The influence of loss to follow-up in autism screening research: Taking stock and moving forward.

BACKGROUND: How best to improve the early detection of autism spectrum disorder (ASD) is the subject of significant controversy. Some argue that universal ASD screeners are highly accurate, whereas others argue that evidence for this claim is insufficient. Relatedly, there is no clear consensus as to the optimal role of screening for making referral decisions for evaluation and treatment. Published screening research can meaningfully inform these questions-but only through careful consideration of children who do not complete diagnostic follow-up. METHODS: We developed two simulation models that re-analyze the results of a large-scale validation study of the M-CHAT-R/F by Robins et al. (2014, Pediatrics, 133, 37). Model #1 re-analyzes screener accuracy across six scenarios, each reflecting different assumptions regarding loss to follow-up. Model #2 builds on this by closely examining differential attrition at each point of the multi-step detection process. RESULTS: Estimates of sensitivity ranged from 40% to 94% across scenarios, demonstrating that estimates of accuracy depend on assumptions regarding the diagnostic status of children who were lost to follow-up. Across a range of plausible assumptions, data also suggest that children with undiagnosed ASD may be more likely to complete follow-up than children without ASD, highlighting the role of clinicians and caregivers in the detection process. CONCLUSIONS: Using simulation modeling as a quantitative method to examine potential bias in screening studies, analyses suggest that ASD screening tools may be less accurate than is often reported. Models also demonstrate the critical importance of every step in a detection process-including steps that determine whether children should complete an additional evaluation. We conclude that parent and clinician decision-making regarding follow-up may contribute more to detection than is widely assumed.

BEhavioral Health Stratified Treatment (B.E.S.T.) to optimize transition to adulthood for youth with intellectual and/or developmental disabilities.

Youth with intellectual and/or developmental disabilities (IDD) often struggle with depression and anxiety, which adversely impacts transition to adulthood. Integrated behavioral health care coordination, wherein care coordinators and behavioral health specialists collaborate to provide systematic, cost-effective, patient-centered care, is a promising strategy to improve access to behavioral health services and address factors that impact transition to adulthood, including depression/anxiety symptoms. Current care coordination models (e.g., Title V Maternal and Child Health Bureau [MCHB]) do not include behavioral health services. The CHECK (Coordinated HealthCarE for Complex Kids) mental health model, hereby refined and renamed BEhavioral Health Stratified Treatment (B.E.S.T.), is a behavioral health intervention delivery program designed for integration into care coordination programs. This study aims to determine whether an integrated behavioral health care coordination strategy (i.e., MCHB care coordination plus B.E.S.T.) would be more acceptable and lead to better youth health and transition outcomes, relative to standard care coordination (i.e., MCHB care coordination alone). Results would guide future investment in improving outcomes for youth with IDD. This study is a two-arm randomized clinical trial of 780 transition-aged youth with IDD (13-20 years) to evaluate the comparable efficacy of MCHB Care Coordination alone vs. MCHB Care Coordination plus B.E.S.T. on the following outcomes: 1) decreased symptoms and episodes of depression and anxiety over time; 2) improved health behaviors, adaptive functioning and health related quality of life; 3) increased health care transition (HCT) readiness; and 4) improved engagement and satisfaction with care coordination among stakeholders.

Effect of Family Navigation on Participation in Part C Early Intervention.

OBJECTIVE: Part C Early Intervention (EI) services have been shown to reduce autism symptoms and promote healthy development among young children. However, EI participation remains low, particularly among children from structurally marginalized communities. We investigated whether family navigation (FN) improved EI initiation following positive primary care screening for autism compared to conventional care management (CCM). METHODS: We conducted a randomized clinical trial among 339 families of children (ages 15-27 months) who screened as having an increased likelihood for autism at 11 urban primary care sites in 3 cities. Families were randomized to FN or CCM. Families in the FN arm received community-based outreach from a navigator trained to support families to overcome structural barriers to autism evaluation and services. EI service records were obtained from state or local agencies. The primary outcome of this study, EI service participation, was measured as the number of days from randomization to the first EI appointment. RESULTS: EI service records were available for 271 children; 156 (57.6%) children were not engaged with EI at study enrollment. Children were followed for 100 days after diagnostic ascertainment or until age 3, when Part C EI eligibility ends; 65 (89%, 21 censored) children in the FN arm and 50 (79%, 13 censored) children in the CCM arm were newly engaged in EI. In Cox proportional hazards regression, families receiving FN were approximately 54% more likely to engage EI than those receiving CCM (1.54 (95% confidence interval: 1.09-2.19), P = .02). CONCLUSIONS: FN improved the likelihood of EI participation among urban families from marginalized communities.

