An HIV-1 risk assessment tool for women aged 15-49 in African countries: A pooled analysis across 15 nationally representative surveys.

BACKGROUND: Women in Africa disproportionately acquire HIV-1. Understanding which women are most likely to acquire HIV-1 can guide focused prevention with pre-exposure prophylaxis (PrEP). Our objective is to identify women at highest risk of HIV-1 and estimate PrEP efficiency at different sensitivity levels. METHODS: Nationally representative data were collected from 2015-2019 from 15 population-based household surveys. This analysis included women aged 15-49 who tested HIV-1 sero-negative or had recent HIV-1. Least absolute shrinkage and selection operator regression models were fit with 28 variables to predict recent HIV-1. Models were trained on the full population and internally cross-validated. Performance was evaluated using area under the receiver-operating-characteristic curve (AUC), sensitivity, and number needed to treat (NNT) with PrEP to avert one infection. RESULTS: Among 209,012 participants 248 had recent HIV-1 infection, representing 118 million women and 402,000 (95% CI: 309,000-495,000) new annual infections. Two variables were retained in the model: living in a subnational area with high HIV-1 viremia and having a sexual partner living outside the home. Full-population AUC was 0.80 (95% CI: 0.76-0.84); cross-validated AUC was 0.79 (95% CI: 0.75-0.84). At a sensitivity of 33%, up to 130,000 cases could be averted if 7.9 million women were perfectly adherent to PrEP; NNT would be 61. At a sensitivity of 67%, up to 260,000 cases could be averted if 25.1 million women were perfectly adherent to PrEP; the NNT would be 96. CONCLUSIONS: This risk assessment tool was generalizable, predictive, and parsimonious with tradeoffs between reach and efficiency.

Chapter 8: Searching for Life Beyond Earth.

The search for life beyond Earth necessitates a rigorous and comprehensive examination of biosignatures, the types of observable imprints that life produces. These imprints and our ability to detect them with advanced instrumentation hold the key to our understanding of the presence and abundance of life in the universe. Biosignatures are the chemical or physical features associated with past or present life and may include the distribution of elements and molecules, alone or in combination, as well as changes in structural components or physical processes that would be distinct from an abiotic background. The scientific and technical strategies used to search for life on other planets include those that can be conducted in situ to planetary bodies and those that could be observed remotely. This chapter discusses numerous strategies that can be employed to look for biosignatures directly on other planetary bodies using robotic exploration including those that have been deployed to other planetary bodies, are currently being developed for flight, or will become a critical technology on future missions. Search strategies for remote observations using current and planned ground-based and space-based telescopes are also described. Evidence from spectral absorption, emission, or transmission features can be used to search for remote biosignatures and technosignatures. Improving our understanding of biosignatures, their production, transformation, and preservation on Earth can enhance our search efforts to detect life on other planets.

Timing of Maternal COVID-19 Vaccine and Antibody Concentrations in Infants Born Preterm.

Importance: COVID-19 vaccine-derived antibodies in pregnant people may protect infants from severe infection in the first 6 months of life via transplacental antibody transfer. Few data exist on maternally derived SARS-CoV-2 antibodies in preterm compared with full-term infants in association with vaccination timing. Objective: To compare SARS-CoV-2 anti-Spike (anti-S) antibody levels in preterm and full-term infants in the context of vaccine dose timing before delivery. Design, Setting, and Participants: This prospective cohort study enrolled pregnant individuals and collected paired maternal and cord blood samples at delivery at the University of Washington between February 1, 2021, and January 31, 2023. Participants who had received at least 2 doses of a messenger RNA COVID-19 vaccine before delivery and did not have a history of prior COVID-19 infection or detectable anti-SARS-CoV-2 nucleocapsid antibodies were included. Exposures: Timing of the last vaccine dose and preterm or full-term gestational age at delivery. Main Outcomes and Measures: Paired maternal and cord samples were tested for anti-S antibody, and linear regression was used to evaluate associations between preterm delivery and anti-S antibody levels. Covariates included timing of last dose, number of doses, insurance status, and immunosuppressing medications. Results: A total of 220 participants (median [IQR] age, 34 [32-37] years; 212 [96.4%] female) with 36 preterm and 184 full-term deliveries were studied. Before delivery, 121 persons received 2 vaccine doses and 99 persons received 3 or more vaccine doses. The geometric mean concentration of maternal anti-S antibodies was 674 (95% CI, 577-787) after 2 doses and 8159 (95% CI, 6636-10 032) after 3 or more doses (P < .001). The cord anti-S antibody geometric mean concentration was 1000 (95% CI, 874-1144) after 2 doses and 9992 (95% CI, 8381-11 914) after 3 or more doses (P < .001). After adjustment for vaccine timing and number of doses before delivery, no association was found between preterm delivery and cord anti-S antibody levels (ß = 0.44; 95% CI, -0.06 to 0.94). Conclusions and Relevance: In this prospective cohort study of pregnant individuals with preterm and full-term deliveries, receipt of 3 or more compared with 2 doses of COVID-19 vaccine before delivery resulted in 10-fold higher cord anti-S antibody levels. Maternal antibody concentration appeared more important than delivery gestational age in determining cord anti-S antibody levels. The number of doses and timing considerations for COVID-19 vaccine in pregnancy should include individuals at risk for preterm delivery.

