Development of a patient-centered conceptual model of the impact of living with autism spectrum disorder

Abstract

The aim of this study was to generate a patient-centered conceptual model of the impact of living with autism spectrum disorder, which can be used to support the selection of outcome measures for clinical trials. Following an initial literature review to identify preliminary concepts and inform an interview guide, in-depth face-to-face interviews were conducted with adolescents and adults with autism spectrum disorder (IQ ⩾ 70) (n = 10), as well as parents of children, adolescents, and adults with autism spectrum disorder (IQ ⩾ 70) (n = 26). Data were analyzed using established qualitative research methods. The resultant conceptual model contains three interrelated domains reflecting core symptoms of autism spectrum disorder (communication deficits, socialization deficits, and restrictive, repetitive patterns of behavior), three domains reflecting associated symptoms of autism spectrum disorder (physical, cognitive, and emotional/behavioral), and three domains representing the impacts of living with autism spectrum disorder (impacts on activities of daily living, school/work, and social life). Interview respondents also cited social communication deficits as priority targets for new treatments. The conceptual model provides a patient-centered perspective of relevant concepts of autism spectrum disorder from the perspectives of people with autism spectrum disorder and their parents and offers a valuable tool for identifying valid patient-centered outcome measures for future clinical trials.

Keywords

autism spectrum disorder conceptual model qualitative research

Introduction

Autism spectrum disorder (ASD) is a neurodevelopmental condition defined by persistent deficits in social communication and social interaction across multiple contexts and by the presence of restricted, repetitive patterns of behavior, interests, or activities. To fulfill the diagnostic criteria, these symptoms must be present in the early developmental period, must cause clinically significant impairments in functioning, and cannot be explained by intellectual disability or global developmental delay (American Psychiatric Association, 2013).

The prevalence of ASD has been increasing in the last decades, and the prevalence estimates vary depending on the methodologies applied. In the United States, there are currently three prevalence monitoring systems using different methodologies: the National Health Interview Survey (NHIS), the Autism and Developmental Disabilities Monitoring (ADDM) Network, and the National Survey of Children’s Health (NSCH). The latest reported estimates from these three efforts are 2.24% (Zablotsky et al., 2015), 1.46% (Christensen et al., 2016), and 2% (Blumberg et al., 2013), respectively. Because children with ASD incur six times higher medical costs than children without ASD (Peacock et al., 2012), this increase in prevalence is having an impact on society and the health care system.

There are currently only two drugs approved by Health Authorities to treat symptoms associated with ASD. The Food and Drug Administration (FDA) has approved risperidone and aripiprazole for the treatment of irritability associated with autistic disorder; neither of these drugs target the core symptoms of ASD and they have not been approved yet in Europe for this indication. Nevertheless, polypharmacy is very common in people with ASD to treat associated symptoms, co-occurring morbidities, or as off-label use with the hope to improve core or associated symptoms (Accordino et al., 2016).

As new pharmacological, psycho-behavioral, and educational intervention treatments for people with ASD are developed, it is necessary that instruments used to measure efficacy are valid, reliable, and grounded in the experiences of the individual and their families. To this end, the FDA recommends that clinical outcome assessments (COAs) are evaluated for selection based on their content validity, that is, the extent to which a measure captures the patient experience of a given concept (FDA, 2009). The guidance documents—which relate to patient-reported outcomes (PROs) but also apply widely to other COAs (e.g. clinician-reported outcomes, observer-reported outcomes, and performance outcomes)—emphasize that instrument development, modification, and selection should be aligned with a conceptual model of a disease or disorder (FDA, 2009).

Earp and Ennett define a conceptual model as a diagram of “… linkages among a set of concepts believed to be related to a particular public health problem” in which concepts refer to an abstract “factor or variable … able to be empirically observed or measured” (Earp and Ennett, 1991: 164). Moreover, Donatti et al. (2008) and Rothman et al. (2007) further elaborate that a conceptual model can be used to delineate the various concepts that are relevant in a particular disease or condition and the hypothesized links between the concepts which provides guidance on what to measure and how to measure it. The FDA Guidance (2009) also states that an

instrument can be used to measure the effect of a medical intervention on one or more concepts (i.e., the thing being measured, such as a symptom or group of symptoms, effects on a particular function or group of functions, or a group of symptoms or functions shown to measure the severity of a health condition). (p. 2) (Note: Emphasis FDA’s own)

To our knowledge, no patient-centered conceptual model on the impact of living with ASD exists. Thus, we sought to generate a conceptual model through empirical evidence from people with ASD and those caring for an individual with ASD.

Methods

Overview of methods

We took a sequential approach to conceptual model development using data from multiple sources and perspectives. A summary of the main steps is depicted in Figure 1. An initial review of the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) criteria and qualitative research in individuals with ASD and/or their caregivers was conducted. Key themes emerging from these sources were used to generate a list of concepts and inform a qualitative interview guide for in-depth interviews with individuals with ASD and their caregivers. The draft conceptual model generated from primary and secondary data sources was finalized following expert review of the content, language, and structure.

Figure 1.

Sequential approach to conceptual model development.

Literature review

A targeted search was conducted on PubMed MEDLINE® to identify relevant articles containing references to qualitative research in individuals with ASD and/or their caregivers. Qualitative research was targeted as we sought to identify authentic patient- or caregiver-reported experiences and thus avoid drawing on evidence that reflected researcher or clinician pre-conceptions of ASD. Search terms were designed to identify the most relevant articles since the literature was expected to be expansive. Two searches were run: (1) a search based on a priori defined key terms of interest in the title/abstract field such as “autism” and “experience” or “qualitative” and (2) a search for “qualitative research” as a Medical Subject Headings (MeSH) term, a National Library of Medicine controlled vocabulary thesaurus used for indexing articles for PubMed (see Table 1) together with search terms for ASD. All searches were limited to English articles published in the past 15 years (1 January 2000–20 February 2015).