Evaluation of clinical assessments of social abilities for use in autism clinical trials by the autism biomarkers consortium for clinical trials.

Clinical trials in autism spectrum disorder (ASD) often rely on clinician rating scales and parent surveys to measure autism-related features and social behaviors. To aid in the selection of these assessments for future clinical trials, the Autism Biomarkers Consortium for Clinical Trials (ABC-CT) directly compared eight common instruments with respect to acquisition rates, sensitivity to group differences, equivalence across demographic sub-groups, convergent validity, and stability over a 6-week period. The sample included 280 children diagnosed with ASD (65 girls) and 119 neurotypical children (36 girls) aged from 6 to 11 years. Full scale IQ for ASD ranged from 60 to 150 and for neurotypical ranged from 86 to 150. Instruments measured clinician global assessment and autism-related behaviors, social communication abilities, adaptive function, and social withdrawal behavior. For each instrument, we examined only the scales that measured social or communication functioning. Data acquisition rates were at least 97.5% at T1 and 95.7% at T2. All scales distinguished diagnostic groups. Some scales significantly differed by participant and/or family demographic characteristics. Within the ASD group, most clinical instruments exhibited weak (≥ |0.1|) to moderate (≥ |0.4|) intercorrelations. Short-term stability was moderate (ICC: 0.5-0.75) to excellent (ICC: >0.9) within the ASD group. Variations in the degree of stability may inform viability for different contexts of use, such as identifying clinical subgroups for trials versus serving as a modifiable clinical outcome. All instruments were evaluated in terms of their advantages and potential concerns for use in clinical trials.

Patterns of Intervention Utilization Among School-Aged Children with Autism Spectrum Disorder: Findings from a Multi-Site Research Consortium.

When designing and interpreting results from clinical trials evaluating treatments for children on the autism spectrum, a complicating factor is that most children receive a range of concurrent treatments. Thus, it is important to better understand the types and hours of interventions that participants typically receive as part of standard of care, as well as to understand the child, family, and geographic factors that are associated with different patterns of service utilization. In this multi-site study, we interviewed 280 caregivers of 6-to-11-year-old school-aged children on the autism spectrum about the types and amounts of interventions their children received in the prior 6 weeks. Reported interventions were coded as "evidence-based practice" or "other interventions," reflecting the level of empirical support. Results indicated that children received a variety of interventions with varying levels of empirical evidence and a wide range of hours (0 to 79.3 hours/week). Children with higher autism symptom levels, living in particular states, and who identified as non-Hispanic received more evidence-based intervention hours. Higher parental education level related to more hours of other interventions. Children who were younger, had lower cognitive ability, and with higher autism symptom levels received a greater variety of interventions overall. Thus, based on our findings, it would seem prudent when designing clinical trials to take into consideration a variety of factors including autism symptom levels, age, cognitive ability, ethnicity, parent education and geographic location. Future research should continue to investigate the ethnic, racial, and socioeconomic influences on school-aged intervention services.

Implementation of a multi-family autism transition program in the high school setting.