Exploring the similarities and differences of burn registers globally: Results from a data dictionary comparison study.

INTRODUCTION: Pooling and comparing data from the existing global network of burn registers represents a powerful, yet untapped, opportunity to improve burn prevention and care. There have been no studies investigating whether registers are sufficiently similar to allow data comparisons. It is also not known what differences exist that could bias analyses. Understanding this information is essential prior to any future data sharing. The aim of this project was to compare the variables collected in countrywide and intercountry burn registers to understand their similarities and differences. METHODS: Register custodians were invited to participate and share their data dictionaries. Inclusion and exclusion criteria were compared to understand each register population. Descriptive statistics were calculated for the number of unique variables. Variables were classified into themes. Definition, method, timing of measurement, and response options were compared for a sample of register concepts. RESULTS: 13 burn registries participated in the study. Inclusion criteria varied between registers. Median number of variables per register was 94 (range 28 - 890), of which 24% (range 4.8 - 100%) were required to be collected. Six themes (patient information, admission details, injury, inpatient, outpatient, other) and 41 subthemes were identified. Register concepts of age and timing of injury show similarities in data collection. Intent, mechanism, inhalational injury, infection, and patient death show greater variation in measurement. CONCLUSIONS: We found some commonalities between registers and some differences. Commonalities would assist in any future efforts to pool and compare data between registers. Differences between registers could introduce selection and measurement bias, which needs to be addressed in any strategy aiming to facilitate burn register data sharing. We recommend the development of common data elements used in an international minimum data set for burn injuries, including standard definitions and methods of measurement, as the next step in achieving burn register data sharing.

Working Towards Holistic Scar Assessment and Improved Shared Decision Making in Global Burn Care.

Cutaneous burn scars impact various aspects of life. Scar treatment is mainly evaluated on scar characteristics. Consensus is needed on which other outcomes to capture, ensuring they are relevant to patients, clinicians, and researchers. The aim of this study was to identify, discuss and analyze outcomes related to cutaneous burn scarring, incorporating the voice of patients and views of healthcare professionals. For this, a Delphi process consisting of two survey rounds and a consensus meeting was initiated. Burn scar-related outcomes were identified from an existing comprehensive list of 100 outcomes by an international panel of patients, healthcare professionals and researchers. Fifty-nine outcomes were identified from the Delphi process as related to scarring (≥60% votes). Outcomes less impactful in relation to scar outcomes included psychosocial issues, sense of normality, understanding of treatment, costs and systemic issues. To represent a holistic assessment of outcomes related to cutaneous burn scarring, this Delphi process established a battery of outcomes currently included in scar quality assessment tools, and an expanded set of less frequently considered outcomes. Future work in this area must include the patient voice from developing countries. This is essential to identify globally applicable outcomes related to scarring.

Differential transcript usage analysis incorporating quantification uncertainty via compositional measurement error regression modeling.

