Eliminating Monitor Overuse (EMO) Type III Effectiveness-Deimplementation Cluster-Randomized Trial: Statistical Analysis Plan

Background: Deimplementing overused health interventions is essential to maximizing quality and value while minimizing harm, waste, and inefficiencies. Three national guidelines discourage continuous pulse oximetry (SpO2) monitoring in children who are not receiving supplemental oxygen, but the guideline-discordant practice remains prevalent, making it a prime target for deimplementation. This paper details the statistical analysis plan for the Eliminating Monitor Overuse (EMO) SpO2 trial, which compares the effect of two competing deimplementation strategies (unlearning only vs. unlearning plus substitution) on the sustainment of deimplementation of SpO2 monitoring in children with bronchiolitis who are in room air. Methods: The EMO Trial is a hybrid type 3 effectiveness-deimplementation trial with a longitudinal cluster-randomized design, conducted in Pediatric Research in Inpatient Settings Network hospitals. The primary outcome is deimplementation sustainment, analyzed as a longitudinal difference-in-differences comparison between study arms. This analysis will use generalized hierarchical mixed-effects models for longitudinal clustering outcomes. Secondary outcomes include the length of hospital stay and oxygen supplementation duration, modeled using linear mixed-effects regressions. Using the well-established counterfactual approach, we will also perform a mediation analysis of hospital-level mechanistic measures on the association between the deimplementation strategy and the sustainment outcome. Discussion: We anticipate that the EMO Trial will advance the science of deimplementation by providing new insights into the processes, mechanisms, and likelihood of sustained practice change using rigorously designed deimplementation strategies. This pre-specified statistical analysis plan will mitigate reporting bias and support data-driven approaches

Differential treatment effects due to post randomization psychological factors: A causal rank preserving modeling approach

Introduction. There are questions on whether the effectiveness of Beck\u27s cognitive behavioral therapy (CBT) on depression in suicidal patients depends on factors early in the CBT process. Purpose. The causal mediation method of Ten Have et al. (2007) is extended with an interaction to identify early post randomization modifiers of the CBT effect on follow-up depression in suicide attempters. Sample. 120 recent suicide attempters were randomized to either cognitive therapy or usual care to prevent future suicide attempts during 18 months of follow-up (Brown et al., 2005). Method. 1- and 3-month hopelessness and social problem orientation measures were examined as effect modifiers of the CBT effect on 6-month depression with a Rank Preserving Model (RPM; Joffe et al., 1998; Ten Have et al., 2007) that included an interaction term between CBT and a post randomization factor. Comparisons were made with a standard interaction regression model, relying on the strong assumption of no unmeasured confounding of the post randomization moderator-outcome relation. The RPM approach does not make such an assumption but does rely on other potentially testable assumptions. Results. The data analysis showed statistically significant effect modification under the RPM, whereas the standard regression model showed less significant effect modification. Simulation results showed unexpectedly good results for the standard regression model under unmeasured confounding. The RPM performed slightly better with respect to bias of the stratified CBT effect, but worse for the interaction effect. The RPM expectedly showed greater variability than the standard regression model in terms of the mean square error. Discussion. Both the RPM and standard regression methods performed well in simulations, whereas there was some disagreement between the methods for the data analysis. The RPM can be used as a check for unmeasured confounding when using the standard regression model

Differential treatment effects due to post randomization psychological factors: A causal rank preserving modeling approach

Introduction. There are questions on whether the effectiveness of Beck\u27s cognitive behavioral therapy (CBT) on depression in suicidal patients depends on factors early in the CBT process. Purpose. The causal mediation method of Ten Have et al. (2007) is extended with an interaction to identify early post randomization modifiers of the CBT effect on follow-up depression in suicide attempters. Sample. 120 recent suicide attempters were randomized to either cognitive therapy or usual care to prevent future suicide attempts during 18 months of follow-up (Brown et al., 2005). Method. 1- and 3-month hopelessness and social problem orientation measures were examined as effect modifiers of the CBT effect on 6-month depression with a Rank Preserving Model (RPM; Joffe et al., 1998; Ten Have et al., 2007) that included an interaction term between CBT and a post randomization factor. Comparisons were made with a standard interaction regression model, relying on the strong assumption of no unmeasured confounding of the post randomization moderator-outcome relation. The RPM approach does not make such an assumption but does rely on other potentially testable assumptions. Results. The data analysis showed statistically significant effect modification under the RPM, whereas the standard regression model showed less significant effect modification. Simulation results showed unexpectedly good results for the standard regression model under unmeasured confounding. The RPM performed slightly better with respect to bias of the stratified CBT effect, but worse for the interaction effect. The RPM expectedly showed greater variability than the standard regression model in terms of the mean square error. Discussion. Both the RPM and standard regression methods performed well in simulations, whereas there was some disagreement between the methods for the data analysis. The RPM can be used as a check for unmeasured confounding when using the standard regression model