LAY ABSTRACT: Transitioning Together is an intervention that supports families of adolescents on the autism spectrum as they prepare for the transition to adulthood. While it has been delivered successfully and shown to result in positive outcomes for families in the university setting, questions remain about whether and how well it can be widely provided to families in real-world settings such as high schools. In this study, we analyzed predictors, facilitators, and barriers to providing Transitioning Together to families at 30 high schools across three US states, all of which received training from a team of researchers to deliver this intervention. Our findings highlight struggles and successes with real-world use of the intervention. Seventeen of the 30 schools were successful in providing Transitioning Together to families. Schools who had higher community socioeconomic status, higher quality family involvement, and higher quality transition planning programming before changing anything for this study were much more likely to provide this new intervention to families. Schools who used the intervention were mostly able to deliver it as designed and received positive feedback from families who participated. Common parts of the intervention that schools struggled with most included following the structure of the sessions, including group problem-solving and dialogue in the sessions, and collecting feedback from families. Future research is needed to learn how to make it even easier for public high schools and other service systems to provide this intervention to families, in a way that also maximizes its effectiveness and accessibility for historically underserved autism spectrum populations.

A method for defining the CORE of a psychosocial intervention to guide adaptation in practice: Reciprocal imitation teaching as a case example.

LAY ABSTRACT: Interventions that support social communication include several "components," or parts (e.g. strategies for working with children and families, targeting specific skills). Some of these components may be essential for the intervention to work, while others may be recommended or viewed as helpful but not necessary for the intervention to work. "Recommended" components are often described as "adaptable" because they can be changed to improve fit in different settings where interventions are offered or with different individuals. We need to understand which parts of an intervention are essential (and which are adaptable) when translating interventions from research to community settings, but it is challenging to do this before studying an intervention in the community. This article presents the CORE (COmponents & Rationales for Effectiveness) Fidelity Method-a new method for defining the essential components of evidence-based interventions-and applies it to a case example of Reciprocal Imitation Teaching, an intervention that parents are taught to deliver with their young children with social communication delays. The CORE Fidelity Method involves three steps: (1) gathering information from multiple sources; (2) integrating information from previous research and theory; and (3) drafting a CORE model for ongoing use. The benefits of using the CORE Fidelity Method may include: (1) improving consistency in intervention and research materials to help all providers emphasize the most important skills or strategies; (2) clarifying which parts of the intervention can be adapted; and (3) supporting future research that evaluates which intervention components work and how they work.

Characterizing Available Tools for Synchronous Virtual Assessment of Toddlers with Suspected Autism Spectrum Disorder: A Brief Report.

The COVID-19 pandemic, and associated social distancing mandates, has placed significant limitations on in-person health services, requiring creative solutions for supporting clinicians engaged in the diagnosis of autism spectrum disorder (ASD). This report describes the five virtual instruments available at the time of manuscript development for use by experienced clinicians making diagnostic determinations of ASD for toddlers across the 12- to 36-months age range. We focus on synchronous virtual assessments in which clinicians guide the child's caregiver through a range of assessment activities and observe spontaneous and elicited behaviors. Assessments are compared on dimensions of targeted behavioral domains, specific activities and presses employed, scoring approaches, and other key logistical considerations to guide instrument selection for use in varied clinical and research contexts.

Family Impact During the Time Between Autism Screening and Definitive Diagnosis.

Over the past 10 years, identification of Autism Spectrum Disorder (ASD) risk has dramatically increased due to the wide-spread implementation of screening programs; yet, there is limited understanding about parent perceptions and experiences during the time period when risk is identified, but prior to receiving a formal diagnosis-a period that can last months to years given the long wait-lists for formal ASD evaluations. The current study aimed to examine parent perceptions of family impact (i.e., the impact their child's behaviors have on the family) between the time of risk-identification and formal diagnosis among 277 children identified as at-risk for ASD through screening positive in primary care. We aimed to compare family impact among those whose child met diagnostic criteria for ASD and those who did not. Parents of children who received a non-ASD diagnosis reported a higher baseline level of family impact (F[1, 274] = 5.82, p = .017); however, perceived difficult child behavior was a stronger predictor of family impact (t[6] = 13.11, p < .001) than later diagnostic group (t[6] = - 2.10, p = .037), and child functioning did not predict family impact (t[6] = -0.31, p = .76). These results suggest that in this population, perceived difficult child behavior is a stronger predictor of family impact than later diagnostic category and should be considered an important factor in family support.