Differential transcript usage (DTU) occurs when the relative expression of multiple transcripts arising from the same gene changes between different conditions. Existing approaches to detect DTU often rely on computational procedures that can have speed and scalability issues as the number of samples increases. Here we propose a new method, CompDTU, that uses compositional regression to model the relative abundance proportions of each transcript that are of interest in DTU analyses. This procedure leverages fast matrix-based computations that make it ideally suited for DTU analysis with larger sample sizes. This method also allows for the testing of and adjustment for multiple categorical or continuous covariates. Additionally, many existing approaches for DTU ignore quantification uncertainty in the expression estimates for each transcript in RNA-seq data. We extend our CompDTU method to incorporate quantification uncertainty leveraging common output from RNA-seq expression quantification tool in a novel method CompDTUme. Through several power analyses, we show that CompDTU has excellent sensitivity and reduces false positive results relative to existing methods. Additionally, CompDTUme results in further improvements in performance over CompDTU with sufficient sample size for genes with high levels of quantification uncertainty, while also maintaining favorable speed and scalability. We motivate our methods using data from the Cancer Genome Atlas Breast Invasive Carcinoma data set, specifically using RNA-seq data from primary tumors for 740 patients with breast cancer. We show greatly reduced computation time from our new methods as well as the ability to detect several novel genes with significant DTU across different breast cancer subtypes.

A framework for the definition and interpretation of the use of surrogate endpoints in interventional trials.

Background: Interventional trials that evaluate treatment effects using surrogate endpoints have become increasingly common. This paper describes four linked empirical studies and the development of a framework for defining, interpreting and reporting surrogate endpoints in trials. Methods: As part of developing the CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) extensions for randomised trials reporting surrogate endpoints, we undertook a scoping review, e-Delphi study, consensus meeting, and a web survey to examine current definitions and stakeholder (including clinicians, trial investigators, patients and public partners, journal editors, and health technology experts) interpretations of surrogate endpoints as primary outcome measures in trials. Findings: Current surrogate endpoint definitional frameworks are inconsistent and unclear. Surrogate endpoints are used in trials as a substitute of the treatment effects of an intervention on the target outcome(s) of ultimate interest, events measuring how patients feel, function, or survive. Traditionally the consideration of surrogate endpoints in trials has focused on biomarkers (e.g., HDL cholesterol, blood pressure, tumour response), especially in the medical product regulatory setting. Nevertheless, the concept of surrogacy in trials is potentially broader. Intermediate outcomes that include a measure of function or symptoms (e.g., angina frequency, exercise tolerance) can also be used as substitute for target outcomes (e.g., all-cause mortality)-thereby acting as surrogate endpoints. However, we found a lack of consensus among stakeholders on accepting and interpreting intermediate outcomes in trials as surrogate endpoints or target outcomes. In our assessment, patients and health technology assessment experts appeared more likely to consider intermediate outcomes to be surrogate endpoints than clinicians and regulators. Interpretation: There is an urgent need for better understanding and reporting on the use of surrogate endpoints, especially in the setting of interventional trials. We provide a framework for the definition of surrogate endpoints (biomarkers and intermediate outcomes) and target outcomes in trials to improve future reporting and aid stakeholders' interpretation and use of trial surrogate endpoint evidence. Funding: SPIRIT-SURROGATE/CONSORT-SURROGATE project is Medical Research Council Better Research Better Health (MR/V038400/1) funded.

Interventions to improve vaccine coverage of pregnant women in Aotearoa New Zealand.

Introduction Maternal vaccination against influenza and pertussis protects mothers and babies from severe disease and is recommended and funded in Aotearoa New Zealand. Despite this, maternal vaccination uptake is low, varies by region and is inequitable, with Maori and Pacific mama (mothers) less likely to receive vaccination. Aim To determine what interventions currently exist to support and encourage maternal vaccination against influenza and pertussis and what changes and interventions could be implemented to improve coverage, with a focus on Maori and Pacific hapu mama (pregnant mothers). Methods Interviews with six participants with diverse roles in the vaccination workforce were conducted. Participants were involved in education, certification and supporting vaccinators, high-level strategising, and vaccination. Interviews aimed to determine what interventions currently exist for hapu mama, what changes need to be made to improve coverage and how Maori and Pacific people have been specifically engaged. Qualitative data analysis was used to determine themes. Results Participants identified that interventions must focus on prioritising and emphasising the importance of maternal vaccination, promoting collaboration and innovation, making interventions accessible, and empowering Maori- and Pacific-driven avenues to vaccination. To create positive foundations, participants identified the importance of building and maintaining trust and affording mothers' time and autonomy in vaccination. Discussion Healthcare professionals need to proactively engage hapu mama about vaccination and collaborate in service delivery. Interventions must be suitably accessible and allow for the autonomy of hapu mama over vaccination decisions. Equity should be considered at the foundation of vaccine interventions to improve the accessibility of vaccines to all communities.

