<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.177715.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>The Autism Mental Status Exam Indonesian Version(AMSE-INA): A Cross-Culturally Validated Pre-Diagnostic Tool for Autism Spectrum Disorder in Resource-Limited Specialist Settings</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Marudur</surname>
                        <given-names>Pengekuten Timbul</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Funding Acquisition</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0009-0004-3945-0938</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sutomo</surname>
                        <given-names>Retno</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Sitaresmi</surname>
                        <given-names>Mei Neni</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Growth and Development Social Pediatrics, Gadjah Mada University Department of Child Health, Yogyakarta, Special Region of Yogyakarta, 55281, Indonesia</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:kutensng@gmail.com">kutensng@gmail.com</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>29</day>
                <month>4</month>
                <year>2026</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2026</year>
            </pub-date>
            <volume>15</volume>
            <elocation-id>636</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>11</day>
                    <month>4</month>
                    <year>2026</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 Marudur PT et al.</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/15-636/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>In many low and middle-income countries (LMICs), diagnosis of autism spectrum disorder (ASD) is hindered by limited access to gold-standard instruments, like the Autism Diagnostic Observation Schedule-2 (ADOS-2), due to cost, training, and licensing barriers. The Autism Mental Status Exam (AMSE) is a brief, observational tool designed to structure clinical observation and support diagnostic decision-making in specialist settings where comprehensive assessments are unavailable.</p>
                </sec>
                <sec>
                    <title>Objective</title>
                    <p>To adapt the AMSE into Indonesian (AMSE-INA) and validate it as a pre-diagnostic tool for use by specialists in secondary/tertiary care settings in Indonesia, where access to gold-standard instruments is constrained.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>This cross-sectional diagnostic accuracy study comprised two phases: (1) rigorous cross-cultural adaptation following Beaton et al. guidelines, and (2) psychometric validation involving 174 children (aged 18&#x00a0;months&#x2013;18&#x00a0;years) referred to a developmental specialist clinic. All participants underwent assessment with the AMSE-INA, the Indonesian version of the Childhood Autism Rating Scale-2 (CARS-2 ST), and a best-estimate clinical diagnosis (BECD) based on DSM-5 criteria by an experienced consultant blinded to AMSE scores. Reliability (internal consistency, inter-rater, test-retest), validity (content, concurrent, discriminant), and diagnostic accuracy (ROC analysis) were evaluated.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>AMSE-INA demonstrated excellent inter-rater reliability (ICC&#x00a0;=&#x00a0;0.97) and test-retest reliability (ICC&#x00a0;=&#x00a0;0.96). Internal consistency was moderate (&#x03b1;&#x00a0;=&#x00a0;0.66), consistent with its multidimensional construct. Content validity was excellent (I-CVI&#x00a0;=&#x00a0;1.00). Concurrent validity with CARS-2 ST was strong (r&#x00a0;=&#x00a0;0.85, p&#x00a0;&lt;&#x00a0;0.001). ROC analysis revealed an AUC of 0.98 (95% CI: 0.96&#x2013;1.00). A cut-off score of &#x2265;6 provided optimal diagnostic utility for specialist settings: sensitivity 88.9%, specificity 94.7%, PPV 95.7%, NPV 86.6%.</p>
                </sec>
                <sec>
                    <title>Conclusion</title>
                    <p>AMSE-INA is a reliable, valid, and culturally appropriate pre-diagnostic tool that can assist specialists in establishing an accurate ASD diagnosis in resource-limited settings. By providing a structured observational framework, it bridges the diagnostic gap when gold-standard tools are inaccessible, improving early intervention access in Indonesia and similar settings.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Autism spectrum disorder</kwd>
                <kwd>autism mental status exam</kwd>
                <kwd>pre-diagnostic tool</kwd>
                <kwd>cross-cultural adaptation</kwd>
                <kwd>validation</kwd>
                <kwd>resource-limited specialist settings</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1" xlink:href="https://doi.org/10.13039/501100014538">
                    <funding-source>Lembaga Pengelola Dana Pendidikan</funding-source>
                </award-group>
                <funding-statement>This research received funding from LPDP (Lembaga Pengelola Dana Pendidikan), Indonesia as a scholarship award. The funder had no role in the study design, data collection, analysis, interpretation, or manuscript preparation.</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec6" sec-type="intro">
            <title>Introduction</title>
            <p>Autism spectrum disorder (ASD) is a complex, lifelong neurodevelopmental condition characterized by persistent deficits in social communication and interaction, alongside restricted, repetitive patterns of behavior, interests, or activities.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> Global prevalence has increased significantly over recent decades, with current estimates suggesting approximately 1&#x2013;2% of children worldwide are affected.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>,
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> This rising prevalence, coupled with the critical importance of early intervention for optimizing long-term outcomes, has placed considerable pressure on diagnostic systems globally.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>,
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup>
            </p>
            <p>In high-income countries, diagnosis is typically achieved through comprehensive multidisciplinary assessment involving gold-standard instruments such as the Autism Diagnostic Observation Schedule-2 (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R).
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>,
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup> These tools, while robust, require extensive training, are time-consuming (often &#x2265;2&#x00a0;hours per assessment), and involve significant costs for materials and licensing.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>,
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup> Consequently, their availability is severely limited in low- and middle-income countries (LMICs), including Indonesia.
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup>
            </p>
            <p>
Indonesia, the world&#x2019;s fourth most populous nation, faces profound challenges in ASD diagnosis. Data on prevalence are limited, but estimates align with global figures, with significant under-identification in rural areas due to scarce specialist services, lack of trained personnel, and financial constraints.
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>,
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> Specialists working in secondary or tertiary referral centers often lack access to ADOS-2 or ADI-R and must rely solely on clinical judgment, which can be subjective and variable, leading to potential over- or underdiagnosis, especially in complex cases with comorbidities.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> Furthermore, widely used screening tools such as the Modified Checklist for Autism in Toddlers, Revised (M-CHAT-R/F) are limited to children under 30&#x00a0;months and rely on parent report, making them unsuitable for older children or as a pre-diagnostic aid for specialists.