Preparing for Group B Streptococcus vaccine. Attitudes of pregnant women in two countries

Group B Streptococcus (GBS) vaccines, designed to be given to pregnant women, are in clinical trials. There is an opportunity to conduct preparatory research now to understand the drivers of and barriers to GBS vaccine acceptance. This will enable targeted interventions so that delays in vaccine uptake might be avoided. A multicenter, mixed-methodology, cross-sectional study evaluated the acceptability of a hypothetical GBS vaccine among pregnant women in two countries with differing health systems. Pregnant women in Philadelphia, US, and Dublin, Ireland, completed an electronic survey and a Discrete Choice Experiment. Five hundred and two women were included in the final analysis. Fifty-three percent of US and 30% of Irish participants reported both awareness and understanding of GBS. The median likelihood score for vaccine receipt (measured on a 10-point scale) was 9 (US: 9 (IQR 7–10), IRL: 9 (IQR 6–10)). Among the US participants, identifying as Black or African American was associated with a lower likelihood of vaccine receipt. Possession of a college degree was associated with increased likelihood of vaccine receipt. Perceived infant benefit was the most important driver of GBS vaccine acceptance. Safety concerns about a novel vaccine was the most prominent barrier identified. Good GBS vaccine uptake is achievable through strong messaging that highlights vaccine safety and the potential infant benefits. Preparation for vaccine implementation should include efforts to increase awareness among pregnant women about GBS infection and a continued focus on improving acceptability of currently recommended maternal vaccines, particularly in population subgroups with low uptake of maternal immunizations

Emerging Methodologies in Pediatric Palliative Care Research: Six Case Studies

Given the broad focus of pediatric palliative care (PPC) on the physical, emotional, and spiritual needs of children with potentially life-limiting illnesses and their families, PPC research requires creative methodological approaches. This manuscript, written by experienced PPC researchers, describes issues encountered in our own areas of research and the novel methods we have identified to target them. Specifically, we discuss potential approaches to: assessing symptoms among nonverbal children, evaluating medical interventions, identifying and treating problems related to polypharmacy, addressing missing data in longitudinal studies, evaluating longer-term efficacy of PPC interventions, and monitoring for inequities in PPC service delivery

Prioritization of pediatric palliative are field-advancement activities in the United States: Results of a national survey

BACKGROUND: The field of pediatric palliative care (PPC) continues to encounter challenges and opportunities to improving access to high-quality PPC services. In early 2019, a workshop identified eleven potential next step actions, and subsequently a national survey-based poll of members of the PPC community was conducted to prioritize these potential actions in terms of their actionable importance. METHODS: Invitations to the survey were distributed in October 2019 to interdisciplinary PPC health care professionals via email to two major listservs, one hosted by the Section of Hospice and Palliative Medicine of the American Academy of Pediatrics, the other by the Center to Advance Palliative Care. Respondents rated the actionable importance of items relative to each other via a discrete choice experiment. Median importance scores are reported for each item. RESULTS: 177 individuals responded to the survey. The majority (62.2%) were physicians, with nurses (16.4%), advanced practice nurses (7.9%), and social workers (7.3%) being the other most common responders. The top 5 potential actions, in descending rank order, were: Determine what parents value regarding PPC (median score of 17.8, out of a total score of all items of 100); Define and disseminate core primary PPC curriculum (median, 15.3); Develop PPC national representation strategy and tactics (median, 12.3); Create PPC-specific program development toolkit (median, 10.9); and, Analyze payment and financing ratios (median, 9.6). CONCLUSIONS: Those seeking to advance the field of PPC should take into account the findings from this study, which suggest that certain actions are more likely to have a beneficial impact on moving the field forward