Developing a Consensus Research Definition for Profound Autism Using a Modified Delphi Method

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Lord, Helen Tager-Flusberg, Judith Ursitti, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8745285/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Background The diagnostic term, autism spectrum disorder, encompasses the full range of impairments associated with the autism spectrum, a significant change from earlier DSM definitions that identified various subtypes of autism. However, the majority of autism-related research and cultural representations in recent years has focused on autistic individuals with strong language and cognitive abilities. In 2021, the administrative term Profound Autism (PA) was proposed by a Lancet Commission to draw attention to autistic people whose impairments require lifelong, round-the-clock care. The definition of PA included a minimum age, an IQ range, nonverbal or minimally verbal skills, and required 24/7 access to an adult to ensure safety. However, researchers are not yet using a consistent definition of PA, based on their interpretation of the Lancet Commission report. Methods To address the need to have studies that use comparable samples and increase clarity in communication and interpretation of results, we carried out a systematic, multi-stage Delphi consensus study with over 70 participants who identified as researchers, caregivers, autistic individuals, and clinicians, to measure consensus on components of a research definition of PA. A series of questions was developed for the primary domains of interest. Results After two rounds of review and voting, 76% of the respondents agreed on a research definition of PA of: adaptive functioning well below age level, requiring adult supervision to ensure physical and mental health, safety and well-being, at least 8 years old, diagnosed with ASD, and having severely impaired cognitive abilities (reflected by IQ score below 50) and/or does not verbally communicate other than single words or fixed phrases predominantly to have their basic needs met. Limitations : Variations in access to measurement tools as well as access to services across the world limits the utility of this definition outside research practices. Conclusions Based on these findings, a new working research definition of profound autism is proposed. This definition will improve specificity in precision medicine treatments for ASD. Autism Spectrum Disorder Profound Autism Delphi Process Figures Figure 1 Figure 2 Background According to the current definition of autism spectrum disorder in the DSM-5, the diagnostic term encompasses the full range of the autism spectrum, levels of impairment, and co-morbidities.( 1 ) This represented a significant change from earlier definitions in DSM III, IIIR and IV in which various subtypes of autism were recognized and defined. In 2021, The Lancet Commission on the Future of Clinical Care in Autism proposed the administrative term Profound Autism (PA) to describe people with autism whose significant impairments require round-the-clock care from an adult. The report highlighted the need to distinguish this group of autistic individuals from those who were more able, with the hope that introducing the term “will spur both the clinical and research global communities to prioritize the needs of this vulnerable and underserved group.”( 2 ) (p.278) The Lancet Commission provided an administrative definition of PA that included a minimum age of 8, an IQ below 50, nonverbal or minimally verbal, and requiring 24/7 care to ensure safety. The Centers for Disease Control followed up on this initial introduction of PA to investigate its prevalence among 8-year-old children, using data collected as part of the Autism and Developmental Disabilities Monitoring Network. Using a definition of IQ below 50 or non/minimally verbal, 26.7% of the autistic children were classified with profound autism.( 3 ) Autistic individuals with intellectual disability or who are non/minimally verbal have been repeatedly shown to have higher rates of medical and psychiatric comorbidities, serious externalizing behaviors, hospitalization, lower adaptive functioning, adult employment and independent living.( 4 – 9 ) It is also widely recognized in the field that the choice of interventions and supports provided to autistic individuals is largely determined by the individual’s verbal and cognitive ability. Despite these wide-ranging challenges, significant needs, and stark differences in appropriate treatment approaches and outcomes, a minority of behavioral or neuroimaging studies of autism have included profoundly autistic participants.( 10 , 11 ) The proportion of treatment studies that include severely affected autistic individuals has declined precipitously over the past two decades.( 10 ) Inclusion of this group in autism research has been limited by a variety of factors, including stigma, perceived challenge, increased costs, researcher familiarity, a paucity of validated assessment tools, and barriers to access and participation for individuals and families, though several publications have identified best practices for enhancing inclusion in research.( 11 ) By recognizing this disparity and providing clear guidance on how profound autism should be defined in a research setting, the goal is to better include these individuals in research and improve diagnosis, treatments, and supports across the lifespan. As an example of such an effort, there was an increase in research projects that included non-verbal individuals following a NICHD workshop and resulting papers in 2013 that worked to better define and operationalize assessment of this group.( 12 ) Progress in a scientific field is critically dependent on rigorous and specific definitions with agreed-upon operationalization.( 13 ) Since it was introduced in 2021, profound autism has been variously defined in subsequent research studies, producing a wide range of prevalence rates across the world based on ascertainment, diagnosis, and other factors (11–58%), difficulty in comparing datasets, and confusion in the field.( 4 ) The lack of a consensus research definition has not only impeded research on profound autism but also has contributed to criticisms of considering profound autism as a distinct subgroup of the autism population.( 14 ) In particular, needs for precision medicines, community integration, employment and housing are being approached with a broad brush and not targeted to different levels of functioning because the term “autism” has become so broad. The lack of a research definition obfuscates the need to develop specific interventions and supports, despite the widely held principle that treatment should be individualized. Whether or not one agrees with distinguishing profound autism from the rest of autism, research including these individuals, which represents a significant gap in our knowledge about autism, is significantly impacted by the lack of a consensus definition. The goal of the current study was to develop a consensus research definition of profound autism, using a modified Delphi methodology,( 15 , 16 ) grounded initially by the criteria in the Lancet report, as determined by a broad group of researchers, clinicians, caregivers, and autistic individuals. Methods The study was carried out over the course of 2024–2025. It was led by a ‘steering committee’ (SC), which included all the authors guided by an independent facilitator with experience conducting Delphi research (Triducive Partners Limited). The study was not registered; all reporting follows the ACCORD guidelines.(17) Fig. 1 summarizes the modified Delphi process that was followed. The modified Delphi differs from a traditional Delphi in that the modified process is used to validate, refine or prioritize existing ideas rather than explore or build consensus from scratch. Specifically, the first rounds were not open ended, it started with a predefined list of items based on the previous Lancet criteria. This resulted in fewer “rounds” being required. The surveys were totally anonymous. Figure 1. Modified Delphi process followed during the study Ethics approval statement: This study did not require registration and ethical approval because neither the assigned interventions nor the outcomes assessed were related to the health of participants. All survey respondents were informed of the purpose of the study and consent to participate was implied by the completion and submission of the survey. This research was conducted according to the principles of the Declaration of Helsinki. Developing Domains and Statements for Inclusion in the Survey The SC convened in March 2024 and reached agreement on the key domains to be considered in developing a research definition of profound autism: 1. Age 2. IQ 3. Language/communication 4. Adaptive functioning 5. Need for adult support 6. Co-morbid diagnoses 7. Severe, intense, dangerous behavior 8. Other Working collaboratively, the SC developed an initial set of 35 statements with support from the facilitator. These statements underwent three rounds of review by members of the SC who categorized them as ‘accept’ ‘remove’ or ‘reword’. During the first round, 10 statements were removed, 7 were added, and 14 were edited. During the second round, 1 statement was removed, 1 was added, and 8 were edited. After a final review, 32 statements were accepted and developed into a survey. Each statement was presented with a 4-point Likert scale (strongly agree, tend to agree, tend to disagree, strongly disagree) to allow responders to indicate their level of agreement and to avoid the ambiguity which can be caused by middle option bias. Following standard Delphi methodology, this survey round was predominantly quantitative and did not seek feedback on the statements from survey respondents. Delphi is considered a consensus group research method, which involves obtaining the views of a group of experts and aims to achieve consensus and agreement as outcomes.(18) Participants The independent facilitator distributed the survey to a large group of individuals identified by members of the SC. They were identified as experts across the world who were experienced clinicians, researchers, caregivers, or clinician-scientists whose expertise (published or presented at scientific meetings) included a focus on autistic individuals who were minimally verbal or had significant cognitive impairment. They were invited to participate and asked to self-identify on the basis of whether they were a researcher, clinician, caregiver, or an autistic individual. 137 individuals agreed to participate, representing 5 geographic regions (US, Canada, Europe, Asia Pacific, and Middle East/Africa), and came from diverse academic and professional backgrounds, ensuring that a comprehensive range of perspectives was included. Procedures As this study only collected anonymous opinions and no identifying or patient health information, it was not submitted to an IRB. No incentives were provided to participants. A statement of consent was included at the beginning of the survey, and consent was assumed to be given by participant completion and submission of the survey. The only demographic information collected on the survey was the respondent’s primary self-identified role and geographic region. The survey opened by asking participants if they were familiar with the term ‘profound autism’ and, in an effort to assess their understanding of the term, were asked the open-ended question: “From your perspective, how is profound autism currently defined?” Participants then rated the 32 statements about Profound Autism using the Likert scale described earlier. Stopping criteria were established a priori as a one-month window within which participants could respond and a minimum of 70 responses were required. Completed surveys were analyzed to determine an overall agreement level for each statement using descriptive statistics. The a priori threshold for consensus was set at 75% and then further defined as ‘strong’ (75%) or ‘very strong’ (90%). For Delphi consensus processes, a level between 70% to 80% is usually adopted and considered to be rigorous.