                <sup>
                    <xref ref-type="bibr" rid="ref16">16</xref>,
                    <xref ref-type="bibr" rid="ref17">17</xref>
                </sup> There is an urgent, unmet need for a tool that can structure the specialist&#x2019;s clinical examination, making it more objective, efficient, and reliable within the constraints of the Indonesian healthcare system.</p>
            <p>The Autism Mental Status Exam (AMSE) is an 8-item, observation-based examination designed to structure the clinical assessment of ASD core symptoms in under 15&#x00a0;minutes.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>,
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> It was developed specifically to enhance the accuracy of clinical judgment in settings where gold-standard tools are impractical.
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> By systematically guiding the observation of social interaction, communication, and repetitive behaviors&#x2014;and incorporating key caregiver report&#x2014;it operationalizes DSM-5 criteria within a routine clinical encounter.
                <sup>
                    <xref ref-type="bibr" rid="ref19">19</xref>
                </sup> Validated in multiple countries (USA, Brazil, China, Turkey, Chile, Sweden and France.), the AMSE has demonstrated consistently high sensitivity (79&#x2013;98%) and specificity (67&#x2013;100%).
                <sup>
                    <xref ref-type="bibr" rid="ref20">20</xref>&#x2013;
                    <xref ref-type="bibr" rid="ref25">25</xref>
                </sup> As an open-access instrument requiring minimal training, it presents a promising solution for specialist diagnostic settings in LMICs.</p>
            <p>A critical and often underexplored aspect of diagnostic tool validation is performance across different developmental stages. ASD symptoms manifest and evolve with age.
                <sup>
                    <xref ref-type="bibr" rid="ref26">26</xref>
                </sup> In toddlers(&lt;3&#x00a0;years), core symptoms may be more categorical and overt (e.g., absence of joint attention, lack of response to name). In preschool and school-aged children (&#x2265;3&#x00a0;years), symptoms often become more nuanced, variable, and influenced by compensatory strategies or comorbid conditions.
                <sup>
                    <xref ref-type="bibr" rid="ref27">27</xref>
                </sup> Tools validated on mixed-age samples may mask important age-related differences in sensitivity and specificity. Therefore, a comprehensive validation must include age-stratified analysis to inform clinicians about the tool&#x2019;s appropriate use across the intended age spectrum.</p>
            <p>However, the use of observational tools is influenced by cultural norms surrounding social behavior, eye contact, communication styles, and play.
                <sup>
                    <xref ref-type="bibr" rid="ref28">28</xref>
                </sup> A direct translation is insufficient; a rigorous cultural adaptation is essential to ensure diagnostic accuracy.
                <sup>
                    <xref ref-type="bibr" rid="ref29">29</xref>
                </sup> No such adaptation or validation exists for the Indonesian context.</p>
            <p>
This study aimed to: (1) perform a comprehensive cross-cultural adaptation of the AMSE into the Indonesian language and context (AMSE-INA), and (2) evaluate its psychometric properties and diagnostic accuracy specifically for use as a pre-diagnostic tool by specialists in Indonesian referral settings where gold-standard instruments are not available.</p>
        </sec>
        <sec id="sec7" sec-type="methods">
            <title>Methods</title>
            <sec id="sec8">
                <title>Study design and setting</title>
                <p>This study employed a cross-sectional diagnostic accuracy design and was conducted in two sequential phases at the Growth and Development-Social Pediatrics Clinic Sardjito Hospital, an academic-tertiary referral center in Yogyakarta, Indonesia from July to December 2025. This study was conducted in two sequential phases. Phase 1 (July&#x2013;September 2025) involved cross-cultural adaptation of the AMSE into Indonesian (AMSE-INA) following Beaton et al. guidelines, including forward translation, expert committee synthesis, back-translation, and pretesting. Pretesting was conducted in routine clinical practice, where clinicians used the adapted tool and provided feedback on its usability and cultural appropriateness; no patient data were systematically collected or used for research purposes during this phase. Phase 1 activities were initiated while the ethical approval application for Phase 2 was under review, as they did not involve research on human subjects.</p>
                <p>Phase 2 (commenced after ethical approval) comprised the psychometric validation study involving human participants. Ethical approval (No. KE/FK/1426/EC/2025) was obtained from the Faculty of Medicine, Public Health, and Nursing Ethics Committee, Universitas Gadjah Mada 
                    <bold>prior to the initiation of Phase 2 data collection</bold>. All Phase 2 procedures were conducted in accordance with the approved protocol, and written informed consent was obtained from all parents/guardians.</p>
            </sec>
            <sec id="sec9">
                <title>Cross-cultural adaptation of the AMSE</title>
                <p>The adaptation strictly followed the internationally recognized 6-step guideline by Beaton et al.