Table 1.

Literature review search terms for PubMed MEDLINE®.

Search no.	Search terms
1	Article title: autism spectrum disorder OR ASD OR autis* OR asperger
2	Article title or abstract: symptom* OR impact OR burden OR effect* OR quality of life OR qol OR health-related quality of life OR hrqol OR hrql OR activities of daily living OR adl OR function* OR caregiver* OR characteristic* OR feature* OR presentation* OR cogniti* OR behavior* OR behaviour* OR emotion* OR psychological
3	Article title: Experience* OR Focus group OR Grounded (for grounded theory) OR Interview* OR Patient report* OR patient-report* OR Perspectiv* OR Phenomenological OR Qualitative OR Self report* OR Self reported* OR Stories OR Story OR Subjective OR Thematic OR Theme*
4	1 AND 2 AND 3
5	Limit 4 to past 15 years (1 January 2000–20 February 2015)
6	Limit 5 to English Language and Humans
7	Limit 6 to exclude in title: NOT (rct OR randomized controlled trial OR clinical trial OR open-label OR epidemiolog* OR prevalen* OR predict* OR gene* OR dna OR rna OR epigenetic OR pathogene* OR risk factor OR neuro* OR neural* OR volumetric* OR brain* OR cortex OR amygdala OR cellular OR de novo OR autonomic OR glial* OR electroencephalography OR eeg OR parietal OR lobule OR protein OR kinase OR rasopathies OR phenotyp* OR genotype* OR chromosome* OR polymorph*)
8	1 AND MeSH term “Qualitative research”⁺
9	Limit 8 to past 15 years (1 January 2000–20 February 2015)
10	7 OR 9
11	Remove duplicates from 10

Search command operator used to retrieve all possible suffix variations of the root word (e.g. Symptom* retrieves symptom, symptoms, symptomatology, symptomatic).

“Qualitative research” is the full and proper MeSH term (“qualitative” [MeSH terms] produces 0 results).

Concepts elicited from the qualitative literature were used to inform topics for discussion within the interview guide.

Qualitative interviews

Recruitment and eligibility

Interview participants (10 individuals with ASD, 26 parents of individuals with ASD) were recruited from three physician’s offices in the United States: New York, NY; Rockville, MD; and San Diego, CA.

Individuals with ASD were only enrolled if they met the following eligibility criteria when screened: provided written informed consent to participate in a 60-min face-to-face interview, were aged 10–65 years, had a clinical diagnosis of ASD as defined by the DSM-5 or International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) criteria for ASD diagnosis, had an IQ of ⩾70, and had sufficient cognitive and linguistic abilities (appropriate to their age and given their ASD diagnosis) necessary to participate in a 1-h interview. Individuals with ASD were excluded if they had a medical history of alcohol and/or substance abuse/dependence, had a significant risk for suicidal behavior, had a concomitant disease or condition that could interfere with the conduct of the study, or were currently participating or had participated within the past 90 days in an investigational drug or device study for ASD.

In order to ensure that insights were consistent across the samples, parents were eligible for the study if his or her son or daughter with ASD met all of the aforementioned criteria, and the parent met the following criteria: provided written informed consent to participate in a 60-min face-to-face interview, was at least 18 years of age, spent significant time supporting the well-being of the person diagnosed with ASD (at least 20 h per week) and had been doing so for the past 6 months (in order to obtain reliable insights about everyday experiences), was not a formal (paid) caregiver, and was able to speak, read, write, and comprehend US English. For parents of individuals with ASD whose son or daughter did not participate in the interviews, the son or daughter with ASD were required to meet all of the aforementioned criteria with the exception of the following: having sufficient cognitive and linguistic abilities, 10–65 years of age (subject with ASD could be as young as 5), and an IQ of ⩾70. Parents were excluded if, in the opinion of the clinician, the parent lacked the ability, cognitive or otherwise, to complete a 60-min interview.

Procedures

All interviews were conducted face-to-face at the physician’s site. In line with industry standards, prior to conducting interviews, all personnel directly involved with the study underwent adverse event (AE) reporting training in the case that any AEs associated with any of the Sponsor’s products (including non-psychiatric medicines) was reported during interviews. Interviewers were experienced in qualitative inquiry and, specifically, in conducting research in people with neurodevelopmental disorders.

Interviews followed a semi-structured concept elicitation interview guide which included open-ended questions designed to encourage spontaneous responses and elicit rich qualitative data. This type of data collection is based on modified grounded theory techniques, a methodology that seeks to construct a theory about a specific phenomenon in which data are gathered inductively, with temporary suspension of existing theory in order to encourage spontaneous emergence of relevant concepts (Charmaz, 1995; Glaser and Strauss, 1967).

Each interview was audio-recorded and lasted approximately 60 min. Following the completion of the interview, participants were compensated US$100 for their time and to cover the costs of travel to the interview locations.

Analysis

Audio-recordings of the interviews were transcribed verbatim and anonymized by removing identifying information such as names and places. In line with the modified grounded theory approach utilized in this study, qualitative data were analyzed by constant comparison of interpretations and codes in which each unit of analysis (one interview transcript) was compared to the next. This followed a pattern of comparing all emerging concepts in previous transcripts to a new transcript, and so on and so forth, until saturation or the point at which a new interview was unlikely to yield new information relevant to the phenomenon in question. Data were collected and analyzed in parallel (i.e. initiating coding of transcripts while interviews are ongoing), and the coding scheme was dictated by the data with regular intervals of harmonization between the two independent coders. Individual cases (unique concepts) were identified and ultimately formed broader categories (domains), which helped to identify and explain patterns and relationships within the data set (the conceptual model) (Morse, 2001).