(19, 20) SC met in August, 2024 to review the findings and, using the consensus level achieved, developed a research definition of PA. This definition, presented in Fig. 2, was tested in a second round of surveys, sent to the same initial group of 137 participants. Figure 2. The finalized definition of profound autism based on the feedback from the second round of survey The proposed definition was presented on the second-round survey, and participants were asked whether or not they agreed with it. If participants disagreed, they were asked to provide qualitative feedback on the definition. The same stopping criteria were used for the second-round survey. Results Initial Survey The initial survey was sent to 137 participants, and 70 responses were received, a response rate of 51% (see Supplementary Figure S1 ). Respondents were predominantly clinicians (n = 30, 45%), followed by researchers (n = 29, 41%), family members (n = 7, 10%), and autistic individuals (n = 2, 3%). Most respondents (n = 62, 89%) were from the United States. Duplicates could be identified by unique identifying numbers assigned by the survey software based on the IP address. (Supplementary Figure S2 ). Second-round Survey The second-round survey was sent to the original 137 participants. It included a definition of profound autism based on the results from the first round, and was completed by 78 participants (57%) (see Supplementary Figures S3 and S4 for demographic details). The majority of respondents agreed with the proposed definition (N = 59; 76%), exceeding the consensus threshold. The SC met one final time in December, 2024 to discuss the feedback from the second-round survey and finalized the research definition of profound autism. The SC considered the high rate of agreement with the surveyed definition and the qualitative comments from some respondents that accompanied the ratings (see Supplementary Table 1) to make slight adjustments to the surveyed definition. The percentage of agreement with each of the 32 statements following the second revision is presented in Table 1 . There was very strong agreement (> 90%) with 12 statements, and strong agreement (> 75%) with an additional 8 statements. 12 statements failed to reach the consensus threshold, and were mostly clustered under the domains of IQ, age, and severe/dangerous behaviors. Table 1 Defined consensus statements and corresponding levels of agreement. Statements which were grouped or paired are indicated with an orange border. Agreement below the consensus threshold (75%) is in pink, agreement which achieved consensus ≥ 75% but < 90% is in blue, agreement ≥ 90% is highlighted in green. No. Statement Agreement Topic A: IQ Considerations 1 A person with Profound Autism should have an IQ score lower than 50 69% 2 A person with Profound Autism should have an IQ score lower than 60 56% 3 A person with Profound Autism should have an IQ score lower than 70 56% 4 Non-verbal IQ is a more inclusive way to ascertain Profound Autism than full scale IQ 63% 5 IQ should not be included in a future definition of Profound Autism 33% Topic B: Language & Communication Considerations 6 A person with Profound Autism does not communicate beyond single words 59% 7 A person with Profound Autism cannot communicate beyond a few single words and fixed phrases, for example “want cookie” 83% 8 A person with Profound Autism primarily verbally communicates only to obtain their basic needs and/or desires 76% 9 A person with Profound Autism could not verbally communicate to an unfamiliar person about basic needs or in an emergency 84% 10 A person with Profound Autism cannot consistently verbally communicate healthcare needs to caregivers or providers. (e.g. express pain) 94% Topic C: The Need for Adult Support 11 A person with Profound Autism is not capable of being left alone in their home without adult supervision due to safety concerns 93% 12 A person with Profound Autism cannot be left alone briefly, for example while their parent/caregiver goes next door to borrow a cup of sugar 74% 13 A person with Profound Autism cannot be left alone in their home for more than 2-hours due to safety concerns 94% 14 A person with Profound Autism requires adult support to meet their basic needs, for example food preparation, dressing, and bathing adequately 97% 15 A person with Profound Autism requires an adult available to them 24/7 to maintain safety, for example due to risk of elopement, self-harm, or lack of environmental awareness 97% Topic D: Age Considerations 16 A person can be identified as having Profound Autism by age 18 months 14% 17 A person can be identified as having Profound Autism by age of 3 years 41% 18 A person can be identified as having Profound Autism by age of 5 years 74% 19 A person can be identified as having Profound Autism by age of 8 years 96% 20 A person with Profound Autism may gain skills over time, but profound autism is a life-long condition 96% Topic E: Adaptive Functioning Considerations 21 A person with Profound Autism cannot independently perform most activities of daily living (e.g. food preparation, dressing, and bathing adequately) 94% 22 A person with Profound Autism has adaptive functioning skills significantly below their age equivalence 99% 23 A person with Profound Autism has on average adaptive skills at least 2-standard deviations below the population mean 89% 24 A person with Profound Autism has on average adaptive skills at least 3-standard deviations below the population mean 90% 25 A person with Profound Autism is unaware of basic social expectations, for example nudity or breaking into neighbors' homes 87% Topic F: Co-morbid Diagnoses Considerations 26 Almost all ASD individuals have some co-morbid medical diagnoses (for example, seizure disorder, sleep disorder, gastrointestinal disorder, but excluding intellectual disability) 76% 27 Co-morbid diagnoses may limit independent functioning in Profound Autism 97% Topic G: Profound Autism Symptomology 28 A person must exhibit periods of intense and dangerous behaviors in order to be diagnosed with Profound Autism 20% 29 Most people with Profound Autism exhibit periods of intense and dangerous behaviors 50% 30 Some people with Profound Autism exhibit periods of intense and dangerous behaviors. 91% Topic H: Other 31 Current diagnostic instruments (like the ADOS) are inadequate to recognize Profound Autism because this population often scores at or below the floor 76% 32 People with Profound Autism struggle to complete assessments e.g. IQ tests 96% Table 1 . Defined consensus statements and corresponding levels of agreement. Statements which were grouped or paired are indicated with an orange border. Agreement below the consensus threshold (75%) is in pink, agreement which achieved consensus ≥ 75% but < 90% is in blue, agreement ≥ 90% is highlighted in green. Discussion Our modified Delphi study led to a consensus research definition of profound autism that states a person with Profound Autism: · meets the diagnostic criteria for autism spectrum disorder, · requires adult supervision to ensure physical and mental health, safety, and well-being, · demonstrates adaptive behavior skills well below age level, with an inability to independently perform most activities of daily living, · has severely impaired cognitive abilities (reflected by IQ score below 50) and/or does not verbally communicate other than single words or fixed phrases, and communicates predominantly to have their basic needs met. · is at least 8 years old (acknowledging that some characteristics consistent with profound autism are evident earlier), · These criteria are neither intermittent nor transient and persist across different environmental settings and situations. Our study confirms the fact that different stakeholders widely recognize profound autism. With a more detailed consensus-based definition, researchers can begin filling the many gaps in our knowledge about people with profound autism across the lifespan, to lay the foundation for the development of novel treatments, behavioral interventions, and supports specific to this group, increasing the chance of effective, individualized intervention and improved outcomes. Of importance, we emphasize this as a research definition for profound autism, as there is a need for more information and guidance before it becomes a practical definition utilized in clinical situations. This includes providing guidance in situations where IQ is not regularly assessed, cannot be assessed, or where verbal ability is ambiguous, and guidance around the definition of a safety concern. This may especially be the case in low-resource or rural communities. This definition aligns closely with the initial definition proposed by the Lancet Commission( 2 ) and offers researchers a more consistent means of operationalizing measurement. Echoing the initial Lancet definition is the requirement for 24/7 access to an adult to maintain health and safety. There was an extremely high level of agreement on this domain, with the broader statements on the need for support to meet basic needs and 24/7 support to maintain safety, achieving 97% agreement. This component of the definition, as simple as it is, achieved such high levels of agreement and garnered so little debate that it suggests that needing access to an adult is a core defining feature of profound autism and is worthy of further assessment and measurement development. Such work will enable us to better understand what this domain represents and how people with this need can be best served and reach their greatest potential by utilizing principles of autonomy, beneficence, and self-direction. Adaptive functioning, the ability to perform tasks of daily living, such as dressing, bathing, navigating streets, using money, etc., was also a domain that achieved extremely high agreement across respondents. While a specific cut-off was not identified, the broader concept of a significant gap between the individual’s adaptive functioning level and that expected for age was highly supported. It has been widely shown that across the spectrum, adaptive functioning generally lags behind developmental norms for age, often by several standard deviations. 97% of respondents agreed that adaptive functioning significantly below age-appropriate levels is a necessary element of the PA definition. Some research suggests that measuring adaptive behavior and executive function is more critical than IQ for understanding variance in social and communication domains in those with ASD.( 21 ) Adaptive functioning at an early age is possibly predictive of functioning category at a later age,( 22 ) which increases its saliency as a component of the PA definition. There was broad agreement that significant language impairment should be part of the definition. To date, creating a universal definition of minimally verbal in ASD has been challenging.( 23 ) In the surveyed definition of PA, respondents expressed concerns about measuring communication deficits in the context of low IQ. Including being minimally verbal as part of the definition of PA will help to motivate researchers to use non-verbal testing and other strategies proposed within the literature to assess and engage with minimally verbal children.