                    <sup>
                        <xref ref-type="bibr" rid="ref29">29</xref>,
                        <xref ref-type="bibr" rid="ref30">30</xref>
                    </sup> to ensure semantic, idiomatic, experiential, and conceptual equivalence. The process included forward translation by independent translators (one clinician, two linguists), synthesis by an expert committee of behavioral-developmental pediatricians, back-translation, and pretesting with clinicians and target patients. The expert committee resolved discrepancies and made key cultural adaptations (e.g., modifying phrasing for &#x201c;pointing&#x201d; to align with local nonverbal communication norms). The final AMSE-INA version and a comprehensive scoring guide with culturally-anchored examples were approved by the original developer. This meticulous process resulted in an instrument with excellent content validity (see Results), confirming its conceptual soundness and cultural appropriateness for Indonesia.</p>
            </sec>
            <sec id="sec10">
                <title>Psychometric validation of AMSE-INA
</title>
                <p>

                    <bold>Participants</bold>
                </p>
                <p>
Children aged 18&#x00a0;months to 18&#x00a0;years who were newly referred during September&#x2013;December 2025 with concerns about social communication, language delay, or restrictive/repetitive behaviors were recruited consecutively. To ensure a clear validation of AMSE against core idiopathic ASD symptoms and avoid confounding variables, children with the following conditions were excluded: 1) severe, uncorrected sensory impairments (e.g., profound deafness, blindness); 2) major neurological deficits (e.g., cerebral palsy with significant motor impairment, progressive neurological disorders); 3) known genetic syndromes strongly associated with a distinct ASD phenotype (e.g., Rett syndrome, Fragile X syndrome). These exclusions are standard in diagnostic validity studies to enhance diagnostic clarity.</p>
                <p>

                    <bold>Sample Size Calculation</bold>
                </p>
                <p>The sample size was calculated for diagnostic sensitivity using the formula by Dahlan,
                    <sup>
                        <xref ref-type="bibr" rid="ref31">31</xref>
                    </sup> assuming a sensitivity of 85%, a 10% margin of error, an alpha of 5%, and an ASD prevalence of 75% in the referral population, targeting a minimum of 72 participants to achieve adequate power
                    <bold>.</bold>
                </p>
                <p>

                    <bold>Procedures and Measures</bold>
                </p>
                <p>Each participant underwent a multi-stage assessment:
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Demographic and Clinical Data:</bold> Collected via parent interview and medical record review.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Index Test:</bold> AMSE-INA was administered by a trained fellow in social pediatrics (Rater A). A subset of participants (n&#x00a0;=&#x00a0;67) was independently assessed by a second trained fellow (Rater B) for inter-rater reliability analysis. Another subset (n&#x00a0;=&#x00a0;61) was reassessed by Rater A after 2&#x2013;4&#x00a0;weeks for test-retest reliability.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Comparator Test:</bold> The Childhood Autism Rating Scale, Second Edition &#x2013; Standard Version (CARS-2 ST) Indonesian version
                                <sup>
                                    <xref ref-type="bibr" rid="ref32">32</xref>
                                </sup> was administered by a senior fellow blinded to AMSE scores. CARS-2 ST is a well-validated 15-item observational scale widely used to assess ASD severity.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Reference Standard (Gold Standard):</bold> A best-estimate clinical diagnosis (BECD) was established by a senior consultant behavioral-developmental pediatrician with over 10&#x00a0;years of experience. The diagnosis was based on a comprehensive review of all available data (developmental history, clinical observation, and CARS-2 ST results) applying DSM-5 criteria.
                                <sup>
                                    <xref ref-type="bibr" rid="ref1">1</xref>
                                </sup> The consultant was blinded to the AMSE-INA scores to avoid incorporation bias.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec11">
                <title>Statistical analysis</title>
                <p>Data were analyzed using IBM SPSS Statistics 30.0. Descriptive statistics summarized participant characteristics. The non-parametric Mann-Whitney U and Kruskal-Wallis tests were used for group comparisons as data were not normally distributed.</p>
                <p>

                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Reliability:</bold> Internal consistency was measured using Cronbach&#x2019;s alpha. Inter-rater and test-retest reliability were assessed using a two-way random-effects Intraclass Correlation Coefficient (ICC) for absolute agreement. ICC values &gt;0.75 were considered excellent.
                                <sup>
                                    <xref ref-type="bibr" rid="ref33">33</xref>
                                </sup>
                            </p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Validity:</bold> Content validity was quantified via the Content Validity Index (CVI) from four independent ASD experts. Concurrent validity was assessed using Spearman&#x2019;s rank correlation between AMSE-INA and CARS-2 ST total scores. Discriminant (known-groups) validity was evaluated by comparing AMSE-INA scores across diagnostic groups (ASD vs. non-ASD) using the Kruskal-Wallis test across diagnostic groups and the Mann-Whitney U Test for two groups of diagnosis (ASD and Non-ASD).</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Diagnostic Accuracy:</bold> Receiver Operating Characteristic (ROC) curve analysis was performed with BECD as the state variable. The Area Under the Curve (AUC) with a 95% Confidence Interval (CI) was calculated. Optimal cut-off scores were identified using Youden&#x2019;s Index (J&#x00a0;=&#x00a0;sensitivity + specificity &#x2013; 1). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and likelihood ratios (LR+, LR-) were calculated for candidate cut-offs.</p>
                        </list-item>
                    </list>
                </p>
            </sec>
        </sec>
        <sec id="sec12" sec-type="results">
            <title>Results</title>
            <sec id="sec13">
                <title>Adaptation product</title>
                <p>The cross-cultural adaptation process yielded the final 
                    <bold>AMSE-INA
</bold>, comprising an administration form and a comprehensive scoring guide with culturally relevant behavioral examples for each item and each score (0, 1, 2). The cross-cultural adaptation yielded a linguistically and culturally appropriate AMSE-INA. Key adjustments included modifying phrasing for pointing behavior (&#x201c;ke arah objek&#x201d; &#x2013; toward the object) to align with Indonesian communication norms. The expert committee confirmed conceptual equivalence with the original AMSE.</p>
            </sec>
            <sec id="sec14">
                <title>Participant characteristics</title>
                <p>
A total of 184 children were recruited, 10 were excluded based on pre-specified criteria: 2 for severe sensory impairment, 5 for major neurological deficits, and 3 for known genetic syndromes, leaving 174 for analysis The cohort had a median age of 4.8&#x00a0;years (range: 1.6&#x2013;16.4) and was predominantly male (149 children, 85.6%), reflecting the known gender disparity in ASD referral patterns. Based on the gold-standard BECD, 99 children (56.9%) were diagnosed with ASD, and 75 children (43.1%) received other developmental diagnoses (e.g., language disorder, ADHD, global developmental delay). For age-stratified analysis, the sample was divided into two groups: children under 3&#x00a0;years (n&#x00a0;=&#x00a0;41, 23.6%) and children 3&#x00a0;years and older (n&#x00a0;=&#x00a0;133, 76.4%). Within the &lt;3&#x00a0;years group, 17 children (41.5%) had ASD. Within the &#x2265;3&#x00a0;years group, 82 children (61.7%) had ASD. No significant demographic differences existed between the ASD and non- ASD groups (p&#x00a0;&gt;&#x00a0;0.05), though clinical characteristics differed significantly (
                    <xref ref-type="table" rid="T1">
Table 1</xref>).</p>
                <table-wrap id="T1" orientation="portrait" position="float">