A new national health system: the opportunity to address data quality issues in maternal immunisation coverage.

AIM: Maternal immunisation coverage is suboptimal in Aotearoa New Zealand. Our objective was to highlight discrepancies resulting from how maternal immunisation coverage for pertussis and influenza is measured in Aotearoa New Zealand. METHOD: A retrospective cohort study of pregnant people was undertaken using administrative datasets. Maternity and immunisation data from three sources (National Immunisation Register [NIR], general practice [GP], and pharmaceutical claims) were linked to determine the proportion of immunisation records not recorded in the NIR but captured in claims data, and to compare this with coverage data available from Te Whatu Ora - Health New Zealand. RESULTS: We found that while increasing numbers of maternal immunisations are being captured in the NIR, around 10% remain unrecorded on the NIR, but within claims datasets. CONCLUSION: Accurate maternal immunisation coverage data is important for public health action. Implementation of the whole-of-life Aotearoa Immunisation Register (AIR) is an important opportunity to improve completeness and consistency of maternal immunisation coverage reporting.

Definitions, acceptability, limitations, and guidance in the use and reporting of surrogate end points in trials: a scoping review.

OBJECTIVE: To synthesize the current literature on the use of surrogate end points, including definitions, acceptability, and limitations of surrogate end points and guidance for their design/reporting, into trial reporting items. STUDY DESIGN AND SETTING: Literature was identified through searching bibliographic databases (until March 1, 2022) and gray literature sources (until May 27, 2022). Data were thematically analyzed into four categories: (1) definitions, (2) acceptability, (3) limitations and challenges, and (4) guidance, and synthesized into reporting guidance items. RESULTS: After screening, 90 documents were included: 79% (n = 71) had data on definitions, 77% (n = 69) on acceptability, 72% (n = 65) on limitations and challenges, and 61% (n = 55) on guidance. Data were synthesized into 17 potential trial reporting items: explicit statements on the use of surrogate end point(s) and justification for their use (items 1-6); methodological considerations, including whether sample size calculations were informed by surrogate validity (items 7-9); reporting of results for composite outcomes containing a surrogate end point (item 10); discussion and interpretation of findings (items 11-14); plans for confirmatory studies, collecting data on the surrogate end point and target outcome, and data sharing (items 15-16); and informing trial participants about using surrogate end points (item 17). CONCLUSION: The review identified and synthesized items on the use of surrogate end points in trials; these will inform the development of the Standard Protocol Items: Recommendations for Interventional Trials-SURROGATE and Consolidated Standards of Reporting Trials-SURROGATE extensions.

Evidence of bacterial biofilms within acute wounds: a systematic review.

OBJECTIVE: The prevalence and role of biofilm formation in acute wounds has seldom been investigated. Understanding the presence of biofilm in acute wounds would allow earlier, biofilm-targeted management, thus decreasing the morbidity and mortality associated with wound infection, improving patient experience and potentially reducing healthcare costs. The purpose of this study was to summarise the evidence for biofilm formation within acute wounds. METHOD: We conducted a systematic literature review for studies which reported evidence of bacterial biofilm formation in acute wounds. An electronic search of four databases was carried out, without restrictions on date. The search terms included 'bacteria', 'biofilm', 'acute' and 'wound'. RESULTS: A total of 13 studies met the inclusion criteria. Of the studies, 69.2% showed evidence of biofilm formation within 14 days of acute wound formation, with 38.5% showing evidence of biofilm 48 hours after wound formed. CONCLUSION: The evidence from this review suggests that biofilm formation plays a greater role within acute wounds than previously considered.

Patient participation impacts outcome domain selection in core outcome sets for research: an updated systematic review.

