Fidelity Measures Research Articles (Page 1)

Purpose: This pilot study examined the feasibility and acceptability of a collaborative social worker–teacher model for delivering group cognitive behavioral therapy for anxiety (GCBT-A) in school settings. Method: Forty-six children (ages 9–11) were randomly allocated to an 8-week GCBT-A or treatment as usual (TAU). Teachers delivered GCBT-A under social worker supervision. Feasibility was assessed through attendance, satisfaction, and fidelity measures. Effectiveness was evaluated using anxiety, depression, and externalizing problem scales. Results: High feasibility was demonstrated with 96.87% attendance, 0% attrition, and high fidelity (0.78–1.00). GCBT-A showed significantly greater improvements than TAU on anxiety, with Cohen's d of −0.66 for Generalized Anxiety Disorder 7-item scale (GAD-7) and −0.56 for SCARED, depression ( d = −0.66), and externalizing problems ( d = −0.56). Qualitative findings indicated high participant satisfaction and perceived benefits from the intervention. Conclusions: The collaborative model is feasible and acceptable with preliminary effectiveness evidence. Larger trials are needed to assess long-term outcomes and scalability in Chinese school settings. The study was registered in the Chinese Clinical Trial Registry (ChiCTR 2300076460), https://www.chictr.org.cn/ .

Recovery Colleges (RCs) are increasingly implemented worldwide, with a fidelity measure recently developed in the United Kingdom (UK). However, RCs may vary based on their operating contexts. In the Netherlands, a key deviation is that RCs are often peer-run rather than co-produced with mental healthcare providers, as outlined in the fidelity measure. This study assessed the measure's suitability in the Dutch context, leading to the development of a reflection tool (Phase 1) which was subsequently evaluated (Phase 2). The development phase involved focus groups with peer facilitators and coordinators from 16 RCs (N = 29) to capture critical elements of Dutch RCs. The tool was piloted (N = 5) and evaluated more broadly (N = 24). The tool provided valuable insights, highlighting shared values among RCs internationally and conceptual differences between Dutch and UK models. The findings raised questions about the boundaries of fidelity in co-created contexts such as RCs.

Introduction Advance care planning (ACP) is supported by evidence, legal and ethical principles and ACP guidelines. However, this complex intervention is often poorly implemented. This article presents a novel fidelity scale to measure the implementation of ACP and reports the preliminary testing of the scale at baseline in a larger trial aiming at implementing ACP in hospitals in Norway. Method The research design conducted was a cross-sectional measurement of fidelity to guidelines, conducted in 12 geriatric hospital units in Norway recruited using purposive sampling. The sample size for the larger trial was determined, based on prior research, to be at least four clusters in each arm. Due to the possibility of unit drop-out during the project period and to secure sufficient power, we included six units in the intervention arm and six in the control arm. For the baseline measurement we developed an ACP fidelity scale including three subscales: implementation, quality and penetration rate, each with 4–11 items. We ensured face and content validity through input from relevant theories and research, experts and users. Items were scored from 1 to 5, with 1 indicating no implementation and 5 indicating full implementation. Data was analyzed using descriptive statistics, Cronbach's alpha and calculation of interrater reliability for the scales. Further psychometric testing could not be conducted at this stage due to the lack of variance in the items. Results The mean score for the implementation subscale was 1.213, with a median of 1, a standard deviation (SD) of 0.08, a standard error (SE) of 0.01, a variance of 0.01, and a range of 0.28 (minimum 1.14 and maximum 1.42). The scores in the subscale showed that none of the units had recommended implementation measures. Only a few professionals reported they had heard of ACP, but not the whole staff. Cronbach's alpha could not be estimated due to the lack of variation in the scores for this subscale. On the quality subscale, which assesses whether ACP is practiced in accordance with practice guidelines, the mean score was 1.11, the median was 1, the SD was 0.48, the SE was 0.06, the variance was 0.13, and the range was 1.27 (minimum 1 and maximum 2.27). The scores in this subscale showed that ACP was practiced sporadically by the palliative care team in only one unit, while the other staff did not engage in this practice at all. Cronbach's alpha for the subscale on quality was 0.887 (11 items) showing an acceptable internal consistency. For the penetration rate subscale, which measures how widespread the practice is, the mean score was 1.08, the median was 1, the SD was 0.28, the SE was 0.05, the variance was 0.08, and the range was from a minimum of 1 to a maximum of 2. Among the total number of admitted geriatric patients, only 10% had received ACP in only one of the 12 units. Also, for this subscale, the model for Cronbach's alpha could not be applied. There was little variation in the low measurements, thus the interrater reliability was high, reflected in the Intraclass Correlation Coefficient (ICC). The ICC was 0,916 [−0,721,0.976] for the implementation subscale, 1.00 for the quality subscale, and 1.00 for the penetration rate subscale. Conclusion Our findings indicate very low implementation of ACP in acute geriatric hospital units in Norway. The newly developed ACP fidelity scale has the potential to serve as an important tool for improving the quality of healthcare services for older patients. However, more data is needed to validate the psychometric properties of the scale. Our study should be considered as a preliminary study, and the scale should be used with caution as long as its properties are not well validated. Clinical Trial Registration ClinicalTrials.gov , NCT05681585.