                    <label>
Table 1. </label>
                    <caption>
                        <title>Demographic and clinical characteristics of the validation sample (N&#x00a0;=&#x00a0;174).</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Characteristics</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Non-ASD (n&#x00a0;=&#x00a0;75)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">ASD (n&#x00a0;=&#x00a0;99)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">p-value
</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Age, years (median, range)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">4.8 (1.6&#x2013;11.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">4.7 (1.6&#x2013;16.4)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.332</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Age group, n (%)</bold>
</td>
                                <td colspan="1" rowspan="1"/>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.022</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;&#x00a0;&lt;&#x00a0;3&#x00a0;years</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">24 (58.5%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">17 (41.5%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;&#x00a0;&#x2265;&#x00a0;3&#x00a0;years</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">51 (38.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">82 (61.7%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Male, n (%)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">64 (85.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">85 (85.9%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.922</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Parental Education (High), n (%)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">31 (41.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">47 (47.5%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.420</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Family History of ASD, n (%)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1 (1.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">9 (9.1%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.045</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Referral Concern, n (%)</bold>
</td>
                                <td colspan="1" rowspan="1"/>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;0.001</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;- Speech Delay</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">38 (50.7%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">24 (24.2%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;- Suspected Autism</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2 (2.7%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">46 (46.5%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;- ADHD</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">24 (32.0%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">12 (12.1%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>CARS-2 ST Severity, n (%)</bold>
</td>
                                <td colspan="1" rowspan="1"/>
                                <td colspan="1" rowspan="1"/>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;0.001</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;- Minimal/None</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">70 (93.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">3 (3.0%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;- Mild-Moderate
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">5 (6.7%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">50 (50.5%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&#x2003;- Severe</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0 (0.0%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">46 (46.5%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>AMSE-INA Score (median, range)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">3 (0&#x2013;8)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">8 (4&#x2013;12)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;0.001</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>

                            <bold>Legend:</bold> ASD&#x00a0;=&#x00a0;Autism Spectrum Disorder; CARS-2 ST&#x00a0;=&#x00a0;Childhood Autism Rating Scale&#x2013;Second Edition Standard Version; AMSE-INA&#x00a0;=&#x00a0;Autism Mental Status Exam Indonesian Version; ADHD&#x00a0;=&#x00a0;Attention-Deficit/Hyperactivity Disorder. p-values were calculated using Mann-Whitney U test for continuous variables and Chi-square test for categorical variable</p>
                    </table-wrap-foot>
                </table-wrap>
            </sec>
            <sec id="sec15">
                <title>Reliability</title>
                <p>The reliability metrics for AMSE-INA were robust, indicating its consistency as a measurement tool.
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Inter-rater Reliability:</bold> For the subset of 67 participants assessed by two independent raters, the ICC was 
                                <bold>0.97</bold> (95% CI: 0.94&#x2013;0.98), indicating 
                                <italic toggle="yes">excellent</italic> agreement.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Test-retest Reliability:</bold> For the subset of 61 participants re-assessed after 2&#x2013;4&#x00a0;weeks, the ICC was 
                                <bold>0.96</bold> (95% CI: 0.93&#x2013;0.97), indicating 
                                <italic toggle="yes">excellent</italic> temporal stability.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Internal Consistency:</bold> Cronbach&#x2019;s alpha for the 8-item scale was 
                                <bold>0.66</bold>. Item analysis revealed that the &#x201c;Pragmatics of Language&#x201d; item had a low corrected item-total correlation (r&#x00a0;=&#x00a0;0.18). Its deletion would increase the scale&#x2019;s alpha to 0.78. In contrast, items like &#x201c;Repetitive/Stereotyped Behavior&#x201d; showed strong item-total correlations (r&#x00a0;=&#x00a0;0.64).</p>
                        </list-item>
                    </list>
                </p>
            </sec>
            <sec id="sec16">
                <title>Validity</title>
                <p>

                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Content Validity:</bold> The scale-level CVI (S-CVI/Ave) was 1.00, and all item-level CVIs (I-CVI) were 1.00, indicating unanimous expert agreement on relevance.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Concurrent Validity:</bold> AMSE-INA total scores correlated strongly with CARS-2 ST total scores (Spearman&#x2019;s rho&#x00a0;=&#x00a0;0.85, p&#x00a0;&lt;&#x00a0;0.001).</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>

                                <bold>Discriminant Validity:</bold> AMSE-INA scores significantly differed across diagnostic groups (Kruskal-Wallis H&#x00a0;=&#x00a0;125.28, p&#x00a0;&lt;&#x00a0;0.001), with highest scores in the ASD group AMSE-INA scores were significantly higher in the ASD group (median&#x00a0;=&#x00a0;8) compared to the non-ASD group (median&#x00a0;=&#x00a0;3) (Mann-Whitney
 U, p&#x00a0;&lt;&#x00a0;0.001).</p>
                        </list-item>
                    </list>
                </p>
                <p>

                    <bold>Diagnostic Accuracy</bold>
                </p>
                <p>ROC analysis indicated outstanding diagnostic performance (
                    <xref ref-type="fig" rid="f1">
Figure 1</xref>). The AUC was 0.978 (95% CI: 0.958&#x2013;0.998, p&#x00a0;&lt;&#x00a0;0.001). The optimal statistical cut-off was &#x2265;5.5 (Youden&#x2019;s Index&#x00a0;=&#x00a0;0.886). For clinical utility, integer cut-offs were evaluated (
                    <xref ref-type="table" rid="T2">
Table 2</xref>).</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>
Figure 1. </label>
                    <caption>
                        <title>Receiver operating characteristic (ROC) curve of AMSE-INA scores for predicting autism spectrum disorder diagnosis against the best estimate clinical diagnosis (BECD) reference standard.</title>
                        <p>The blue curve represents the AMSE-INA performance across different cut-off scores. The diagonal dashed line represents the reference line (area&#x00a0;=&#x00a0;0.5), indicating no discriminatory power. The Area Under the Curve (AUC) was 0.978 (95% CI: 0.958&#x2013;0.998, p&#x00a0;&lt;&#x00a0;0.001), demonstrating outstanding diagnostic accuracy. The optimal cut-off score of &#x2265;6 (Youden&#x2019;s Index&#x00a0;=&#x00a0;0.886) is indicated by the point nearest the top-left corner of the curve.</p>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/195982/4570a7e7-da92-4b23-bb19-23eb3b67cd18_figure1.gif"/>