In order to evaluate conceptual saturation—the point at which additional interviews are unlikely to generate new information thereby justifying the sample size in qualitative research—concepts spontaneously emerging from the interviews were analyzed (separately for both individuals with ASD and parent samples) and compared in sets in the order the data were collected (Charmaz, 1995; Glaser and Strauss, 1967). For example, concepts reported in the first three interviews with individuals with ASD were compared to the next two interviews conducted. Both of these sets of interviews (n = 5) were compared with the next three interviews, and subsequently, all of these interviews (n = 8) were compared to the last two interviews. Conceptual saturation was achieved for both samples, thus no further interviews were conducted.

Ethics

This study was approved by a centralized review board: Copernicus Group Independent Review Board (reference number: EOS1-15-352). All interview participants were required to provide written informed consent. For underage participants who participated in interviews (10–17 years old), the parent had to give written permission and consent for his or her child to participate as well as the child providing written assent.

Results

Literature search

A total of 253 abstracts were identified of which 29 were retained and reviewed (see Figure 2). Article selection was based on content, that is, only articles that reported on original qualitative primary research with individuals with ASD or caregivers of individuals with ASD, or those that contained excerpts or quotes from other qualitative studies were included; articles that contained direct quotes from individuals with ASD regarding an experimental treatment (e.g. music therapy), as opposed to sharing immediate experience about ASD, were excluded.

Figure 2.

Literature review search results.

DSM-5 diagnostic criteria were used as a framework for grouping concepts that fell under the core symptoms of the disorder (social communication impairments and restricted repetitive patterns of behavior). The remaining concepts were grouped based on the themes which emerged from the literature and were combined with core symptom domains into preliminary list of concepts and domains. A total of 108 unique concepts were identified in the published literature. These were organized into 14 domains:

Deficits in social-emotional reciprocity (DSM-5 Criterion A.1);

Deficits in non-verbal communicative behaviors (DSM-5 Criterion A.2);

Deficits in developing, maintaining, and understanding relationships (DSM-5 Criterion A.3);

Other verbal communication deficits;

Stereotyped or repetitive motor movements, use of objects, or speech (DSM-5 Criterion B.1);

Insistence on sameness, inflexible adherence to routines, or ritualized patterns of verbal or non-verbal behavior (DSM-V Criterion B.2);

Highly restricted, fixated interests that are abnormal in intensity or focus (DSM-V Criterion B.3);

Hyper- or hyporeactivity to sensory input or unusual interest in sensory aspects of the environment (DSM-V Criterion B.4);

Deficits in cognitive abilities;

Emotional impacts of ASD;

Physical manifestations of ASD;

Other behavioral manifestations of ASD;

Miscellaneous impacts/consequences of ASD, for example, independence;

Developmental delays associated with ASD.

The resultant list of concepts also contributed to the development of the interview guides (separate guides for individuals with ASD and parent samples) which were designed to facilitate discussion around key domains. The interview guides included topics, questions, and probes designed to understand signs and symptoms of ASD, as well as impacts and experiences related to the condition from an individual’s perspective. Key topics included experiences related to:

Communication and social interaction and related impacts;

Restricted, repetitive patterns of behavior, interests or activities and related impacts;

Sensory symptoms and related impacts;

Cognitive symptoms and related impacts;

Physical symptoms and related impacts;

Emotional symptoms and related impacts;

General impacts.

To provide further insight into the relative importance of the concepts and domains discussed, respondents were also asked to identify which symptoms or impacts of ASD they would most like to be improved.

Expert review

The draft conceptual model was discussed during a therapeutic area expert (TAE) advisory board in September 2016 (attended by seven experts in ASD from the United States and the United Kingdom). The TAE panel included academic researchers, ASD measurement experts, practicing clinicians, and individuals with ASD.

During a half-day session, the expert panel were presented with the qualitative study results (literature review and interviews) and asked to critique the draft conceptual model. Minor changes to the model were recommended by the panel. These included amendments to concept and domain labels (e.g. to ensure concept labels were more patient-centered) and structure (e.g. combining concepts under larger domain labels).

Qualitative interviews

Demographic characteristics

Table 2 describes the demographic characteristics of the 26 parents. The average age was 53 years old and the majority of parents were female (n = 20, 76.9%) and White (n = 23, 88.5%). Five parents (19.2%) were Hispanic or Latino. A wide range of education levels were represented, from high school diploma (or test of General Education Development (GED)) or less (n = 3, 11.5%) to graduate degree (n = 13, 50.0%). All participants identified themselves as a parent of the person with ASD that he or she cared for with most individuals with ASD being male (n = 21, 80.8% male vs n = 5, 19.2% female). Ages of the individuals with ASD the parent cared for ranged from 7 to 31 years old with more than half being under 18 years old (n = 15, 57.7%).

Table 2.

Parent demographic characteristics.

Characteristic	Parents (N = 26)n (%)
Age
Average (SD)	53.0 (7.83)
Gender
Male	6 (23.1%)
Female	20 (76.9%)
Race (specified)
White	23 (88.5%)
American Indian or Alaska Native	1 (3.8%)
Asian	1 (3.8%)
Black or African American	1 (3.8%)
Ethnicity
Hispanic or Latino	5 (19.2%)
Education
High school diploma (or GED) or less	3 (11.5%)
Some college or certificate program	4 (15.4%)
College or university degree (2- or 4-year)	6 (23.1%)
Graduate degree	13 (50.0%)
Marital status
Married	21 (80.8%)
Divorced/separated	3 (11.5%)
Single	2 (7.7%)
Work status^a
Full time	9 (34.6%)
Part time	8 (30.8%)
Homemaker	8 (30.8%)
On disability	2 (7.7%)
Retired	2 (7.7%)
Unemployed	1 (3.8%)
Age of person with ASD who parent is caring for
7 year old	1 (3.8%)
9 year old	1 (3.8%)
10 year old	1 (3.8%)
12 year old	2 (7.7%)
13 year old	5 (19.2%)
14 year old	3 (11.5%)
16 year old	1 (3.8%)
17 year old	1 (3.8%)
21 year old	2 (7.7%)
22 year old	4 (15.4%)
25 year old	1 (3.8%)
26 year old	1 (3.8%)
28 year old	1 (3.8%)
30 year old	1 (3.8%)
31 year old	1 (3.8%)

SD: standard deviation; GED: General Education Development.