Parent stress and coping trajectories in Hispanic and non-Hispanic families of children at risk of autism spectrum disorder.

LAY ABSTRACT: Little is known about parent experiences throughout the diagnostic process for autism or how these parent experiences may help explain the disparities that exist between Hispanic and non-Hispanic families in time-to-diagnosis among children identified as at risk for autism. The current study examined trajectories of parenting stress, coping, and perceived family impact over time, throughout the autism diagnostic process among Hispanic and non-Hispanic families. Hispanic families reported lower levels of parenting stress, coping, and negative family impact across time. Further, there were differences in the change in use of coping and the amount of negative family impact reported between Hispanic and non-Hispanic parents over time. These differences shed light on the unique experiences and strengths of Hispanic families demonstrate. Interventions that leverage those strengths and focus on education, empowerment, and resilience might be particularly beneficial for Hispanic families and may also better inform work to increase resilience.

What Happens After a Positive Primary Care Autism Screen Among Historically Underserved Families? Predictors of Evaluation and Autism Diagnosis.

OBJECTIVE: Families, pediatric providers, and service systems would benefit from expanded knowledge regarding (1) who is most likely to receive a recommended diagnostic evaluation after a positive primary care-administered autism screen and (2) of those who screen positive, who is most likely to be diagnosed with autism? METHOD: Participants included 309 predominantly low-income, racial/ethnic minority parents and their child, aged 15 to 27 months, who screened positive on the Modified Checklist for Autism in Toddlers, Revised with Follow-Up (M-CHAT-R/F). Generalized estimating equations were used to fit models of predictors for each binary outcome: receiving a diagnostic evaluation and receiving an autism diagnosis on evaluation. RESULTS: Significant predictors of diagnostic evaluation receipt included the parent being older or non-Hispanic and the child having private insurance, lower child communication functioning, or receiving Early Intervention services. Significant predictors of an autism diagnosis on evaluation included male child, lower child communication functioning, screening directly in the parent's preferred language, White/non-Hispanic parent, and no parent history of mood disorder. CONCLUSION: Children with younger parents, Hispanic ethnicity, relatively higher communication skills, public insurance, and no Early Intervention services were less likely to receive recommended diagnostic care. Reduced likelihood of autism diagnosis after a positive screen in non-White/non-Hispanic subgroups supports previous research indicating issues with M-CHAT-R/F positive predictive power for racial/ethnic minorities. The use of telephonic interpreters to administer screens, as opposed to directly screening in families' preferred languages, may lead to identification of fewer true autism cases. Thus, multilingual clinical staff capacity may improve positive predictive power of autism screening.

Effect of Family Navigation on Diagnostic Ascertainment Among Children at Risk for Autism: A Randomized Clinical Trial From DBPNet.