OBJECTIVES: The importance of including patients, carers, and the public in health research is well recognized, including the need to consider outcomes in health care research that reflect the priorities of patients. Core outcome sets (COS) define the minimum set of outcomes that should be measured and reported in research of a given condition, determined through consensus among key stakeholders. The Core Outcome Measures in Effectiveness Trials Initiative undertakes an annual systematic review (SR) to identify newly published COS to update its online database of COS for research. The objective of this study was to assess the impact of patient participation on COS. STUDY DESIGN AND SETTING: SR methods used in previous updates were applied to identify research studies published or indexed in 2020 and 2021 (conducted as separate reviews) that report development of a COS, regardless of any specifications relating to condition, population, intervention, or setting. Studies were assessed according to published standards for COS development, and core outcomes extracted from study publications were categorized according to an outcome taxonomy and added to an existing database of core outcome classifications of all previously published COS. The effect of patient participation on core domains was examined. RESULTS: Searches identified 56 new studies published in 2020 and 54 in 2021. All studies met all four minimum standards for scope, and 42 (75%) of the 2020 studies and 45 (83%) of the 2021 studies met all three standards for stakeholders involved. However, only 19 (34%) of the 2020 studies and 18 (33%) of the 2021 studies met all four standards for the consensus process. COS that involved patients or their representatives are more likely to include life impact outcomes (239, 86%) than COS without patient participation (193, 62%). Physiological/clinical outcomes are almost always specified at a granular level, whereas life impact outcomes are often described at a higher level. CONCLUSION: This study adds to the body of evidence demonstrating the importance and impact of including patients, carers, and the public in COS development, in particular by demonstrating that the impact of interventions on patients' lives is more likely to be represented in COS that involve patients or their representatives. COS developers are encouraged to pay increased attention to methods and reporting relating to the consensus process. Further work is required to understand the appropriateness and rationale for the discrepancy in granularity levels between outcome domains.

Exploring the similarities and differences of variables collected by burn registers globally: protocol for a data dictionary review study.

INTRODUCTION: Burn registers can provide high-quality clinical data that can be used for surveillance, research, planning service provision and clinical quality assessment. Many countrywide and intercountry burn registers now exist. The variables collected by burn registers are not standardised internationally. Few international burn register data comparisons are completed beyond basic morbidity and mortality statistics. Data comparisons across registers require analysis of homogenous variables. Little work has been done to understand whether burn registers have sufficiently similar variables to enable useful comparisons. The aim of this project is to compare the variables collected in countrywide and intercountry burn registers internationally to understand their similarities and differences. METHODS AND ANALYSIS: Burn register custodians will be invited to participate in the study and to share their register data dictionaries. Study objectives are to compare patient inclusion and exclusion criteria of each participating burn register; determine which variables are collected by each register, and if variables are required or optional, identify common variable themes; and compare a sample of variables to understand how they are defined and measured. All variable names will be extracted from each register and common themes will be identified. Detailed information will be extracted for a sample of variables to give a deeper insight into similarities and differences between registers. ETHICS AND DISSEMINATION: No patient data will be used in this project. Permission to use each register's data dictionary will be sought from respective register custodians. Results will be presented at international meetings and published in open access journals. These results will be of interest to register custodians and researchers wishing to explore international data comparisons, and countries wishing to establish their own burn register.

Exploring what is important during burn recovery: a qualitative study investigating priorities of patients and healthcare professionals over time.

OBJECTIVES: This qualitative study aimed to investigate: (1) priorities of patients and healthcare professionals during recovery from a burn injury, (2) how priorities change over time and (3) how priorities map to outcomes currently reported in burns research. DESIGN: Semi-structured interviews were conducted. Interviews were audio recorded, transcribed and analysed thematically. SETTING, PARTICIPANTS: A total of 53 patients and healthcare professionals were recruited from four National Health Service (NHS) burn services across England and Wales across England and Wales. Patient participants (n=32) included adults, adolescents and parents of paediatric patients, with a variety of burn injuries in terms of severity and cause of burn injury. Healthcare professionals (n=21) were NHS staff members involved in burn care and included professionals with a range of clinical experience and roles (eg, nurses, surgeons, occupational therapists, physiotherapist, administration). RESULTS: Ten themes relating to priorities (outcomes) during recovery from a burn injury were identified for patients and professionals. Of those, six were identified for patients and professionals ('pain and discomfort', 'psychological well-being', 'healing', 'scarring', 'function', 'infection'), three were unique to professionals ('patient knowledge, understanding and support', 'sense of control', 'survival') and one was unique to patients ('uncertainty'). Results highlighted that importance of these priorities changes over time (eg, 'survival' was only a concern in the short term). Likewise, priorities differed between patients and professionals (eg, 'pain' was important to patients throughout their recovery, but not for professionals). Seven out of 10 themes overlapped with outcomes commonly assessed in burn research. CONCLUSION: Professionals' and patients' priorities (important outcomes) change over time after burn injury and differ between those groups. Burn care research should consider measuring outcomes at different time points during the recovery from a burn injury to accurately reflect complexity of burn recovery.