( 24 ) There was also a high level of agreement on excluding several domains in the consensus definition. Severe, intense or challenging behaviors are a significant concern with individuals across the spectrum and are particularly prevalent in the profound autism group. Among the many issues raised by these behaviors, an insidious and perhaps most impairing aspect is that the behaviors can result in exclusion from the very activities, experiences, health care, and interventions that the individual needs in order to maintain basic health and connection and reach their full potential. Many caregivers report that it is these behaviors, rather than the autism, that are the primary source of distress and impairment for the individual and family and are of greatest concern.( 25 ) Given this, it was notable that there was a high level of agreement that the presence of these behaviors should not be included in the definition of PA, as there are individuals who do not engage in these behaviors but still need 24/7 support for safety. Identifying what distinguishes this group from the majority that do engage in these behaviors is a critical research opportunity, as clarification of genetic, relational or experiential factors that initiate or accelerate the pathway to these behaviors could lead to broad early intervention guidance that seeks to prevent or ameliorate their occurrence and consequently increase community participation, family and individual well-being, and decrease exclusion from the community, educational settings, intervention programs and healthcare. Co-occurring diagnoses are common in ASD, and some studies have reported higher rates of medical and psychiatric co-occurring disorders in those with characteristics that are consistent with profound autism, including higher rates of epilepsy, constipation, and ADHD.( 26 , 27 ) Despite their prevalence, it was widely agreed among respondents that these co-morbidities should not be included as criteria for profound autism, as there is wide variability in the prevalence of each co-morbidity, and individuals in the profound group who lack these co-morbidities. The area of most significant disagreement and debate was the use of an IQ score cut-off in defining PA. There was the most agreement with an IQ score lower than 50 (68%), which had greater agreement than a cut-off of 60 (58%) or 70 (57%), but no cut-off value achieved the consensus threshold. Despite the disagreements, respondents felt IQ should be included (“IQ should not be included” scored only 32% agreement) in order for researchers to have the ability to use existing databases that include IQs, but not more open-ended questions about support needs. In terms of clinical care and other research, however, respondents expressed concern with both the constraints in access to IQ testing and the validity of testing for those with low cognitive functioning and/or minimal verbal ability. Survey respondents had a very high level of agreement that individuals with PA struggle to complete assessments like IQ tests (96%). Overall, the lack of consensus on an appropriate IQ cut-off reflected philosophical and measurement challenges that have long been debated within the field, and IQ was included as part of criterion 5 as an “and/or” with minimal verbal ability. Another area of significant debate was the lower age bound appropriate for application of the term profound autism. Most respondents felt that PA could be identified by age 5 (74%). However, this statement did not reach the consensus threshold, due to the lack of agreement from researchers (57%) compared to caregivers (86%) and autistic individuals (100%). The disagreements among researchers were characterized by three themes. The primary scientific concern was that, in multiple studies, some key elements of the profound autism definition, such as verbal ability or IQ score, are not stable in children under 8 years old.( 28 , 29 ) As such, providing a reliable profound autism diagnosis before that age was determined to be unsupported by current data. Participants also noted that round-the-clock adult support is developmentally appropriate for children under the age of 8. A third theme of concern was that if profound autism was diagnosed in young children, health insurance companies or policy makers might utilize the term to limit access to more intensive or particular interventions, similar to how some have misused the ADOS and other measures requirements for establishing an autism diagnosis, which creates barriers to diagnosis and subsequent services.( 30 ) As there currently are no measures that have been shown to reliably predict later profound autism status in those under 8 years old, the consensus was to constrain the definition to individuals 8 and older. This study has several strengths and limitations that are worth noting. Strengths of the study include the use of an evidence-based methodology for establishing scientific consensus, a relatively high response rate, a range of participants including researchers, clinicians, caregivers, autistic individuals, and others, and a result based on broad agreement above the a priori threshold for the specified domains. Limitations of this study include the relatively smaller proportion of participants who self-identified as autistic, the fact that most participants were from the US despite attempts to reach a global audience, and that several participants acknowledged they may have answered differently if better measures or data for challenging areas, such as IQ or age of reliable symptom ascertainment, were available in the field. A major challenge, and a source of debate among respondents, is how to utilize existing data when applying a new definition, which may not be well-measured in current datasets. While new measures and empirical investigation of definitional domains are essential in the future, researchers, caregivers and others were understandably concerned about ensuring that existing data, such as IQ scores or adaptive functioning scores, could be effectively utilized for research or clinical needs when considering profound autism. Our study provides several clear foci for future research to further operationalize and better understand the definition, measure key domains not well-represented by current measures, and answer critical questions, such as the age at which symptoms of profound autism are reliably predictive of future group inclusion. Needing 24/7 access to an adult to ensure safety and well-being is a concept that is not well-represented by current measures and presents an opportunity for both reliable measure development and parsing the critical and predictive elements captured by this concept. Notably, caregivers of autistic children and adults who participated in the study were in 97% agreement as to the critical nature of this domain, suggesting it captures something essential for the concept and experience of PA. Valid and reliable measurement of IQ in individuals with significant cognitive and/or language impairments remains a major challenge for the field and is also an area for further measure development. Equally important is the opportunity to explore the concurrent validity of other more accessible measures that could adequately indicate or represent level of cognitive impairment. Given the barriers to obtaining valid IQ scores using current measures, respondents engaged in the most debate about whether to include IQ in the definition of profound autism, and future research on representation with and without IQ measurement would be instructive. Another area that the definition of profound autism highlights as needing further development is efficient, quantitative measurement of verbal ability across the full spectrum. Currently studies use a wide range of measures, which inhibits progress and focus on this primary area of functioning.( 10 ) Nevertheless, among researchers who focus on minimally verbal autism, there is growing agreement that natural language samples represent the best approach to capturing the communicative abilities, including speech and language in this population.( 31 ) A key area for further research is identifying at what age symptoms appear that are predictive of meeting the definition of profound autism. Establishing this could widen the age range of research participation and enhance the ability to provide focused and possibly more intensive early intervention for those with the highest likelihood of future impairment, which is a critical need in the field to inform decisions on dose, duration, and cost of early intervention for a particular individual. It is also critically important, given our study’s determination that the need for adult support is a core concept of profound autism, to develop measures with greater specificity for this domain and to parse the items that may carry the most variance, such as the ability to communicate in an emergency.( 32 ) Finally, the development of sensitive and specific screeners for profound autism across the lifespan would be beneficial for both research and clinical settings, allowing for the rapid identification of at-risk individuals, potentially increasing recruitment efficiency and participation in research, and highlighting critical domains for individualizing treatment. Limitations Despite the rigor of the process, there are limitations to the existing study design. There is geographic and cultural variation in diagnosis and access to services and varying tools to assess intellectual disability measurements which may make an IQ measurement difficult, especially in those who are profoundly affected. There were not sufficient respondents from countries outside the US to incorporate different regional or cultural viewpoints into this definition to ensure that international consensus was reached.. We emphasize that these guidelines for diagnosis should be used for research purposes and they do not impact clinician best practices when determining an autism diagnosis. Conclusions A large and varied group of researchers, clinicians, caregivers, and autistic individuals agreed that Profound Autism is a meaningful term and reached consensus above the a priori specified level on key components of a research definition. The highest levels of agreement were reached on the requirement of 24/7 access to an adult for health and safety, as well as significant impairment in adaptive functioning. The consensus definition creates the opportunity to compare existing datasets and health records and to spur the creation of new measures, both of which will enable an increased focus on the research questions and clinical needs of an unresearched and underserved portion of the autism spectrum. As there is evidence that the outcomes, needs, interventions, and supports for those with Profound Autism are distinct, it logically follows that clarity in identification increases the opportunity to improve those areas for both those with profound autism and those without. Abbreviations ADHD - Attention Deficit Hyperactivity Disorder ADOS – Autism Diagnostic Observation Scale ASD - Autism Spectrum Disorder DSM – Diagnostic and Statistical Manual for Mental Disorders IDD – Intellectual Disability IQ – Intellectual Quotient NICHD - National Institute of Child Health and Human Development PA -Profound Autism SC – Steering Committee Declarations Since we are collecting no PHI, we received an exception from the Triducive IRB committee. Disclosure: Catherine L. Lord receives royalties from sales of the ADI-R and ADOS/ADOS-2. She has also received support from the Longitudinal Study of Caregivers NIH Grant #4-441587-CL-29304. Helen Tager-Flusberg is supported by NIH Grant P50 DC 18006. Matthew Siegel Funding: This research was funded by The Autism Science Foundation and Profound Autism Alliance. This study was presented at the International Meeting for Autism Research; April 30-May 3, 2025; Seattle, Washington. Author Contribution All authors approve to the submitted version of the work and to be personally accountable for their contributions. All authors contributed to the conception, design, acquisition and analysis of the work. MS drafted the paper and all authors substantially revised it. Acknowledgement The authors wish to acknowledge Dal Singh, BA and Katie Larner, PhD from Triducive (www.triducive.com) for guiding the authors in the Delphi Method and collecting and analyzing the results. They also acknowledge Katie Madgett, BS for her editorial support. Data Availability The dataset supporting the conclusions of this article may be available following a request to the corresponding author. References American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders [Internet]. Fifth Edition. American Psychiatric Association. 