                </fig>
                <table-wrap id="T2" orientation="portrait" position="float">
                    <label>
Table 2. </label>
                    <caption>
                        <title>Diagnostic accuracy of AMSE-INA at different cut-off scores (N&#x00a0;=&#x00a0;174).</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Parameter</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Cut-off &#x2265;5</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Cut-off &#x2265;6</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Sn [%, (95% CI)]</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">93.9 (90.4&#x2013;97.5)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">88.9 (84.2&#x2013;93.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Sp [%, (95% CI)]</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">86.7 (81.7&#x2013;92.7)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">94.7 (91.3&#x2013;98.0)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>PPV [%, (95% CI)]</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">90.3 (85.9&#x2013;94.7)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">95.7 (92.5&#x2013;98.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>NPV [%, (95% CI)]</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">91.5 (87.4&#x2013;95.7)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">86.6 (81.5&#x2013;92.7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>Accuracy [%, (95% CI)]</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">90.8 (86.5&#x2013;95.1)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">91.4 (87.2&#x2013;95.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>LR+ (95% CI)</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">7.1 (4.0&#x2013;12.6)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">16.7 (6.4&#x2013;43.7)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="middle">
                                    <bold>LR- (95% CI)</bold>
</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">0.07 (0.03&#x2013;0.15)</td>
                                <td align="char" char="(" colspan="1" rowspan="1" valign="middle">0.12 (0.07&#x2013;0.20)</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>

                            <bold>Legend:</bold> Sn&#x00a0;=&#x00a0;sensitivity; Sp&#x00a0;=&#x00a0;specificity; PPV&#x00a0;=&#x00a0;positive predictive value; NPV&#x00a0;=&#x00a0;negative predictive value; LR+&#x00a0;=&#x00a0;positive likelihood ratio; LR-&#x00a0;=&#x00a0;negative likelihood ratio; CI&#x00a0;=&#x00a0;confidence interval. Optimal cut-off (&#x2265;6) was determined using Youden&#x2019;s Index.</p>
                    </table-wrap-foot>
                </table-wrap>
                <p>Age-Stratified Diagnostic Accuracy
                    <bold>:</bold>

                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Children &lt;3&#x00a0;years: The diagnostic accuracy was perfect, with an AUC of 1.00.</p>
                        </list-item>
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Children &#x2265;3&#x00a0;years: The diagnostic accuracy remained excellent, with an AUC of 0.97 (95% CI: 0.93&#x2013;0.99).</p>
                        </list-item>
                    </list>
                </p>
                <p>A cut-off of &#x2265;6 provided an optimal balance for a pre-diagnostic tool in a specialist setting, maximizing specificity (94.7%) and PPV (95.7%) to minimize false positives, while maintaining high sensitivity (88.9%). A cut-off of &#x2265;5 could be considered for high-sensitivity screening in lower-prevalence settings (
                    <xref ref-type="table" rid="T3">
Table 3</xref>).</p>
                <table-wrap id="T3" orientation="portrait" position="float">
                    <label>
Table 3. </label>
                    <caption>
                        <title>Diagnostic accuracy of AMSE-INA at cut-off &#x2265;6, Overall and by age group.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Parameter</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Overall sample (N&#x00a0;=&#x00a0;174)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Children &lt;3&#x00a0;years (n&#x00a0;=&#x00a0;41)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Children &#x2265;3&#x00a0;years (n&#x00a0;=&#x00a0;133)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>Sn [%, (95% CI)]</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">88.9 (84.2&#x2013;93.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">94.1(73.0&#x2013;99.0)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">87.8 (79.0&#x2013;93.2)|</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>Sp [%, (95% CI)]</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">94.7 (91.3&#x2013;98.0)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">100 (85.7&#x2013;100)
                                    <xref ref-type="table-fn" rid="tfn1">*</xref>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">92.2 (81.2&#x2013;97.8)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>PPV [%, (95% CI)]</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">95.7 (92.5&#x2013;98.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">100 (79.4&#x2013;100)
                                    <xref ref-type="table-fn" rid="tfn1">*</xref>
                                </td>
                                <td align="left" colspan="1" rowspan="1" valign="top">94.7 (86.8&#x2013;98.5)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>NPV [%, (95% CI)]</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">86.6 (81.5&#x2013;92.7)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">96.0 (80.5&#x2013;99.3)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">82.5 (69.8&#x2013;91.3)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>Accuracy [%, (95% CI)]</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">91.4 (87.2&#x2013;95.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">97.6 (87.4&#x2013;99.6)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">89.5 (83.1&#x2013;93.6)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>LR+ (95% CI)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">16.7 (6.4&#x2013;43.7)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&gt;100 (5.0- &#x221e;)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">11.3 (4.3&#x2013;28.8)</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">
                                    <bold>LR- (95% CI)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.12 (0.07&#x2013;0.20)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.06 (0.002&#x2013;0.29)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.13 (0.07&#x2013;0.24)</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>

                            <bold>Legend:</bold> Sn&#x00a0;=&#x00a0;sensitivity; Sp&#x00a0;=&#x00a0;specificity; PPV&#x00a0;=&#x00a0;positive predictive value; NPV&#x00a0;=&#x00a0;negative predictive value; LR+&#x00a0;=&#x00a0;positive likelihood ratio; LR-&#x00a0;=&#x00a0;negative likelihood ratio. The LR+ for children &lt;3&#x00a0;years approaches infinity due to 100% specificity in this subgroup.</p>
                        <fn-group content-type="footnotes">
                            <fn id="tfn1">
                                <label>*</label>
                                <p>Note: Confidence intervals for proportions were calculated using the Wilson score method, except for values of 100% where exact binomial (Clopper&#x2013;Pearson) intervals are reported.</p>
                            </fn>
                        </fn-group>
                    </table-wrap-foot>
                </table-wrap>
            </sec>
        </sec>
        <sec id="sec17" sec-type="discussion">
            <title>Discussion</title>
            <p>This study successfully adapted and validated the AMSE for use in Indonesia. The resulting AMSE-INA is not merely a screening questionnaire but a 
                <bold>structured pre-diagnostic examination tool</bold> with robust psychometric properties, specifically designed to aid clinical decision-making by specialists in settings where gold-standard instruments like ADOS-2 are inaccessible. The age-stratified analysis offers novel and crucial insights for its application across different developmental stages.</p>
            <p>The cultural adaptation process was vital to this success. Modifications like clarifying &#x201c;pointing toward an object&#x201d; rather than &#x201c;at an object&#x201d; account for local nonverbal communication norms, ensuring behavioral anchors are meaningful.
