Advances in wearables and digital technology now make it possible to deliver behavioral mobile health interventions to individuals in their everyday life. The micro-randomized trial (MRT) is increasingly used to provide data to inform the construction of these interventions. In an MRT, each individual is repeatedly randomized among multiple intervention options, often hundreds or even thousands of times, over the course of the trial. This work is motivated by multiple MRTs that have been conducted, or are currently in the field, in which the primary outcome is a longitudinal binary outcome. The primary aim of such MRTs is to examine whether a particular time-varying intervention has an effect on the longitudinal binary outcome, often marginally over all but a small subset of the individual's data. We propose the definition of causal excursion effect that can be used in such primary aim analysis for MRTs with binary outcomes. Under rather restrictive assumptions one can, based on existing literature, derive a semiparametric, locally efficient estimator of the causal effect. We, starting from this estimator, develop an estimator that can be used as the basis of a primary aim analysis under more plausible assumptions. Simulation studies are conducted to compare the estimators. We illustrate the developed methods using data from the MRT, BariFit. In BariFit, the goal is to support weight maintenance for individuals who received bariatric surgery.

Objective

This study tested the effect of beginning treatment with a speech-generating device (SGD) in the context of a blended, adaptive treatment design for improving spontaneous, communicative utterances in school-aged, minimally verbal children with autism.

Method

A total of 61 minimally verbal children with autism, aged 5 to 8 years, were randomized to a blended developmental/behavioral intervention (JASP+EMT) with or without the augmentation of a SGD for 6 months with a 3-month follow-up. The intervention consisted of 2 stages. In stage 1, all children received 2 sessions per week for 3 months. Stage 2 intervention was adapted (by increased sessions or adding the SGD) based on the child's early response. The primary outcome was the total number of spontaneous communicative utterances; secondary measures were the total number of novel words and total comments from a natural language sample.

Results

Primary aim results found improvements in spontaneous communicative utterances, novel words, and comments that all favored the blended behavioral intervention that began by including an SGD (JASP+EMT+SGD) as opposed to spoken words alone (JASP+EMT). Secondary aim results suggest that the adaptive intervention beginning with JASP+EMT+SGD and intensifying JASP+EMT+SGD for children who were slow responders led to better posttreatment outcomes.

Conclusion

Minimally verbal school-aged children can make significant and rapid gains in spoken spontaneous language with a novel, blended intervention that focuses on joint engagement and play skills and incorporates an SGD. Future studies should further explore the tailoring design used in this study to better understand children's response to treatment. Clinical trial registration information-Developmental and Augmented Intervention for Facilitating Expressive Language (CCNIA); http://clinicaltrials.gov/; NCT01013545.

Background

To combat the opioid epidemic in the USA, unprecedented federal funding has been directed to states and territories to expand access to prevention, overdose rescue, and medications for opioid use disorder (MOUD). Similar to other states, California rapidly allocated these funds to increase reach and adoption of MOUD in safety-net, primary care settings such as Federally Qualified Health Centers. Typical of current real-world implementation endeavors, a package of four implementation strategies was offered to all clinics. The present study examines (i) the pre-post effect of the package of strategies, (ii) whether/how this effect differed between new (start-up) versus more established (scale-up) MOUD practices, and (iii) the effect of clinic engagement with each of the four implementation strategies.

Methods

Forty-one primary care clinics were offered access to four implementation strategies: (1) Enhanced Monitoring and Feedback, (2) Learning Collaboratives, (3) External Facilitation, and (4) Didactic Webinars. Using linear mixed effects models, RE-AIM guided outcomes of reach, adoption, and implementation quality were assessed at baseline and at 9 months follow-up.

Results

Of the 41 clinics, 25 (61%) were at MOUD start-up and 16 (39%) were at scale-up phases. Pre-post difference was observed for the primary outcome of percent of patient prescribed MOUD (reach) (β_time = 3.99; 0.73 to 7.26; p = 0.02). The largest magnitude of change occurred in implementation quality (ES = 0.68; 95% CI = 0.66 to 0.70). Baseline MOUD capability moderated the change in reach (start-ups 22.60%, 95% CI = 16.05 to 29.15; scale-ups -4.63%, 95% CI = -7.87 to -1.38). Improvement in adoption and implementation quality were moderately associated with early prescriber engagement in Learning Collaboratives (adoption: ES = 0.61; 95% CI = 0.25 to 0.96; implementation quality: ES = 0.55; 95% CI = 0.41 to 0.69). Improvement in adoption was also associated with early prescriber engagement in Didactic Webinars (adoption: ES = 0.61; 95% CI = 0.20 to 1.05).