2013 [cited 2025 Aug 11]. 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Woolley AW, Chabris CF, Pentland A, Hashmi N, Malone TW. Evidence for a Collective Intelligence Factor in the Performance of Human Groups. Science. 2010;330(6004):686–8. Gattrell WT, Logullo P, Van Zuuren EJ, Price A, Hughes EL, Blazey P, et al. ACCORD (ACcurate COnsensus Reporting Document): A reporting guideline for consensus methods in biomedicine developed via a modified Delphi. PLOS Med. 2024;21(1):e1004326. Shang Z. Use of Delphi in health sciences research: A narrative review. Med (Baltim). 2023;102(7):e32829. Falzarano M, Pinto Zipp G. Seeking consensus through the use of the Delphi technique in health sciences research. J Allied Health. 2013;42(2):99–105. Grisham T. The Delphi technique: a method for testing complex and multifaceted topics. Int J Manag Proj Bus. 2009;2(1):112–30. Bertollo JR, Yerys BE, More Than IQ. Executive Function Explains Adaptive Behavior Above and Beyond Nonverbal IQ in Youth With Autism and Lower IQ. Am J Intellect Dev Disabil. 2019;124(3):191–205. Mandelli V, Landi I, Busuoli EM, Courchesne E, Pierce K, Lombardo MV. Prognostic early snapshot stratification of autism based on adaptive functioning. Nat Ment Health. 2023;1(5):327–36. Koegel LK, Bryan KM, Su PL, Vaidya M, Camarata S. Definitions of Nonverbal and Minimally Verbal in Research for Autism: A Systematic Review of the Literature. J Autism Dev Disord. 2020;50(8):2957–72. McKinney A, Weisblatt EJ, Hotson KL, Bilal Ahmed Z, Dias C, BenShalom D, et al. Overcoming hurdles to intervention studies with autistic children with profound communication difficulties and their families. Autism. 2021;25(6):1627–39. Zablotsky B, Bramlett M, Blumberg SJ. Factors associated with parental ratings of condition severity for children with autism spectrum disorder. Disabil Health J. 2015;8(4):626–34. Coury D, Jones NE, Klatka K, Winklosky B, Perrin JM. Healthcare for children with autism: the Autism Treatment Network. Curr Opin Pediatr. 2009;21(6):828–32. Simonoff E, Jones CRG, Baird G, Pickles A, Happé F, Charman T. The persistence and stability of psychiatric problems in adolescents with autism spectrum disorders. J Child Psychol Psychiatry. 2013;54(2):186–94. Pickles A, McCauley JB, Pepa LA, Huerta M, Lord C. The adult outcome of children referred for autism: typology and prediction from childhood. J Child Psychol Psychiatry. 2020;61(7):760–7. Simonoff E, Kent R, Stringer D, Lord C, Briskman J, Lukito S, et al. Trajectories in Symptoms of Autism and Cognitive Ability in Autism From Childhood to Adult Life: Findings From a Longitudinal Epidemiological Cohort. J Am Acad Child Adolesc Psychiatry. 2020;59(12):1342–52. Kovic Y, Dallas GD, Andrade JL, Lloveras LA, Peters KP, Soda T. The Rapid Autism Assessment: Reducing Barriers to Behavioral Intervention Services. J Am Acad Child Adolesc Psychiatry. 2025;S0890-8567(25)00124-8. Barokova M, Tager-Flusberg H, Commentary. Measuring Language Change Through Natural Language Samples. J Autism Dev Disord. 2020;50(7):2287–306. Sterrett K, Clarke E, Nofer J, Piven J, Lord C. Toward a functional classification for autism in adulthood. Autism Res. 2024;17(10):2105–19. Additional Declarations No competing interests reported. Supplementary Files SUPPLEMENTARYFIGURES.docx SUPPLEMENTARYTABLES.docx Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8745285","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":594626171,"identity":"09db0892-5739-4002-8e20-47e0e2b445b6","order_by":0,"name":"Matthew Siegel","email":"","orcid":"","institution":"Boston Children’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Matthew","middleName":"","lastName":"Siegel","suffix":""},{"id":594626172,"identity":"0cf79470-744c-4803-8bbf-2bc22cee7233","order_by":1,"name":"Catherine L. Lord","email":"","orcid":"","institution":"University of California","correspondingAuthor":false,"prefix":"","firstName":"Catherine","middleName":"L.","lastName":"Lord","suffix":""},{"id":594626173,"identity":"9583436c-bae6-4bbf-91f2-70dd6cffa108","order_by":2,"name":"Helen Tager-Flusberg","email":"","orcid":"","institution":"Boston University","correspondingAuthor":false,"prefix":"","firstName":"Helen","middleName":"","lastName":"Tager-Flusberg","suffix":""},{"id":594626174,"identity":"5d49f130-9838-4bef-ac98-1b56ae815cbf","order_by":3,"name":"Judith Ursitti","email":"","orcid":"","institution":"Profound Autism Alliance","correspondingAuthor":false,"prefix":"","firstName":"Judith","middleName":"","lastName":"Ursitti","suffix":""},{"id":594626175,"identity":"0d79959e-6d85-425d-aa0a-c6efef6b78f3","order_by":4,"name":"Alycia Halladay","email":"","orcid":"","institution":"Autism Science Foundation","correspondingAuthor":false,"prefix":"","firstName":"Alycia","middleName":"","lastName":"Halladay","suffix":""},{"id":594626176,"identity":"51e81332-ebb8-4de1-a48b-dddea8b39d86","order_by":5,"name":"Alison T. Singer","email":"data:image/png;base64,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","orcid":"","institution":"Autism Science Foundation","correspondingAuthor":true,"prefix":"","firstName":"Alison","middleName":"T.","lastName":"Singer","suffix":""}],"badges":[],"createdAt":"2026-01-30 23:23:06","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8745285/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8745285/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103724343,"identity":"aa9c9447-f2ee-47e8-b9ca-07b98d5cc4dc","added_by":"auto","created_at":"2026-03-02 07:56:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1107575,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eModified Delphi process followed during the study\u003c/u\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8745285/v1/68391aaf1856d74cf6c087d8.png"},{"id":103724412,"identity":"858f8253-9ccd-49c1-ab7c-d9ff74f72888","added_by":"auto","created_at":"2026-03-02 07:57:13","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":384407,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cu\u003eThe finalized definition of profound autism based on the feedback from the second round of survey\u003c/u\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8745285/v1/5087940eddbc2d7a90e0794e.png"},{"id":103724451,"identity":"88806f0b-d3cb-45a1-92e2-0a4bfe3a4e0b","added_by":"auto","created_at":"2026-03-02 07:57:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2196367,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8745285/v1/e42fde5b-571a-487d-a82b-d1e486ea8f24.pdf"},{"id":103724347,"identity":"4eee4f7a-0675-4075-9b2f-5e1294eb1918","added_by":"auto","created_at":"2026-03-02 07:56:54","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":33000,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYFIGURES.docx","url":"https://assets-eu.researchsquare.com/files/rs-8745285/v1/d0f5173c5b93d2d7f57d3d41.docx"},{"id":103724368,"identity":"61d05188-52e6-447b-9285-641ee04da152","added_by":"auto","created_at":"2026-03-02 07:57:03","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":20777,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPLEMENTARYTABLES.docx","url":"https://assets-eu.researchsquare.com/files/rs-8745285/v1/c9dab630f6faad0a3aabc26f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Developing a Consensus Research Definition for Profound Autism Using a Modified Delphi Method","fulltext":[{"header":"Background","content":"\u003cp\u003eAccording to the current definition of autism spectrum disorder in the DSM-5, the diagnostic term encompasses the full range of the autism spectrum, levels of impairment, and co-morbidities.(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) This represented a significant change from earlier definitions in DSM III, IIIR and IV in which various subtypes of autism were recognized and defined. In 2021, \u003cem\u003eThe Lancet Commission on the Future of Clinical Care in Autism\u003c/em\u003e proposed the administrative term Profound Autism (PA) to describe people with autism whose significant impairments require round-the-clock care from an adult. The report highlighted the need to distinguish this group of autistic individuals from those who were more able, with the hope that introducing the term \u0026ldquo;will spur both the clinical and research global communities to prioritize the needs of this vulnerable and underserved group.\u0026rdquo;(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e)\u003csup\u003e(p.278)\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe Lancet Commission provided an administrative definition of PA that included a minimum age of 8, an IQ below 50, nonverbal or minimally verbal, and requiring 24/7 care to ensure safety. The Centers for Disease Control followed up on this initial introduction of PA to investigate its prevalence among 8-year-old children, using data collected as part of the Autism and Developmental Disabilities Monitoring Network. Using a definition of IQ below 50 or non/minimally verbal, 26.7% of the autistic children were classified with profound autism.(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e Autistic individuals with intellectual disability or who are non/minimally verbal have been repeatedly shown to have higher rates of medical and psychiatric comorbidities, serious externalizing behaviors, hospitalization, lower adaptive functioning, adult employment and independent living.(\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) It is also widely recognized in the field that the choice of interventions and supports provided to autistic individuals is largely determined by the individual\u0026rsquo;s verbal and cognitive ability. Despite these wide-ranging challenges, significant needs, and stark differences in appropriate treatment approaches and outcomes, a minority of behavioral or neuroimaging studies of autism have included profoundly autistic participants.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) The proportion of treatment studies that include severely affected autistic individuals has declined precipitously over the past two decades.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Inclusion of this group in autism research has been limited by a variety of factors, including stigma, perceived challenge, increased costs, researcher familiarity, a paucity of validated assessment tools, and barriers to access and participation for individuals and families, though several publications have identified best practices for enhancing inclusion in research.