Social spending refers to public or private funds aimed at helping vulnerable groups. Evidence-based decision-making supports social spending by applying existing evidence to inform funding and involves integrating relevant information from various sources, such as experimental studies and community feedback. Online clearinghouses support evidence-based decision-making by synthesizing evidence on what works, though manually updating literature is incomplete. In addition, passively summarizing evaluations is insufficient for end-users to implement preventive solutions that achieve population impacts. A responsive platform and a dissemination plan are needed to encourage the uptake of equitable and culturally relevant preventive interventions grounded in transparency and rigorous evidence of effectiveness. A two-part conceptual framework is proposed for a clearinghouse platform that integrates stepwise, interactive, AI-driven capabilities safeguarded by human touchpoints. First, clearinghouses should adopt a "living" review to automatically update evaluations-an approach embraced globally by organizations such as the World Health Organization, Cochrane Collaboration, and the U.N.'s Pan American Health Organization. The second component involves adding a chatbot to support assessment and implementation guidance and make recommendations on (1) the provision of all evidence-based preventive interventions (EBPIs) and their key activities, (2) EBPIs shown to achieve equitably distributed outcomes, (3) culturally relevant EBPIs that align with the values and needs of a target population, (4) implementation support, such as materials, training, and fidelity measures, and (5) delivery costs. The resulting platform will ethically expedite the translational process of identifying and scaling EBPIs, leading to a more complete, comprehensive, and accessible body of evidence on effective preventive strategies.

Generative Artificial Intelligence (AI) has the potential to address the limited availability of dental radiographs for the development of Dental AI systems by creating clinically realistic synthetic dental radiographs (SDRs). Evaluation of artificially generated images requires both expert review and objective measures of fidelity. A stepwise approach was used to processing 10,000 dental radiographs. First, a single dentist screened images to determine if specific image selection criterion was met; this identified 225 images. From these, 200 images were randomly selected for training an AI image generation model. Second, 100 images were randomly selected from the previous training dataset and evaluated by four dentists; the expert review identified 57 images that met image selection criteria to refine training for two additional AI models. The three models were used to generate 500 SDRs each and the clinical realism of the SDRs was assessed through expert review. In addition, the SDRs generated by each model were objectively evaluated using quantitative metrics: Fréchet Inception Distance (FID) and Kernel Inception Distance (KID). Evaluation of the SDR by a dentist determined that expert-informed curation improved SDR realism, and refinement of model architecture produced further gains. FID and KID analysis confirmed that expert input and technical refinement improve image fidelity. The convergence of subjective and objective assessments strengthens confidence that the refined model architecture can serve as a foundation for SDR image generation, while highlighting the importance of expert-informed data curation and domain-specific evaluation metrics.

