Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Shared Decision Making Following a Large-Scale EBP Implementation Effort in Publicly-Funded Children’s Mental Health Services: A Focus on Latinx Caregivers

This dissertation used observational methods to examine shared-decision making (SDM) as a potential engagement strategy for caregivers of Latinx youth within the context of multiple EBP delivery. Results revealed that community therapists used SDM in most sessions about varied types of decisions, but only at modest levels. We did not find an association between global measurements of SDM and therapeutic bond elements

Recommendations for Writing a National Institutes of Health Individual Predoctoral Fellowship (F31) Training Grant in Dissemination and Implementation Science

Early career training is an essential component of building the future of dissemination and implementation (D&I) science. The United States National Institutes of Health Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (F31) award offers a mechanism for doctoral students to acquire specialized D&I training and mentorship, to pursue independent research in D&I science, and to receive financial support for their graduate studies. Due to scarce resources on preparing early career grant proposals focused on D&I science, this commentary offers guidance to doctoral students on developing a successful application for a specific type of early career proposal - the NIH F31 mechanism. We offer strategies for the research and training components based on themes identified across six funded F31 grant applications and on our experiences in the application process (grants funded from 2019-2020). We are from diverse fields (clinical psychology, school psychology, public health, and epidemiology) with varied research foci (global health, mental health, and infectious diseases). Applications were funded on both the F31 and F31-Diversity mechanisms. Funded F31 research projects included dissemination strategies, treatment adaptions, piloting new methods, and pre-implementation inquiry. Common training goals included developing content expertise in D&I science, understanding specific D&I science methodologies, learning strategies for working with community partners, and enhancing knowledge of analytic methods. D&I training activities included journal clubs, meeting with consultants, attending D&I science trainings, and attending conferences. Mentored research training is essential for learning D&I science methods and developing research-practice partnerships as students

Comparing organization-focused and state-focused financing strategies on provider-level reach of a youth substance use treatment model: a mixed-method study.

BACKGROUND: Financial barriers in substance use disorder service systems have limited the widespread adoption-i.e., provider-level reach-of evidence-based practices (EBPs) for youth substance use disorders. Reach is essential to maximizing the population-level impact of EBPs. One promising, but rarely studied, type of implementation strategy for overcoming barriers to EBP reach is financing strategies, which direct financial resources in various ways to support implementation. We evaluated financing strategies for the Adolescent Community Reinforcement Approach (A-CRA) EBP by comparing two US federal grant mechanisms, organization-focused and state-focused grants, on organization-level A-CRA reach outcomes. METHOD: A-CRA implementation took place through organization-focused and state-focused grantee cohorts from 2006 to 2021. We used a quasi-experimental, mixed-method design to compare reach between treatment organizations funded by organization-focused versus state-focused grants (164 organizations, 35 states). Using administrative training records, we calculated reach as the per-organization proportion of trained individuals who received certification in A-CRA clinical delivery and/or supervision by the end of grant funding. We tested differences in certification rate by grant type using multivariable linear regression models that controlled for key covariates (e.g., time), and tested threats to internal validity from our quasi-experimental design through a series of sensitivity analyses. We also drew on interviews and surveys collected from the treatment organizations and (when relevant) interviews with state administrators to identify factors that influenced reach. RESULTS: The overall certification rates were 27 percentage points lower in state-focused versus organization-focused grants (p = .01). Sensitivity analyses suggested these findings were not explained by confounding temporal trends nor by organizational or state characteristics. We did not identify significant quantitative moderators of reach outcomes, but qualitative findings suggested certain facilitating factors were more influential for organization-focused grants (e.g., strategic planning) and certain barrier factors were more impactful for state-focused grants (e.g., states finding it difficult to execute grant activities). DISCUSSION: As the first published comparison of EBP reach outcomes between financing strategies, our findings can help guide state and federal policy related to financing strategies for implementing EBPs that reduce youth substance use. Future work should explore contextual conditions under which different financing strategies can support the widespread implementation of EBPs for substance use disorder treatment

Comparing organization-focused and state-focused financing strategies on provider-level reach of a youth substance use treatment model: a mixed-method study

Abstract Background Financial barriers in substance use disorder service systems have limited the widespread adoption—i.e., provider-level reach—of evidence-based practices (EBPs) for youth substance use disorders. Reach is essential to maximizing the population-level impact of EBPs. One promising, but rarely studied, type of implementation strategy for overcoming barriers to EBP reach is financing strategies, which direct financial resources in various ways to support implementation. We evaluated financing strategies for the Adolescent Community Reinforcement Approach (A-CRA) EBP by comparing two US federal grant mechanisms, organization-focused and state-focused grants, on organization-level A-CRA reach outcomes. Method A-CRA implementation took place through organization-focused and state-focused grantee cohorts from 2006 to 2021. We used a quasi-experimental, mixed-method design to compare reach between treatment organizations funded by organization-focused versus state-focused grants (164 organizations, 35 states). Using administrative training records, we calculated reach as the per-organization proportion of trained individuals who received certification in A-CRA clinical delivery and/or supervision by the end of grant funding. We tested differences in certification rate by grant type using multivariable linear regression models that controlled for key covariates (e.g., time), and tested threats to internal validity from our quasi-experimental design through a series of sensitivity analyses. We also drew on interviews and surveys collected from the treatment organizations and (when relevant) interviews with state administrators to identify factors that influenced reach. Results The overall certification rates were 27 percentage points lower in state-focused versus organization-focused grants (p = .01). Sensitivity analyses suggested these findings were not explained by confounding temporal trends nor by organizational or state characteristics. We did not identify significant quantitative moderators of reach outcomes, but qualitative findings suggested certain facilitating factors were more influential for organization-focused grants (e.g., strategic planning) and certain barrier factors were more impactful for state-focused grants (e.g., states finding it difficult to execute grant activities). Discussion As the first published comparison of EBP reach outcomes between financing strategies, our findings can help guide state and federal policy related to financing strategies for implementing EBPs that reduce youth substance use. Future work should explore contextual conditions under which different financing strategies can support the widespread implementation of EBPs for substance use disorder treatment