(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e) By recognizing this disparity and providing clear guidance on how profound autism should be defined in a research setting, the goal is to better include these individuals in research and improve diagnosis, treatments, and supports across the lifespan. As an example of such an effort, there was an increase in research projects that included non-verbal individuals following a NICHD workshop and resulting papers in 2013 that worked to better define and operationalize assessment of this group.(\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eProgress in a scientific field is critically dependent on rigorous and specific definitions with agreed-upon operationalization.(\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Since it was introduced in 2021, profound autism has been variously defined in subsequent research studies, producing a wide range of prevalence rates across the world based on ascertainment, diagnosis, and other factors (11\u0026ndash;58%), difficulty in comparing datasets, and confusion in the field.(\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e) The lack of a consensus research definition has not only impeded research on profound autism but also has contributed to criticisms of considering profound autism as a distinct subgroup of the autism population.(\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) In particular, needs for precision medicines, community integration, employment and housing are being approached with a broad brush and not targeted to different levels of functioning because the term \u0026ldquo;autism\u0026rdquo; has become so broad. The lack of a research definition obfuscates the need to develop specific interventions and supports, despite the widely held principle that treatment should be individualized. Whether or not one agrees with distinguishing profound autism from the rest of autism, research including these individuals, which represents a significant gap in our knowledge about autism, is significantly impacted by the lack of a consensus definition.\u003c/p\u003e \u003cp\u003eThe goal of the current study was to develop a consensus research definition of profound autism, using a modified Delphi methodology,(\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) grounded initially by the criteria in the Lancet report, as determined by a broad group of researchers, clinicians, caregivers, and autistic individuals.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThe study was carried out over the course of 2024\u0026ndash;2025. It was led by a \u0026lsquo;steering committee\u0026rsquo; (SC), which included all the authors guided by an independent facilitator with experience conducting Delphi research (Triducive Partners Limited). The study was not registered; all reporting follows the ACCORD guidelines.(17) Fig.\u0026nbsp;1 summarizes the modified Delphi process that was followed. The modified Delphi differs from a traditional Delphi in that the modified process is used to validate, refine or prioritize existing ideas rather than explore or build consensus from scratch. Specifically, the first rounds were not open ended, it started with a predefined list of items based on the previous Lancet criteria. This resulted in fewer \u0026ldquo;rounds\u0026rdquo; being required. The surveys were totally anonymous.\u003c/p\u003e\n\u003cp\u003eFigure 1. Modified Delphi process followed during the study\u003c/p\u003e\n\u003cdiv id=\"Sec3\"\u003e\n \u003ch2\u003eEthics approval statement:\u003c/h2\u003e\n \u003cp\u003eThis study did not require registration and ethical approval because neither the assigned interventions nor the outcomes assessed were related to the health of participants. All survey respondents were informed of the purpose of the study and consent to participate was implied by the completion and submission of the survey. This research was conducted according to the principles of the Declaration of Helsinki.\u003c/p\u003e\n\u003c/div\u003e\n\u003ch3\u003eDeveloping Domains and Statements for Inclusion in the Survey\u003c/h3\u003e\n\u003cp\u003eThe SC convened in March 2024 and reached agreement on the key domains to be considered in developing a research definition of profound autism:\u003c/p\u003e\n\u003cdiv\u003e\n \u003cp\u003e1. Age\u003c/p\u003e\n\u003c/div\u003e\n\u003cp\u003e2. IQ\u003c/p\u003e\n\u003cp\u003e3. Language/communication\u003c/p\u003e\n\u003cp\u003e4. Adaptive functioning\u003c/p\u003e\n\u003cp\u003e5. Need for adult support\u003c/p\u003e\n\u003cp\u003e6. Co-morbid diagnoses\u003c/p\u003e\n\u003cp\u003e7. Severe, intense, dangerous behavior\u003c/p\u003e\n\u003cp\u003e8. Other\u003c/p\u003e\n\u003cp\u003eWorking collaboratively, the SC developed an initial set of 35 statements with support from the facilitator. These statements underwent three rounds of review by members of the SC who categorized them as \u0026lsquo;accept\u0026rsquo; \u0026lsquo;remove\u0026rsquo; or \u0026lsquo;reword\u0026rsquo;. During the first round, 10 statements were removed, 7 were added, and 14 were edited. During the second round, 1 statement was removed, 1 was added, and 8 were edited. After a final review, 32 statements were accepted and developed into a survey. Each statement was presented with a 4-point Likert scale (strongly agree, tend to agree, tend to disagree, strongly disagree) to allow responders to indicate their level of agreement and to avoid the ambiguity which can be caused by middle option bias. Following standard Delphi methodology, this survey round was predominantly quantitative and did not seek feedback on the statements from survey respondents. Delphi is considered a consensus group research method, which involves obtaining the views of a group of experts and aims to achieve consensus and agreement as outcomes.(18)\u003c/p\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eThe independent facilitator distributed the survey to a large group of individuals identified by members of the SC. They were identified as experts across the world who were experienced clinicians, researchers, caregivers, or clinician-scientists whose expertise (published or presented at scientific meetings) included a focus on autistic individuals who were minimally verbal or had significant cognitive impairment. They were invited to participate and asked to self-identify on the basis of whether they were a researcher, clinician, caregiver, or an autistic individual. 137 individuals agreed to participate, representing 5 geographic regions (US, Canada, Europe, Asia Pacific, and Middle East/Africa), and came from diverse academic and professional backgrounds, ensuring that a comprehensive range of perspectives was included.\u003c/p\u003e\n\u003ch3\u003eProcedures\u003c/h3\u003e\n\u003cp\u003eAs this study only collected anonymous opinions and no identifying or patient health information, it was not submitted to an IRB. No incentives were provided to participants. A statement of consent was included at the beginning of the survey, and consent was assumed to be given by participant completion and submission of the survey. The only demographic information collected on the survey was the respondent\u0026rsquo;s primary self-identified role and geographic region.\u003c/p\u003e\n\u003cp\u003eThe survey opened by asking participants if they were familiar with the term \u0026lsquo;profound autism\u0026rsquo; and, in an effort to assess their understanding of the term, were asked the open-ended question: \u0026ldquo;From your perspective, how is profound autism currently defined?\u0026rdquo; Participants then rated the 32 statements about Profound Autism using the Likert scale described earlier. Stopping criteria were established \u003cem\u003ea priori\u003c/em\u003e as a one-month window within which participants could respond and a minimum of 70 responses were required.\u003c/p\u003e\n\u003cp\u003eCompleted surveys were analyzed to determine an overall agreement level for each statement using descriptive statistics. The \u003cem\u003ea priori\u003c/em\u003e threshold for consensus was set at 75% and then further defined as \u0026lsquo;strong\u0026rsquo; (75%) or \u0026lsquo;very strong\u0026rsquo; (90%). For Delphi consensus processes, a level between 70% to 80% is usually adopted and considered to be rigorous.(19, 20) SC met in August, 2024 to review the findings and, using the consensus level achieved, developed a research definition of PA. This definition, presented in Fig.\u0026nbsp;2, was tested in a second round of surveys, sent to the same initial group of 137 participants.\u003c/p\u003e\n\u003cp\u003eFigure 2. The finalized definition of profound autism based on the feedback from the second round of survey\u003c/p\u003e\n\u003cp\u003eThe proposed definition was presented on the second-round survey, and participants were asked whether or not they agreed with it. If participants disagreed, they were asked to provide qualitative feedback on the definition. The same stopping criteria were used for the second-round survey.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eInitial Survey\u003c/h2\u003e \u003cp\u003eThe initial survey was sent to 137 participants, and 70 responses were received, a response rate of 51% (see Supplementary Figure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e). Respondents were predominantly clinicians (n\u0026thinsp;=\u0026thinsp;30, 45%), followed by researchers (n\u0026thinsp;=\u0026thinsp;29, 41%), family members (n\u0026thinsp;=\u0026thinsp;7, 10%), and autistic individuals (n\u0026thinsp;=\u0026thinsp;2, 3%). Most respondents (n\u0026thinsp;=\u0026thinsp;62, 89%) were from the United States. Duplicates could be identified by unique identifying numbers assigned by the survey software based on the IP address. (Supplementary Figure \u003cspan refid=\"MOESM2\" class=\"InternalRef\"\u003eS2\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSecond-round Survey\u003c/h3\u003e\n\u003cp\u003eThe second-round survey was sent to the original 137 participants. It included a definition of profound autism based on the results from the first round, and was completed by 78 participants (57%) (see Supplementary Figures S3 and S4 for demographic details). The majority of respondents agreed with the proposed definition (N\u0026thinsp;=\u0026thinsp;59; 76%), exceeding the consensus threshold. The SC met one final time in December, 2024 to discuss the feedback from the second-round survey and finalized the research definition of profound autism. The SC considered the high rate of agreement with the surveyed definition and the qualitative comments from some respondents that accompanied the ratings (see Supplementary Table\u0026nbsp;1) to make slight adjustments to the surveyed definition.\u003c/p\u003e \u003cp\u003eThe percentage of agreement with each of the 32 statements following the second revision is presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. There was very strong agreement (\u0026gt;\u0026thinsp;90%) with 12 statements, and strong agreement (\u0026gt;\u0026thinsp;75%) with an additional 8 statements. 12 statements failed to reach the consensus threshold, and were mostly clustered under the domains of IQ, age, and severe/dangerous behaviors.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDefined consensus statements and corresponding levels of agreement. Statements which were grouped or paired are indicated with an orange border. Agreement below the consensus threshold (75%) is in pink, agreement which achieved consensus\u0026thinsp;\u0026ge;\u0026thinsp;75% but \u0026lt;\u0026thinsp;90% is in blue, agreement\u0026thinsp;\u0026ge;\u0026thinsp;90% is highlighted in green.