Some individuals marked more than one response, thus percentages total more than 100.0%.

The parents of all 10 individuals with ASD who participated in the interviews also acted as respondents in the parent sample. The demographic characteristics of the 10 individuals with ASD are presented in Table 3. Their ages ranged from 13 to 31 years old (five adolescents aged 13–17 years old, and five adults aged 22–31 years old), with mean age of 19.9 years. They were predominantly male (n = 9, 90.0%) and white (n = 8, 80.0%). One individual (10.0%) was Hispanic or Latino. Education levels ranged from middle or high school (n = 5, 50.0%) to college or university degree (n = 1, 10.0%). One individual worked full time (10%) and the majority of individuals lived with family or friends (90.0%).

Table 3.

Subject demographic characteristics.

Characteristic	Individuals with ASD (N = 10)n (%)
Age
Average (SD)	19.9 (6.23)
Adolescents (13–17 years)	5 (50%)
Adults (22–31 years)	5 (50%)
Gender
Male	9 (90.0%)
Female	1 (10.0%)
Race
American Indian or Alaska Native	1 (10.0%)
White	8 (80.0%)
Other	1 (10.0%)^a
Ethnicity
Hispanic or Latino	1 (10.0%)
Education
Currently in middle or high school	5 (50.0%)
High school diploma (or GED)	3 (30.0%)
Some college	1 (10.0%)
College or university degree (2- or 4-year)	1 (10.0%)
Living situation
With family or friends	9 (90.0%)
Alone	1 (10.0%)
Work status^b
Part time	2 (20.0%)
Student	2 (20.0%)
Unemployed	2 (20.0%)
Full time	1 (10.0%)
Other	1 (10.0%)

ASD: autism spectrum disorder; SD: standard deviation; GED: General Education Development.

One subject selected other and wrote in Italian and Lithuanian.

Information not available for all individuals.

Interview findings

The final conceptual model of the impact of living with ASD is presented in Figure 3. Specific to the aim of this study, the conceptual model organizes the most frequently reported concepts and domains. Thus, we have included concepts that were reported by 25% or more of the total sample. This allows focus on the most pertinent concepts to individuals with ASD and their parents in an effort to focus the future measurement of key concepts that are relevant to the majority of individuals. In line with this aim, and to facilitate comparison between the different groups included in this study (i.e. adults and adolescents with ASD and parents caring for an individual with ASD), we also present the proportion of respondents in each sample who reported each salient concept along with more detailed illustrative quotes.

Figure 3.

Conceptual model of the impact of living with ASD.

Core symptoms of ASD

Communication-related symptoms

“Difficulty with conversations” was the most frequently reported communication concept among the 26 parents of adults (90.9%) and adolescents/children with ASD (86.7%) and also the most frequently reported concept by adolescents with ASD (80.0%) (see Figure 4). “Difficulty with conversations” was often described as an inappropriate or awkward social approach and/or using inappropriate details, topics, or responses in conversation. One parent described that their child had “very little understanding of what sort of topics he can talk openly about” (Parent of 13 year old with ASD). Adults and adolescents with ASD explained that their difficulty with conversation included feeling like they were “kind of butting in” (22 year old with ASD) and that they did not know “when to come in and when to be allowed to get out [of conversation] … And I have no idea when the conversation will end” (13 year old with ASD). One individual with ASD explained,

And again, my hardest—my biggest difficulty with that is starting, and in a discussion, someone’s already started it. That’s where I sort—that’s sort of wound up saying I felt like I was kind of butting in, because my usual method of entering conversation is sort of interjecting one topic I would know about that they didn’t have an immediate answer for. (22 year old with ASD)

Figure 4.

Frequency of communication-related symptoms reported during qualitative interviews.

Difficulty “recognizing/interpreting non-verbal cues” was another widely reported concept (reported by 58.3% of the total sample). One individual with ASD described the difficulty they experienced in trying to read facial expressions and other non-verbal body language cues:

I tend to find it pretty difficult to read, just I’ve—it’s not consistent with every person what their facial expression is or what their stance is when they’re feeling a specific thing. So people will be upset and I’ll have no clue. … If somebody’s completely angry or downright depressed, I’ll usually pick up on that, but it has to be at the extreme end of every emotion for me to pick up on it. (26 year old with ASD)

Parents also discussed similar experiences in relation to their child’s difficulties recognizing non-verbal cues:

… because he can’t seem to get that hint, because he’s clueless, literally. And he doesn’t understand people’s expressions. (Parent of 13 year old with ASD)

Socialization symptoms

All parents (100.0%) and most individuals with ASD (90.0%) reported at least one socialization symptom. Out of the total sample, the concept of being “withdrawn in social settings” was the most frequently reported socialization symptom (83.3%) (see Figure 5). It was also the most frequently reported socialization symptom among parents of adolescents with ASD (93.3%), adults with ASD (80.0%), and adolescents with ASD (60.0%). “Withdrawn in social settings” included engaging in “isolated play” (Parent of 13 year old with ASD) and not “particularly participating” in group conversation (Parent of 13 year old with ASD).

Figure 5.

Frequency of socialization-related symptoms reported during qualitative interviews.