Conclusions

Rather than providing an all-clinics-get-all-components package of implementation strategies, these data suggest that it may be more efficient and effective to tailor the provision of implementation strategies based on the needs of clinic. Future implementation endeavors could benefit from (i) greater precision in the provision of implementation strategies based on contextual determinants, and (ii) the inclusion of strategies targeting engagement.

Many preventive trials randomize individuals to intervention condition which is then delivered in a group setting. Other trials randomize higher levels, say organizations, and then use learning collaboratives comprised of multiple organizations to support improved implementation or sustainment. Other trials randomize or expand existing social networks and use key opinion leaders to deliver interventions through these networks. We use the term contextually driven to refer generally to such trials (traditionally referred to as clustering, where groups are formed either pre-randomization or post-randomization - i.e., a cluster-randomized trial), as these groupings or networks provide fixed or time-varying contexts that matter both theoretically and practically in the delivery of interventions. While such contextually driven trials can provide efficient and effective ways to deliver and evaluate prevention programs, they all require analytical procedures that take appropriate account of non-independence, something not always appreciated. Published analyses of many prevention trials have failed to take this into account. We discuss different types of contextually driven designs and then show that even small amounts of non-independence can inflate actual Type I error rates. This inflation leads to rejecting the null hypotheses too often, and erroneously leading us to conclude that there are significant differences between interventions when they do not exist. We describe a procedure to account for non-independence in the important case of a two-arm trial that randomizes units of individuals or organizations in both arms and then provides the active treatment in one arm through groups formed after assignment. We provide sample code in multiple programming languages to guide the analyst, distinguish diverse contextually driven designs, and summarize implications for multiple audiences.

Objective

We sought to examine predictors and moderators of treatment outcomes among 488 youths ages 7-17 years (50% female; 74% ≤ 12 years) meeting Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; American Psychiatric Association, 2000) criteria for diagnoses of separation anxiety disorder, social phobia, or generalized anxiety disorder who were randomly assigned to receive either cognitive behavioral therapy (CBT), sertraline (SRT), their combination (COMB), or medication management with pill placebo (PBO) in the Child/Adolescent Anxiety Multimodal Study (CAMS).

Method

Six classes of predictor and moderator variables (22 variables) were identified from the literature and examined using continuous (Pediatric Anxiety Ratings Scale; PARS) and categorical (Clinical Global Impression Scale-Improvement; CGI-I) outcome measures.

Results

Three baseline variables predicted better outcomes (independent of treatment condition) on the PARS, including low anxiety severity (as measured by parents and independent evaluators) and caregiver strain. No baseline variables were found to predict Week 12 responder status (CGI-I). Participants' principal diagnosis moderated treatment outcomes but only on the PARS. No baseline variables were found to moderate treatment outcomes on Week 12 responder status (CGI-I).

Discussion

Overall, anxious children responded favorably to CAMS treatments. However, having more severe and impairing anxiety, greater caregiver strain, and a principal diagnosis of social phobia were associated with less favorable outcomes. Clinical implications of these findings are discussed.

Objective

To evaluate changes in the trajectory of youth anxiety following the introduction of specific cognitive-behavior therapy (CBT) components: relaxation training, cognitive restructuring, and exposure tasks.

Method

Four hundred eighty-eight youths ages 7-17 years (50% female; 74% ≤ 12 years) were randomly assigned to receive either CBT, sertraline (SRT), their combination (COMB), or pill placebo (PBO) as part of their participation in the Child/Adolescent Anxiety Multimodal Study (CAMS). Youths in the CBT conditions were evaluated weekly by therapists using the Clinical Global Impression Scale-Severity (CGI-S; Guy, 1976) and the Children's Global Assessment Scale (CGAS; Shaffer et al., 1983) and every 4 weeks by blind independent evaluators (IEs) using the Pediatric Anxiety Ratings Scale (PARS; RUPP Anxiety Study Group, 2002). Youths in SRT and PBO were included as controls.

Results

Longitudinal discontinuity analyses indicated that the introduction of both cognitive restructuring (e.g., changing self-talk) and exposure tasks significantly accelerated the rate of progress on measures of symptom severity and global functioning moving forward in treatment; the introduction of relaxation training had limited impact. Counter to expectations, no strategy altered the rate of progress in the specific domain of anxiety that it was intended to target (i.e., somatic symptoms, anxious self-talk, avoidance behavior).

Conclusions

Findings support CBT theory and suggest that cognitive restructuring and exposure tasks each make substantial contributions to improvement in youth anxiety. Implications for future research are discussed. (PsycINFO Database Record