RAADS Sensitivity (6 false negatives) Specificity (0 false positives) ASD 201 COMPARISON % 100% Constantino SRS-A Sensitivity (3 false negatives) ASD %

17 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 17 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.

18 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 18 Mean RAADS-R Scores and Ranges by Research Center: ASD Subjects Research centerN RAADS-R Scores MeanMinMax UCLA Yale Mount Sinai University of Utah Monsah University, Australia Aspect, Sydney Griffith University, Australia Geneva Center, Canada University of London

19 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 19 Mean RAADS-R Scores and Ranges – Autism, Asperger and, ASD N RAADS-R Scores MeanMinMax All ASD subjects All Autistic subjects All Asperger subjects

20 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 20 Mean RAADS-R Scores and Ranges – Comparison Subjects N RAADS MeanMinMax No DSM-IV-TR diagnosis Other DSM-IV-TR diagnoses Total All Comparison subjects

21 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 21 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) CenterDiagnosisNSexSchoolSRSIQRAADS-R YaleAsperger19MHS GriffithAsperger23MHS AspecAutistic18MHS GriffithAsperger19MHS YaleAsperger20MCOL YaleAsperger19MCOL 11660

22 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 22 Conclusions  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 < ) 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%.

23 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 23 Conclusions  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.

24 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 24 Summary  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.

25 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 25 Clinical Implications of RAADS Scores 66 OR ABOVE HIGHLY LIKELY TO HAVE ASD HIGHLY LIKELY TO HAVE ASD 65 OR BELOW HIGHLY UNLIKELY TO HAVE ASD HIGHLY UNLIKELY TO HAVE ASD Sensitivity = 97% (6 false negatives) Specificity = 100% (no false positives)

26 © Ariella Riva Ritvo, Ph.D. Yale; Edward R. Ritvo, MD 2010 Slide 26 The Ritvo Autism Asperger Diagnostic Scale-R RAADS SCORES ASD N = 201OTHER DX N = 302NO OTHER DX N = 276 SENSITIVITY = 97%SPECIFICITY = 100% MEAN 134 MEAN 22 MEAN 30 65

27 © The Ritvo Autism Asperger Diagnostic Scale Revised (RAADS-R) 2010 Thank you.


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