One adult with ASD described how they sometimes passively observed social settings rather than fully engaging with others:

Like even with close friends, I can definitely have moments where I’m just like kind of a passive observer and other times where I’m—I think it’s most pronounced with meeting new people, like—but like there—and I don’t think there’s any real rhyme nor reason to that. Like sometimes I’ll be super outgoing, and I—other times, I’m just like I’m going to—yeah, people are doing things, and I’m just going to be a wallflower here. (25 year old with ASD)

“Difficulty conforming to social norms” was the most frequently reported socialization symptom among parents of adults with ASD (90.9%). This included behaving in a way that could be “considered harassment” (Parent of 28 year old with ASD) or not respecting personal boundaries:

… she was—I would consider it, yeah, a girlfriend—for a really brief time. And he was so clingy. And he would just like want to lay on her—and just kind of doesn’t know like the boundaries or when that’s appropriate type of thing, so. (Parent of 22 year old with ASD)

Other parents described that their child often made comments during inappropriate times such as when “watching a movie in a theater” (Parent of 13 year old with ASD) or announced inappropriate things in public, for example, shouting in an elevator “I need pee-pee in front of everybody” (Parent of 13 year old with ASD).

Restrictive, repetitive patterns of behavior symptoms

Out of the total sample, “obsessive/restricted interest” was the most frequently reported concept overall and within the restrictive, repetitive patterns of behaviors domain (97.2%). It was also the most frequently reported concept among all sub-groups: parents of adults with ASD (90.9%), parents of adolescents/children with ASD (100.0%), adults with ASD (100.0%), and adolescents with ASD (100.0%) (see Figure 6). Obsessive interests often included various “collections” (26 year old with ASD) such as “40 or 50 cameras” (Parent of 16 year old with ASD) and “purses, bags” (Parent of 13 year old with ASD) as well as “playing the same videogame or watching YouTube videos over and over and over and over again” (Parent of 10 year old with ASD). Restricted interests included individuals only talking about a specific interest, leading to a lack of communication with others. As one parent stated, “He will communicate mostly when he wants to be heard, since he has a marked interest in certain areas and he wants to talk about those things all the time” (Parent of 13 year old with ASD).

Figure 6.

Frequency of repetitive/restrictive behavior symptoms reported during qualitative interviews.

The concept of “atypical sensitivity to stimuli” was reported by 90.9% of parents of high-functioning adults with ASD, 80.0% of parents of high-functioning adolescents with ASD, 100.0% of high-functioning adults with ASD, and 100.0% of high-functioning adolescents with ASD. “Atypical sensitivity to stimuli” included hyper-sensitivity to texture as well as hyper-sensitivity to loud noises such as “booms and bangs and … unexpected noises” (Parent of 10 year old with ASD), and more subtle and/or persistent noises such as “buzzing insects, like flies or bees” (Parent of 10 year old with ASD) and “an echo” or “the sound of the ocean” (Parent of 7 year old with ASD).

The negative impact and distressing nature of experiencing hypersensitivity to sound was described by one individual with ASD:

I mean, a while ago, like you know there was a—you know, like around July 4th, there was a fireworks display, and that like really—I hated it. You know, boom, boom, boom. That—you mean—you know what I mean? You know, the soldiers, you know, the PTSD—you know, they hear the boom, boom, boom. You know, they—anyway, that just like really got to me—the boom, boom, boom. (16 year old with ASD)

Associated symptoms of ASD

Among the total sample, “difficulty learning” was the most frequently reported cognitive symptom (63.9%) and was reported by the majority of parents of adults (72.7%) and adolescents/children with ASD (66.7%). Individuals with ASD and their parents described difficulty learning either in reference to a certain subject such as math or English, or a general difficulty learning new skills:

But it’s stuff like English, stuff that like—you know, stuff that there’s no like, you know, formula for or—that’s the stuff that I trip up on. (16 year old with ASD)

So I think that the reading is easier for him than math. He is, seems to have a lot of struggle with abstract mathematical concepts, you know, beyond just like listing the numbers and he’s barely able to do addition, you know. He was sort of learning multiplication but kind of stopped and any kind of word problem, very, very difficult. (Parent of 12 year old with ASD)

Getting “easily agitated/angered” was the most frequently reported concept in the “emotional/behavioral” domain (52.8%) and was reported predominantly by parents of adults (63.6%) and adolescents/children with ASD (60.0%). The concept was not as frequently reported by adults (20.0%) or adolescents (40.0%) with ASD. Parents stated that individuals with ASD would “yell … curse. And/or, at the same time, he will just be really, really down” (Parent of 17 year old with ASD), “get physically aggressive … use insulting language” (Parent of 30 year old with ASD), or “a bit of annoyance in the beginning can lead to frustration … quickly turn into just a bit of anger and he can stalk off” (Parent of 13 year old with ASD). Individuals with ASD stated that they had a “fairly short fuse … get pretty agitated, get pretty angry” (26 year old with ASD) or would get frustrated in situations such as in which “I’m working on something and I know I’m right” (16 year old with ASD).

Among the five adults with ASD, concepts of “anxiety” (60.0%), feeling “overly self-consciousness” (60.0%), and “depression” (40.0%) were reported:

… but I’m just like—it like—I’m 25. I still live with my parents. I don’t have a job. Like so—it’s like—it’s hard to judge that when you have like—whether you’re being anxious and depressed for no reason when you have legitimate sources of things to be anxious and depressed about. (25 year old with ASD)

Among all physical symptoms, “decreased motor skills” was the most frequently reported concept (72.2%). “Decreased motor skills” mostly referred to difficulty with fine motor skills such as handwriting, with parents describing their child’s handwriting as “very sketchy … very juvenile” or grasping a pen “very tight and so you’d see his fingers turning red or white” (Parent of 13 year old with ASD). One individual with ASD compared his handwriting to that of a doctor, stating that it is “chicken scratch, basically” (22 year old with ASD). Difficulty with fine motor skills such as handwriting also impacted other important aspects of life including school work:

Writing has always been really difficult for him. He was never able to do homework because of that. When we still had homework sent home, I w—he would dictate, and I would type, and that was only after probably at least an hour of screaming and crying, maybe. Really, really hard. So his handwriting is atrocious. It’s very sketchy, like, you know—it looks like he’s sketching. Very hard to decipher. Very, very juvenile. (Parent of 17 year old with ASD)