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStatement\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAgreement\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eTopic A: IQ Considerations\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e1\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism should have an IQ score lower than 50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e69%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e2\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism should have an IQ score lower than 60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e56%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e3\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism should have an IQ score lower than 70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e56%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e4\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-verbal IQ is a more inclusive way to ascertain Profound Autism than full scale IQ\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e63%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e5\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIQ should not be included in a future definition of Profound Autism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e33%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic B: Language \u0026amp; Communication Considerations\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e6\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism does not communicate beyond single words\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e59%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e7\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism cannot communicate beyond a few single words and fixed phrases, for example \u0026ldquo;want cookie\u0026rdquo;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e83%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e8\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism primarily verbally communicates only to obtain their basic needs and/or desires\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e76%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e9\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism could not verbally communicate to an unfamiliar person about basic needs or in an emergency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e84%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e10\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism cannot consistently verbally communicate healthcare needs to caregivers or providers. (e.g. express pain)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e94%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic C: The Need for Adult Support\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e11\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism is not capable of being left alone in their home without adult supervision due to safety concerns\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e93%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e12\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism cannot be left alone briefly, for example while their parent/caregiver goes next door to borrow a cup of sugar\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e74%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e13\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism cannot be left alone in their home for more than 2-hours due to safety concerns\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e94%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e14\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism requires adult support to meet their basic needs, for example food preparation, dressing, and bathing adequately\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e97%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e15\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism requires an adult available to them 24/7 to maintain safety, for example due to risk of elopement, self-harm, or lack of environmental awareness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e97%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic D: Age Considerations\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e16\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person can be identified as having Profound Autism by age 18 months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e14%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e17\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person can be identified as having Profound Autism by age of 3 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e41%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e18\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person can be identified as having Profound Autism by age of 5 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e74%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e19\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person can be identified as having Profound Autism by age of 8 years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e96%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e20\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism may gain skills over time, but profound autism is a life-long condition\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e96%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic E: Adaptive Functioning Considerations\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e21\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism cannot independently perform most activities of daily living (e.g. food preparation, dressing, and bathing adequately)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e94%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e22\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism has adaptive functioning skills significantly below their age equivalence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e99%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e23\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism has on average adaptive skills at least 2-standard deviations below the population mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e89%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e24\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism has on average adaptive skills at least 3-standard deviations below the population mean\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e90%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e25\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person with Profound Autism is unaware of basic social expectations, for example nudity or breaking into neighbors' homes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e87%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic F: Co-morbid Diagnoses Considerations\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e26\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAlmost all ASD individuals have some co-morbid medical diagnoses (for example, seizure disorder, sleep disorder, gastrointestinal disorder, but excluding intellectual disability)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e76%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e27\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCo-morbid diagnoses may limit independent functioning in Profound Autism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e97%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic G: Profound Autism Symptomology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e28\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eA person must exhibit periods of intense and dangerous behaviors in order to be diagnosed with Profound Autism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e20%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e29\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMost people with Profound Autism exhibit periods of intense and dangerous behaviors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e50%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e30\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSome people with Profound Autism exhibit periods of intense and dangerous behaviors.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e91%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopic H: Other\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e31\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCurrent diagnostic instruments (like the ADOS) are inadequate to recognize Profound Autism because this population often scores at or below the floor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e76%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003e32\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePeople with Profound Autism struggle to complete assessments e.g. IQ tests\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e96%\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. \u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDefined consensus statements and corresponding levels of agreement. Statements which were grouped or paired are indicated with an orange border. Agreement below the consensus threshold (75%) is in pink, agreement which achieved consensus\u0026thinsp;\u0026ge;\u0026thinsp;75% but \u0026lt;\u0026thinsp;90% is in blue, agreement\u0026thinsp;\u0026ge;\u0026thinsp;90% is highlighted in green.\u003c/span\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur modified Delphi study led to a consensus research definition of profound autism that states a person with Profound Autism:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e\u0026middot; meets the diagnostic criteria for autism spectrum disorder,\u003c/p\u003e\u003cp\u003e\u0026middot; requires adult supervision to ensure physical and mental health, safety, and well-being,\u003c/p\u003e\u003cp\u003e\u0026middot; demonstrates adaptive behavior skills well below age level, with an inability to independently perform most activities of daily living,\u003c/p\u003e\u003cp\u003e\u0026middot; has severely impaired cognitive abilities (reflected by IQ score below 50)\u003c/p\u003e\u003cp\u003eand/or\u003c/p\u003e\u003cp\u003edoes not verbally communicate other than single words or fixed phrases, and\u003c/p\u003e\u003cp\u003ecommunicates predominantly to have their basic needs met.\u003c/p\u003e\u003cp\u003e\u0026middot; is at least 8 years old (acknowledging that some characteristics consistent with profound autism are evident earlier),\u003c/p\u003e\u003cp\u003e\u0026middot; These criteria are neither intermittent nor transient and persist across different environmental settings and situations.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eOur study confirms the fact that different stakeholders widely recognize profound autism. With a more detailed consensus-based definition, researchers can begin filling the many gaps in our knowledge about people with profound autism across the lifespan, to lay the foundation for the development of novel treatments, behavioral interventions, and supports specific to this group, increasing the chance of effective, individualized intervention and improved outcomes. Of importance, we emphasize this as a research definition for profound autism, as there is a need for more information and guidance before it becomes a practical definition utilized in clinical situations. This includes providing guidance in situations where IQ is not regularly assessed, cannot be assessed, or where verbal ability is ambiguous, and guidance around the definition of a safety concern. This may especially be the case in low-resource or rural communities. This definition aligns closely with the initial definition proposed by the Lancet Commission(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) and offers researchers a more consistent means of operationalizing measurement. Echoing the initial Lancet definition is the requirement for 24/7 access to an adult to maintain health and safety. There was an extremely high level of agreement on this domain, with the broader statements on the need for support to meet basic needs and 24/7 support to maintain safety, achieving 97% agreement. This component of the definition, as simple as it is, achieved such high levels of agreement and garnered so little debate that it suggests that needing access to an adult is a core defining feature of profound autism and is worthy of further assessment and measurement development. Such work will enable us to better understand what this domain represents and how people with this need can be best served and reach their greatest potential by utilizing principles of autonomy, beneficence, and self-direction.