Importance: Early identification of autism spectrum disorder (ASD) is associated with improved cognitive and behavioral outcomes. Targeted strategies are needed to support equitable access to diagnostic services to ensure that children from low-income and racial/ethnic minority families receive the benefits of early ASD identification and treatment. Objective: To test the efficacy of family navigation (FN), an individually tailored, culturally informed care management strategy, to increase the likelihood of achieving diagnostic ascertainment among young children at risk for ASD. Design, Setting, and Participants: This randomized clinical trial of 249 families of children aged 15 to 27 months who had positive screening results for possible ASD was conducted in 11 urban primary care sites in 3 cities. Data collection occurred from February 24, 2015, through November 5, 2018. Statistical analysis was performed on an intent-to-treat basis from November 5, 2018, to July 27, 2020. Interventions: Families were randomized to FN or conventional care management (CCM). Families receiving FN were assigned a navigator who conducted community-based outreach to families to address structural barriers to care and support engagement in recommended services. Families receiving CCM were assigned to a care manager, who did limited telephone outreach. Families received FN or CCM after positive initial screening results and for 100 days after diagnostic ascertainment. Main Outcomes and Measures: The primary outcome, diagnostic ascertainment, was measured as the number of days from randomization to completion of the child's clinical developmental evaluation, when a diagnosis of ASD or other developmental disorder was determined. Results: Among 250 families randomized, 249 were included in the primary analysis (174 boys [69.9%]; mean [SD] age, 22.0 [3.5] months; 205 [82.3%] publicly insured; 233 [93.6%] non-White). Children who received FN had a greater likelihood of reaching diagnostic ascertainment over the course of 1 year (FN, 108 of 126 [85.7%]; CCM, 94 of 123 [76.4%]; unadjusted hazard ratio [HR], 1.39 [95% CI, 1.05-1.84]). Site (Boston, New Haven, and Philadelphia) and ethnicity (Hispanic vs non-Hispanic) moderated the effect of FN (treatment × site interaction; P = .03; Boston: HR, 2.07 [95% CI, 1.31-3.26]; New Haven: HR, 1.91 [95% CI, 0.94-3.89]; and Philadelphia: HR, 0.91 [95% CI, 0.60-1.37]) (treatment × ethnicity interaction; P < .001; Hispanic families: HR, 2.81 [95% CI, 2.23-3.54] vs non-Hispanic families: HR, 1.49 [95% CI, 1.45-1.53]). The magnitude of FN's effect was significantly greater among Hispanic families than among non-Hispanic families (diagnostic ascertainment among Hispanic families: FN, 90.9% [30 of 33], and CCM, 53.3% [16 of 30]; vs non-Hispanic families: FN, 89.7% [35 of 39], and CCM, 77.5% [31 of 40]). Conclusions and Relevance: Family navigation improved the likelihood of diagnostic ascertainment among children from racial/ethnic minority, low-income families who were detected as at risk for ASD in primary care. Results suggest differential effects of FN by site and ethnicity. Trial Registration: ClinicalTrials.gov Identifier: NCT02359084.

A commentary on interpreting the United States preventive services task force autism screening recommendation statement.

In 2016, the US Preventive Services Task Force concluded that there was "insufficient" ("I" statement) evidence to support universal primary care screening for autism spectrum disorder. The statement led to controversy among research and clinical communities. Although a number of papers have since been published arguing for the potential benefit of autism spectrum disorder screening, none adequately address the potential harms of autism spectrum disorder screening. This evidence gap may relate to confusion regarding how the US Preventive Services Task Force conceptualizes and evaluates potential harm. In this commentary, we explore how the US Preventive Services Task Force operationalizes harm and discuss how the potential for harm was described in the "I" statement on autism spectrum disorder screening. This information can serve as a guide for investigators working to study the benefits and harms of autism spectrum disorder screening in order to fill the research gaps cited by the US Preventive Services Task Force report. Finally, we recommend future research directions for exploring harms of autism spectrum disorder screening, filling cited research gaps, and ultimately ensuring that the benefits of autism spectrum disorder screening truly outweigh the harms for all children and their families.

Improving Family Navigation for Children With Autism: A Comparison of Two Pilot Randomized Controlled Trials.

OBJECTIVE: Family navigation (FN), a care management strategy, helps families overcome systems and person-level barriers to care. We previously demonstrated FN's feasibility, acceptability, and potential efficacy for increasing access and reducing time to autism-related diagnostic services among low-income, minority children. In this paper, we describe modifications to FN in response to concerns raised in our first pilot randomized controlled trial (RCT), and then assess these modifications in a second pilot RCT. METHODS: An advisory group recommended modifications to recruitment procedures and study conditions. Forty parent-child dyad participants with autism-related concerns were randomized to receive modified usual care (UC) or modified FN. We compared whether the first and second pilot RCTs differed in: participant enrollment, satisfaction with clinical care, and timely completion of the diagnostic assessment. RESULTS: Recruitment improved under the modified protocol with significantly fewer potentially eligible families refusing (19.5% vs 4.8%, P < .05) or being excluded from study enrollment (43.6% vs 0%, P < .01). Comparing the first and second pilot RCTs, regardless of study arm, families in the second pilot were more likely to complete diagnostic assessment (UC: hazard ratio [HR] 3.41, 95% confidence intervals [CI 1.20, 9.68]; FN: HR 2.64, 95% CI [1.31, 5.30]) and report greater satisfaction with clinical care. In the second pilot, compared to UC, FN continued increase the likelihood of completing the diagnostic assessment (HR: 2.57; 95% CI [1.22, 5.40]). CONCLUSIONS: Easy-to-implement system-level enhancements improved study recruitment, satisfaction with care, and completion of a diagnostic assessment. With enhancement, FN continued to confer benefits to families.