“Sleep problems” were also frequently reported by adolescents with ASD (80.0%) and parents of adolescents/children with ASD (53.3%). Parents described sleep problems in relation to both difficulty waking and difficulty sleeping: “wasn’t waking up in the morning. Like he was in a coma” (Parent of 17 year old with ASD) or “not unusual for him to show up in our room at 4:00 or 5:00 in the morning” (Parent of 10 year old with ASD). “Sleep problems” were described as having a negative impact on school attendance and also on the individual’s family:

Things got really bad around January and February … he wasn’t moving until 2:00 or 3:00 in the afternoon. So he would miss school. He’d miss school. He’d miss—he started missing school again, and he wound up in XXXX Partial Adolescent Program. He did three weeks at a day treatment program because we—it was—it was horrible. Just horrible. He’s—we’re better now. We’re still not great. (Parent of 17 year old with ASD)

When he was young, and he was initially diagnosed, we went through two or three years of not getting a full night of sleep. He would wake up around 2:00 and be literally bouncing off the walls until about 5:00 in the morning. That’s one of the reasons we got a house, because we needed two different bedrooms. We just couldn’t do that anymore. (Parent of 22 year old with ASD)

“Disruptive/aggressive behavior” was also reported by 69.2% of parents and 60.0% of people with ASD. Parents described “disruptive/aggressive behavior” as “a lot of loud screaming and throwing himself on the floor and punching himself in the face” (Parent of 12 year old with ASD), “explosive behavior, anger, a breakdown, weeping, screaming, cursing … head-banging” (Parent of 17 year old with ASD), or “slam a door and walk out” (Parent of 22 year old with ASD). One parent described their son’s aggression toward others:

And I’ve found in the past like when some neighbors came over and they were all jumping on the trampoline and they’re—they were kind of bigger kids, so they were kind of wrestling and stuff, but then XXXX just got so angry and exploded like of anger, yelling at them, that kind of stuff, because for him he just couldn’t figure that out. Like it’s either he’s in there having fun, but then he’s frustrated and doesn’t know how to manage them, that, to say, I’m done. (Parent of 13 year old with ASD)

Impacts of ASD

In total, 84.6% of parents reported concerns around at least one daily living skill or concerns about limited independence. The most frequently reported impacts of ASD by parents were “difficulty with self-care/hygiene” (42.3%), “restricted clothing choices” (34.6%), and “decreased independence” (34.6%). Of note, individuals with ASD were less likely to report concerns in these areas; no adults or adolescents with ASD reported “difficulty with self-care/hygiene” and only one adult with ASD discussed “restricted clothing choices.”

The negative impact on self-care/hygiene was described by caregivers in terms of frequency “And otherwise he doesn’t really shower until I yell at him …” (Parent of 26 year old with ASD), quality “He’ll come out very quickly … And you can tell he didn’t wash with soap” (Parent of 13 year old with ASD), and conceptually

Her hygiene, because we’re taking care of it most of the time, is good. Not great, because she doesn’t really know, nor understand the importance of it. She understands the routine of it. She’ll think I have to brush my teeth, but she doesn’t really understand the importance of it. (Parent of 13 year old with ASD)

We’ve just gone through a whole months long battle with him of you should use deodorant in the morning. So we finally have him doing that and that was only after multiple people kind of commented that he was odiferous. (Parent of 13 year old with ASD)

“Decreased work/school attendance” and/or “decreased work/school performance” was reported by almost half of parents (42.3%) and individuals with ASD (40.0%). A variety of factors contributed to the negative impact on work/school attendance and/or performance. One parent described that their son “missed about 125 days of school because … [he] was too anxious” (Parent of 17 year old with ASD), while another parent described that their son wouldn’t complete homework tasks:

Even when—I’ve s—when he was a little kid, I could see him just sitting there at his desk with the homework, and he’d lay everything out the way he wants, and he was just ready to go, and he’d sit there for hours, and it was a simple homework that he could do and wouldn’t finish it. But he would be like playing around with little gadgets or—you know? And then he’d go back to it, and he would get frustrated at the end of the day, because he’s just like, how is it that I can’t finish this? (Parent of 21 year old with ASD)

Individuals with ASD described that they “missed quite a few days [of school] from sleeping in” (17 year old with ASD) or would have homework that “has a certain amount of time to be done, and … it takes me a little bit longer” (13 year old with ASD). Older individuals talked about how the symptoms of their ASD impacted their ability to work:

When I was at the bakery, there were certain doughs that sometimes I would help mix that had a horrible texture to them. [laughter] Q: The doughs? The—A: Yeah. Q: Yeah. So it definitely affected you at work? A: Mm. Yeah, it could be pretty stressful. When I wasn’t working in the bakery, I worked—because it was in a grocery store and when I wasn’t doing that, I was up front helping with customer service, which certainly could be stressful with the noise level and having to communicate. (26 year old with ASD)

Concepts of ASD that respondents would most like to see improve

Respondents identified a number of concepts that they would most like to see improved. Although a total of 49 different concepts were reported, Table 4 shows the most frequently reported concepts in each sub-group. Across the sample, core social communication symptoms were of greatest importance; half of parents of individuals with ASD identified that improvements in conversation skills or improvements in expression and processing of emotions were the most important treatment targets. Similarly, 80% of adults with ASD identified that improvements in conversation skills were most important. Within the adolescent sub-group, the most frequently reported concept that this group wanted to improve was social interactions (40%).

Table 4.

Frequently reported concepts which respondents would most like to be improved by a new treatment.