BackgroundAutism and ADHD are heritable, co-occurrent, and associated with difficulties with executive functioning (cognitive and self-regulation skills which enable us to set and work toward goals). Executive function difficulties, and their negative impacts across cognitive, health and social domains, extend to individuals with first-degree relatives who are autistic or have ADHD, even if they do not meet thresholds for a clinical diagnosis themselves. Supporting executive function development in children with elevated autism traits, or a first-degree relative with autism or ADHD, addresses community priorities for early support to help achieve the best mental health, education and life outcomes.MethodsThis study will evaluate the feasibility and acceptability of a randomized controlled trial (RCT) of a parent-toddler programme entitled “Supporting Toddlers with a connection to autism or ADHD to develop strong Attention, Regulation and Thinking skills” (START). START is a neurodiversity-affirming programme, co-refined through extensive Patient and Public Involvement. Sixty parent-child dyads, in Oxford or Southampton (UK), will be randomized using Sealed Envelope by a researcher not involved in recruitment, delivery or outcome data collection to receive START or usual practice, on a 1:1 ratio. Children (20 months old) will be assessed using questionnaires completed by the parent (not blind to allocation) post-intervention (within 2 weeks of the end of the active intervention wave, when children are aged 27–31 months), and using parent questionnaires and a battery of executive function measures administered by researchers blind to allocation at baseline and follow-up (36 months old). START will be delivered in small groups to 30 parent-child dyads, in community settings.DiscussionWe will assess the feasibility of recruiting eligible participants to the study, the reliability of measures of implementation fidelity and degree of implementation fidelity achieved, the appropriateness of proposed outcome and mechanism measures, the acceptability of an RCT of the programme, parental adherence to the programme, logistics of programme delivery, and the acceptability of START, using mixed-method measures of engagement and satisfaction. Results will inform the design and implementation of a definitive RCT of START, and yield broader insights into the delivery and evaluation of complex early-years interventions in community settings.Trial registrationISRCTN registry ISRCTN99820028 https://doi.org/10.1186/ISRCTN99820028.

A framework for monitoring intervention fidelity: The NOURISH trial.

Fidelity measurement is critical to ensuring that mental health interventions are delivered as intended and achieve meaningful outcomes. However, conventional fidelity tools often face challenges in real-world mental health settings, including limited usability, high resource demands, and poor contextual fit. Human-centered design (HCD) offers a promising, participatory approach to developing pragmatic fidelity tools that are usable, acceptable, and sustainable. HCD emphasizes empathy, co-creation, iterative testing, and stakeholder engagement—principles that align closely with implementation science priorities in mental health. This mini-review synthesizes current applications of core elements of HCD in fidelity measurement for mental health interventions. Drawing on case examples from youth services, community mental health, culturally adapted programs, and digital health platforms, we illustrate how HCD can enhance tool relevance, promote equity, and support sustained adoption. We also explore tensions in co-design processes, including balancing scientific rigor with adaptability, and managing resource constraints. Despite these challenges, integrating HCD into fidelity work can improve alignment with service realities, increase stakeholder ownership, and ultimately strengthen intervention quality and equity. We recommend embedding HCD principles within implementation frameworks and expanding support for participatory fidelity development. By tailoring fidelity tools to the dynamic contexts of mental health care, HCD can help bridge the gap between evidence and practice and improve mental health outcomes across diverse populations.

Recovery Colleges (RCs) offer an innovative model of mental health support that blends co-production with adult learning to promote personal recovery and social inclusion. While evidence supports their effectiveness, most RC research and practice have been developed in Western contexts, raising concerns about cross-cultural applicability. The RECOLLECT Change Model (RCM) and RECOLLECT Fidelity Measure (RFM) were developed in England to characterise RC mechanisms and assess fidelity. Our previous studies have identified cultural influences on the RC operational model, however how to address these influences remains unknown. Given the increasing global interest in RCs, the aims of this study are to (a) identify the level of cultural influence on the RCM mechanisms and RFM items, and (b) provide recommendations to inform cross-cultural applicability of RCM and RFM. This global Delphi study follows Belton's six-step methodology and uses a decentring approach to cross-cultural research that seeks to extend the relevance of tools developed in a single culture to multiple cultural contexts. Experts will be recruited via the RECOLLECT International Research Consortium, covering 31 countries across six continents. We aim to recruit approximately 100 panellists with at least three years' RC experience. Data collection will occur via Microsoft Forms across iterative Delphi rounds. Panellists will rate the importance and cultural difficulty of RCM and RFM items, provide feedback on culturally aligned response types, and suggest revisions for improved cultural fit. Quantitative data will be analysed using non-parametric statistics and a collapsed three-point Likert scale to address cross-cultural response bias. Qualitative responses will be analysed using descriptive content analysis informed by Hofstede's cultural dimension theory. Member checking will be conducted after the final round to enhance trustworthiness. This study will identify which RCM and RFM components are cross-culturally applicable and which require adjustment, contributing to the balance between fidelity and fit in mental health approaches. By developing culturally informed recommendations, this study aims to expand the accessibility and relevance of RC frameworks across diverse settings. Findings will benefit RC practitioners, researchers, and policymakers seeking to improve service delivery and recovery outcomes in culturally meaningful ways.