Social Determinants of Health and the Role of Routine Pediatric Care in a Medically Complex Toddler.

CASE: Late on a Friday afternoon, a new family presents to your practice for urgent care. They come with their youngest child Mai, a 2-year-old girl, who, although born in the United States at 36 weeks gestation, has resided in Laos with her grandparents for the past 16 months. Your triage nurse tells you that she has a fever and was found to have profound anemia while at the WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) office earlier today.On walking into the room, you describe Mai as "listless" and "sickly." Her vitals were notable for fever (102°F), tachycardia (140 beats per minute), and tachypnea (35 breaths per minute). On physical examination, she was grunting with a systolic ejection murmur and without hepatosplenomegaly. Laboratory test results revealed hemoglobin of 2.2 g/dL, hematocrit of 12%, mean corpuscular volume of 50 fL, red cell distribution width of 27%, reticulocyte count of 3%, ferritin of <2 ng/mL, iron of 15 µg/dL, total iron binding count of 420 µg/dL, white blood cell count of 13.5 K/µL, and platelets of 605 K/µL. Her evaluation was consistent with severe iron deficiency anemia (IDA), which was further supported by reported restrictive diet and excessive cow milk intake of 35 ounces daily. She was admitted to the Pediatric Intensive Care Unit in high-output cardiac failure and was slowly transfused with 15 mL/kg of packed red blood cells over 2 days with careful monitoring. Once stabilized, she was transferred to the inpatient floor for further nutritional evaluation and supplementation. Additional workup, including hemoglobin electrophoresis, fecal occult blood test, celiac studies, and stool parasite testing were normal. The clinical picture was consistent with a viral infection in the setting of profound IDA and malnutrition.Although her clinical status had improved, she remained inpatient for nutritional optimization. Her height was at the 54th percentile (z-score: 0.11), weight was at the first percentile (z-score: -2.25), and body mass index was below the first percentile (z-score: -3.18), diagnostic of severe protein-calorie malnutrition. She was evaluated by an interdisciplinary growth and nutrition team, received multivitamin and mineral supplements, and was monitored for refeeding syndrome. She was noted to be "difficult to engage," "resistant to new faces," and made little progress on expanding her dietary choices. Concerns about a possible diagnosis of autism spectrum disorder were raised by her treating team. What would you do next? REFERENCE: 1. Bouma S. Diagnosing pediatric malnutrition: paradigm shifts of etiology-related definitions and appraisal of the indicators. Nutr Clin Pract. 2017;32:52-67.

The Cultural Adaptation of a Transition Program for Latino Families of Youth with Autism Spectrum Disorder.

During the transition to adulthood, effective and culturally relevant supports are critical for families of youth with autism spectrum disorder (ASD). There is a dearth of documented program development and research on supports for Spanish-speaking Latino families during this life stage. The present work describes the cultural adaptation process of an evidence-based transition program for Latino families of youth with ASD. A model of the actions necessary to meaningfully conduct a cultural adaptation in this context is described. After implementing the culturally adapted program titled Juntos en la Transición with five Spanish-speaking families, parents reported high social validity of the program through surveys and interviews. The cultural adaptation process followed in this work is important for the further development of programs that address the transition needs of Latino youth with ASD and their families. Our impressions may also be useful to those who aim to develop culturally sensitive and ecologically valid multifamily group intervention programs for families from cultural and linguistic minority groups.