Sub-group	Most frequently reported concepts	Example quote
Parents of individuals with ASD	Improved conversation skills (13/26, 50.0%)	“I would like to see her have a little bit more of a normal life or a normal dialogue and conversation with others, because for her, the social and the communication delay impacts everything. It impacts her school. It impacts her relationships.” (Parent of 14 year old with ASD)
Parents of individuals with ASD	Improved expression and processing of emotions (13/26, 50.0%)	“No, but even from like this conversation, it just comes back to this like, the communication, the ability to tell me what’s wrong, why it’s wrong um, how he feels.” (Parent of 12 year old with ASD)
Adults with ASD	Improved conversation skills (4/5, 80.0%)	“That really depends on the conversation you have. I don’t know. I guess—but any change is helpful. But again I want to know—I guess just like a little sort of a—again, just a little start to improvement and I can probably work from there … I guess knowing how to change topics, keep it in their interest, as opposed to mostly—as opposed to only what I would know.” (22 year old with ASD)
Adolescents with ASD	Improved social interactions (2/5, 40.0%)	“Probably being social more … Probably be around friends more … probably maybe doing stuff with them—probably finding out what they’re talking about.” (13 year old with ASD)

ASD: autism spectrum disorder.

Discussion

The primary aim of this study was to generate a patient-centered conceptual model of the impact of living with ASD through qualitative insights of individuals with ASD and their caregivers. The conceptual model presented here explicitly outlines the discrete, relevant qualities of living with ASD and provides a framework with which to assess the content of efficacy assessments for use in clinical trials. Drawing together initial insights from the published literature, the perspectives of people with ASD and their caregivers, and expert clinical review, helps to ensure the conceptual model is grounded in current thinking on the characterization of ASD, while remaining centered on the individual.

The in-depth interviews conducted in this study highlight the possible negative impacts associated with the core symptoms of ASD and provide a rich insight into how these symptoms are experienced by adults and adolescents with ASD. Consistent with extant literature, difficulties with communication and social situations were among the most commonly reported symptoms, as well as sensitivity to sensory stimuli (Baranek et al., 2006; Calder et al., 2012). Respondents in this study, across all sub-groups (parents, adults, and adolescents), also indicated that core social communication difficulties were the most important ASD symptoms that they would like to be improved by a new treatment. Such insights provide additional support that core symptoms, particularly social communication, should be the target of new interventions (Anagnostou et al., 2015).

The qualitative interviews in this study emphasize the importance of associated symptoms of ASD (e.g. physical, cognitive, emotional/behavioral) as well resulting impacts (e.g. on activities of daily living (ADLs), school/work, and social life). Of note, impacts on ADLs and functional independence appear to be of particular importance to parents of children, adolescents, and adults with ASD, but less so among individuals with ASD. Although >40% of parents reported difficulties in their child’s self-care/hygiene, no individuals with ASD reported the concept. For example, parents in this study reported that their child avoided showering altogether or only spent a limited time in the shower. Previous research has posited that impacts on self-care tasks, including showering, may in part be related to atypical responses to stimuli, for example, avoiding showering due to a dislike of transitioning from hot to cold water (Ashburner et al., 2013). Findings from this study support that atypical responses to stimuli were widely reported within the sample; 100% of adults and adolescents with ASD discussed this concept during the interviews.

It is notable that individuals with ASD tended to report fewer concepts than parents, but this cannot be explained by failure to achieve conceptual saturation as the research was designed to allow exhaustive discussion of concepts of importance and interviews continued until no new concepts arose. While this finding may be explained simply as a reflection of differing priorities between individuals with ASD and their parents, there are a number of other potential explanations for this observation. For example, it has been asserted that people with ASD may lack self-insight (Frith and Happé, 1999) and may not be fully aware of their symptoms, while their parents may have become “expert observers,” particularly if they have participated in psychoeducational programs or therapeutic interventions which encourage parent participation. However, recent research by Schriber et al. (2014) has challenged this hypothesis by finding that individuals with ASD have similar levels of insight as typically developing individuals—a finding supported by the detailed descriptions of ASD-related symptoms and impacts described by the individuals with ASD interviewed in this study. Moreover, Schriber et al. posit that parents of people with ASD—what the authors describe as “the measure of the ‘truth’”—may actually be hypersensitive to the challenges their child faces. In other words, the years of learning about and living with a child with ASD might lead parents to be more knowledgeable of, observant of, and acutely sensitive to autism-related traits and other “perceived shortcomings” in their children (Schriber et al., 2014). This may explain, at least in part, why parents reported specific issues with ADLs—challenges that many parents of typically developing children and adolescents might also report.

In line with Schriber et al.’s (2014) findings, it is possible that people with ASD interviewed in this study may have been fully aware of the challenges they faced but may struggle to communicate them. Although every effort was made to conduct interviews in a way that facilitated open and honest dialogue between the respondent and the interviewer (e.g. asking clear questions, allowing plenty of time for spontaneous responses, taking breaks, and providing the option to split the interview across more than one session; as per guidance from Cridland et al., 2015), it is possible that one-to-one semi-structured interviews were not optimal forums for some individuals with specific communication difficulties. Future research may wish to build upon these findings through the use of alternative qualitative approaches such as Conversation Analysis or Discourse Analysis (O’Reilly et al., 2016), utilizing augmented communication approaches such as high-tech (e.g. Digital Storytelling; De Vecchi et al., 2016) or low-tech resources (e.g. Talking Mats; Hallberg et al., 2013), or including people with ASD and their families in data analysis through member checking (Dockett et al., 2009).

Following guidance from a recent editorial in Autism on the value of qualitative inquiry in ASD research (Bölte, 2014), our study sought to achieve rigor by demonstrating the concepts of triangulation, trustworthiness, saturation, flexibility, and applicability (Kisely and Kendall, 2011). With regard to triangulation, our data included insights from adults and adolescents with ASD, the parents of individuals with ASD, and those of clinical experts. Thus, we were able to explore importance of concepts from multiple perspectives and generate a conceptual model which considered insights from the sample as a whole. This research also sought to stay truthful to the voices of the real experts—individuals experiencing first-hand what it means to live with ASD on a daily basis. The interviews were semi-structured and conducted by experienced qualitative interviewers, thus allowing open discussion of concepts of importance to respondents. Moreover, we also sought to obtain insights from parents who had regular contact with their child and who could provide detailed, first-hand accounts of the impacts of ASD on their child and their family. Finally, although the data presented here provide a rich account of the experiences of living with ASD, our study was designed to meet a specific application: the development of a conceptual model which could support the future selection or development of COAs that measure what matters to people with ASD. Thus, we have chosen to highlight concepts according to those most frequently reported within the sample in order to facilitate future measurement of concepts (in clinical trial settings) that are relevant to most people with ASD, as well as those individuals who care for and support them.