\u003c/p\u003e \u003cp\u003eAdaptive functioning, the ability to perform tasks of daily living, such as dressing, bathing, navigating streets, using money, etc., was also a domain that achieved extremely high agreement across respondents. While a specific cut-off was not identified, the broader concept of a significant gap between the individual\u0026rsquo;s adaptive functioning level and that expected for age was highly supported. It has been widely shown that across the spectrum, adaptive functioning generally lags behind developmental norms for age, often by several standard deviations. 97% of respondents agreed that adaptive functioning significantly below age-appropriate levels is a necessary element of the PA definition. Some research suggests that measuring adaptive behavior and executive function is more critical than IQ for understanding variance in social and communication domains in those with ASD.(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) Adaptive functioning at an early age is possibly predictive of functioning category at a later age,(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) which increases its saliency as a component of the PA definition.\u003c/p\u003e \u003cp\u003eThere was broad agreement that significant language impairment should be part of the definition. To date, creating a universal definition of minimally verbal in ASD has been challenging.(\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) In the surveyed definition of PA, respondents expressed concerns about measuring communication deficits in the context of low IQ. Including being minimally verbal as part of the definition of PA will help to motivate researchers to use non-verbal testing and other strategies proposed within the literature to assess and engage with minimally verbal children.(\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eThere was also a high level of agreement on excluding several domains in the consensus definition. Severe, intense or challenging behaviors are a significant concern with individuals across the spectrum and are particularly prevalent in the profound autism group. Among the many issues raised by these behaviors, an insidious and perhaps most impairing aspect is that the behaviors can result in exclusion from the very activities, experiences, health care, and interventions that the individual needs in order to maintain basic health and connection and reach their full potential. Many caregivers report that it is these behaviors, rather than the autism, that are the primary source of distress and impairment for the individual and family and are of greatest concern.(\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e) Given this, it was notable that there was a high level of agreement that the presence of these behaviors should not be included in the definition of PA, as there are individuals who do not engage in these behaviors but still need 24/7 support for safety. Identifying what distinguishes this group from the majority that do engage in these behaviors is a critical research opportunity, as clarification of genetic, relational or experiential factors that initiate or accelerate the pathway to these behaviors could lead to broad early intervention guidance that seeks to prevent or ameliorate their occurrence and consequently increase community participation, family and individual well-being, and decrease exclusion from the community, educational settings, intervention programs and healthcare. Co-occurring diagnoses are common in ASD, and some studies have reported higher rates of medical and psychiatric co-occurring disorders in those with characteristics that are consistent with profound autism, including higher rates of epilepsy, constipation, and ADHD.(\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e) Despite their prevalence, it was widely agreed among respondents that these co-morbidities should not be included as criteria for profound autism, as there is wide variability in the prevalence of each co-morbidity, and individuals in the profound group who lack these co-morbidities.\u003c/p\u003e \u003cp\u003eThe area of most significant disagreement and debate was the use of an IQ score cut-off in defining PA. There was the most agreement with an IQ score lower than 50 (68%), which had greater agreement than a cut-off of 60 (58%) or 70 (57%), but no cut-off value achieved the consensus threshold. Despite the disagreements, respondents felt IQ should be included (\u0026ldquo;IQ should not be included\u0026rdquo; scored only 32% agreement) in order for researchers to have the ability to use existing databases that include IQs, but not more open-ended questions about support needs. In terms of clinical care and other research, however, respondents expressed concern with both the constraints in access to IQ testing and the validity of testing for those with low cognitive functioning and/or minimal verbal ability. Survey respondents had a very high level of agreement that individuals with PA struggle to complete assessments like IQ tests (96%). Overall, the lack of consensus on an appropriate IQ cut-off reflected philosophical and measurement challenges that have long been debated within the field, and IQ was included as part of criterion 5 as an \u0026ldquo;and/or\u0026rdquo; with minimal verbal ability.\u003c/p\u003e \u003cp\u003eAnother area of significant debate was the lower age bound appropriate for application of the term profound autism. Most respondents felt that PA could be identified by age 5 (74%). However, this statement did not reach the consensus threshold, due to the lack of agreement from researchers (57%) compared to caregivers (86%) and autistic individuals (100%). The disagreements among researchers were characterized by three themes. The primary scientific concern was that, in multiple studies, some key elements of the profound autism definition, such as verbal ability or IQ score, are not stable in children under 8 years old.(\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) As such, providing a reliable profound autism diagnosis before that age was determined to be unsupported by current data. Participants also noted that round-the-clock adult support is developmentally appropriate for children under the age of 8. A third theme of concern was that if profound autism was diagnosed in young children, health insurance companies or policy makers might utilize the term to limit access to more intensive or particular interventions, similar to how some have misused the ADOS and other measures requirements for establishing an autism diagnosis, which creates barriers to diagnosis and subsequent services.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) As there currently are no measures that have been shown to reliably predict later profound autism status in those under 8 years old, the consensus was to constrain the definition to individuals 8 and older.\u003c/p\u003e \u003cp\u003eThis study has several strengths and limitations that are worth noting. Strengths of the study include the use of an evidence-based methodology for establishing scientific consensus, a relatively high response rate, a range of participants including researchers, clinicians, caregivers, autistic individuals, and others, and a result based on broad agreement above the \u003cem\u003ea priori\u003c/em\u003e threshold for the specified domains. Limitations of this study include the relatively smaller proportion of participants who self-identified as autistic, the fact that most participants were from the US despite attempts to reach a global audience, and that several participants acknowledged they may have answered differently if better measures or data for challenging areas, such as IQ or age of reliable symptom ascertainment, were available in the field. A major challenge, and a source of debate among respondents, is how to utilize existing data when applying a new definition, which may not be well-measured in current datasets. While new measures and empirical investigation of definitional domains are essential in the future, researchers, caregivers and others were understandably concerned about ensuring that existing data, such as IQ scores or adaptive functioning scores, could be effectively utilized for research or clinical needs when considering profound autism.\u003c/p\u003e \u003cp\u003eOur study provides several clear foci for future research to further operationalize and better understand the definition, measure key domains not well-represented by current measures, and answer critical questions, such as the age at which symptoms of profound autism are reliably predictive of future group inclusion. Needing 24/7 access to an adult to ensure safety and well-being is a concept that is not well-represented by current measures and presents an opportunity for both reliable measure development and parsing the critical and predictive elements captured by this concept. Notably, caregivers of autistic children and adults who participated in the study were in 97% agreement as to the critical nature of this domain, suggesting it captures something essential for the concept and experience of PA. Valid and reliable measurement of IQ in individuals with significant cognitive and/or language impairments remains a major challenge for the field and is also an area for further measure development. Equally important is the opportunity to explore the concurrent validity of other more accessible measures that could adequately indicate or represent level of cognitive impairment. Given the barriers to obtaining valid IQ scores using current measures, respondents engaged in the most debate about whether to include IQ in the definition of profound autism, and future research on representation with and without IQ measurement would be instructive.\u003c/p\u003e \u003cp\u003e Another area that the definition of profound autism highlights as needing further development is efficient, quantitative measurement of verbal ability across the full spectrum. Currently studies use a wide range of measures, which inhibits progress and focus on this primary area of functioning.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e) Nevertheless, among researchers who focus on minimally verbal autism, there is growing agreement that natural language samples represent the best approach to capturing the communicative abilities, including speech and language in this population.(\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eA key area for further research is identifying at what age symptoms appear that are predictive of meeting the definition of profound autism. Establishing this could widen the age range of research participation and enhance the ability to provide focused and possibly more intensive early intervention for those with the highest likelihood of future impairment, which is a critical need in the field to inform decisions on dose, duration, and cost of early intervention for a particular individual. It is also critically important, given our study\u0026rsquo;s determination that the need for adult support is a core concept of profound autism, to develop measures with greater specificity for this domain and to parse the items that may carry the most variance, such as the ability to communicate in an emergency.