                <sup>
                    <xref ref-type="bibr" rid="ref28">28</xref>,
                    <xref ref-type="bibr" rid="ref30">30</xref>
                </sup> The development of a detailed, culturally relevant scoring guide based on pre-test feedback was crucial for achieving high inter-rater reliability, transforming the tool from a simple translation into an operational clinical instrument.
                <sup>
                    <xref ref-type="bibr" rid="ref30">30</xref>
                </sup>
            </p>
            <p>The perfect content validity (CVI&#x00a0;=&#x00a0;1.00) is a direct outcome of the rigorous adaptation process and confirms that AMSE-INA is culturally and conceptually appropriate for Indonesia. Key adaptations, such as refining the description of pointing behavior, mirror the essential work done in other cultural validations, ensuring the tool measures ASD symptoms rather than cultural misfit.
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>,
                    <xref ref-type="bibr" rid="ref23">23</xref>
                </sup> This step is non-negotiable; a tool&#x2019;s ecological validity in a new setting depends on such careful localization of behavioral anchors.</p>
            <p>The observed internal consistency (Cronbach&#x2019;s &#x03b1;&#x00a0;=&#x00a0;0.66) warrants a nuanced interpretation that is common in the validation of multidimensional diagnostic tools. A moderate alpha is not indicative of a flawed tool but reflects its intentional design to capture the distinct, heterogeneous domains of ASD as defined by the DSM-5. The AMSE is not a unidimensional scale measuring a single latent trait; it is a structured clinical checklist that operationalizes two relatively independent symptom domains: 
                <bold>social-communication deficits</bold> and 
                <bold>restricted, repetitive behaviors (RRBs)</bold>. This pattern is 
                <bold>consistent with global AMSE validations</bold>, in which Cronbach&#x2019;s alpha typically ranges from 0.61 to 0.80 rather than exceeding 0.90. For instance, studies in Chile and China reported alphas of 0.61 and 0.65, respectively,
                <sup>
                    <xref ref-type="bibr" rid="ref21">21</xref>,
                    <xref ref-type="bibr" rid="ref23">23</xref>
                </sup> while Brazil reported 0.74,
                <sup>
                    <xref ref-type="bibr" rid="ref20">20</xref>
                </sup> and Turkey reported 0.80.
                <sup>
                    <xref ref-type="bibr" rid="ref22">22</xref>
                </sup>
            </p>
            <p>The moderate internal consistency (&#x03b1;&#x00a0;=&#x00a0;0.66) is consistent with previous AMSE validations and reflects its intentional design to measure related but distinct clinical domains of ASD (social communication and restricted/repetitive behaviors).
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>,
                    <xref ref-type="bibr" rid="ref21">21</xref>,
                    <xref ref-type="bibr" rid="ref22">22</xref>
                </sup> The low contribution of the &#x201c;Pragmatics&#x201d; item is a known characteristic of the tool across cultures and may relate to the challenge of reliably observing this domain in a brief examination.
                <sup>
                    <xref ref-type="bibr" rid="ref20">20</xref>,
                    <xref ref-type="bibr" rid="ref34">34</xref>
                </sup> The high content validity confirms that Indonesian experts view the AMSE-INA items as fully representative of core ASD symptoms within the local context.</p>
            <p>The consistently low item-total correlation for the &#x201c;Pragmatics of Language&#x201d; item across studies (including ours) is a known characteristic, likely due to its conditional scoring and the subtle, culturally-influenced nature of pragmatic deficits. Therefore, the internal consistency result should be interpreted as evidence that AMSE-INA&#x2019;s total score is a composite of semi-independent domains, which is appropriate for its purpose. This stands in clear contrast to its excellent inter-rater and test-retest reliability, which confirms that clinicians can apply the scoring rules for each individual item with very high consistency.</p>
            <p>The core strength of AMSE-INA lies in its 
                <bold>excellent reliability and high diagnostic accuracy</bold>. The inter-rater and test-retest ICCs (&gt;0.95) exceed those of many established clinical tools and indicate that AMSE-INA can yield consistent scores across clinicians and over time, a critical feature for a reliable diagnostic aid.
                <sup>
                    <xref ref-type="bibr" rid="ref35">35</xref>,
                    <xref ref-type="bibr" rid="ref36">36</xref>
                </sup> The AUC of 0.98 is exceptional and aligns with findings from validation studies in Brazil (AUC&#x00a0;=&#x00a0;0.99) and Turkey (AUC&#x00a0;=&#x00a0;0.98).
                <sup>
                    <xref ref-type="bibr" rid="ref22">22</xref>,
                    <xref ref-type="bibr" rid="ref24">24</xref>
                </sup> This confirms that the adapted instrument retains a near-perfect ability to discriminate between ASD and non-ASD cases within a referral population.</p>
            <p>The proposed cut-off of &#x2265;6 is strategically chosen for the tool&#x2019;s intended use. In a specialist referral clinic where the pre-test probability of ASD is high (57% in this sample), the priority is to confirm the diagnosis with high confidence to justify resource-intensive interventions and family counselling. A specificity of 94.7% and a PPV of 95.7% mean that a child scoring &#x2265;6 has a very high probability of having ASD, effectively &#x201c;ruling in&#x201d; the disorder. The high positive likelihood ratio (LR+&#x00a0;=&#x00a0;16.7) signifies a &#x201c;conclusive&#x201d; shift in post-test probability.