Durante la transición a la adultez, las adaptaciones eficaces y culturalmente relevantes son fundamentales para las familias de jóvenes con trastorno del espectro autista (TEA). Hay una escasez de investigaciones y desarrollo de programas documentados sobre las adaptaciones para las familias latinas de habla hispana durante esta etapa de la vida. El presente trabajo describe el proceso de adaptación cultural de un programa de transición de base fáctica para familias latinas de jóvenes con TEA. Se describe un modelo de las medidas necesarias para llevar a cabo significativamente una adaptación cultural en este contexto. Después de implementar el programa adaptado culturalmente y titulado Juntos en la Transición con cinco familias de habla hispana, los padres informaron una alta validez social del programa mediante encuestas y entrevistas. El proceso de adaptación cultural seguido en este trabajo es importante para el futuro desarrollo de programas que aborden las necesidades de transición de los jóvenes latinos con TEA y sus familias. Nuestras impresiones también pueden ser útiles para aquellos que desean desarrollar programas de intervención en grupos multifamiliares ecológicamente válidos y culturalmente adaptados para familias de grupos culturales y lingüísticos minoritarios.

Simulation and minimization: technical advances for factorial experiments designed to optimize clinical interventions.

BACKGROUND: The Multiphase Optimization Strategy (MOST) is designed to maximize the impact of clinical healthcare interventions, which are typically multicomponent and increasingly complex. MOST often relies on factorial experiments to identify which components of an intervention are most effective, efficient, and scalable. When assigning participants to conditions in factorial experiments, researchers must be careful to select the assignment procedure that will result in balanced sample sizes and equivalence of covariates across conditions while maintaining unpredictability. METHODS: In the context of a MOST optimization trial with a 2x2x2x2 factorial design, we used computer simulation to empirically test five subject allocation procedures: simple randomization, stratified randomization with permuted blocks, maximum tolerated imbalance (MTI), minimal sufficient balance (MSB), and minimization. We compared these methods across the 16 study cells with respect to sample size balance, equivalence on key covariates, and unpredictability. Leveraging an existing dataset to compare these procedures, we conducted 250 computerized simulations using bootstrap samples of 304 participants. RESULTS: Simple randomization, the most unpredictable procedure, generated poor sample balance and equivalence of covariates across the 16 study cells. Stratified randomization with permuted blocks performed well on stratified variables but resulted in poor equivalence on other covariates and poor balance. MTI, MSB, and minimization had higher complexity and cost. MTI resulted in balance close to pre-specified thresholds and a higher degree of unpredictability, but poor equivalence of covariates. MSB had 19.7% deterministic allocations, poor sample balance and improved equivalence on only a few covariates. Minimization was most successful in achieving balanced sample sizes and equivalence across a large number of covariates, but resulted in 34% deterministic allocations. Small differences in proportion of correct guesses were found across the procedures. CONCLUSIONS: Based on the computer simulation results and priorities within the study context, minimization with a random element was selected for the planned research study. Minimization with a random element, as well as computer simulation to make an informed randomization procedure choice, are utilized infrequently in randomized experiments but represent important technical advances that researchers implementing multi-arm and factorial studies should consider.

Using the Multiphase Optimization Strategy (MOST) framework to test intervention delivery strategies: a study protocol.