This study has a number of limitations. First, more caregivers were recruited than people with autism and some concepts included in the final model were reported only by caregivers. While direct qualitative evidence from patients is generally preferred, contemporary use of the term “patient-centered” includes caregiver perspectives (Fleurence et al., 2013), especially when patients may find it challenging to explain their symptoms. Patient-centered outcomes may or may not be measured by patient self-report, but are defined as “those outcomes important to patients’ survival, function, or feelings as identified or affirmed by the patients themselves, or judged to be in patients’ best interests by providers and caregivers when patients cannot report for themselves” (Patrick, 2013). Our decision to include concepts that were not reported by individuals with ASD reflects the important role of family and friends in supporting an individual with ASD, as well as the unique insight they provide as “observers” of ASD symptoms and impacts; many of outcome measures used in clinical trials in ASD rely on a caregiver or study-partner to report on observable behavior, even for clinician-rated assessments (Anagnostou et al., 2015). Nevertheless, the rigor of this research was supported by evidence of conceptual saturation within both samples (Kisely and Kendall, 2011).

Second, the study included no data pertaining to the experiences of younger children (<7 years) or older adults (>31 years) with ASD, or in individuals with IQ < 70, and was conducted in the United States only on a predominantly White, post-secondary educated (caregiver) sample. This limits the application of the conceptual model to all populations and, as is the case for all hypothetical models, further qualitative work should be conducted to test the applicability of this model to broader populations. With regard to IQ, although we would expect concepts reported in the conceptual model to be similar in individuals with IQ < 70, the severity would likely be more pronounced, particularly in those with difficulties with verbal communication. We also hypothesize that the concepts identified in this study would be broadly consistent in younger children or older adults; however, it is likely that specific real-world examples and priorities of concepts will vary by age, for example, types of play may vary in younger children, and influence of family may differ in middle- and older-aged individuals.

Third, it is important to acknowledge that this research sought to identify the impacts of ASD (to support efficacy assessment) and not to evaluate strengths. As Shore (2010) asserts, the challenges of ASD in some individuals can be seen as strengths in others. For example, if an individual experiences challenges in grasping the “big” picture, others may consider this to be a strength, for example, having a greater attention to detail. While it is important to focus on the efficacy of interventions in their ability to improve the impacts of a disease or disorder, any interventions should also allow the strengths (and “special interests”) of an individual to be maintained. Moreover, given the focus of this research was to reflect important measurement concepts to support selection of outcome measures for clinical trials, we did not seek to explore the influences of wider environmental issues, for example, support services or concurrent pharmacological or behavioral interventions. Future research should be undertaken to explore further how these external factors interact with the symptom and impact concepts identified through this research and how geographic or socio-demographic factors influence.

Fourth, as the main focus was the identification of relevant concepts for measurement, we have not attempted to represent the complex inter-relationships that may exist between concepts, beyond the assertion that core and associated symptoms of ASD lead to a range of impacts. However, such causal linkages are important to the conceptualization of ASD and may be an area that warrants further attention.

In summary, this research provides in-depth qualitative data describing the complex, multidimensional nature of the impact of ASD, as well as the high unmet need for both individuals with ASD and their caregivers. As such, this research provides further emphasis on the need for new treatments to address the symptoms and impacts of ASD. Although it merits further iteration and refinement (e.g. testing of its application to broader populations), the conceptual model presented in this article provides an important starting point as a reference for the selection of fit-for-purpose outcome measures for future clinical trials of novel therapies. In line with the multidimensional conceptual model presented in this article, a multidimensional measurement strategy assessing the broad range of relevant concepts is likely needed; while this study highlights that social communication difficulties are among the most important treatment and measurement targets for trials in ASD, the heterogeneity of the disorder necessitates the measurement of core symptoms, associated symptoms, and wider impacts of ASD on the individual and their families.

Supplemental Material

AUT718987_Lay_Abstract – Supplemental material for Development of a patient-centered conceptual model of the impact of living with autism spectrum disorder

Supplemental material, AUT718987_Lay_Abstract for Development of a patient-centered conceptual model of the impact of living with autism spectrum disorder by Fiona McDougall, Thomas Willgoss, Steve Hwang, Federico Bolognani, Lorraine Murtagh, Evdokia Anagnostou and Diana Rofail in Autism

Footnotes

Acknowledgements

We would like to acknowledge and thank the following individuals for their contributions to this research: Elisabeth Piault-Louis and our other colleagues at Roche for their support in planning and interpreting this research; Drs Carpenter, Payakachat, Schultz, Scahill, Tilford, Shore, Kuhlthau, and Pellicano without compensation for their valuable input on the conceptual model; Endpoint Outcomes for supporting the design and execution of the research; and, most importantly, the individuals who participated in the interviews.

Declaration of conflicting interests

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: F.M., T.W., and D.R. are employees of Roche Products Ltd, UK. F.B. and L.M. are employees of F. Hoffmann-La Roche Ltd, Switzerland. S.H. is an employee of Endpoint Outcomes, a research consultancy who acted as consultants in this study. E.A. has consulted to Seaside Therapeutics, Novartis, and F. Hoffmann-La Roche Ltd. She has received grant funding from Sanofi Canada, book royalties from APPI and Springer, and support from AMO Pharma. F. M., T. W., F. B. and L. M. have shares and/or share options in Roche.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by F. Hoffmann-La Roche Ltd, Switzerland.

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