This study aimed to assess the feasibility and preliminary outcomes of the SEE Learning® (Social, Emotional, and Ethical Learning) program among elementary school-aged children. A quasi-experimental design was employed, with 685 4th- and 5th-grade students across 33 classrooms (344 students received the 12-week SEE Learning program; 341 students were wait-list controls). Assessments of compassion for self and others, social and emotional competencies, and the degree to which students perceived their classrooms as supportive were collected before and after program implementation. Measures of dosage, fidelity, and acceptability were assessed via teachers' weekly lesson diaries. Teachers reported the program was feasible to implement. They demonstrated high lesson completion and fidelity rates with minimal preparation time and strong adherence to the lesson structure. Most program activities fit within a 50-minute timeframe or less, reflecting the program's suitability for elementary school settings. Student reports showed preliminary impacts of the program. Those who received SEE Learning reported significant improvements in self-compassion, perspective-taking, empathic concern (e.g., compassion for others), intrinsic prosocial motivation, and academic goal setting compared to students in the wait-list control group. This study is among the first to demonstrate the feasibility and preliminary student impacts of the compassion-focused SEE Learning program in an elementary school setting. Future investigations might explore the implementation and effects of the SEE Learning program using randomized-controlled experimental designs and longer-term follow-ups. In addition, studies evaluating program implementation and impacts in diverse cultural-contextual settings, and among students of different ages, are needed. In sum, the SEE Learning program shows evidence of promise for impacting elementary school students' prosocial skills and competencies.

BackgroundDigital adherence technologies (DATs) are promising tools for supporting tuberculosis (TB) treatment. DATs can serve as reminders for people with TB to take their medication and act as proxies for adherence monitoring. Strong engagement with DATs, from both the person with TB and health care provider (HCP) perspectives, is essential for ensuring intervention fidelity. The Adherence Support Coalition to End TB (ASCENT) project evaluated 2 types of DATs, pillboxes and medication labels (99DOTS), in cluster-randomized trials across 5 countries.ObjectiveThis study aims to investigate participant and HCP engagement with DATs for TB treatment, stratified by DAT type and country.MethodsThis study is a subanalysis of data generated through the ASCENT trials, which enrolled adults with drug-susceptible TB. A digital dose was defined as either a pillbox opening (for pillbox users) or a dosing confirmation SMS text message sent by the participant (for label users), both of which were recorded on the adherence platform. Descriptive analysis was used to provide an overview of dose-day outcomes. DAT engagement was assessed from both participant and HCP perspectives. To enhance participant engagement, we summarized the frequency of digital engagement overall and by treatment phase, as well as the frequency of consecutive days without engagement. For HCP engagement, we summarized the frequency of doses added manually, the number of days between the actual dose day and when a manual dose was added, and instances of consecutive manual dosing lasting more than 3 and more than 7 days, where doses were added more than 1 week after the dose day.ResultsOf the 9511 participants included, 6719 (70.64%) were using the pillbox, 3544 (37.26%) were female, and the median age was 40 years. Across DAT types, there were 1,384,879 dose days, with 973,876 (70.32%) contributed by pillbox users. Of all dose days, 1,165,195 (84.14%) were recorded as digital, 156,664 (11.31%) as manual, 59,045 (4.26%) had no information, and 3975 (0.29%) were confirmed as missed. Digital dosing decreased slightly from the intensive to the continuation phase. The percentage of digital dose days was higher among pillbox users (851,496/973,876, 87.43%) compared with label users (313,699/411,003, 76.33%). Among label users, manual dosing was most common in the Philippines (37,919/171,786, 22.07%) and least common in Tanzania (11,108/76,231, 14.57%). Among pillbox users, manual dosing was most common in the Philippines (24,015/208,130, 11.54%) and Ukraine (13,209/111,901, 11.80%). Overall, 512 out of 2792 (18.34%) label users and 588 out of 6719 (8.75%) pillbox users experienced a run of more than 7 consecutive nondigital dose days that were resolved more than 1 week after the dose day. The highest occurrence was observed in the Philippines (368/1142, 32.22%, for label users and 224/1351, 16.58%, for pillbox users).ConclusionsThere was considerable variation in DAT engagement across countries and DAT types, reflecting differences in how the intervention was implemented. Further refinement of the intervention and improvements in its delivery may be necessary to enhance outcomes.