                <sup>
                    <xref ref-type="bibr" rid="ref37">37</xref>
                </sup> This addresses a key need: reducing diagnostic uncertainty and subjective variability when gold-standard tools are absent.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>,
                    <xref ref-type="bibr" rid="ref38">38</xref>
                </sup>
            </p>
            <p>The age-stratified analysis provides one of the most significant and actionable findings of this study. The perfect diagnostic accuracy (AUC&#x00a0;=&#x00a0;1.00) in children under 3&#x00a0;years is exceptionally promising. At the recommended cut-off of &#x2265;6, AMSE-INA achieved 94.1% sensitivity, 100% specificity, and PPV in this young cohort. This indicates that when a toddler scores 6 or higher on AMSE-INA, the clinician can be virtually certain of an ASD diagnosis, a powerful asset for early, confident identification.</p>
            <p>This superb performance in very young children likely stems from the nature of early ASD symptoms. In toddlers, core deficits (e.g., absent joint attention, lack of response to name, limited social smiling) are often more categorical, severe, and easily observable within a brief clinical interaction.
                <sup>
                    <xref ref-type="bibr" rid="ref27">27</xref>,
                    <xref ref-type="bibr" rid="ref39">39</xref>,
                    <xref ref-type="bibr" rid="ref40">40</xref>
                </sup> The structured observation of AMSE-INA effectively captures these clear behavioral markers. This finding is crucial for Indonesia, as it suggests AMSE-INA is not just a general tool but one with particular strength in facilitating early detection within specialist settings, directly addressing the national problem of late diagnosis.</p>
            <p>For children aged 3&#x00a0;years and older, accuracy remained excellent (AUC&#x00a0;=&#x00a0;0.97), though specificity at the &#x2265;6 cut-off was slightly lower (92.2%) than in the younger group. This is clinically understandable. As children develop, ASD symptoms can become more nuanced, variable, and intertwined with comorbid conditions (e.g., ADHD, anxiety) or intellectual disability.
                <sup>
                    <xref ref-type="bibr" rid="ref26">26</xref>
                </sup> Some children may develop compensatory strategies that mask core social deficits during brief observations. Furthermore, the &#x201c;Pragmatics of Language&#x201d; item, which is more frequently scorable in this verbal older group, has known reliability challenges, potentially contributing to score variability. This does not diminish the tool&#x2019;s value for older children but underscores that 
                <bold>clinical judgment must always integrate the AMSE-INA score with a comprehensive developmental history</bold>. A score just below 6 in an older child with strong historical evidence of ASD should not rule out the diagnosis.</p>
            <p>The strong correlation with CARS-2 ST supports the convergent validity of AMSE-INA with an established ASD assessment tool. However, future validation against gold-standard instruments like ADOS-2 would strengthen the evidence, though pragmatic constraints in LMICs often limit such comparisons.</p>
            <p>AMSE-INA fills a specific niche in Indonesia&#x2019;s diagnostic ecosystem. Widely-used tools like M-CHAT-R/F are parent-reported and age-restricted, serving as initial population screens.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>,
                    <xref ref-type="bibr" rid="ref41">41</xref>
                </sup> In contrast, AMSE-INA is a 
                <bold>clinician-driven, specialist-level observational tool</bold>. It does not replace a comprehensive clinical evaluation but structures and objectifies it, directly addressing the over-reliance on unstructured clinical judgment that can lead to diagnostic delays and errors in resource-limited settings.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>,
                    <xref ref-type="bibr" rid="ref42">42</xref>,
                    <xref ref-type="bibr" rid="ref43">43</xref>
                </sup> For a specialist who cannot administer an ADOS-2, the 15-minute AMSE-INA provides a standardized framework for systematically assessing DSM-5 criteria, integrating caregiver reports, and generating a quantifiable score that strongly predicts the final diagnosis.</p>
            <p>AMSE-INA&#x2019;s role must be understood within the existing Indonesian diagnostic landscape. Tools like the M-CHAT-R/F are vital for Level 1 screening in community or primary care settings. In contrast, AMSE-INA is a Level 2, specialist-administered, observational tool. It does not replace a full clinical evaluation but structures and objectifies it. For specialists who cannot access an ADOS-2, AMSE-INA provides a standardized, evidence-based framework for efficiently gathering and synthesizing diagnostic information during a consultation. Its 15-minute administration time makes it feasible in busy public hospital settings, and its zero cost eliminates a major barrier to adoption. It effectively bridges the gap between a positive screening result and a definitive, specialist-level diagnosis.</p>
            <sec id="sec18">
                <title>Limitations and future directions</title>
                <p>This study has limitations. The single-center, tertiary-care sample may affect generalizability to primary care or other regions. The gender imbalance, while reflective of global ASD epidemiology and referral bias, indicates a need for conscious effort to validate tools in female populations. While BECD is a well-accepted reference standard, future research directly comparing AMSE-INA with ADOS-2 in Indonesia would strengthen the evidence base. The sample size for the &lt;3&#x00a0;years subgroup, while adequate for initial analysis, warrants replication in a larger, prospective study of toddlers. Furthermore, implementation science research is needed to study the rollout, training, and real-world impact of integrating AMSE-INA into routine practice across different healthcare tiers in Indonesia.</p>
            </sec>
        </sec>
        <sec id="sec19" sec-type="conclusion">
            <title>Conclusion</title>
            <p>This study provides a comprehensive cross-cultural adaptation and validation of the Autism Mental Status Exam for Indonesia. AMSE-INA is a reliable, valid, and diagnostically accurate pre-diagnostic tool across a wide age range that equips specialists with a structured, rapid, and accurate method for assessing ASD when access to gold-standard instruments is constrained. By providing a standardized framework to guide observation and clinical judgment, it has the potential to significantly improve diagnostic consistency and accuracy, reduce delays, and facilitate earlier intervention pathways for children with ASD in Indonesia and similar resource-limited settings. Its open-access nature and minimal training requirements make it a feasible and scalable solution for bridging the diagnostic gap in specialist care. Its widespread implementation in secondary and tertiary healthcare settings is strongly recommended.</p>
        </sec>
    </body>
    <back>
        <sec id="sec22" sec-type="data-availability">
            <title>Data availability statement</title>
            <p>The anonymized dataset supporting this study is available in Zenodo. All data and supporting materials underlying this study are openly available in Zenodo under a 
                <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license (CCBY4.0)</ext-link>: 
                <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.19104529">https://doi.org/10.5281/zenodo.19104529</ext-link>.