Research priority setting in plastic and reconstructive surgery: A systematic review.

BACKGROUND: The health research agenda has historically been led by researchers; however, their priorities may not necessarily align with those of patients, caregivers and clinicians. Research priority setting initiatives identify and prioritise topics which lack evidence. This is particularly important in plastic surgery, a speciality lacking high-quality evidence to definitively answer many common clinical questions. Research priorities direct research activity and funding, so their selection process must be representative and transparent. This review appraised all priority setting initiatives in plastic surgery using the reporting guideline for priority setting of health research (REPRISE). METHODS: OVID Medline, EMBASE, CINAHL and the James Lind Alliance (JLA) repository were searched (inception - 11/06/21) using search terms for 'research priority setting' and 'plastic and reconstructive surgery'. Dual-author screening and data extraction were conducted, according to PRISMA. RESULTS: Of 3899 de-duplicated citations, 17 were included. Most studies were conducted in national (14/17), high-income (16/17) settings. More priority setting initiatives focussed on burns (6/17) and hand surgery (4/17) than other subspecialties. The JLA (5/17) and qualitative (5/17) approaches were most used for prioritisation, followed by Delphi techniques (3/17), other surveys (3/17) and mixed methods (1/17). A minority included patient (8/17) or multi-disciplinary (8/17) stakeholders. Few reported strategies for implementing research priorities (6/17) or measuring their impact (2/17). CONCLUSIONS: Stakeholders from lower-income countries are underrepresented in priority setting initiatives for plastic surgery, despite the global burden of disease. Future studies should recruit more patient and multidisciplinary stakeholders, to achieve meaningful consensus. Clear implementation strategies are needed to maximise impact.

The association between gestational age and maternal adverse outcomes in patients undergoing trial of labor after cesarean.

BACKGROUND: Although successful trial of labor after cesarean (TOLAC) resulting in vaginal birth after cesarean (VBAC) can lead to improved maternal and neonatal outcomes, an unsuccessful TOLAC is associated with increased risk of uterine rupture, higher blood loss, and increased risk of infection. Data remain limited in terms of whether differences in gestational age of patients who attempt TOLAC affect maternal morbidity. Out objective was to examine the association between gestational age and maternal adverse outcomes in women undergoing trial of labor after cesarean. METHODS: This population-based cross-sectional study used birth data from the U.S. National Vital Statistics from 2014 to 2018. Women with liveborn singleton gestation who underwent TOLAC at 23 - 41 weeks' gestation were included in the analytic population. The primary outcome was a composite of maternal adverse outcomes: admission to the intensive care unit, blood transfusion, uterine rupture, or unplanned hysterectomy. Secondary outcomes were individual measures within the primary composite outcome. Outcomes were compared between patients who underwent TOLAC at term (37-41 weeks gestational age) and those who underwent TOLAC at preterm (23-36 weeks gestational age). Multivariable analyses adjusted for demographic and obstetric differences between the two groups. RESULTS: 455,284 patients met inclusion criteria for the study; 39,589 (8.7%) were at a preterm gestational age (GA) and 415,695 (91.3%) were at a term GA. The overall composite maternal adverse outcome was significantly higher for patients undergoing TOLAC at preterm GA (12.0 per 1,000 live births) compared to term GA (8.0 per 1,000 live births; aRR1.42; 95% CI 1.29-1.56). Among individual conditions within the primary composite outcome, preterm gestational age was associated with increased risk of admission to the intensive care unit, blood transfusion, and unplanned hysterectomy. CONCLUSIONS: In patients who underwent TOLAC, preterm gestational age was associated with increased risk of adverse maternal outcomes.

Scoping and targeted reviews to support development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: protocol.