(\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e) Finally, the development of sensitive and specific screeners for profound autism across the lifespan would be beneficial for both research and clinical settings, allowing for the rapid identification of at-risk individuals, potentially increasing recruitment efficiency and participation in research, and highlighting critical domains for individualizing treatment.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eDespite the rigor of the process, there are limitations to the existing study design. There is geographic and cultural variation in diagnosis and access to services and varying tools to assess intellectual disability measurements which may make an IQ measurement difficult, especially in those who are profoundly affected. There were not sufficient respondents from countries outside the US to incorporate different regional or cultural viewpoints into this definition to ensure that international consensus was reached.. We emphasize that these guidelines for diagnosis should be used for research purposes and they do not impact clinician best practices when determining an autism diagnosis.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eA large and varied group of researchers, clinicians, caregivers, and autistic individuals agreed that Profound Autism is a meaningful term and reached consensus above the \u003cem\u003ea priori\u003c/em\u003e specified level on key components of a research definition. The highest levels of agreement were reached on the requirement of 24/7 access to an adult for health and safety, as well as significant impairment in adaptive functioning. The consensus definition creates the opportunity to compare existing datasets and health records and to spur the creation of new measures, both of which will enable an increased focus on the research questions and clinical needs of an unresearched and underserved portion of the autism spectrum. As there is evidence that the outcomes, needs, interventions, and supports for those with Profound Autism are distinct, it logically follows that clarity in identification increases the opportunity to improve those areas for both those with profound autism and those without.\u003c/p\u003e "},{"header":"Abbreviations","content":" \u003cp\u003eADHD - Attention Deficit Hyperactivity Disorder\u003c/p\u003e \u003cp\u003eADOS \u0026ndash; Autism Diagnostic Observation Scale\u003c/p\u003e \u003cp\u003eASD - Autism Spectrum Disorder\u003c/p\u003e \u003cp\u003eDSM \u0026ndash; Diagnostic and Statistical Manual for Mental Disorders\u003c/p\u003e \u003cp\u003eIDD \u0026ndash; Intellectual Disability\u003c/p\u003e \u003cp\u003eIQ \u0026ndash; Intellectual Quotient\u003c/p\u003e \u003cp\u003eNICHD - National Institute of Child Health and Human Development\u003c/p\u003e \u003cp\u003ePA -Profound Autism\u003c/p\u003e \u003cp\u003eSC \u0026ndash; Steering Committee\u003c/p\u003e \u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eSince we are collecting no PHI, we received an exception from the Triducive IRB committee.\u003c/p\u003e\u003cp\u003e \u003ch2\u003eDisclosure:\u003c/h2\u003e \u003cp\u003eCatherine L. Lord receives royalties from sales of the ADI-R and ADOS/ADOS-2. She has also received support from the Longitudinal Study of Caregivers NIH Grant #4-441587-CL-29304. Helen Tager-Flusberg is supported by NIH Grant P50 DC 18006. Matthew Siegel\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eThis research was funded by The Autism Science Foundation and Profound Autism Alliance.\u003c/p\u003e \u003cp\u003eThis study was presented at the International Meeting for Autism Research; April 30-May 3, 2025; Seattle, Washington.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors approve to the submitted version of the work and to be personally accountable for their contributions. All authors contributed to the conception, design, acquisition and analysis of the work. MS drafted the paper and all authors substantially revised it.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors wish to acknowledge Dal Singh, BA and Katie Larner, PhD from Triducive (www.triducive.com) for guiding the authors in the Delphi Method and collecting and analyzing the results. They also acknowledge Katie Madgett, BS for her editorial support.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe dataset supporting the conclusions of this article may be available following a request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAmerican Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders [Internet]. Fifth Edition. American Psychiatric Association. 2013 [cited 2025 Aug 11]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://psychiatryonline.org/doi/book/\u003c/span\u003e\u003cspan address=\"https://psychiatryonline.org/doi/book/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1176/appi.books.9780890425596\u003c/span\u003e\u003cspan address=\"10.1176/appi.books.9780890425596\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLord C, Charman T, Havdahl A, Carbone P, Anagnostou E, Boyd B, et al. The Lancet Commission on the future of care and clinical research in autism. Lancet. 2022;399(10321):271\u0026ndash;334.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHughes MM, Shaw KA, DiRienzo M, Durkin MS, Esler A, Hall-Lande J et al. The Prevalence and Characteristics of Children With Profound Autism, 15 Sites, United States, 2000\u0026ndash;2016. Public Health Rep. 2023;003335492311635.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eClarke EB, McCauley JB, Lutz A, Gotelli M, Sheinkopf SJ, Lord C. Understanding profound autism: implications for stigma and supports. Front Psychiatry. 2024;15:1287096.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLord C, McCauley JB, Pepa LA, Huerta M, Pickles A. Work, living, and the pursuit of happiness: Vocational and psychosocial outcomes for young adults with autism. Autism. 2020;24(7):1691\u0026ndash;703.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMicai M, Fatta LM, Gila L, Caruso A, Salvitti T, Fulceri F, et al. Prevalence of co-occurring conditions in children and adults with autism spectrum disorder: A systematic review and meta-analysis. 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Clin Neuropsychol. 2018;32(7):1226\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStedman A, Taylor B, Erard M, Peura C, Siegel M. Are Children Severely Affected by Autism Spectrum Disorder Underrepresented in Treatment Studies? An Analysis of the Literature. J Autism Dev Disord. 2019;49(4):1378\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThurm A, Halladay A, Mandell D, Maye M, Ethridge S, Farmer C. Making Research Possible: Barriers and Solutions For Those With ASD and ID. J Autism Dev Disord. 2022;52(10):4646\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKasari C, Brady N, Lord C, Tager-Flusberg H. Assessing the minimally verbal school-aged child with autism spectrum disorder. Autism Res Off J Int Soc Autism Res. 2013;6(6):479\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiesefeld HR, Lamy D, Gaspelin N, Geng JJ, Kerzel D, Schall JD, et al. 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J Autism Dev Disord. 2020;50(7):2287\u0026ndash;306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSterrett K, Clarke E, Nofer J, Piven J, Lord C. Toward a functional classification for autism in adulthood. Autism Res. 2024;17(10):2105\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"molecular-autism","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mola","sideBox":"Learn more about [Molecular Autism](http://molecularautism.biomedcentral.com/)","snPcode":"13229","submissionUrl":"https://submission.nature.com/new-submission/13229/3","title":"Molecular Autism","twitterHandle":"@MolecularAutism","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Autism Spectrum Disorder, Profound Autism, Delphi Process","lastPublishedDoi":"10.21203/rs.3.rs-8745285/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8745285/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe diagnostic term, autism spectrum disorder, encompasses the full range of impairments associated with the autism spectrum, a significant change from earlier DSM definitions that identified various subtypes of autism. However, the majority of autism-related research and cultural representations in recent years has focused on autistic individuals with strong language and cognitive abilities. In 2021, the administrative term Profound Autism (PA) was proposed by a Lancet Commission to draw attention to autistic people whose impairments require lifelong, round-the-clock care. The definition of PA included a minimum age, an IQ range, nonverbal or minimally verbal skills, and required 24/7 access to an adult to ensure safety. However, researchers are not yet using a consistent definition of PA, based on their interpretation of the Lancet Commission report.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eTo address the need to have studies that use comparable samples and increase clarity in communication and interpretation of results, we carried out a systematic, multi-stage Delphi consensus study with over 70 participants who identified as researchers, caregivers, autistic individuals, and clinicians, to measure consensus on components of a research definition of PA. A series of questions was developed for the primary domains of interest.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter two rounds of review and voting, 76% of the respondents agreed on a research definition of PA of: adaptive functioning well below age level, requiring adult supervision to ensure physical and mental health, safety and well-being, at least 8 years old, diagnosed with ASD, and having severely impaired cognitive abilities (reflected by IQ score below 50) and/or does not verbally communicate other than single words or fixed phrases predominantly to have their basic needs met.\u003c/p\u003e\u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003e: Variations in access to measurement tools as well as access to services across the world limits the utility of this definition outside research practices.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eBased on these findings, a new working research definition of profound autism is proposed. This definition will improve specificity in precision medicine treatments for ASD.\u003c/p\u003e","manuscriptTitle":"Developing a Consensus Research Definition for Profound Autism Using a Modified Delphi Method","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-02 07:55:17","doi":"10.21203/rs.3.rs-8745285/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"molecular-autism","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mola","sideBox":"Learn more about [Molecular Autism](http://molecularautism.biomedcentral.com/)","snPcode":"13229","submissionUrl":"https://submission.nature.com/new-submission/13229/3","title":"Molecular Autism","twitterHandle":"@MolecularAutism","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e0f62650-9b65-4279-b68d-cf7676b5c790","owner":[],"postedDate":"March 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-09T16:23:27+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-02 07:55:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8745285","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8745285","identity":"rs-8745285","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}