BACKGROUND: Delivery of behavioral interventions is complex, as the majority of interventions consist of multiple components used either simultaneously, sequentially, or both. The importance of clearly delineating delivery strategies within these complex interventions-and furthermore understanding the impact of each strategy on effectiveness-has recently emerged as an important facet of intervention research. Yet, few methodologies exist to prospectively test the effectiveness of delivery strategies and how they impact implementation. In the current paper, we describe a study protocol for a large randomized controlled trial in which we will use the Multiphase Optimization Strategy (MOST), a novel framework developed to optimize interventions, i.e., to test the effectiveness of intervention delivery strategies using a factorial design. We apply this framework to delivery of Family Navigation (FN), an evidence-based care management strategy designed to reduce disparities and improve access to behavioral health services, and test four components related to its implementation. METHODS/DESIGN: The MOST framework contains three distinct phases: Preparation, Optimization, and Evaluation. The Preparation phase for this study occurred previously. The current study consists of the Optimization and Evaluation phases. Children aged 3-to-12 years old who are detected as "at-risk" for behavioral health disorders (n = 304) at a large, urban federally qualified community health center will be referred to a Family Partner-a bicultural, bilingual member of the community with training in behavioral health and systems navigation-who will perform FN. Families will then be randomized to one of 16 possible combinations of FN delivery strategies (2 × 2 × 2× 2 factorial design). The primary outcome measure will be achieving a family-centered goal related to behavioral health services within 90 days of randomization. Implementation data on the fidelity, acceptability, feasibility, and cost of each strategy will also be collected. Results from the primary and secondary outcomes will be reviewed by our team of stakeholders to optimize FN delivery for implementation and dissemination based on effectiveness, efficiency, and cost. DISCUSSION: In this protocol paper, we describe how the MOST framework can be used to improve intervention delivery. These methods will be useful for future studies testing intervention delivery strategies and their impact on implementation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03569449. Registered on 26 June 2018.

Diagnostic Uncertainty in a Complex Young Man: Autism Versus Psychosis.

CASE: James is a 7½-year-old boy born in Vietnam to a mother with mental illness. Little is known about his early history; he spent the first 6 months of his life in an orphanage, followed by foster care and a disrupted adoption. He moved to the U.S. at age 1½ and joined his current adoptive family at age 4 years. Shortly thereafter, James' psychiatric nurse practitioner diagnosed him with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). Pragmatic language and syntax deficits were also noted from an early age.James is now exhibiting anxiety, perseverative beliefs, and regression in his toileting. He began "talking to himself in his room" and using neologisms. A school-based evaluation resulted in educational diagnoses of ADHD and ASD based on social disconnectedness and invading others' personal space. James' parents felt "something else was going on" and sought a second opinion with a multidisciplinary team (consisting of a pediatric psychologist and a developmental pediatrician). Considering James' history, previous assessments, and their assessment battery (Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, and Autism Diagnostic Observation Schedule, and Rorschach Inkblot Test), the team characterized his current symptoms as an emerging psychotic disorder.Several consultations occurred over the next 9 months of the school term. First, clinicians in the psychiatry department confirmed symptoms of functional decline, cognitive disorganization, and hallucinations, which were attributed to post-traumatic stress rather than a psychotic disorder. Second, adding to the diagnostic uncertainty, when James started an atypical antipsychotic medication and was under good symptom control, the school team believed that ADHD-not psychosis-best accounted for his presentation. There was significant contention between the medical team and consulting school psychologist regarding the extent to which data from the parental history and Rorschach should be considered in formulating the patient's diagnosis.Two-and-a-half years later, James was weaned off risperidone to manage a new side effect of tics. He subsequently manifested significant paranoia with reactive aggression toward peers for imagined slights and insults that he could "swear he heard." A different school-contracted psychologist's re-evaluation corroborated the diagnosis of schizophrenia based on the several years of unfolding clinical observations. Acting from the supposition that early-onset psychosis was too rare and too stigmatizing a condition to apply to a "kid who's just having trouble paying attention," the first school psychologist remained adamant that ADHD and ASD were the most appropriate diagnoses, and James would be ill-served "pumped full of neuroleptics."He returns now to the original Developmental Behavioral Pediatric consulting team. What would you do to try to bridge this impasse?

Brief Report: Mapping Systems of Support and Psychological Well-Being of Mothers of Adolescents with Autism Spectrum Disorders.

Parents of children with autism spectrum disorders are generally known to experience elevated levels of stress and poorer psychological well-being. To provide treatments and resources that most effectively support parent mental health, it is critical to understand how parents' connections with various networks and systems impact their well-being. This study examined the relationship between the psychological well-being of mothers of adolescents with ASD (n = 20) and their systems of support from an ecological systems theoretical framework. Findings indicated that most connections across mothers' ecosystems were strong in nature. However, the presence of strong connections was not significantly related to psychological well-being. In contrast, stressful/weak connections were significantly related to elevated levels of depressive symptoms, perceived stress, and sense of burden.