ABSTRACTThe present study is the first systematic review of instructional coaching components, methodologies, and outcomes reported in experimental and quasi‐experimental group design studies examining the impact of coaching for school personnel supporting elementary‐grade students with reading difficulties. Published and unpublished investigations (n = 30) from 2000 to 2023, which included 1863 teachers and interventionists and 21,133 kindergarten through 5‐grade students with reading difficulties, were reviewed. All studies were reviewed using a structured review coding system with four dimensions (i.e., sample characteristics, coaching model elements, methodologies used, and outcomes reported; n = 77 variables). Strengths of reviewed coaching studies were the inclusion of multicomponent professional development with implementation training, diversity in student samples, and the use of statistical testing and reporting of effect sizes. Overall, 27 studies (90%) reported positive improvements in student reading performance at post‐intervention. However, details reported for implementer and student characteristics, professional development components, and reading interventions implemented varied. Weaknesses of the literature were a lack of the following: participant inclusion and exclusion criteria, utilization of coaching in the use of reading screening and diagnostic measures to identify student skill‐specific needs, implementation fidelity measurement, and follow‐up data collection. Implications for research and practice are offered.

We explore the principles of many-body Hamiltonian complexity reduction via downfolding on an effective low-dimensional representation. We show that the renormalization factor provides a unique measure of the quality of the compression as it directly represents the projection between the approximate stationary state of the many-body Hamiltonian and the full many-body wavefunction. Hence, the renormalization factor is a measure of fidelity between the effective (reduced-rank) description and the full many-body treatment for arbitrary (i.e., ground and excited) states. When the entire problem is mapped on a system of interacting quasiparticles [Romanova et al., npj Comput. Mater. 9, 126 (2023)], the effective Hamiltonians can faithfully reproduce the physics only when a clear energy scale separation exists between the subsystems and their environment. We also demonstrate that it is necessary to include quasiparticle renormalization at distinct energy scales, capturing the distinct interaction between subsystems and their surrounding environments. Numerical results from simple, exactly solvable models highlight the limitations and strengths of this approach, particularly for ground and low-lying excited states. This work lays the groundwork for applying dynamical downfolding techniques to problems concerned with (quantum) interfaces.

Monitoring treatment fidelity is critical to the development and delivery of high-quality interventions. A growing body of research has emerged related to the development and implementation of treatment fidelity measures. The present study extends the implementation of science literature by developing and piloting a multidimensional treatment fidelity measure unique to social competence interventions. The evaluation process involved the assessment of interrater reliability, fidelity scores across groups, and student outcomes within a randomized control trial study. Results encompass two years of data collection and articulate the use of the fidelity measure during the delivery of core components of social competence programming.

BackgroundMultisite implementation research in justice and health settings often does not systematically assess differential degrees of project involvement among participating sites, despite its implications for both research and the intervention. Tracking organization and participant involvement across sites, when attempted, has typically entailed the use of discrete and sometimes disjointed fidelity measures that may not accurately reflect engagement with a project. This article advances a more comprehensive and sophisticated conceptual model for measuring and monitoring site engagement. This conceptual model was developed from a literature review of the implementation science and related disciplines while being informed by multisite project implementation experience. We propose the Site Engagement Activity Model Leveraging Implementation Science (SEAMLIS), a conceptual model that holistically identifies the breadth of agency participation (diverse activities such as trainings, meetings, etc.) and duration of site engagement (participation levels from inception to completion) to be measured, assessed, and reported.Case presentationWe also describe Juvenile Justice Translational Research on Interventions for Adolescents in the Legal System (JJ-TRIALS), a 36-site implementation research project, as an illustrative case example of our proposed model. We then operationalize all proposed domains and subdomains and specify key measures from the project.ConclusionsWe provide analytical recommendations for the application and future research of the proposed model in health and justice settings. In multisite implementation research, site engagement could be fruitfully used as an independent, dependent, or intervening (moderating or mediating) variable.Trial registrationNCT02672150, February 3, 2016.

“How do you know you know that you're doing ACT?” An experimental study of simulated therapy sessions to explore the measurement properties of the Acceptance and Commitment Therapy Fidelity Measure (ACT-FM)

Serious workforce shortages in youth mental health widen the gap between demand and use, and exacerbate health disparities. A strategy to address this is training and integrating youth and young adult (Y/YA) peers to deliver services. This paper reviews international scientific studies on Y/YA services targeting mental health conditions or health promotion. We applied systematic criteria including controlled designs (RCTs or quasi-experimental), active intervention delivered by a young person, key search terms, and peer-reviewed publication between 2012 and 2023. The review yielded 32 studies meeting criteria, encompassing six domains: eating disorders, health promotion, depression/anxiety, suicidal risk, serious mental illness (SMI) and "other." The most consistent evidence for effectiveness was for eating disorders; findings in the other domains were mixed. Training manuals, fidelity measurement, reporting of demographic data, and consistency in outcome measurement were largely absent, limiting both replicability and generalizability. The acceleration of scientific attention to youth/young adult peer services over the past decade and emerging support for its effectiveness is encouraging, however, and it bodes well for mitigating workforce shortages and, more importantly, for improving the quality of services for young people.