                <sup>
                    <xref ref-type="bibr" rid="ref44">44</xref>
                </sup>
            </p>
            <p>The deposit includes anonymized participant data (Excel), instrument PDFs (AMSE-INA, CARS-2 ST Indonesian), permission letters, ethics approval, SPSS output, adaptation records, pretesting feedback form, and a comprehensive README file.</p>
            <p>Data are available under the terms of the 
                <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license (CC BY 4.0)</ext-link>.</p>
        </sec>
        <ack>
            <title>Acknowledgements</title>
            <p>The authors wish to acknowledge the following individuals for their contributions:
                <list list-type="bullet">
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Braghmandita Widya Indraswari contributed as a member of the expert committee during the instrument adaptation process and participated in patient diagnosis.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>David Grodberg, as the license holder of the AMSE instrument, was involved in the cross-cultural adaptation process.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>Professional translators were engaged for linguistic adaptation and were compensated for their services; they were not involved in determining the adaptation outcomes.</p>
                    </list-item>
                    <list-item>
                        <label>&#x2022;</label>
                        <p>The manuscript was drafted with the assistance of Deepseek AI, but all content was reviewed, edited, and is the sole responsibility of the authors.</p>
                    </list-item>
                </list>
            </p>
        </ack>
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    </back>
    <sub-article article-type="reviewer-report" id="report495117">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.195982.r495117</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Gunturu</surname>
                        <given-names>Sasidhar</given-names>
                    </name>
                    <xref ref-type="aff" rid="r495117a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-6867-2394</uri>
                </contrib>
                <aff id="r495117a1">
                    <label>1</label>Bronx-Lebanon Hospital Center, New York, New York, USA</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>6</day>
                <month>7</month>
                <year>2026</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 Gunturu S</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport495117" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.177715.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>
                <bold>Major revision</bold>.</p>
            <p> 
                <bold>Introduction</bold>
            </p>
            <p> The Introduction presents a compelling rationale for the study. The authors clearly identify an important clinical problem: standardized ASD diagnostic tools such as ADOS-2 and ADI-R are difficult to access in many low- and middle-income settings because they require training, licensing, time, and financial resources. The manuscript also appropriately explains why a shorter structured observational tool such as AMSE may be clinically useful in Indonesia and similar settings.</p>
            <p> However, the intended role of AMSE-INA should be stated more clearly. Is the tool meant to support triage, standardize specialist observation, increase confidence in clinical diagnosis, or function as a Level 2 pre-diagnostic instrument?</p>
            <p> 
                <bold>Methods &#x2014; study design and setting</bold>
            </p>
            <p> I would strongly recommend that the authors explicitly report the study according to STARD guidelines. A participant flow diagram would be particularly helpful. Readers should be able to see how many patients were assessed for eligibility, how many were excluded, how many completed AMSE-INA, how many completed CARS-2 ST, how many received BECD, and whether any data were missing. As a reader, It is important to know whether AMSE-INA, CARS-2 ST, and BECD were performed on the same day or across different visits, because clinical status could have changed between assessments.</p>
            <p> 
                <bold>Methods &#x2014; cross-cultural adaptation</bold>
            </p>
            <p> The cross-cultural adaptation process is one of the manuscript&#x2019;s strengths.</p>
            <p> &#x00a0;At present, the reader receives only a general description of the adaptation process. I would recommend adding a table that documents the main adaptation decisions. For example:</p>
            <p> 
                <bold>AMSE item</bold>
            </p>
            <p> 
                <bold>Translation issue</bold>
            </p>
            <p> 
                <bold>Cultural concern</bold>
            </p>
            <p> 
                <bold>Final Indonesian wording</bold>
            </p>
            <p> 
                <bold>Rationale</bold>
            </p>
            <p> </p>
            <p> The pretesting process also needs more explanation. The authors should state how many clinicians participated, how many patients or families were involved, what type of feedback was collected, and what changes were made after pretesting. If no formal patient data were collected during pretesting, that should be clearly explained.</p>
            <p> 
                <bold>Methods &#x2014; index test, comparator, and reference standard</bold>
            </p>
            <p> This is the most important methodological section to strengthen.</p>
            <p> The relationship between CARS-2 ST and the reference standard needs a more transparent explanation. The manuscript states that best-estimate clinical diagnosis was based on developmental history, clinical observation, and CARS-2 ST, while CARS-2 ST was also used to assess concurrent validity with AMSE-INA. This creates a risk of partial circularity or criterion contamination. In other words, if CARS-2 ST helps inform the reference diagnosis and is also used as a comparator, the relationship among AMSE-INA, CARS-2 ST, and BECD may not be fully independent.</p>
            <p> This does not invalidate the study, but it should be acknowledged directly.</p>
            <p> The manuscript should also clearly describe blinding. It states that the consultant establishing BECD was blinded to AMSE scores, which is important. The authors should also specify whether AMSE-INA raters were blinded to CARS-2 ST results and final diagnosis, and whether CARS-2 ST assessors were blinded to AMSE-INA scores.</p>
            <p> 
                <bold>&#x00a0;Results &#x2014; participant characteristics</bold>
            </p>
            <p> There is one important wording issue. The manuscript states that there were no significant demographic differences between ASD and non-ASD groups, but the table appears to show significant differences for some variables, including age group and family history.</p>
            <p> 
                <bold>Discussion</bold>
            </p>
            <p> Well written section, however, several passages are too promotional for a scientific manuscript. Words and phrases such as &#x201c;superb,&#x201d; &#x201c;powerful asset,&#x201d; &#x201c;virtually certain,&#x201d; and &#x201c;strongly recommended&#x201d; should be softened. The data are strong enough that the authors do not need promotional language. The Discussion should also include a clearer paragraph on potential bias.</p>
            <p> The authors can say that AMSE-INA &#x201c;may have the potential&#x201d; to support earlier assessment, but they should not present this as demonstrated.</p>
            <p> </p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Partly</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>No</p>
            <p>Reviewer Expertise:</p>
            <p>Psychiatry</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
    </sub-article>
</article>