INTRODUCTION: Using a surrogate endpoint as a substitute for a primary patient-relevant outcome enables randomised controlled trials (RCTs) to be conducted more efficiently, that is, with shorter time, smaller sample size and lower cost. However, there is currently no consensus-driven guideline for the reporting of RCTs using a surrogate endpoint as a primary outcome; therefore, we seek to develop SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) extensions to improve the design and reporting of these trials. As an initial step, scoping and targeted reviews will identify potential items for inclusion in the extensions and participants to contribute to a Delphi consensus process. METHODS AND ANALYSIS: The scoping review will search and include literature reporting on the current understanding, limitations and guidance on using surrogate endpoints in trials. Relevant literature will be identified through: (1) bibliographic databases; (2) grey literature; (3) handsearching of reference lists and (4) solicitation from experts. Data from eligible records will be thematically analysed into potential items for inclusion in extensions. The targeted review will search for RCT reports and protocols published from 2017 to 2021 in six high impact general medical journals. Trial corresponding author contacts will be listed as potential participants for the Delphi exercise. ETHICS AND DISSEMINATION: Ethical approval is not required. The reviews will support the development of SPIRIT and CONSORT extensions for reporting surrogate primary endpoints (surrogate endpoint as the primary outcome). The findings will be published in open-access publications.This review has been prospectively registered in the OSF Registration DOI: 10.17605/OSF.IO/WP3QH.

Protocol for the development of SPIRIT and CONSORT extensions for randomised controlled trials with surrogate primary endpoints: SPIRIT-SURROGATE and CONSORT-SURROGATE.

INTRODUCTION: Randomised controlled trials (RCTs) may use surrogate endpoints as substitutes and predictors of patient-relevant/participant-relevant final outcomes (eg, survival, health-related quality of life). Translation of effects measured on a surrogate endpoint into health benefits for patients/participants is dependent on the validity of the surrogate; hence, more accurate and transparent reporting on surrogate endpoints is needed to limit misleading interpretation of trial findings. However, there is currently no explicit guidance for the reporting of such trials. Therefore, we aim to develop extensions to the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) and CONSORT (Consolidated Standards of Reporting Trials) reporting guidelines to improve the design and completeness of reporting of RCTs and their protocols using a surrogate endpoint as a primary outcome. METHODS AND ANALYSIS: The project will have four phases: phase 1 (literature reviews) to identify candidate reporting items to be rated in a Delphi study; phase 2 (Delphi study) to rate the importance of items identified in phase 1 and receive suggestions for additional items; phase 3 (consensus meeting) to agree on final set of items for inclusion in the extensions and phase 4 (knowledge translation) to engage stakeholders and disseminate the project outputs through various strategies including peer-reviewed publications. Patient and public involvement will be embedded into all project phases. ETHICS AND DISSEMINATION: The study has received ethical approval from the University of Glasgow College of Medical, Veterinary and Life Sciences Ethics Committee (project no: 200210051). The findings will be published in open-access peer-reviewed publications and presented in conferences, meetings and relevant forums.

Protocol for a Global Burns Research Priority Setting Partnership to agree the most important unanswered questions in international burns care.

INTRODUCTION: Burns affect 11 million people globally and can result in long-term disability with substantial associated healthcare costs. There is limited research funding to support trials to provide evidence for clinical decision-making. Research prioritisation ensures that research focuses on the topics most important to stakeholders, addressing issues of research waste and evidence gaps. The aim of this project is to agree the global top 10 research priorities important to international patients, carers and clinicians from all income status countries. METHODS AND ANALYSIS: The Global Burns Research Priority Setting Partnership will use James Lind Alliance methods to establish the top 10 research priorities in global burns care. An initial international online multilingual survey will collect candidate research priorities from stakeholders. To increase equity in participation, the survey will also be available via the social media app WhatsApp. Additionally, interviews will be conducted. Data will be analysed to identify and collate research questions and to verify that the priorities are true clinical uncertainties. This list will then be ranked by stakeholders in order of importance via a second online survey. Finally, a consensus meeting will identify the top 10 research priorities. ETHICS AND DISSEMINATION: The University of Bristol Medical School Faculty Ethical Committee has approved this project. Research into burn care should be prioritised to ensure that funding is focused where most needed. This should be undertaken internationally, to ensure inclusion of the views of professionals and patients from lower income countries, where the incidence of thermal burns is highest. The involvement of the James Lind Alliance will ensure that the methodology is robust and that the patient voice is heard. The final top 10 priorities will be disseminated to funders, governments and researchers internationally to inform future global burns research.