Adolescents face increased vulnerability to mental health conditions, particularly when exposed to multidimensional poverty and trauma and pronounced treatment gaps. Waves for Change, a Sport for Development (SfD) intervention, employs task-sharing through its ‘5-Pillar Method’ to build resilience and prevent mental health conditions among at-risk adolescents in South Africa. This study assessed the implementation outcomes of this Method using a mixed-methods design, incorporating interviews, focus groups, self-report questionnaires, document reviews and routine site assessments, with 69 stakeholders including staff, peer coaches, mental healthcare providers, social workers, teachers, and adolescents. A thematic analysis revealed key facilitators to successful implementation, including: a year-long preventative approach, creation of safe spaces for learning self-regulation skills, employment of youth coaches from local communities, incorporation of fun, group-based physical activities, modelling and repetition of desired skills, provision of transport and meals, government partnerships, and consistent weekly training and supervision. Implementation challenges included coach capacity, due to their education levels and own trauma experiences, measurement of fidelity to the Method and of adolescents’ emotional experiences, and some concerns around ocean safety. These findings provide valuable insights for implementing community-based SfD interventions for adolescents facing adversity, and contributes towards global evidence supporting task-shared mental health approaches in LMICs.

BackgroundRespiratory illness is consistently the leading cause of death and hospitalization in severe cerebral palsy (CP). Respiratory Exacerbations-Plan for Action and Care Transitions (RE-PACT) is a just-in-time adaptive intervention to prevent respiratory illness in severe CP. RE-PACT combines early illness detection with rapid clinical response to address varying causes of respiratory illness early enough to modify illness trajectory. This study’s objective was to determine RE-PACT’s feasibility, acceptability, fidelity, and estimated effect size.MethodsThis two-site randomized controlled trial occurred from April 2022-February 2024 in demographically and geographically distinct locations. Caregiver-child pairs were recruited from complex care programs, and children had both gross motor function classification system level 4–5 CP and either pulmonologist care or daily respiratory treatments. Children were randomized to usual care or RE-PACT for six months. Primary outcomes were feasibility, acceptability, and fidelity measures having a priori definitions of success. The primary clinical outcome was the severe respiratory illness (SRI) event rate, defined as hospitalizations due to respiratory diagnoses. Clinicaltrials.gov registration is NCT05292365.ResultsSixty children were enrolled, of which 26 were randomized into RE-PACT. Measures confirmed RE-PACT’s feasibility, acceptability, and fidelity, e.g., text message response rates were 97.5%, and no action planning or clinical responder activities were missed. System usability scale scores were “good to excellent” (mean [SD], 79.5 [11.7]). The RE-PACT SRI event rate (95% confidence interval, CI) was 0.71 (0.36–1.14) per person-year compared to the usual care event rate 1.08 (0.61–1.91) per person-year, a risk ratio of 0.66 (0.28–1.56). Secondary outcomes and qualitative data reinforced RE-PACT’s positive impact.ConclusionsRE-PACT is a feasible, acceptable intervention that can be delivered with high fidelity to diverse families caring for children with severe CP. These data inform the sample and design characteristics needed for efficacy testing of RE-PACT’s ability to prevent severe respiratory illness.

SummaryWe present a method that quantifies nearly all pairwise amino acid substitutions, revealing the rates and spectra of mistranslation per amino acid and per codon. While determining error rates is illuminating, understanding why certain mistranslation events are enriched requires further exploration, particularly in relation to the translation-accuracy hypothesis. We found that codons favored in highly expressed genes are not predictive of translational fidelity and are not selected for translational accuracy. We evaluated our method using historically characterized ribosomal variants of Escherichia coli reported to differ in translation fidelity. However, we found no significant differences among their overall translation-error rates, estimated here to be ~2 per 1,000 amino acids. Instead they each exhibited unique mistranslation profiles, which likely led to prior overestimates of the translation error-rate in the putative error-prone variant. Together, these results underscore the significance of a direct, proteome-wide measure of translation fidelity.